Cirrosis BMJ

Cirrhosis
Straight to the point of care
Last updated: Feb 23, 2023

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 5
Classification 6
Case history 7
Diagnosis 9
Approach 9
History and exam 20
Risk factors 23
Investigations 25
Differentials 31
Criteria 32
Management 35
Approach 35
Treatment algorithm overview 44
Treatment algorithm 45
Emerging 49
Primary prevention 49
Secondary prevention 49
Patient discussions 50
Follow up 51
Monitoring 51
Complications 52
Prognosis 58
Guidelines 59
Diagnostic guidelines 59
Treatment guidelines 61
References 65
Images 81
Disclaimer 89
Cirrhosis Overview
Summary
Cirrhosis is the pathological end-stage of any chronic liver disease and most commonly results from chronic
hepatitis B and C, alcohol-related liver disease, and non-alcoholic fatty liver disease.
OVERVIEW
The main complications of cirrhosis are related to the development of liver insufficiency and portal
hypertension and include ascites, variceal haemorrhage, jaundice, portosystemic encephalopathy, acute
kidney injury and hepatopulmonary syndromes, and the development of hepatocellular carcinoma.
Once a patient with cirrhosis develops signs of decompensation, survival is significantly impaired.
Management of cirrhosis includes treating underlying liver disease, avoiding superimposed injury, and
managing complications. Timely referral for liver transplantation may be the only curative treatment option for
patients with decompensated cirrhosis.
Chronic liver disease and cirrhosis are significant causes of premature mortality.
Definition
Cirrhosis is a diffuse pathological process, characterised by fibrosis and conversion of normal liver
architecture to structurally abnormal nodules known as regenerative nodules.[1]
It can arise from a variety of causes and is the final stage of any chronic liver disease. It can lead to portal
hypertension, liver failure, and hepatocellular carcinoma. In general, it is considered to be irreversible in its
advanced stages, although there can be significant recovery if the underlying cause is treated.
Laparoscopic view of a cirrhotic liver

Courtesy of Dr Eugene Schiff and Dr Lennox Jeffers; used with permission
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Cirrhosis Theory
Epidemiology
Cirrhosis is an important cause of morbidity and mortality. An estimated 1.5 billion people globally
have chronic liver disease, with an age-standardised incidence of chronic liver disease and cirrhosis
THEORY
of 20.7/100,000.[2] In 2017, the global prevalence of compensated and decompensated cirrhosis was
estimated to be 112 million cases and 10.6 million cases, respectively. Cirrhosis caused more than 2.2
million deaths worldwide in 2017.[3]
Hospital admissions related to liver cirrhosis have increased in the US, from 3056 per 100,000 hospital
admissions in 2012 to 3757 per 100,000 hospital admissions in 2016.[4]
In the UK, cirrhosis is a significant cause of premature mortality and years of working life lost.[5]
The majority of cases of chronic liver disease are accounted for by viral hepatitis, alcohol-related liver
disease, and non-alcoholic fatty liver disease (NAFLD).[3] Cirrhosis due to viral hepatitis is decreasing
following implementation of successful vaccination programmes.[2] The prevalence of NAFLD has increased
in parallel with the obesity epidemic. If this trend continues it is expected that NAFLD will become the most
common cause of advanced liver disease and liver failure in the 21st century.[6] [7]
In the US, deaths attributable to hepatocellular carcinoma doubled from 5112 in 1999 to 11,073 in 2016.[8]
Hepatocellular carcinoma is the leading cause of death in patients with hepatitis C virus (HCV)-related
cirrhosis.[6]
In Europe, cirrhosis related to either viral infection (21% [13% HCV infection; 7% hepatitis B virus infection]),
or alcohol abuse (19%) are the main indications for liver transplant. Dual aetiology liver cirrhosis caused by
viral hepatitis and alcohol-related related liver disease (ArLD) represents 3% of cases.[9]
Aetiology
Any chronic liver disease may cause cirrhosis. The most common causes of cirrhosis are alcohol-related liver
disease, non-alcoholic fatty liver disease (NAFLD), and chronic viral hepatitis.[2] [10]
Other less common but important causes of cirrhosis include cholestatic, autoimmune, and metabolic liver
diseases.
When the aetiology of cirrhosis cannot be determined, it is considered 'cryptogenic'. The number of cases of
cryptogenic cirrhosis is significantly declining, in part because it is becoming more evident that many cases
are undiagnosed NAFLD.
The various causes of cirrhosis are listed below.
• Chronic viral hepatitis: hepatitis type C and B (with or without coexisting hepatitis D).
• Alcohol-related liver disease.
• Metabolic disorders: NAFLD, haemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency,
glycogen storage diseases, abetalipoproteinaemia.
• Cholestatic and autoimmune liver diseases: primary biliary cholangitis, primary sclerosing cholangitis,
autoimmune hepatitis, autoimmune cholangiopathy, immunoglobulin G4 (IgG4)-related disease.
• Biliary obstruction: mechanical obstruction, biliary atresia, cystic fibrosis.
• Hepatic venous outflow obstruction: Budd-Chiari syndrome, veno-occlusive disease, right-sided heart
failure.
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 23, 2023.
Cirrhosis Theory
• Drugs and toxins: amiodarone, methotrexate.
• Intestinal bypass: anastomosis of the jejunum to the ileum to shorten the length of the digestive tract in
class III obesity (body mass index ≥40 kg/m²), or to bypass a diseased area or blockage.
• Indian childhood cirrhosis (environmental copper poisoning, now rare).
THEORY
• Cryptogenic cirrhosis.
Pathophysiology
Hepatic fibrosis occurs in most patients with any type of chronic liver injury and may ultimately evolve into
cirrhosis with nodule formation.
The central event in hepatic fibrosis is the activation of hepatic stellate cells, which are the major source of
extracellular matrix. This leads to an accumulation of collagen types I and III in the hepatic parenchyma and
space of Disse.
The result of collagen deposition in the space of Disse is termed 'capillarisation' of the sinusoids, a process
in which the hepatic sinusoids lose their characteristic fenestration, thereby altering the exchange between
hepatocytes and plasma. With activation, hepatic stellate cells become contractile, which may be a major
determinant of increased portal resistance during liver fibrosis and cirrhosis.[11]
Laparoscopic view of a cirrhotic liver

This process is usually progressive and perturbs blood flow through the liver, thereby leading to increased
pressure within the portal venous system, as well as shunting blood away from the liver.
In addition to architectural changes causing a fixed component of portal hypertension, dynamic changes
to vascular tone resulting from an acute insult such as infection can influence portal pressure and result in
acute decompensation.
These changes lead to portal hypertension, which underlies the development of ascites and gastro-
oesophageal varices, and promotes the diversion of nutrient-carrying blood away from the liver, contributing
to hepatic encephalopathy.
Cirrhosis can lead to malnutrition, and most importantly sarcopenia. This leads to frailty, which is increasingly
recognised as a poor prognostic marker.[12] [13] Sarcopenia results from anorexia; hypermetabolism;
5
Cirrhosis Theory
hyperammonaemia; malabsorption due to intraluminal bile acid deficiency and/or chronic pancreatitis; altered
macronutrient metabolism; and micronutrient deficiencies.[14]
Inadequate synthesis due to hepatic impairment combined with a catabolic state results in
THEORY
hypoalbuminaemia, which can worsen complications of liver cirrhosis such as ascites.
Cirrhosis is a dynamic disease state with potential for reversibility if ongoing liver injury is halted. For
example, a patient with decompensated cirrhosis related to alcohol may clinically recompensate with
abstinence.[15] Similarly, serial biopsy studies have shown improvement of liver fibrosis following treatment
of chronic viral hepatitis.[16]
There is likely a point after which liver cirrhosis is considered irreversible and the only treatment at that
stage is liver transplantation. This may relate to the deposition of hepatic elastin, which is more resistant to
remodelling.[17]
Hepatocellular carcinoma
The pathophysiology of hepatocellular carcinoma is complex and multifactorial, but much more likely in the
context of cirrhosis than in a non-cirrhotic liver. The pro-oncogenic environment likely relates to a state of
chronic inflammation, telomere shortening, and cell senescence.
Additional oncogenic factors may relate to the underlying aetiology of liver disease, such as integration of
hepatitis B virus DNA into the host genome, resulting in pro-oncogenic mutations.[18]
Classification
Compensated cirrhosis
In compensated cirrhosis, biochemical, radiological, or histological findings consistent with the pathological
process of cirrhosis are present. Liver synthetic function is preserved and there is no evidence of
complications related to portal hypertension, such as ascites, gastro-oesophageal varices and variceal
bleeding, hepatic encephalopathy, and/or jaundice.
Decompensated cirrhosis
Cirrhosis is regarded as decompensated when there is evidence of the development of complications of
liver dysfunction with reduced hepatic synthetic function and portal hypertension including ascites, variceal
bleeding, hepatic encephalopathy, and/or jaundice. Decompensated cirrhosis is an umbrella term for a
spectrum of disease.
Cirrhosis Theory
THEORY
Icterus or jaundice
CDC. Dr Thomas F. Sellers/Emory University; used with permission
Case history
Case history #1
A 56-year-old man with a remote history of intravenous drug use presents to an initial visit complaining
of increased abdominal girth but denies jaundice. He drinks about 2 to 4 glasses of wine with dinner
and recalls having had abnormal liver enzymes in the past. Physical examination reveals spider naevi, a
palpable firm liver, mild splenomegaly, and shifting dullness consistent with the presence of ascites. Liver
function is found to be deranged with elevated aminotransferases (aspartate aminotransferase [AST]: 90
U/L, alanine aminotransferase [ALT]: 87 U/L), and the patient is positive for anti-hepatitis C antibody.
Case history #2
A 60-year-old woman with a past medical history of obesity, diabetes, and dyslipidaemia is noted to have
abnormal liver enzymes with elevated aminotransferases (ALT: 68 U/L, AST: 82 U/L), and normal alkaline
phosphatase and bilirubin. She denies significant alcohol consumption, and tests for viral hepatitis and
autoimmune markers are negative. An abdominal ultrasound reveals evidence of fatty infiltration of the
liver and slight enlargement of the spleen.
7
Cirrhosis Theory
Other presentations
In the early stages of cirrhosis, patients may be completely asymptomatic or complain of unexplained
fatigue, weakness, and/or weight loss.
THEORY
Liver enzymes may show only mild abnormality, if any.
Cirrhosis Diagnosis
Approach
The evaluation of a patient with suspected chronic liver disease and cirrhosis should begin with a detailed
history identifying the presence of risk factors for the different causes of cirrhosis. Patients should then
undergo a thorough physical examination in order to elicit any signs of chronic liver disease or complications
of cirrhosis.
A full panel of blood tests should be undertaken to establish the aetiology of chronic liver disease and to
ascertain the degree of disease severity. Liver imaging and screening endoscopy may be required.
Cirrhosis should be differentiated from non-cirrhotic conditions that can also lead to portal hypertension.
These include disorders such as constrictive pericarditis; vascular disorders such as Budd-Chiari syndrome,
portal vein and splenic vein thrombosis, and inferior vena cava obstruction; infectious agents such as
schistosomiasis; and sarcoidosis, nodular regenerative hyperplasia, and idiopathic portal hypertension, also
known as hepatoportal sclerosis. It is important to exclude exposure to substances that may cause portal
hypertension such as vitamin A intoxication, arsenic, and vinyl chloride toxicity.
Certain non-hepatic conditions may lead to the development of cirrhosis, as is the case with congestive
hepatopathy where congestive heart failure or cardiopulmonary disease lead to passive hepatic congestion,
which may lead to cirrhosis with time.
History
Presenting features
• Patients with cirrhosis may be asymptomatic or have non-specific constitutional symptoms, such as
fatigue, weakness, and weight loss, as well as recurrent infections and decreased libido.
• Symptoms of decompensation include:
• Abdominal distension due to ascites

• Vomiting of blood (haematemesis) and black stool (melaena) secondary to variceal
haemorrhage
DIAGNOSIS
• Altered mental status in hepatic encephalopathy
• Peripheral oedema
• Jaundice.
• Less common symptoms associated with pulmonary complications of portal hypertension include
dyspnoea on exertion. In patients with hepatopulmonary syndrome, platypnoea (shortness of
breath with sitting up) and orthodeoxia (deoxygenation with sitting up) are classically described;
patients may also develop clubbing and cyanosis. In portopulmonary hypertension patients may
develop syncope and chest pain/pressure.
Past medical history
• Check whether the patient has already been diagnosed with a chronic liver disease.
• Elicit any history of metabolic syndromes (diabetes, dyslipidaemia, obesity, hypertension) or
autoimmune disorders.
• Knowledge of the patient's past medical history may be helpful in identifying exposure to
hepatotoxic drugs.
• Patients should be asked about previous history of blood transfusion.
9
Cirrhosis Diagnosis
Drug history
• A complete drug history should be taken. Long-term use of methotrexate and amiodarone have
been implicated in the development of liver cirrhosis.[19]
• It is important to elicit the use of over-the-counter medications, vitamins, and herbal and dietary
supplementation, which may account for liver injury and may not be volunteered by the patient.[20]
Family history
• A family history of haemochromatosis, Wilson's disease, or alpha-1 antitrypsin deficiency provides

an important diagnostic clue.
• Chronic hepatitis B may be transmitted from mother to child, and asking about a family history of
viral hepatitis is important.
• Patients should be asked whether there is a family history of liver cirrhosis or hepatocellular
carcinoma as genetic susceptibility to liver injury is likely to play a role in risk.
• A history of metabolic risk factors in the family, particularly diabetes, should raise suspicion for non-
alcoholic fatty liver disease.
Social history and risk factors
• Patients should be asked sensitively about risk-taking behaviours, such as intravenous drug use,
unprotected intercourse, and tattoos.
• A detailed alcohol history should be taken in order to assess the patient's level and pattern of
alcohol consumption, and the number of units consumed per week should be documented.
• A thorough travel history should also be taken, including country of birth and ethnic origin of
parents, as well as a history of dental or surgical procedures performed abroad.
• A history of patterns of weight gain/loss should be taken.
Physical examination
Chronic liver disease and cirrhosis have a variety of physical characteristics, some of which are specific to
the underlying causative disease.
DIAGNOSIS
Hand and nail features
• Leukonychia (white nails) secondary to hypoalbuminaemia

• Polished nails secondary to excessive scratching in pruritus
• Palmar erythema
• Spider naevi
• Bruising
• Finger clubbing and cholesterol deposits in palmar creases in primary biliary cholangitis
• Dupuytren contracture in alcohol-related liver disease
• Cyanosis and finger clubbing in patients with hepatopulmonary syndrome.
Cirrhosis Diagnosis
Liver palms erythema of adult alcoholic

Dr P. Marazzi / Science Photo Library; used with permission
DIAGNOSIS
11
Cirrhosis Diagnosis
Preoperative view of a small finger flexion contracture

From the collection of Dr C.M. Rodner; used with permission
Facial features
• Telangiectasia
• Spider naevi
• Bruising
• Rhinophyma (lobulated and hypertrophied appearance of the nose secondary to sebaceous gland
hyperplasia)
DIAGNOSIS
• Parotid gland swelling

• Glossitis
• Skin has the appearance of a US dollar note ('paper-money' skin, randomly distributed thready
blood vessels)
• Seborrhoeic dermatitis
• Jaundiced sclerae
• Xanthelasma in primary biliary cholangitis.
Cirrhosis Diagnosis
Icterus or jaundice
Chest wall features
• Gynaecomastia (tender and firm enlarged breast bud) and loss of secondary sexual hair in men
• Breast atrophy in women.
Abdominal features
DIAGNOSIS
• Collateral circulation of the abdominal wall around the umbilicus (caput medusa)
• Bruising
• Hepatomegaly
• Splenomegaly
• Abdominal distension (particularly in the flanks) with shifting dullness and fluid thrill secondary to
ascites
• Hepatic bruit may be present with a vascular hepatoma
• Loss of secondary sexual hair and testicular atrophy in men.
13
Cirrhosis Diagnosis
Caput medusa: dilated superficial (superior and inferior)

epigastric veins radiating from a central large venous varix
Singh NK, Cheema U, Khalil A. Caput medusae. Case
Reports. 2010;2010:bcr0320102795; used with permission
DIAGNOSIS
Cirrhosis Diagnosis
Ascites. View of the abdomen of a female patient with alcoholic liver

disease and cirrhosis, showing swelling due to ascites (accumulation of
fluid in the peritoneal cavity), jaundice (yellowing of the skin), and bruising
Science Photo Library; used with permission
Other physical findings include hepatic fetor, muscle wasting, and peripheral oedema, and findings of
elevated right heart pressure such as elevated jugular venous pulse, increased split of the second heart
sound, and pulsatile liver in patients with portopulmonary hypertension.
DIAGNOSIS
Blood tests
All patients should receive a liver screen on presentation in order to identify the underlying cause and
severity of the cirrhosis.
Liver function tests
These tests show characteristic results depending on the nature of the hepatic insult.
• Aminotransferases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) levels

increase with hepatocellular damage and are usually elevated to some degree.
• Normal AST and ALT levels do not preclude the diagnosis of cirrhosis.[21]
• Aminotransferase levels bear little to no relationship to frequency of complications or
death.[22]
• ALT levels are greater than those of AST in most chronic liver diseases (except for alcohol-
related liver disease), but this finding may be reversed with progression of liver disease.
15
Cirrhosis Diagnosis
• An AST/ALT ratio of ≥1 is thought to be a predictor of cirrhosis.[23]
• Alkaline phosphatase and gamma-glutamyl transferase (GGT) levels increase in cholestasis
(resulting from primary biliary cholangitis and primary sclerosing cholangitis), with minimal
derangement of AST and ALT.
• Total bilirubin may be normal in patients with compensated cirrhosis, but as the cirrhosis
progresses, serum levels generally rise.
• It is important to recognise that these tests can be elevated in conditions other than liver disease.
For example, aminotransferases can be elevated in systemic diseases without primary liver
involvement, such as thyroid disease, muscle disorders (including cardiac ischaemia), and coeliac
disease. Alkaline phosphatase can be elevated with bone disease and total bilirubin will be
elevated in the setting of haemolysis.
Gamma-glutamyl transferase (GGT)
• Increase in this liver microsomal enzyme represents enzyme activation, which can be induced by
alcohol and certain drugs, and is also observed in metabolic liver disease/non-alcoholic fatty liver
disease (NAFLD).
• GGT is increased in cholestasis along with alkaline phosphatase (ALP).
• GGT is not significantly present in bone, such that concomitant elevated GGT and ALP indicates
the liver as the source of the ALP.
Albumin
• A decrease in serum albumin is a marker of hepatic synthetic dysfunction.

Electrolytes
• Hyponatraemia is a common finding in cirrhotic patients with associated ascites, and worsens as
the liver disease progresses.
• Hyperkalaemia is frequently observed in patients with cirrhosis (12% to 14% of those hospitalised
with cirrhosis).[24] It may indicate a poor prognosis, and can present a challenge to treat.[24] [25]
DIAGNOSIS
Full blood count and clotting
• Prolongation of the prothrombin time is a marker of hepatic synthetic dysfunction. (Although

prothrombin time can be prolonged in patients with vitamin K deficiency, it is readily reversed by
vitamin K replacement, which does not occur in the setting of hepatic dysfunction.)
• Coagulopathy in liver disease is complex. A prolonged prothrombin time does not necessarily mean
that the patient is at increased risk of bleeding, and correction of coagulopathy with blood products
outside the context of acute bleeding is not usually warranted.[26]
• The presence of thrombocytopenia (platelet count <150,000/microlitre) is the most sensitive and
specific laboratory finding for the diagnosis of cirrhosis in the setting of chronic liver disease and
results from portal hypertension with hypersplenism and platelet sequestration.[27]
Viral serology
• Presence of immunoglobulin G (IgG) antibodies to hepatitis C virus (confirmed with hepatitis C

virus RNA) is indicative of chronic hepatitis C infection.[28] Hepatitis C genotype is ordered once
infection is confirmed in order to guide treatment decisions.
Cirrhosis Diagnosis
• A detectable hepatitis B surface antigen (HBsAg) or viraemia on a highly sensitive hepatitis B DNA
assay indicates chronic hepatitis B infection.[28] Hepatitis B e-antigen/e-antibody, genotype, and
viral load should be measured to assess disease phase and guide further treatment.[28]
Iron studies
• The initial screening tests for haemochromatosis are total iron and TIBC, in order to calculate the
transferrin saturation (iron/TIBC), and serum ferritin. If the transferrin saturation and ferritin are
elevated, HFE genotyping is performed.[29]
Auto-antibody screen
• Auto-antibodies: antinuclear (ANA) and antismooth muscle (SMA) for autoimmune hepatitis;
antimitochondrial (AMA) for primary biliary cholangitis, more specifically the M2 antibody.
Serum immunoglobulins
• Assessment of serum immunoglobulins (IgA, IgG, and IgM) should be undertaken. Levels are
frequently elevated in patients with cirrhosis.[30]
Ceruloplasmin
• Serum ceruloplasmin is decreased in Wilson's disease.

Alpha-1 antitrypsin
• Approximately 15% of adults with alpha-1 antitrypsin deficiency develop cirrhosis.[31]

• Plasma alpha-1 antitrypsin levels are used as a screening test.
• Alpha-1 antitrypsin is an acute phase protein and may be elevated in inflammation.
• Further testing can be done to confirm the diagnosis with protein electrophoresis and phenotyping.
Alpha-fetoprotein
• The finding of elevated alpha-fetoprotein in a patient with cirrhosis should raise concern for the
DIAGNOSIS
development of hepatocellular carcinoma.[32] However, this tumour marker may also be elevated
on the basis of chronic liver disease and inflammation in the absence of hepatocellular carcinoma;
therefore, cross-sectional imaging is indicated to exclude the presence of hepatic lesions.
Endoscopy
An upper gastrointestinal endoscopy should be performed in selected patients with cirrhosis to screen
for oesophagogastric varices. The selection of these patients is based on non-invasive assessment
of their liver comprising platelet count and liver stiffness measurement.[33] In particular, patients with
compensated cirrhosis, who have a liver stiffness <20 kPa (as measured by transient elastography) and
platelet count >150 × 10⁹ cells/L, have a very low risk of having varices requiring treatment and can avoid
screening endoscopy.[33] In practice, however, many centres still offer baseline endoscopy to all patients
with liver cirrhosis. Meta-analysis has shown that ultra-thin gastroscopy may be a better tolerated method
for screening for varices where indicated.[34]
Patients with cirrhosis have historically been offered baseline upper gastrointestinal endoscopy
for screening of gastro-oesophageal varices at the time of diagnosis, and at 1- to 3-year intervals
thereafter.[35] However, guideline recommendations vary regarding screening intervals.
17
Cirrhosis Diagnosis
Primary prophylaxis (to prevent variceal bleeding) with either non-selective beta-blockers (propranolol,
nadolol, or carvedilol) or endoscopic variceal ligation (EVL), which requires several sessions to obliterate
varices, should be implemented if high-risk gastro-oesophageal varices are present.[36] One meta-
analysis reported that, for primary prevention of variceal bleeding, variceal-band ligation plus beta-blocker
resulted in a lower bleed rate compared with beta-blocker alone, but was also associated with a higher
adverse event rate.[37] Combination therapy is not currently recommended for primary prophylaxis.
Imaging
Signs of advanced cirrhosis may be detected using ultrasound, computed tomography (CT) scan,
and magnetic resonance imaging (MRI).[38] [39] The choice of imaging modality is dependent on the
pathology requiring investigation and physician preference.
Ultrasound with Doppler assessment of flow within the hepatic vasculature is the preferred test for the
initial evaluation of patients with suspected cirrhosis. It avoids radiation and contrast risks associated with
other imaging modalities.
If there are features suspicious for hepatocellular carcinoma on ultrasound, or if the patient has
unexplained abdominal pain, further evaluation with CT or MRI is recommended.[40]
Liver surface nodularity or a small liver with or without hypertrophy of the left/caudate lobe is detectable
on ultrasound, CT, and MRI. Signs of advanced cirrhosis may be detected using ultrasound, CT scan, or
MRI.
There is no radiological test sensitive enough to be used as the sole diagnostic tool for cirrhosis. However,
the radiological findings described above, in combination with a strong clinical suspicion, suffice for the
diagnosis of cirrhosis without the need for a confirmatory liver biopsy.
Imaging studies in patients with cirrhosis are an important tool for early detection of hepatocellular
carcinoma and are routinely used for surveillance of this condition.
Liver biopsy
DIAGNOSIS
Liver biopsy remains the most specific and sensitive test for the diagnosis of cirrhosis. However, it is
not necessary in patients with advanced liver disease and typical clinical, laboratory, and/or radiological
findings of cirrhosis, unless there is a need to determine the degree of inflammation.
In addition to confirming the diagnosis, liver biopsy may help to determine the aetiology of the underlying
liver disease, although this is not always possible as characteristic features of the primary insult (e.g.,
non-alcoholic fatty liver disease or autoimmune hepatitis) may no longer be detectable by the time the
procedure is carried out.
Liver biopsy is also helpful in diagnosing coexistent liver diseases (e.g. fatty liver and viral hepatitis,
haemochromatosis and viral hepatitis) and autoimmune overlap syndromes, as well as infiltrative and
infectious disorders.
Liver biopsy may help guide management of specific causes of chronic liver disease and cirrhosis. In
patients with cirrhosis and hepatic lesions, liver biopsy may be necessary in some cases in order to
differentiate benign lesions from primary liver cancer and metastatic liver disease.
Liver biopsy is associated with risk of bleeding, perforation, and pneumothorax, among other
complications.[41]
Cirrhosis Diagnosis
Severity scoring
The two most commonly used scoring systems to determine disease severity are the Child-Pugh-Turcotte
(CPT) and, more recently, the Model of End-Stage Liver Disease (MELD). Other scoring systems continue
to be evaluated.[42] [43] [44] [45]
Child-Pugh-Turcotte (CPT)
Based on the presence of ascites and hepatic encephalopathy, serum bilirubin, albumin, and clotting
(prothrombin time and international normalised ratio [INR]) and is divided into Child A, B, and C with
increasing disease severity.
Child-Pugh-Turcotte scoring system

From the collection of Dr Keith Lindor; used with permission
Model of End-Stage Liver Disease (MELD)
DIAGNOSIS
Electronically calculated from the serum bilirubin, sodium, creatinine, and clotting (INR and prothrombin
time) by a specific computer programme.[45] [46] This is the classification system used for the allocation
of livers for transplantation in the US.
Non-invasive tests
Serological and indirect markers of fibrosis have a good negative predictive value for cirrhosis, and are
often used in community settings to risk stratify patients with risk factors for liver disease.
Fibrosis markers
Several fibrosis markers have been assessed. Some of these use combinations of routinely collected
blood tests (e.g., NAFLD fibrosis score, fibrosis-4 [FIB-4], AST to platelet ratio index [APRI], AST/
ALT ratio). Others use specific molecular markers of fibrogenesis (e.g., enhanced liver fibrosis [ELF]).
The utility of these markers is predominantly for excluding severe fibrosis, with normal values being
reassuring. They do not perform well at differentiating intermediate stages of fibrosis.
Imaging techniques to detect fibrosis
19
Cirrhosis Diagnosis
Transient elastography is an ultrasound-based technique for detecting hepatic fibrosis and cirrhosis
without the need for liver biopsy.
As with non-invasive blood tests for fibrosis evaluation, transient elastography has best diagnostic
performance in excluding liver cirrhosis. The accuracy falls in intermediate stages of fibrosis. The Society
of Radiologists in Ultrasound recommends a low cut-off value to exclude significant fibrosis, and a high
cut-off value to indicate compensated advanced chronic liver disease.[47] Meta-analyses and prospective
studies of transient elastography report excellent diagnostic accuracy for the diagnosis of cirrhosis
(independent of the underlying disease) and the identification of fibrosis in patients with recurrent hepatitis
C after liver transplantation.[48] [49] [50] [51] [52] [53] [54] [55] [56]
As with transient elastography, acoustic radiation force impulse (ARFI) imaging employs ultrasound to
perform elastography.
Magnetic resonance elastography is effective in measuring fibrosis, but its application is limited by cost,
and it may not be possible if older metal prostheses are present in the patient. Staging of fibrosis may be
possible using gadoxetic acid-enhanced MRI.[57]
History and exam

Key diagnostic factors
presence of risk factors (common)
• Risk factors include alcohol misuse, intravenous drug use, unprotected intercourse, obesity, and blood
transfusion.
abdominal distension (common)

• Symptom of decompensated cirrhosis secondary to ascites in portal hypertension.
jaundice and pruritus (common)

DIAGNOSIS
• Suggestive of decompensated cirrhosis secondary to reduced hepatic excretion of conjugated bilirubin

into the biliary tree. Pruritus is secondary to impaired bile secretion.
Cirrhosis Diagnosis
Icterus or jaundice
blood in vomit (haematemesis) and black stool (melaena) (common)

• Symptoms of decompensated cirrhosis secondary to gastrointestinal haemorrhage from gastro-
oesophageal varices in portal hypertension.
hand and nail features (e.g., leukonychia, palmar erythema, spider naevi)
DIAGNOSIS
(common)
• Characteristic physical findings in the hands and nails in chronic liver disease include: leukonychia
(white nails) secondary to hypoalbuminaemia, polished nails secondary to excessive scratching in
pruritus, palmar erythema (redness of thenar and hypothenar eminences), spider naevi (blanch on
pressure and spider-like branches fill from a central arteriole), bruising, finger clubbing, and cholesterol
deposits in palmar creases in primary biliary cholangitis, and Dupuytren contracture in alcohol-related
liver disease.
21
Cirrhosis Diagnosis
Preoperative view of a small finger flexion contracture

facial features (e.g., telangiectasia, spider naevi, jaundiced sclera) (common)

• Characteristic physical findings in the face in chronic liver disease include: telangiectasia (red focal
lesions resulting from irreversible dilatation of small blood vessels in the skin), spider naevi (blanch
on pressure and spider-like branches fill from a central arteriole), bruising, rhinophyma, parotid gland
swelling, paper-money appearance of the skin (randomly distributed thready blood vessels), and red
tongue in alcohol-related liver disease; seborrhoeic dermatitis, jaundiced sclera, and xanthelasma
DIAGNOSIS
(yellow plaques on eyelids secondary to lipid deposition) in primary biliary cholangitis.
abdominal features (e.g., collateral circulation, hepatosplenomegaly,

distension) (common)
• Characteristic physical findings in the abdomen in chronic liver disease include: collateral circulation
of the abdominal wall around the umbilicus (caput medusa), bruising, hepatomegaly, splenomegaly,
abdominal distension (particularly in the flanks) with shifting dullness and fluid thrill secondary to
ascites, hepatic bruit (may be present with a vascular hepatoma), and loss of secondary sexual hair
and testicular atrophy in men.
altered mental status (uncommon)

• Symptom of decompensated cirrhosis secondary to portosystemic encephalitis.
Cirrhosis Diagnosis
Other diagnostic factors

constitutional symptoms (common)
• Patients with cirrhosis may be asymptomatic or have non-specific constitutional symptoms such as
fatigue, weakness, and weight loss.
lower extremity swelling (common)

• Symptom of decompensated cirrhosis secondary to peripheral oedema due to hypoalbuminaemia.
hepatic fetor (common)

• Sweet, putrid smell of the breath in decompensated cirrhosis secondary to portosystemic shunting.
muscle wasting (common)

• Common physical finding in chronic liver disease secondary to malnutrition and a hypercatabolic state.
peripheral oedema (common)

• Sign of decompensated cirrhosis secondary to salt retention and reduced hepatic synthetic function
leading to hypoalbuminaemia.
recurrent infections (uncommon)

• Can be present in patients with decompensated cirrhosis secondary to impaired cellular immunity.
decreased libido (uncommon)

• Symptom of decompensated cirrhosis secondary to hormonal changes and testicular atrophy, most
commonly seen in patients with alcohol-related liver disease and haemochromatosis.
chest wall features (e.g., gynaecomastia) (uncommon)

• Characteristic physical findings in the chest in chronic liver disease include gynaecomastia (tender and
firm enlarged breast bud) and loss of secondary sexual hair in men, and breast atrophy in women.
dyspnoea (uncommon)
DIAGNOSIS
• Dyspnoea on exertion is an uncommon symptom associated with pulmonary complications of portal
hypertension. In patients with hepatopulmonary syndrome, platypnoea and orthodeoxia are classically
described; patients may also develop clubbing and cyanosis. Dyspnoea may occur with hepatic
hydrothorax.
chest pain (uncommon)

• May occur in portopulmonary hypertension.
syncope (uncommon)
• May occur in portopulmonary hypertension.
Risk factors
Strong
23
Cirrhosis Diagnosis
alcohol misuse
• Alcohol-related liver disease, secondary to excessive alcohol consumption, is one of the most common
causes of cirrhosis in the developed world.[2] [10]
intravenous drug use

• People who inject drugs are at risk of contracting hepatitis B and C, both of which are known to cause
cirrhosis.
unprotected intercourse
• Intercourse without the use of barrier contraception puts people at risk of contracting hepatitis B and
C, both of which are known to cause cirrhosis.
obesity
• Non-alcoholic fatty liver disease, secondary to obesity and diabetes, is one of the most common
causes of cirrhosis.[2] [7]
country of birth
• Hepatitis B and C are endemic in certain global regions.
Weak
blood transfusion
• Hepatitis B or C, both of which are known causes of cirrhosis, may be contracted from contaminated
blood products, although this risk is extremely small due to the routine screening of blood donors and
products for viral hepatitides. Blood transfusion before 1992, or clotting factor transfusion before 1987,
are risk factors in the US.
tat tooing
• Tattooing is a risk factor when universal precautions are not adequately observed. Patients should be
counselled about this.
DIAGNOSIS
Cirrhosis Diagnosis
Investigations
1st test to order
Test Result
liver function tests usually deranged
• Aminotransferase (aspartate aminotransferase [AST] and alanine
aminotransferase [ALT]) levels increase with hepatocellular damage.
Normal AST and ALT levels do not preclude the diagnosis of
cirrhosis.[21] Aminotransferase levels bear little to no relationship to
frequency of complications or death.[22]
• ALT levels are greater than those of AST in most chronic liver
diseases (except for alcohol-related liver disease), but this finding
may be reversed with progression of liver disease. An AST/ALT ratio
of ≥1 is thought to be a predictor of cirrhosis.[23]
• Alkaline phosphatase and gamma-glutamyl transferase (GGT) levels
increase in cholestasis (resulting from primary biliary cholangitis and
primary sclerosing cholangitis), with minimal derangement of AST
and ALT.
• Total bilirubin may be normal in patients with compensated cirrhosis,
but as the cirrhosis progresses, serum levels generally rise.
gamma-glutamyl transferase (GGT) elevated
• Increase in this liver microsomal enzyme represents enzyme
activation, which can be induced by alcohol and certain drugs and
is also observed in metabolic liver disease/non-alcoholic fatty liver
disease (NAFLD).
• Increased in cholestasis along with alkaline phosphatase (ALP).
• GGT is not significantly present in bone, such that concomitant
elevated GGT and ALP indicates the liver as the source of the ALP.
serum albumin reduced
• A decrease in serum albumin is a marker of hepatic synthetic
dysfunction.
DIAGNOSIS
serum sodium reduced
• Hyponatraemia is a common finding in cirrhotic patients with
associated ascites, and worsens as the liver disease progresses.
serum potassium may be elevated
• Hyperkalaemia is frequently observed in patients with cirrhosis (12%
to 14% of those hospitalised with cirrhosis).[24] It may indicate a poor
prognosis, and can present a challenge to treat.[24] [25]
prothrombin time prolonged
• Prolongation of the prothrombin time is a marker of hepatic synthetic
dysfunction.
platelet count reduced
• The presence of thrombocytopenia (platelet count <150,000/
microlitre) is the most sensitive and specific laboratory finding for
the diagnosis of cirrhosis in the setting of chronic liver disease and
results from portal hypertension with hypersplenism and platelet
sequestration.[27]
25
Cirrhosis Diagnosis
Test Result
antibodies to hepatitis C virus present
• Presence of immunoglobulin G (IgG) antibodies to hepatitis C
virus (confirmed with hepatitis C virus-RNA) is indicative of chronic
hepatitis C infection.[28]
hepatitis B surface antigen ± hepatitis B DNA assay HBsAg present or
• A detectable HBsAg or viraemia on a highly sensitive hepatitis B DNA hepatitis B viraemia
detected
assay indicates chronic hepatitis B infection.[28]
• Hepatitis B e-antigen/e-antibody, genotype, and viral load should be
measured to assess disease phase and guide further treatment.
DIAGNOSIS
Cirrhosis Diagnosis
Other tests to consider
Test Result
total iron, total iron binding capacity (TIBC), transferrin elevated transferrin
saturation, and serum ferritin saturation and
elevated ferritin in
• The initial screening tests for haemochromatosis are total iron
haemochromatosis
and total iron binding capacity, in order to calculate the transferrin
saturation (iron/TIBC), and serum ferritin.
• If the transferrin saturation is elevated (>45%), further testing with
ferritin and possible genetic testing (C282Y and H63D mutation
analysis) should be undertaken.
• If the transferrin saturation and ferritin are elevated, HFE genotyping
is performed.[29]
antinuclear antibody present in autoimmune
hepatitis
• Tests for autoimmune hepatitis
antismooth muscle antibody present in autoimmune
hepatitis
antimitochondrial antibody present in primary biliary

cholangitis
• Specifically the M2 antibody.
serum immunoglobulins frequently elevated in
patients with cirrhosis
• IgA, IgG, and IgM levels should be evaluated.
serum ceruloplasmin low in Wilson's disease
plasma alpha-1 antitrypsin reduced in alpha-1

antitrypsin deficiency
• Approximately 15% of adults with alpha-1 antitrypsin deficiency
develop cirrhosis.[31]
• Plasma alpha-1 antitrypsin levels are used as a screening test.
• Alpha-1 antitrypsin is an acute phase protein and may be elevated in
inflammation.
• Further testing can be done to confirm the diagnosis with protein
DIAGNOSIS
electrophoresis and phenotyping.
alpha-fetoprotein normal or raised
• The finding of elevated alpha-fetoprotein in a patient with cirrhosis
should raise concern for the development of hepatocellular
carcinoma.[32] However, this tumour marker may also be elevated
on the basis of chronic liver disease and inflammation in the absence
of hepatocellular carcinoma; therefore, cross-sectional imaging is
indicated to exclude the presence of hepatic lesions.
abdominal ultrasound liver surface nodularity,
small liver, possible
• Signs of advanced cirrhosis may be detected using abdominal
hypertrophy of left/
ultrasound.
caudate lobe, ascites,
• Signs of portal hypertension: ascites, splenomegaly, increased
splenomegaly, increased
diameter of the portal vein (≥13 mm), or collateral vessels.
diameter of the portal vein
• In combination with a strong clinical suspicion, the above findings
(≥13 mm), or collateral
suffice for the diagnosis of cirrhosis without the need for a
vessels
confirmatory liver biopsy.
• A normal abdominal ultrasound does not exclude significant liver
disease.
27
Cirrhosis Diagnosis
Test Result
abdominal CT liver surface nodularity,
• Signs of advanced cirrhosis may be detected using abdominal cross-
sectional imaging.
caudate lobe, evidence
• Signs of portal hypertension: ascites, splenomegaly, collateral
of ascites, or collateral
circulation.
circulation
suffice for the diagnosis of cirrhosis without the need of a
abdominal MRI liver surface nodularity,
• Signs of advanced cirrhosis may be detected using MRI of the liver.
• Signs of portal hypertension: ascites, splenomegaly, collateral
caudate lobe, evidence
circulation.
of ascites, or collateral
circulation
suffice for the diagnosis of cirrhosis without the need of a
upper gastrointestinal endoscopy gastro-oesophageal
varices, portal
• Identifies the presence of gastro-oesophageal varices or portal
hypertensive gastropathy secondary to portal hypertension in patients hypertensive gastropathy
with chronic liver disease, thus aiding the diagnosis of cirrhosis.
• The Baveno VII criteria have been validated in several patient cohorts
(with compensated advanced chronic liver disease) and suggest
that screening endoscopy could be reserved for specific patients,
based on liver stiffness measurement (LSM) and platelet count
assessment.[33] In particular, patients with compensated cirrhosis,
who have a liver stiffness <20 kPa (as measured by transient
elastography) and platelet count >150 × 10⁹ cells/L, have a very low
risk of having varices requiring treatment and can avoid screening
endoscopy.[33] In practice, however, many centres still offer baseline
endoscopy to all patients with liver cirrhosis.
• In compensated patients with no or small varices at screening
endoscopy, expanded Baveno VI criteria recommend screening for
gastro-oesophageal varices at 1- to 3-year intervals thereafter.[58]
DIAGNOSIS
• Baveno VII consensus guidelines conclude that patients who avoid

screening endoscopy can be followed up by yearly repetition of
transient elastography and platelet count. If LSM increases (≥20
Cirrhosis Diagnosis
Test Result
kPa) or platelet count declines (≤150 x 109 L), these patients should
undergo screening endoscopy.[33]
•
Oesophageal varices in a patient with portal hypertension

From the collection of Douglas G. Adler, MD
liver biopsy architectural distortion of
the liver parenchyma with
• Liver biopsy remains the most specific and sensitive test for the
formation of regenerative
diagnosis of cirrhosis. However, it is not necessary in patients
nodules
with advanced liver disease and typical clinical, laboratory, and/or
radiological findings of cirrhosis unless there is a need to determine
the degree of inflammation.
DIAGNOSIS
• In addition to confirming the diagnosis, liver biopsy may help to
determine the aetiology of the underlying liver disease, although this
is not always possible as characteristic features of the primary insult
(e.g., non-alcoholic fatty liver disease or autoimmune hepatitis) may
no longer be detectable by the time the procedure is carried out.
• Liver biopsy is associated with risk of bleeding, perforation, and
pneumothorax, among other complications.[41]
non-invasive tests of liver elasticity serological marker
and ultrasound-based
• Ultrasound-based elastography is a useful tool for detecting hepatic
elastography evidence of
fibrosis and cirrhosis without the need for liver biopsy. Meta-analyses
fibrosis
and prospective studies of transient elastography report excellent
diagnostic accuracy for the diagnosis of cirrhosis (independent of the
underlying disease) and the identification of fibrosis in patients with
recurrent hepatitis C after liver transplantation.[48] [49] [50] [51] [52]
[53] [54] [55] [56]
• As with transient elastography, acoustic radiation force impulse
(ARFI) imaging employs ultrasound to perform elastography.
Magnetic resonance elastography is effective in measuring fibrosis,
but its application is limited by cost, and it may not be possible if older
29
Cirrhosis Diagnosis
Test Result
metal prostheses are present in the patient. Staging of fibrosis may
be possible using gadoxetic acid-enhanced MRI.[57]
• Several fibrosis markers have been assessed. Some of these use
combinations of routinely collected blood tests (e.g., non-alcoholic
fatty liver disease [NAFLD] fibrosis score, fibrosis-4 [FIB-4], AST
to platelet ratio index [APRI], AST/ALT ratio). Others use specific
molecular markers of fibrogenesis (e.g., enhanced liver fibrosis
[ELF]). The utility of these markers is predominantly for excluding
severe fibrosis, with normal values being reassuring. They do not
perform well at differentiating intermediate stages of fibrosis.
DIAGNOSIS
Cirrhosis Diagnosis
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Budd-Chiari syndrome • Abdominal pain, diarrhoea, • Doppler ultrasound and
and progressively worsening abdominal CT: absence of
ascites. hepatic vein filling.
• Abdominal CT: rapid contrast
clearing of caudate lobe.
Portal vein thrombosis • Signs and symptoms of the • Magnetic resonance

underlying cause such as (indirect) or direct
acute pancreatitis (severe angiography: normal hepatic
upper abdominal pain venous pressure gradient
radiating through to the (measure of portal pressure).
back, vomiting, absent • Doppler ultrasound and
bowel sounds, pyrexia, abdominal CT: portal vein
hypovolaemic shock, skin filling defect, absence of flow
discoloration periumbilically in the portal vein.
[Cullen's sign] and in the
flanks [Grey Turner's sign]),
ascending cholangitis
(pyrexia, malaise, rigors,
right upper quadrant pain,
jaundice, dark urine, and
pale stools), or abdominal
sepsis (pyrexia, abdominal
pain, signs of peritonism).
Splenic vein thrombosis • Signs and symptoms • Abdominal ultrasound and

of pancreatitis: severe CT: evidence of splenic vein
upper abdominal pain thrombosis.
radiating through to the • Magnetic resonance
back, vomiting, absent (indirect) or direct
DIAGNOSIS
bowel sounds, pyrexia, angiography: normal hepatic
hypovolaemic shock, venous pressure gradient
and skin discoloration (measure of portal pressure).
periumbilically (Cullen's
sign) and in the flanks
(Grey Turner's sign) in
acute pancreatitis; non-
specific abdominal pain
exacerbated by eating,
diarrhoea, steatorrhoea,
weight loss, and mild pyrexia
in chronic pancreatitis.
Nodular regenerative • No differentiating signs and • Liver biopsy: small

hyperplasia symptoms. regenerative nodules with
minimal or no fibrosis on
reticulin staining.
Idiopathic portal • No differentiating signs and • Liver biopsy: no evidence of

hypertension symptoms. cirrhosis.
(hepatoportal sclerosis)
31
Cirrhosis Diagnosis
Condition Differentiating signs / Differentiating tests

symptoms
Constrictive pericarditis • Raised jugular venous • ECG: tachycardia, atrial
pressure, tachycardia, and fibrillation, low-voltage
atrial fibrillation. QRS complexes, T-wave
• Heart sounds: quiet, third abnormalities.
heart sound (ventricular • Doppler ultrasound:
knock) present. ventricular filling
abnormalities.
Inferior vena cava (IVC) • Signs and symptoms of • Abdominal ultrasound

obstruction renal cell carcinoma: classic and CT: evidence of IVC
triad of haematuria, flank obstruction.
pain, and flank/abdominal
mass with weight loss and
hypertension.
Schistosomiasis • History of travel to endemic • Magnetic resonance

areas. (indirect) or direct
• Constitutional symptoms angiography: normal hepatic
of febrile illness: malaise, venous pressure gradient
rigors, sweating, weight (measure of portal pressure).
loss, anorexia, vomiting,
diarrhoea, headache,
muscular aches and
weakness, and abdominal
pain.
• Signs of febrile illness:
urticarial rash, pyrexia, and
lymphadenopathy.
Sarcoidosis • Lung involvement: dry cough • Chest x-ray findings are

and dyspnoea. dependent on the stage of
• Skin involvement: altered disease progression: hilar
pigmentation (hypo- lymphadenopathy, diffuse
DIAGNOSIS
or hyperpigmented); reticulonodular shadowing

maculopapular skin (parenchymal disease), and
lesions on face, back, and upper lobe fibrosis.
extremities; and erythema • Liver biopsy: non-
nodosum on legs. necrotising/caseating
• Eye involvement: anterior or granulomas.
posterior uveitis, dry eyes
(sicca), and glaucoma.
Vitamin A intoxication, • No differentiating signs and • History generally reveals

arsenic, and vinyl symptoms. exposure.
chloride toxicity
Criteria
Child-Pugh-Turcot te (CPT)[42] [43]
One of the most commonly used scoring systems to determine disease severity in cirrhosis.[42] [43] The
CPT score is based on the presence of ascites and hepatic encephalopathy, serum bilirubin, albumin, and
clotting (prothrombin time and international normalised ratio [INR]) and is divided into Child A, B, and C with
increasing disease severity.
Cirrhosis Diagnosis
Child-Pugh-Turcotte scoring system

Model of End-Stage Liver Disease (MELD)[46]

A more recent scoring system for the determination of severity in cirrhosis, the MELD score is electronically
calculated from the serum bilirubin, sodium, creatinine, and clotting (INR and prothrombin time) by a
specific computer programme.[45] [46] This is the classification system used for the allocation of livers for
transplantation in the US.
Acute kidney injury-hepatorenal syndrome (AKI-HRS)

Acute kidney injury (AKI) is an absolute increase in serum creatinine of ≥26.4 micromoles/L (≥0.3 mg/dL)
in less than 48 hours, or a percentage increase in serum creatinine of at least 1.5-fold from baseline in less
DIAGNOSIS
than 7 days, or a reduction in urine output of 0.5 mL/kg/h for more than 6 hours.[59] [60] [61] AKI has three
stages, as defined by the International Club of Ascites (ICA-AKI criteria):[62]
• Stage 1: an increase in serum creatinine ≥26.4 micromoles/L (≥0.3 mg/dL) or an increase in serum
creatinine ≥1.5-fold to twofold from baseline at diagnosis of AKI
• Stage 2: an increase in serum creatinine greater than twofold to threefold from baseline
• Stage 3: an increase of serum creatinine greater than threefold from baseline or serum creatinine ≥352
micromoles/L (≥4.0 mg/dL) with an acute increase ≥26.4 micromoles/L (≥0.3 mg/dL) or initiation of
renal replacement therapy.
European Association for the Study of the Liver (EASL) guidelines recommend using an adapted staging
system for AKI that splits AKI stage 1 into stage 1A and 1B according to a serum creatinine value of <133
micromoles/L (<1.5 mg/dL) or ≥133 micromoles/L (≥1.5 mg/dL), respectively.[59]
International Club of Ascites (ICA) diagnostic criteria for AKI-HRS:[60]
• Cirrhosis with ascites

• Diagnosis of AKI according to ICA-AKI criteria (stage 2 or 3 AKI, or stage 1 AKI that has progressed
despite close monitoring, removal of risk factors, and correction of hypovolaemia)
33
Cirrhosis Diagnosis
• No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with
albumin
• Absence of shock
• No current or recent use of nephrotoxic drugs (non-steroidal anti-inflammatory drugs, aminoglycosides,
or iodinated contrast media)
• No macroscopic signs of structural kidney injury. Structural kidney injury is indicated by proteinuria
(>500 mg/day), micro-haematuria (>50 red blood cells per high-power field), and/or abnormal renal
ultrasonography.
DIAGNOSIS
Cirrhosis Management
Approach
The mainstay of therapy for liver cirrhosis remains the treatment of the underlying chronic liver disease, when
possible, and prevention of superimposed hepatic insult, which could result in acute-on-chronic liver failure.
Early detection, control, and treatment of complications is essential; patients who develop complications
should be referred for liver transplant evaluation.
Patients should be advised of the necessity for adequate nutrition, regular exercise, and the avoidance of
hepatotoxins.[63]
Treatment of underlying chronic liver disease and prevention of

superimposed hepatic insult
As cirrhosis is the pathological end-stage of any chronic liver disease, it is essential to treat the underlying
causative condition in order to slow or halt the progression of cirrhosis. Oral direct-acting antivirals are
considered a first-line treatment for chronic hepatitis C virus infection. Regimens depend on the genotype
and presence or absence of cirrhosis.[64] Local guidance should be consulted. Antivirals, such as
tenofovir and entecavir, are indicated to treat cirrhosis due to chronic hepatitis B.[65] [66]
Superimposed hepatic insult may be prevented through the avoidance of alcohol and other hepatotoxic
drugs (e.g., non-steroidal anti-inflammatory drugs [NSAIDs] and high doses of paracetamol [>2 g/day]),
immunisation against hepatitis A and B for susceptible patients, management of metabolic risk factors,
maintenance of adequate nutrition, and regular exercise.
Monitoring for complications

Cirrhosis is associated with serious complications including portal hypertension causing ascites
(further complicated by spontaneous bacterial peritonitis and hepatic hydrothorax), gastro-oesophageal
varices and portosystemic encephalopathy, acute kidney injury and hepatopulmonary syndromes,
portopulmonary hypertension, acute-on-chronic liver failure, and hepatocellular carcinoma.
Prompt detection and treatment of these complications is essential in order to minimise related morbidity
and mortality. Imaging tests include:
• Abdominal ultrasound for the detection of ascites

• Upper gastrointestinal endoscopy for the detection of gastro-oesophageal varices
• Abdominal ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) for the
detection of hepatocellular carcinoma
Other specialised tests may be required depending on individual symptoms.
Ascites
The most common complication of cirrhosis.
Every patient with new-onset ascites should undergo a diagnostic paracentesis: cell count with
differential, albumin, and total protein should be measured in the ascitic fluid. Ascitic fluid should also be
MANAGEMENT
sent for culture and cytology.
The serum-ascites albumin gradient (SAAG) should be calculated: a SAAG of ≥11 g/L with low ascitic
fluid total protein is consistent with portal hypertension secondary to cirrhosis.
35
Ascites develops in part due to activation of the renin-angiotensin-aldosterone system, resulting in sodium
retention. Evidence suggests that severe dietary sodium restriction may be more harmful than beneficial,
and many clinicians advise a no-added-salt diet rather than a low-salt diet.[72] This means excluding
additional table salt being added to foods and avoidance of foods with high salt content, such as crisps
and some processed meals. This results in a moderate sodium restriction with daily intake of not more
than 5 to 6.5 g.
First-line choice of diuretic should be spironolactone due to its effects on aldosterone and maintaining
normal serum potassium.[72] Furosemide may be added in patients who do not respond. Renal function
and electrolytes should be monitored carefully when initiating diuretics and after dose escalation.
NSAIDs, ACE inhibitors, and other nephrotoxins should be avoided in patients with ascites.[61]
Large volume refractory ascites
Some patients may develop large volume ascites refractory to medical treatment because of lack of
efficacy, or unacceptable adverse effects or complications. These patients may require recurrent large-
volume paracentesis (LVP) and albumin replacement for symptom control.[73]
Patients not suitable for liver transplantation should be considered for transjugular intrahepatic
portosystemic shunt (TIPSS) placement.[74] Meta-analyses indicate that TIPSS is more effective
than paracentesis for control of refractory ascites, but is associated with a higher incidence of hepatic
encephalopathy.[74] [75] [76] [77] [78] [79] [80] Overall mortality does not appear to differ between the
two interventions, but TIPSS may confer a modest benefit with respect to transplant-free survival.[74]
[75] [76] [77] [78] [79] [80] A Cochrane systematic review and network meta-analysis reported that the
overall certainty (quality) of evidence was very low, primarily because of unclear or high risk of bias in
trials assessing interventions for the treatment of refractory ascites in patients with cirrhosis.[74] Disease
severity at the time of TIPSS placement is an important predictive factor for outcomes.[81]
The prognosis of patients with refractory ascites is poor. If TIPSS/transplantation are not viable options,
then long-term drain placement for intermittent small-volume paracentesis may be considered as a
palliative measure.[82] Prospective randomised controlled trials are warranted.
The use of vaptans (vasopressin V2-receptor antagonists) may have a slight beneficial effect on ascites
and hyponatraemia, but they do not reduce mortality, liver complications, or renal failure.[83] [84]
Gastro-oesophageal varices
Varices are present in 50% of patients with cirrhosis. Variceal bleeding is the most common lethal
complication of cirrhosis with an associated mortality of 20% at 6 weeks.[85] Patients with cirrhosis have
historically been offered upper gastrointestinal endoscopy for screening of gastro-oesophageal varices at
the time of diagnosis, and at 1- to 3-year intervals thereafter.[35] However, guideline recommendations
vary regarding screening intervals.
The Baveno VII criteria suggest that screening endoscopy could be reserved for a subgroup of patients,
based on liver stiffness measurement (LSM) and platelet count assessment.[33] In particular, patients
MANAGEMENT
with compensated cirrhosis, who have a liver stiffness <20 kPa (as measured by transient elastography)
and platelet count >150 × 10⁹ cells/L, have a very low risk of having varices requiring treatment and can
avoid screening endoscopy.[33] In practice, however, many centres still offer baseline endoscopy to all
patients with liver cirrhosis.
In compensated patients with no or small varices at screening endoscopy, expanded Baveno VI criteria
recommend screening for gastro-oesophageal varices at 1- to 3-year intervals thereafter.[58]
Baveno VII consensus guidelines conclude that patients who avoid screening endoscopy can be followed
up by yearly repetition of transient elastography and platelet count. If LSM increases (≥20 kPa) or platelet
count declines (≤150 x 109 L), these patients should undergo screening endoscopy.[33]
Oesophageal varices in a patient with portal hypertension

Primary prophylaxis of bleeding
Prophylaxis with either non-selective beta-blockers (propranolol, nadolol, or carvedilol) or endoscopic

variceal ligation (EVL), which requires several sessions to obliterate varices, should be implemented
if high-risk oesophageal varices are present, due to the increased risk of variceal bleeding.[36] High-
risk varices include small varices with red signs, medium or large varices irrespective of Child-Pugh
MANAGEMENT
classification, or small varices in Child-Pugh C patients.[59]
Non-selective beta-blockers
37
Advantages of non-selective beta-blockers include low cost and ease of administration. Once a
patient is on a non-selective beta-blocker, there is no need for repeat oesophagogastroduodenoscopy
(OGD), and haemodynamic responders to non-selective beta-blockers have a lower incidence of
decompensation and death. Disadvantages are that approximately 15% of patients may have absolute
or relative contraindications to therapy, and another 15% require dose reduction or discontinuation
attributed to common adverse effects (e.g., fatigue, weakness, and shortness of breath) that resolve upon
discontinuation, but that may discourage patients and their physicians from using these drugs.[86]
Monitoring haemodynamic response while treating a patient with beta-blockers is associated with a
lower risk of variceal bleeding, but large cohort randomised controlled trials are required to confirm these
findings.[87] There is ongoing debate regarding the safety of non-selective beta-blockers in patients
with cirrhosis and refractory ascites. The expanded Baveno VI criteria proposed that in patients with
refractory ascites and (i) systolic blood pressure <90 mmHg, or (ii) serum creatinine >133 micromoles/
L (>1.5 mg/dL), or (iii) hyponatraemia <130 millimoles/L, the beta-blocker should be reduced in dose or
even temporarily discontinued.[58] However, there is evidence to suggest that the risk of harm may not be
significant.[88] [89] [90] [91]
Endoscopic variceal ligation (EVL)
Advantages of EVL are that it can theoretically be done in the same session as screening endoscopy
and has few contraindications. Disadvantages include the risks associated with sedation, plus the risk of
causing dysphagia, oesophageal ulceration, strictures, and bleeding. Although the number of side effects
is greater with non-selective beta-blockers, the severity of side effects is greater with EVL, with reports of
deaths resulting from EVL-induced bleeding ulcers. In addition, because EVL is a local therapy that does
not act on the pathophysiology of portal hypertension, not only is it unable to prevent complications other
than variceal haemorrhage but also, after variceal eradication, surveillance endoscopies are necessary at
least annually to detect variceal recurrence, which approaches 90%.[86] Child-Pugh class C, ascites, or
low prothrombin index are all indicators for high risk of early bleeding following EVL.[92]
The choice of whether to use non-selective beta-blockers or EVL should be based on local resources
and expertise, patient preference and characteristics, contraindications, and adverse events.[58] A
meta-analysis that included 1023 patients compared prophylactic EVL with beta-blockers and found that
there was no difference between the treatments with regard to gastrointestinal haemorrhage, all-cause
mortality, or haemorrhage-related mortality. While there was a decrease in variceal haemorrhage with
EVL compared with beta-blockers (relative risk [RR] 0.72, 95% CI 0.4 to 0.96), variceal haemorrhage was
not significantly different between the two groups when only high-quality trials were considered (RR 0.84,
95% CI 0.60 to 1.17).[93] Subjective factors influence the physician's choice in selecting non-selective
beta-blockers versus EVL, as illustrated in an interview-based study in which gastroenterologists who
spent at least half their time performing endoscopy were more likely to choose EVL, whereas physicians
who had a less procedural-based practice were more likely to choose non-selective beta-blockers.[94]
Transjugular intrahepatic portosystemic shunts (TIPSS)
TIPSS are not recommended for primary prophylaxis of variceal haemorrhage.[86] Evidence obtained
from trials of prophylactic surgical shunt therapy show a significantly higher rate of encephalopathy and a
MANAGEMENT
tendency for a higher mortality in patients randomised to shunt surgery.[95]
Due to very low‐certainty evidence, conclusions cannot be drawn about the benefits and harms of
portosystemic shunts compared with endoscopic interventions for people with cirrhosis and previous
hypertensive portal bleeding (i.e., secondary prophylaxis).
Gastric varices
Gastric varices are present in about 20% of patients with cirrhosis and can present either as isolated
gastric varices or as gastro-oesophageal varices.[96] In the latter, the oesophageal varices extend below
the cardia into the lesser curvature of the stomach (type 1 gastro-oesophageal varices [GOV 1]) or
into the fundus (type 2 gastro-oesophageal varices [GOV 2]).[96] They have different physiology and
clinical characteristics compared with oesophageal varices. Gastric varices bleed less frequently but
more significantly than oesophageal varices. Bleeding is less directly related to the degree of portal
hypertension and more related to the size of the varix and wall tension.[96] There is little literature
regarding the management of gastric varices compared with oesophageal varices. Hence, most
recommendations are based on expert opinion.[96] Currently, non-selective beta-blockers are suggested
for primary prevention of variceal bleeding from GOV 2 or isolated gastric varices. Treatment for GOV 1
should follow the above guidance for oesophageal varices.
Acute variceal haemorrhage
An episode of acute variceal haemorrhage should be managed as a medical emergency with

intravascular volume support, blood transfusion (with the aim of keeping the haemoglobin around 70-80 g/
L [7-8 g/dL]), and a combination of endoscopic and pharmacological therapy.[97] [98]
Terlipressin (a vasopressin analogue), or somatostatin (or its analogue octreotide) should be initiated as
soon as a variceal bleed is suspected and continued for 3-5 days if it is confirmed.
Upper gastrointestinal endoscopy should be performed within 24 hours to confirm the diagnosis and allow
treatment with EVL or sclerotherapy.[99]
Short-term (up to 7 days) antibiotic prophylaxis should be instituted in all patients following a
gastrointestinal haemorrhage (regardless of the presence of ascites) as this has been shown to decrease
the rate of bacterial infections and increase survival.[100] Ceftriaxone is the first choice in patients with
decompensated cirrhosis, in those already on fluoroquinolone prophylaxis, and in hospital settings with
high prevalence of fluoroquinolone-resistant bacterial infections. Oral fluoroquinolones should be used in
the remaining patients.[101] [102]
Life-threatening bleeding may be controlled with a Sengstaken-Blakemore tube or a Danis stent until
haemostasis can be achieved endoscopically, or with TIPSS with or without embolisation.[103]
Malnutrition and sarcopenia

It is recommended that patients hospitalised with cirrhosis receive formal dietician assessment, and
steps should be taken to minimise the fasting period prior to procedures (e.g., by giving them a pre-
bedtime snack or early-morning snack if the procedure will be in the late afternoon).[104] Parenteral
supplementation may be required for those who cannot meet their nutritional intake needs orally.
MANAGEMENT
Recommended protein intake for adults with cirrhosis is 1.2 to 1.5 g/kg (ideal body weight) per day, and
1.2 to 2 g/kg (ideal body weight) per day if critically ill.
39
Hepatocellular carcinoma
See Hepatocellular carcinoma (Management approach) .
Spontaneous bacterial peritonitis

A peritoneal fluid absolute neutrophil count >250 cells/mm³ is the accepted criterion for the diagnosis for
spontaneous bacterial peritonitis.[59]
Treatment is with intravenous antibiotics, such as cefotaxime or a fluoroquinolone, and intravenous

human albumin solution. Albumin has been shown to reduce mortality in one randomised controlled
trial.[105]
All patients who have survived an episode of spontaneous bacterial peritonitis require lifelong secondary
antibiotic prophylaxis.
Patients with ascites and an ascitic fluid total protein level of ≤10 g/L are at high risk of developing
spontaneous bacterial peritonitis, and should be considered for primary antibiotic prophylaxis.[59] [106]
[107] High-quality evidence for this intervention is lacking and further trials are needed to establish
whether antibiotic prophylaxis for people with cirrhosis is beneficial.[108]
See Spontaneous bacterial peritonitis (Management approach) .
Hepatic hydrothorax
Occurs in approximately 5% to 10% of patients with cirrhosis, usually in patients with ascites.[109]
Hepatic hydrothorax may cause dyspnoea. Management is similar to that of ascites. In some patients,
long-term indwelling pleural catheters are required for symptomatic management.[110] Patients with
hepatic hydrothorax should be evaluated for liver transplantation.[111]
Portosystemic hepatic encephalopathy

Approximately 11% of patients with cirrhosis have hepatic encephalopathy at the time of cirrhosis
diagnosis.[112] Around 30% to 40% of patients with cirrhosis have an episode of hepatic encephalopathy
during their illness, and there is a 30% to 40% chance of recurrence in the following year.[113]
Hepatic encephalopathy is characterised by changes in consciousness, behaviour, and personality

with disorientation, drowsiness, forgetfulness, confusion, agitation, and eventual coma. Slurred speech,
asterixis (liver flap), increased muscle tone, and extensor plantar reflexes may be present.
Precipitating factors include gastrointestinal haemorrhage, constipation, diarrhoea and vomiting,

hypoglycaemia, and electrolyte imbalance; drugs (diuretics, sedatives) and medical procedures
(paracentesis, TIPSS); infection, anaemia, hypoxia, and hypotension. Serum ammonia levels are usually
elevated, but there is poor correlation between ammonia level and the degree of encephalopathy. There
appears to be an increased risk of hepatic encephalopathy with the use of proton-pump inhibitors.[114]
[115]
Treatment involves identification and correction of reversible precipitating factors and lactulose, used
MANAGEMENT
alone or in combination with antibiotics such as rifaximin.[116] [117] Dietary protein restriction is not
recommended.[118]
See Hepatic encephalopathy (Management approach) .
Acute kidney injury-hepatorenal syndrome (AKI-HRS)
In patients with cirrhosis, the causes of acute kidney injury can be hypovolaemia, acute tubular necrosis,
or hepatorenal syndrome with either acute kidney injury or acute kidney disease. Investigations to
determine the cause include a careful history, physical examination, blood biochemistry, microscopic
examination and chemical analysis of urine, select urine biomarkers and renal ultrasound.[61]
AKI-HRS (formerly known as type-1 hepatorenal syndrome) can be diagnosed if patients meet the
following criteria, as defined by the International Club of Ascites (ICA):[60]
• Cirrhosis with ascites

• Diagnosis of AKI according to ICA-AKI criteria (i.e., increase in serum creatinine ≥26.4 micromoles/
L [≥0.3 mg/dL] within 48 hours; or a percentage increase in serum creatinine ≥50% from baseline
which is known, or presumed, to have occurred within the previous 7 days); the American
Gastroenterological Association (AGA) also include a reduction of urine output to below 0.5 mL/kg/
h for >6 hours[61]
• No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with
albumin
• Absence of shock
• No current or recent use of nephrotoxic drugs (NSAIDs, aminoglycosides, or iodinated contrast
media)
• No macroscopic signs of structural kidney injury. Structural kidney injury is indicated by proteinuria
(>500 mg/day), microhaematuria (>50 red blood cells per high-power field), and/or abnormal renal
ultrasonography.
Measures can be taken to prevent AKI-HRS from developing in patients with cirrhosis, and include:[61]
• Advising patients to avoid alcohol

• Monitoring serum creatinine levels and electrolytes when diuretics are given and avoiding excessive
diuretics
• Avoiding large-volume paracentesis without albumin replacement
• Giving prophylactic antibiotics when infection is strongly suspected (investigations should include
diagnostic paracentesis to evaluate for spontaneous bacterial peritonitis)
• Avoiding use of non-selective beta-blockers and nephrotoxic medications (e.g., ACE inhibitors,
angiotensin-II receptor antagonists, and NSAIDs).
Once diagnosed, treatment of the precipitating cause should be initiated and any non-selective
beta-blockers, diuretics, and NSAIDs held or stopped. Fluid losses should be replaced and fluid
status monitored.[61] Vasoconstrictors and albumin are recommended in all patients and should be
expeditiously used. Terlipressin plus albumin should be considered as the first-line therapeutic option.
Noradrenaline (norepinephrine) can be an alternative to terlipressin. However, there are several limitations
MANAGEMENT
associated with its use. Midodrine plus octreotide can be an option when terlipressin or noradrenaline
are unavailable, but its efficacy is much lower than that of terlipressin.[59] [119] For further information,
see Hepatorenal syndrome (Management approach) .
41
Hyponatraemia
Patients with cirrhosis commonly develop hyponatraemia, especially with progression of liver disease.
Hyponatraemia is usually well tolerated.
Initial management consists of discontinuation of diuretic therapy once serum sodium <130 mEq/L. Fluid
restriction is usually necessary for serum sodium levels <115-120 mEq/L.
In patients with severe hyponatraemia treatment with vaptans may increase serum sodium, but their use
does not reduce mortality, liver complications or renal failure.[59] [120]
Hyperkalaemia
Hyperkalaemia is frequently observed in patients with cirrhosis (12% to 14% of those hospitalised with
cirrhosis).[24] It may indicate a poor prognosis and can present a challenge to treat.[24] [25] The standard
treatment of an insulin-glucose protocol to reduce serum potassium may be ineffective in the setting of
cirrhosis, and therefore adjunct treatments may be preferred.[121]
Hepatopulmonary syndrome
Results from portal hypertension and occurs in at least 5% of patients awaiting liver transplantation.[122]
Symptoms include dyspnoea and platypnoea. The diagnosis includes the finding of hypoxaemia with
increased alveolar-arterial gradient, orthodeoxia, and the determination of intrapulmonary vascular dilation
on contrast-enhanced echocardiography.
The presence of hepatopulmonary syndrome should prompt immediate evaluation for liver
transplantation. The condition usually resolves following liver transplantation.[123]
Portopulmonary hypertension
This complication is diagnosed when findings of unexplained pulmonary hypertension are present
in association with portal hypertension. Unlike hepatopulmonary syndrome, this condition may not
completely resolve following liver transplantation.
Patients with severe pulmonary hypertension that does not improve with the use of vasodilators such as
epoprostenol, bosentan, iloprost, or sildenafil are not candidates for liver transplantation in view of the
high risk of death associated with the procedure.
In one randomised controlled trial, macitentan, an endothelin-receptor antagonist, significantly reduced

pulmonary vascular resistance in patients with portopulmonary hypertension compared with placebo.[124]
Acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is a potentially reversible condition that can occur in people with
chronic liver disease. It is a heterogeneous syndrome; affected patients have features of hepatic failure
(coagulopathy, elevated bilirubin) and may also have extrahepatic organ failure (kidney, lung, brain,
or circulation). ACLF may be precipitated by alcohol, viral hepatitis, drug-induced liver injury, surgery,
ischaemia, or infection.
MANAGEMENT
Treatment includes resuscitation, treatment of the precipitating factor, support of failing organs, and
assessment for and early treatment of infection. Patients should be cared for in the intensive care unit.
Some patients may benefit from early liver transplantation.[125]
Treatment of shock in ACLF can be challenging. Society of Critical Care Medicine guidelines recommend
using albumin as a resuscitation fluid over other fluids, particularly when serum albumin is below 3 mg/
dL.[126] The guidelines also recommend aiming for a mean arterial pressure of 65 mmHg alongside
invasive haemodynamic monitoring. If vasopressors are required, noradrenaline is more effective than
dopamine in reversing hypotension. Low-dose vasopressin can be added to noradrenaline in patients
with ACLF who remain hypotensive despite fluid resuscitation. The possible mortality benefit with the
addition of vasopressin must be weighed against increased risk of digital ischaemia, however. As well as
addressing the treatment of shock, the guidelines also provide recommendations for managing endocrine,
haematological, pulmonary, and renal features of ACLF in the intensive care unit setting.[126] See Acute
liver failure (Management approach) .
Liver transplantation
Patients who develop complications of cirrhosis such as hepatocellular carcinoma or signs of
decompensation (ascites, jaundice, variceal haemorrhage, portal systemic encephalopathy,
hepatopulmonary syndrome or hepatorenal syndrome) should be referred for liver transplant evaluation
without delay. Transplant assessment may be a prolonged process and early referral is preferable. Some
patients with acute-on-chronic liver failure may benefit from early liver transplantation.[125]
Orthotopic liver transplantation remains the only curative treatment option for patients with
decompensated cirrhosis.
Systems of liver allocation vary. In the US, liver allocation is based on the Model for End-Stage Liver
Disease (MELD) score, which estimates the risk of 3-month mortality.[46] A survival benefit from
undergoing liver transplantation is seen when the MELD score is ≥15.
There is, however, a shortage of organ donors. In 2021, 9236 liver transplants were performed in the
US, with the current waiting list standing at 11,185 candidates.[127] As a result, a significant number of
patients die while waiting for an organ donor.
Palliative care
As cirrhosis is a life-limiting condition, palliative care should be offered alongside other curative therapies,
and may be relevant for patients with compensated cirrhosis and decompensated cirrhosis.[128] The
American Gastroenterological Association and the American Association for the Study of Liver Disease
have both published guidelines on palliative care in patients with cirrhosis. These promote advanced care
planning, assessment and management of symptoms (including pain, breathlessness, muscle cramps,
sexual dysfunction, insomnia, daytime sleepiness, fatigue, pruritus, anxiety, and depression), screening
for carer needs, and early liaison with local palliative care teams.[128] [129] Particular note is given to
chronic pain management in the setting of diminished liver function and novel treatments for refractory
ascites.[129]
MANAGEMENT
43
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Ongoing ( summary )
all patients
1st treatment of underlying chronic liver

disease and prevention of superimposed
hepatic insult
plus monitoring for complications
plus supportive and palliative care
adjunct sodium restriction and diuretic therapy for

ascites
2nd liver transplantation
2nd transjugular intrahepatic portosystemic

shunt (TIPSS)
MANAGEMENT
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Ongoing
all patients
1st treatment of underlying chronic liver

disease and prevention of superimposed
hepatic insult
» As cirrhosis is the pathological end-stage of

any chronic liver disease, it is essential to treat
the underlying causative condition.
» Oral direct-acting antivirals are considered a

first-line treatment for chronic hepatitis C virus
infection. Regimens depend on the genotype
and presence or absence of cirrhosis.[64] Local
guidance should be consulted. Antivirals such
as tenofovir and entecavir are indicated to treat
cirrhosis due to chronic hepatitis B.[65] [66]
» Superimposed hepatic insult may be prevented

through the avoidance of alcohol and other
hepatotoxic drugs (e.g., non-steroidal anti-
inflammatory drugs [NSAIDs] and high doses
of paracetamol [>2 g/day]), immunisation
against hepatitis A and B for susceptible
patients, management of metabolic risk factors,
maintenance of adequate nutrition, and regular
exercise.
plus monitoring for complications
Treatment recommended for ALL patients in
selected patient group
» Cirrhosis is associated with serious
complications including portal hypertension
causing ascites (further complicated by
spontaneous bacterial peritonitis and hepatic
hydrothorax), gastro-oesophageal varices
and portosystemic encephalopathy, acute
kidney injury and hepatopulmonary syndromes,
portopulmonary hypertension, hepatocellular
carcinoma, and acute-on-chronic liver failure.
» Prompt detection and treatment of these

complications is essential in order to minimise
related morbidity and mortality. Imaging tests
include: abdominal ultrasound for the detection
MANAGEMENT
of ascites; upper gastrointestinal endoscopy

in selected patients for the detection of gastro-
oesophageal varices; and abdominal ultrasound,
computed tomography (CT), or magnetic
resonance imaging (MRI) for the detection of
hepatocellular carcinoma.
45
Ongoing
» Other specialised tests may be required
depending on individual symptoms.
» See Oesophageal varices , Spontaneous

bacterial peritonitis , Hepatic encephalopathy
, Hepatorenal syndrome , Hepatocellular
carcinoma , and Acute liver failure .
plus supportive and palliative care
Treatment recommended for ALL patients in
» It is recommended that patients hospitalised
with cirrhosis receive formal dietician
assessment, and steps should be taken to
minimise the fasting period prior to procedures
(e.g., by giving them a pre-bedtime snack
or early-morning snack if the procedure will
be in the late afternoon).[104] Parenteral
supplementation may be required for those who
cannot meet their nutritional intake needs orally.
Recommended protein intake for adults with
cirrhosis is 1.2 to 1.5 g/kg (ideal body weight)
per day, and 1.2 to 2 g/kg (ideal body weight) per
day if critically ill.
» As cirrhosis is a life-limiting condition, palliative

care should be offered alongside other curative
therapies, and may be relevant for patients with
compensated cirrhosis and decompensated
cirrhosis.[128] The American Gastroenterological
Association and the American Association for
the Study of Liver Disease have both published
guidelines on palliative care in patients with
cirrhosis. These promote advanced care
planning, assessment and management of
symptoms (including pain, breathlessness,
muscle cramps, sexual dysfunction, insomnia,
daytime sleepiness, fatigue, pruritus, anxiety,
and depression), screening for carer needs, and
early liaison with local palliative care teams.[128]
[129] Particular note is given to chronic pain
management in the setting of diminished liver
function and novel treatments for refractory
ascites.[129]
adjunct sodium restriction and diuretic therapy for
ascites
Treatment recommended for SOME patients in
Primary options
MANAGEMENT
» spironolactone: 100 mg orally once daily

initially, titrate as needed every 3-5 days,
maximum 400 mg/day
OR
Ongoing
» spironolactone: 100 mg orally once daily

initially, titrate as needed every 3-5 days,
maximum 400 mg/day
-and-
» furosemide: 40 mg orally once daily initially,
titrate as needed every 3-5 days, maximum
160 mg/day
» Ascites is the most common complication of

cirrhosis.
» Every patient with new-onset ascites should

undergo a diagnostic paracentesis: cell count
with differential, albumin, and total protein should
be measured in the ascitic fluid. Ascitic fluid
should also be sent for culture and cytology.
» The serum-ascites albumin gradient (SAAG)

should be calculated: a SAAG of ≥11 g/L with
low ascitic fluid total protein is consistent with
portal hypertension secondary to cirrhosis.
» Treatment involves a no-added-salt diet (daily

intake of not more than 5 to 6.5 g) and the use
of diuretics.[72] First-line diuretic should be
spironolactone due to its effects on aldosterone
and maintaining normal serum potassium.
Furosemide may be added to patients who do
not respond to spironolactone.[72] Once-daily
dosing is typically preferred. The doses of both
oral diuretics can be increased simultaneously
every 3-5 days (maintaining the 100 mg to
40 mg ratio) if weight loss and natriuresis are
inadequate.[130] Serum sodium, potassium, and
creatinine should be monitored.
» Non-steroidal anti-inflammatory drugs

(NSAIDs), ACE inhibitors, and other
nephrotoxins should be avoided in patients with
ascites.[61]
2nd liver transplantation
» Patients who develop complications of

cirrhosis such as hepatocellular carcinoma or
signs of decompensation (ascites, jaundice,
variceal haemorrhage, hepatopulmonary
syndrome, hepatic hydrothorax, portal systemic
encephalopathy, or hepatorenal syndrome)
should be referred for liver transplant evaluation
without delay. Transplant assessment may
MANAGEMENT
be a prolonged process and early referrals

are preferable. Some patients with acute-on-
chronic liver failure may benefit from early liver
transplantation.[125]
47
Ongoing
» Orthotopic liver transplantation remains the
only curative treatment option for patients with
decompensated cirrhosis.
» A survival benefit from undergoing liver

transplantation is seen when the Model of End-
Stage Liver Disease (MELD) score is ≥15.
2nd transjugular intrahepatic portosystemic
shunt (TIPSS)
» Patients not suitable for liver transplantation

should be considered for transjugular
intrahepatic portosystemic shunt (TIPSS)
placement.[74]
» Meta-analyses indicate that TIPSS is more

effective than paracentesis for control of
refractory ascites, but is associated with a higher
incidence of hepatic encephalopathy.[74] [75]
[76] [77] [78] [79] [80] Overall mortality does not
appear to differ between the two interventions,
but TIPSS may confer a modest benefit with
respect to transplant-free survival.[74] [75] [76]
[77] [78] [79] [80] A Cochrane systematic review
and network meta-analysis reported that the
overall certainty (quality) of evidence was very
low, primarily because of unclear or high risk
of bias in trials assessing interventions for the
treatment of refractory ascites in patients with
cirrhosis.[74]
» Disease severity at the time of TIPSS

placement is an important predictive factor for
outcomes.[81]
MANAGEMENT
Emerging
Antifibrotic agents
There are many antifibrotic agents being considered for therapeutic use in chronic liver disease, (e.g.,
silymarin, transforming growth factor [TGF]-beta antagonists, endothelin-receptor antagonists, ACE inhibitors,
and relaxin). As it stands, there are no clinically approved therapies for liver fibrosis. Several are in phase
2 and 3 clinical trials, including drugs targeting the farnesoid X receptor, peroxisome proliferator-activated
receptors (PPARs), and chemokine receptors.[131] Macitentan, an endothelin-receptor antagonist, may
benefit patients with portopulmonary hypertension, but is not approved for this indication.[124]
Pentoxifylline
Pentoxifylline is a phosphodiesterase inhibitor with anti-inflammatory properties that lowers blood viscosity
and improves erythrocyte flexibility. Pro-inflammatory cytokines, including tumour necrosis factor (TNF)-alpha
and interleukin-6, are elevated in patients with cirrhosis in response to endotoxaemia. These cytokines lead
to a pro-inflammatory, hyperdynamic state. Pentoxifylline has been shown not only to decrease levels of TNF-
alpha but also to increase systemic vascular resistance, directly opposing splanchnic vasodilation without
precipitating an increase in the pressure in the portal venous system. In a randomised placebo-controlled
trial of patients with advanced cirrhosis, pentoxifylline reduced the risk of complications, including bacterial
infections, renal insufficiency, hepatic encephalopathy, and gastrointestinal haemorrhage, compared with
placebo.[132] It did not improve short-term mortality.[132] Pentoxifylline added to the standard care of volume
expansion with albumin and vasoconstriction appeared to be safe in a small randomised controlled trial of
patients with type-1 hepatorenal syndrome, but further large-scale prospective studies are needed to validate
the efficacy of this treatment.[133]
Cyanoacrylate injection
Although a single study suggested that cyanoacrylate injection is more effective than propranolol in
preventing first bleeding in patients with large type 2 gastro-oesophageal varices or isolated gastric varices,
there were no differences in survival, and further research is necessary.[33]
Primary prevention
Methods of primary prevention include:
• Prevention strategies aimed at reducing excessive alcohol consumption, intravenous drug use, and
unprotected intercourse
• Vaccination programmes for hepatitis B
• Public health strategies to control the rising incidence of obesity and diabetes
• Screening patients with risk factors for liver disease with non-invasive markers of liver fibrosis to
identify liver disease before cirrhosis develops
• Treatment of any underlying chronic liver disease to prevent the progression to cirrhosis
• Appropriate screening of family members of patients with cirrhosis secondary to haemochromatosis or
Wilson’s disease
• See Haemochromatosis (screening) and Wilson’s disease (screening)

• Screening of blood donors and products for viral hepatitides.
MANAGEMENT
Secondary prevention
The following secondary preventive strategies are aimed at minimising the level of superimposed hepatic
insult in an established cirrhotic liver:
49
• Treatment of any underlying chronic liver disease

• Avoidance of alcohol and other hepatotoxins such as non-steroidal anti-inflammatory drugs and high
doses of paracetamol (>2 g/day)
• Immunisation against hepatitis A and B for susceptible patients.
• In particular, the US Advisory Committee on Immunization Practices recommends that all

patients with cirrhosis should be vaccinated against hepatitis A and B.[146]
There is some evidence to suggest that long-term treatment with beta-blockers (propranolol or carvedilol)
increases decompensation-free survival, compared with placebo, in patients with compensated cirrhosis and
clinically significant portal hypertension.[147]
Patient discussions
Patients with cirrhosis should be advised of the following in order to minimise any further insult to the liver:
• Avoidance of alcohol and other hepatotoxins such as non-steroidal anti-inflammatory drugs and
high doses of paracetamol (>2 g/day).
• Careful nutritional intake with adequate lean protein and a carbohydrate-based snack before bed.
Decompensated patients should be advised to adhere to a no-added-salt diet.[143] Patients with
compensated cirrhosis and obesity should be advised to lose weight.
• Attendance for immunisation against influenza and pneumococcus.
• Regular exercise. Exercise appears to be safe for patients with cirrhosis and can increase
endurance.[144] [145]
MANAGEMENT
Cirrhosis Follow up
Monitoring
Monitoring
FOLLOW UP
Patients with cirrhosis should be monitored every 6 to 12 months with laboratory tests (renal function/
electrolytes, liver function tests, albumin, full blood count, prothrombin time, alpha-fetoprotein) and
imaging studies (6 monthly abdominal ultrasound) to check for:
• Signs and symptoms of advanced liver disease

• Disease progression
• Development of complications of portal hypertension such as ascites, hepatic encephalopathy,
jaundice, and variceal bleeding.
All patients with cirrhosis, especially those with viral hepatitis (type B and C), alcohol-related liver disease,
and haemochromatosis, are at high risk of developing hepatocellular carcinoma and should undergo
surveillance with ultrasound, with or without alpha-fetoprotein, every 6 months.[136] In clinical practice,
computed tomography (CT) is used as a second-line diagnostic imaging modality. However, it may lack
accuracy in ruling out hepatocellular carcinoma (HCC); one meta-analysis found that if CT is used in the
detection of HCC of any size and stage, 22.5% of people with HCC would be missed, and 8.7% of people
without HCC would be unnecessarily treated. However, all included studies were judged to be at high risk
of bias, limiting the authors’ ability to confidently draw conclusions based on these results.[142]
51
Cirrhosis Follow up
Complications
Complications Timeframe Likelihood

FOLLOW UP
ascites variable high
The most common complication of cirrhosis. Treatment involves a no-added-salt diet and diuretics.
Evidence suggests that severe dietary sodium restriction may be more harmful than beneficial, and many
clinicians advise a no-added-salt diet rather than a low-salt diet.[72] This means excluding additional
table salt being added to foods and avoidance of foods with high salt content, such as crisps and some
processed meals. This results in a moderate sodium restriction with daily intake of not more than 5 to 6.5
g. First-line choice of diuretic should be spironolactone due to its effects on aldosterone. Furosemide may
be added in patients who do not respond. Renal function and electrolytes should be monitored carefully
when initiating diuretics and after dose escalation. Non-steroidal anti-inflammatory drugs, ACE inhibitors,
and other nephrotoxins should be avoided in patients with ascites.
Every patient with new-onset ascites should undergo a diagnostic paracentesis: cell count with differential,
albumin, and total protein should be measured in the ascitic fluid. Ascitic fluid should also be sent for
culture and cytology.
Patients with refractory ascites (maximum diuretic doses not sufficient to control ascites or unacceptable
adverse effects/complications with diuretic therapy) can be managed with large-volume paracentesis
(LVP) and albumin replacement for symptom control. Patients not suitable for liver transplantation should
be considered for transjugular intrahepatic portosystemic shunt (TIPSS) placement.[74] Meta-analyses
indicate that TIPSS is more effective than paracentesis for control of refractory ascites, but is associated
with a higher incidence of hepatic encephalopathy.[74] [75] [76] [77] [78] [79] [80] Overall mortality does
not appear to differ between the two interventions, but TIPSS may confer a modest benefit with respect
to transplant-free survival.[74] [75] [76] [77] [78] [79] [80] A Cochrane systematic review and network
meta-analysis reported that the overall certainty (quality) of evidence was very low, primarily because
of unclear or high risk of bias in trials assessing interventions for the treatment of refractory ascites in
patients with cirrhosis.[74] Disease severity at the time of TIPSS placement is an important predictive
factor for outcomes.[81]
Long-term abdominal drains may be used in the palliative care setting.[82] Prospective randomised
controlled trials are warranted.
The use of vaptans (vasopressin V2-receptor antagonists) may have a slight beneficial effect on ascites
and hyponatraemia, but they do not reduce mortality, liver complications, or renal failure.[83] [84]
gastro-oesophageal varices variable high
Varices are present in 50% of patients with cirrhosis, and variceal bleeding is the most common lethal
complication of cirrhosis with an associated mortality of 20% at 6 weeks.[85] Patients with cirrhosis have
historically been offered upper gastrointestinal endoscopy for screening of gastro-oesophageal varices at
the time of diagnosis, and at 1- to 3-year intervals thereafter.[35] However, guideline recommendations
vary regarding screening intervals. The Baveno VII criteria suggest that screening endoscopy could
be reserved for a subgroup of patients, based on liver stiffness measurement and platelet count
assessment.[33] In particular, patients with compensated cirrhosis, who have a liver stiffness <20 kPa (as
measured by transient elastography) and platelet count >150 × 10⁹ cells/L, have a very low risk of having
varices requiring treatment and can avoid screening endoscopy.[33] In practice, however, many centres
still offer baseline endoscopy to all patients with liver cirrhosis.
Prophylaxis of bleeding
Prophylaxis with either non-selective beta-blockers (propranolol, nadolol, or carvedilol) or endoscopic

variceal ligation (EVL), which requires several sessions to obliterate varices, should be implemented
if high-risk oesophageal varices are present, due to the increased risk of variceal bleeding.[36] High-
Cirrhosis Follow up

risk varices include small varices with red signs, medium or large varices irrespective of Child-Pugh
classification, or small varices in Child-Pugh C patients.[59] Isolated gastric varices or oesophageal
FOLLOW UP
varices extending below the cardia into the gastric fundus should also be considered for non-selective
beta-blockers for primary prophylaxis.[33]
Advantages of non-selective beta-blockers include low cost and ease of administration. In addition, once
a patient is on non-selective beta-blockers, there is no need for repeat oesophagogastrosduodenoscopy
(OGD), and haemodynamic responders to non-selective beta-blockers have a lower incidence of
decompensation and death. Disadvantages are that approximately 15% of patients may have absolute
or relative contraindications to therapy, and another 15% require dose reduction or discontinuation
attributed to common adverse effects (e.g., fatigue, weakness, and shortness of breath) that resolve upon
discontinuation, but that may discourage patients and their physicians from using these drugs.[86]
Monitoring haemodynamic response while treating a patient with beta-blockers is associated with a
lower risk of variceal bleeding, but large cohort randomised controlled trials are required to confirm these
findings.[87]
There is ongoing debate regarding the safety of non-selective beta-blockers in patients with cirrhosis
and refractory ascites. The expanded Baveno VI criteria proposed that in patients with refractory ascites
and (i) systolic blood pressure <90 mmHg, or (ii) serum creatinine >133 micromoles/L (>1.5 mg/dL), or
(iii) hyponatraemia <130 millimoles/L, the beta-blocker should be reduced in dose or even temporarily
discontinued.[58] However, there is evidence to suggest that the risk of harm may not be significant.[88]
[89] [90] [91]
Endoscopic variceal ligation (EVL) is an alternative to non-selective beta-blockers. Advantages of

EVL are that it can theoretically be done in the same session as screening endoscopy and has few
contraindications. Disadvantages include the risks associated with sedation, plus the risk of causing
dysphagia, oesophageal ulceration, strictures, and bleeding. Although the number of side effects is greater
with non-selective beta-blockers, the severity of side effects is greater with EVL, with reports of deaths
resulting from EVL-induced bleeding ulcers. In addition, because EVL is a local therapy that does not act
on the pathophysiology of portal hypertension, not only is it unable to prevent complications other than
variceal haemorrhage but also, after variceal eradication, surveillance endoscopies are necessary at least
annually to detect variceal recurrence, which approaches 90%.[86] Child-Pugh class C, ascites, or low
prothrombin index are all indicators for high risk of early bleeding following EVL.[92]
The choice of whether to use non-selective beta-blockers or EVL should be based on local resources
and expertise, patient preference and characteristics, contraindications, and adverse events.[58] A
meta-analysis that included 1023 patients compared prophylactic EVL with beta-blockers and found that
there was no difference between the treatments with regard to gastrointestinal haemorrhage, all-cause
mortality, or haemorrhage-related mortality. While there was a decrease in variceal haemorrhage with EVL
compared with beta-blockers (relative risk [RR] 0.72, 95% CI 0.4 to 0.96), variceal haemorrhage was not
significantly different between the two groups when only high-quality trials were considered (RR 0.84, 95%
CI 0.60 to 1.17).[93] Subjective factors influence the physician's choice in selecting non-selective beta-
blockers versus EVL, as illustrated in an interview-based study in which gastroenterologists who spent at
least half their time performing endoscopy were more likely to choose EVL, whereas physicians who had a
less procedural-based practice were more likely to choose non-selective beta-blockers.[94]
Transjugular intrahepatic portosystemic shunts (TIPSS)
TIPSS are not recommended for primary prophylaxis of variceal haemorrhage.[86] Evidence obtained
from trials of prophylactic surgical shunt therapy show a significantly higher rate of encephalopathy and a
tendency for a higher mortality in patients randomised to shunt surgery.[95]
Management of acute variceal haemorrhage
An episode of acute variceal haemorrhage should be managed as a medical emergency with intravascular
volume support, blood transfusion (with the aim of keeping the haemoglobin around 70-80 g/L [7-8 g/dL]),
and a combination of endoscopic and pharmacological therapy.[98] Terlipressin (a vasopressin analogue),
53
Cirrhosis Follow up

or somatostatin (or its analogue octreotide) should be initiated as soon as a variceal bleed is suspected
and continued for 3-5 days if it is confirmed. Upper gastrointestinal endoscopy should be performed within
FOLLOW UP
24 hours to confirm the diagnosis and allow treatment with EVL or sclerotherapy.[99]
Short-term (up to 7 days) antibiotic prophylaxis should be instituted in all patients following a
gastrointestinal haemorrhage (regardless of the presence of ascites) as this has been shown to decrease
the rate of bacterial infections and increase survival.[100] Ceftriaxone is the first choice in patients with
decompensated cirrhosis, in those already on fluoroquinolone prophylaxis, and in hospital settings with
high prevalence of fluoroquinolone-resistant bacterial infections. Oral fluoroquinolones should be used in
the remaining patients.[101] [102]
Life-threatening bleeding may be controlled with a Sengstaken-Blakemore tube or a Danis stent until
haemostasis can be achieved endoscopically, or with TIPSS with or without embolisation.[103]
malnutrition and sarcopenia variable high
It is recommended that patients hospitalised with cirrhosis receive formal dietician assessment, and
steps should be taken to minimise the fasting period prior to procedures (e.g., by giving them a pre-
bedtime snack or early-morning snack if the procedure will be in the late afternoon).[104] Parenteral
supplementation may be required for those who cannot meet their nutritional intake needs orally.
Recommended protein intake for adults with cirrhosis is 1.2 to 1.5 g/kg (ideal body weight) per day, and 1.2
to 2 g/kg (ideal body weight) per day if critically ill.
hepatocellular carcinoma variable high
Patients with cirrhosis, especially those with viral hepatitis (type B and C), alcohol-related liver disease,
and haemochromatosis, are at high risk of developing hepatocellular carcinoma and should therefore
undergo surveillance with ultrasound, with or without alpha-fetoprotein, every 6 months.[136] Alpha-
fetoprotein cannot be recommended as a single test because it is neither sensitive nor specific for
hepatocellular carcinoma.
There are several different treatment options for hepatocellular carcinoma depending on its stage and the
degree of liver dysfunction. These include liver transplantation, surgical resection, radiofrequency ablation,
microwave ablation, and transarterial chemoembolisation. Advanced hepatocellular carcinoma may be
treated using sorafenib as palliative chemotherapy.
The Barcelona Clinic Liver Center (BCLC) classification for staging and treatment of hepatocellular
carcinoma is endorsed by the American Association for the Study of Liver Diseases and the European
Association for the Study of the Liver.[40] [136] The BCLC staging system correlates each of its stages
with treatment modalities and estimates the life expectancy based on prior studies.[136]
bleeding and thrombosis variable high
The haemostatic balance in liver disease is fragile, and the risk of bleeding/thrombosis is poorly predicted
by routinely used diagnostic tests, such as international normalised ratio (INR).
Patients with advanced liver disease often have thrombocytopenia due to hypersplenism. There is a
concurrent reduction in synthesis of clotting factors, leading to elevations in INR. Portal hypertension
or hyperfibrinolysis may give rise to bleeding. Lusutrombopag and avatrombopag are approved for
thrombocytopenia in adults with chronic liver disease undergoing invasive procedures.[140]
Anticoagulation is frequently withheld from hospitalised patients with cirrhosis because of concerns over
laboratory parameters. Thromboelastography may ultimately have a role in the evaluation of clotting in
patients with cirrhosis, but validated target levels are lacking.[141] It has been increasingly recognised that
patients with cirrhosis are at significant risk of venous thromboembolism (VTE), with typical incidence rates
of 0.5% to 1.9%, but in some studies considerably higher.[26] In hospitalised patients with cirrhosis who
Cirrhosis Follow up

otherwise meet standard guidelines for the use of VTE prophylaxis, standard anticoagulation prophylaxis
should be used.[26]
FOLLOW UP
The American Gastroenterological Association has published guidelines with recommendations
for achieving haemostasis, as well as the prevention and treatment of thrombosis, in patients with
cirrhosis.[26]
spontaneous bacterial peritonitis variable medium
A peritoneal fluid absolute neutrophil count >250 cells/mm³ is the accepted criterion for the diagnosis for
spontaneous bacterial peritonitis.[59]
Treatment is with intravenous antibiotics, such as cefotaxime or a fluoroquinolone, and intravenous human
albumin solution. Albumin has been shown to reduce mortality in one randomised controlled trial.[105]
All patients who have survived an episode of spontaneous bacterial peritonitis require lifelong secondary
antibiotic prophylaxis.[137]
Patients with ascites and an ascitic fluid total protein level of ≤10 g/L are at high risk of developing
spontaneous bacterial peritonitis and should be considered for primary antibiotic prophylaxis.[59] [106]
[107] High-quality evidence for this intervention is lacking and further trials are needed to establish
whether antibiotic prophylaxis for people with cirrhosis is beneficial.[108]
hepatic hydrothorax variable medium
Occurs in approximately 5% to 10% of cirrhotic patients, usually in patients with ascites.[109]
Hepatic hydrothorax may cause dyspnoea.
Management is similar to that of ascites. In some patients, long-term indwelling catheters are required
for symptomatic management. Patients with hepatic hydrothorax should be evaluated for liver
transplantation.[110]
portosystemic encephalopathy variable medium
Approximately 11% of patients with cirrhosis have hepatic encephalopathy at the time of cirrhosis
diagnosis.[112] Around 30% to 40% of patients with cirrhosis have an episode of hepatic encephalopathy
during their illness, and there is a 30% to 40% chance of recurrence in the following year.[113]
Hepatic encephalopathy is characterised by changes in consciousness, behaviour, and personality

with disorientation, drowsiness, forgetfulness, confusion, agitation, and eventual coma. Slurred speech,
asterixis (liver flap), increased muscle tone, and extensor plantar reflexes may be present.
Precipitating factors include gastrointestinal haemorrhage, constipation, diarrhoea and vomiting,

hypoglycaemia, and electrolyte imbalance; drugs (diuretics, sedatives) and medical procedures
(paracentesis, transjugular intrahepatic portosystemic shunt [TIPSS]); infection, anaemia, hypoxia, and
hypotension.
Serum ammonia levels are usually elevated, but there is poor correlation between ammonia level and the
degree of encephalopathy.
There appears to be an increased risk of hepatic encephalopathy with the use of proton-pump
inhibitors.[114] [115]
55
Cirrhosis Follow up

Treatment involves identification and correction of reversible precipitating factors and lactulose, used
alone or in combination with antibiotics such as rifaximin.[116] [117] [138] Dietary protein restriction is not
FOLLOW UP
recommended.[118]
acute kidney injury-hepatorenal syndrome (AKI-HRS) variable medium
AKI-HRS (formerly known as type-1 hepatorenal syndrome) can be diagnosed if patients meet the
following criteria, as defined by the International Club of Ascites: cirrhosis with ascites; diagnosis of AKI
according to ICA-AKI criteria (i.e., increase in serum creatinine ≥26.4 micromoles/L [≥0.3 mg/dL] within 48
hours, or a percentage increase in serum creatinine ≥50% from baseline which is known, or presumed,
to have occurred within the previous 7 days; [the American Gastroenterological Association (AGA) also
include a reduction of urine output to below 0.5 mL/kg/h for >6 hours]); no response after 2 consecutive
days of diuretic withdrawal and plasma volume expansion with albumin; absence of shock; no current or
recent use of nephrotoxic drugs (non-steroidal anti-inflammatory drugs, aminoglycosides, or iodinated
contrast media); no macroscopic signs of structural kidney injury (structural kidney injury is indicated by
proteinuria [>500 mg/day], microhaematuria [>50 red blood cells per high-power field], and/or abnormal
renal ultrasonography).[60] [61]
Measures can be taken to prevent AKI-HRS from developing in patients with cirrhosis, and include:[61]
Advising patients to avoid alcohol
Monitoring serum creatinine levels and electrolytes when diuretics are given and avoiding excessive
diuretics
Avoiding large-volume paracentesis without albumin replacement
Giving prophylactic antibiotics when infection is strongly suspected (investigations should include
diagnostic paracentesis to evaluate for spontaneous bacterial peritonitis)
Avoiding use of non-selective beta-blockers and nephrotoxic medications (e.g. ACE inhibitors, angiotensin
II receptors blockers, and NSAIDs).
Once diagnosed, treatment of the precipitating cause should be initiated and any non-selective beta-
blockers, diuretics and NSAIDS held or stopped. Fluid losses should be replaced and fluid status
monitored.[61]
Vasoconstrictors and albumin are recommended in all patients and should be expeditiously used.
Terlipressin plus albumin should be considered as the first-line therapeutic option. Noradrenaline
(norepinephrine) can be an alternative to terlipressin. However, there are several limitations associated
with its use. Midodrine plus octreotide can be an option when terlipressin or noradrenaline are unavailable,
but its efficacy is much lower than that of terlipressin.[59] [139]
hepatopulmonary syndrome variable low
Results from portal hypertension and occurs in at least 5% of patients awaiting liver transplantation.[122]
Symptoms include dyspnoea and platypnoea. The diagnosis includes the finding of hypoxaemia with
increased alveolar-arterial gradient, orthodeoxia, and the determination of intrapulmonary vascular
dilatation on contrast-enhanced echocardiography.
The presence of hepatopulmonary syndrome should prompt immediate evaluation for liver transplantation.
Cirrhosis Follow up

The condition usually resolves following liver transplantation.[123]
FOLLOW UP
portopulmonary hypertension variable low
This complication is diagnosed when findings of unexplained pulmonary hypertension are present in
association with portal hypertension.
Unlike hepatopulmonary syndrome, this condition may not completely resolve following liver
transplantation. Patients with severe pulmonary hypertension that does not improve with the use
of vasodilators such as epoprostenol, bosentan, iloprost, or sildenafil are not candidates for liver
transplantation in view of the high risk of death associated with the procedure.
In one randomised controlled trial, macitentan, an endothelin-receptor antagonist, significantly reduced

pulmonary vascular resistance in patients with portopulmonary hypertension compared with placebo.[124]
acute-on-chronic liver failure variable low
Acute-on-chronic liver failure (ACLF) is a potentially reversible condition that can occur in people with
chronic liver disease. It is a heterogeneous syndrome; affected patients have features of hepatic failure
(coagulopathy, elevated bilirubin) and may also have extrahepatic organ failure (kidney, lung, brain,
or circulation). ACLF may be precipitated by alcohol, viral hepatitis, drug-induced liver injury, surgery,
ischaemia, or infection. Treatment includes resuscitation, treatment of the precipitating factor, support of
failing organs, and assessment for and early treatment of infection. Patients should be cared for in the
intensive care unit. Some patients may benefit from early liver transplantation.[125]
Treatment of shock in ACLF can be challenging. Society of Critical Care Medicine guidelines recommend
using albumin as a resuscitation fluid over other fluids, particularly when serum albumin is below 3 mg/
dL.[126] The guidelines also recommend aiming for a mean arterial pressure of 65 mmHg alongside
invasive haemodynamic monitoring. If vasopressors are required, noradrenaline (norepinephrine) is more
effective than dopamine in reversing hypotension. Low-dose vasopressin can be added to noradrenaline
in patients with ACLF who remain hypotensive despite fluid resuscitation. The possible mortality benefit
with the addition of vasopressin must be weighed against increased risk of digital ischaemia, however. As
well as addressing the treatment of shock, the guidelines also provide recommendations for managing
endocrine, haematological, pulmonary, and renal features of ACLF in the intensive care unit setting.[126]
hypogonadism and feminisation variable low
Cirrhosis is associated with an oestrogenic/androgenic imbalance with reduced circulating levels of

testosterone and a relative increase in oestrogen. This leads to hypogonadism and feminisation in men.
Hypogonadism is characterised by testicular atrophy, impotence, and loss of libido, while gynaecomastia
and a female pattern of hair distribution are features of feminisation. Testicular atrophy and reduced libido
are most commonly seen in patients with underlying alcohol-related liver disease and haemochromatosis.
In women, this endocrine imbalance may cause amenorrhoea, infertility, acne vulgaris, and the
development of benign breast cysts.
hepatic osteodystrophy variable low
This is the term given to the combination of osteoporosis and osteomalacia associated with chronic liver
disease. Hepatic osteodystrophy most commonly occurs with underlying cholestatic disease (primary
biliary cholangitis and primary sclerosing cholangitis), but can occur with any chronic liver disease.
Osteoporosis results from reduced bone mineralisation and formation secondary to decreased activity of
57
Cirrhosis Follow up

osteoblasts. This leads to pathological fractures, particularly of the vertebrae; back pain; and kyphosis.
Osteomalacia is less common and results from reduced bone mineralisation. Its main symptom is bone
FOLLOW UP
pain. Vitamin D deficiency is a contributory factor in the development of hepatic osteodystrophy.
Prognosis
Overall prognosis
The overall median survival of patients with cirrhosis is approximately 10 years, but prognosis depends on
the stage of the disease.
The 10-year survival rate in patients with compensated cirrhosis is approximately 90%, and the likelihood of
transitioning to decompensated cirrhosis within 10 years is 50%.[134] The median survival time in patients
with decompensated cirrhosis is approximately 2 years.[134] [135]
In clinical practice, the Child-Pugh-Turcotte score and the Model for End-Stage Liver Disease score are the
most commonly used scoring systems for the prediction of mortality related to liver disease.
Four clinical stages of cirrhosis have been identified and each is associated with a different prognosis.[134]
Stage 1
• Patients without gastro-oesophageal varices or ascites have a mortality of approximately 1% per year.
Stage 2
• Patients with gastro-oesophageal varices (but no bleeding) and no ascites have a mortality of
approximately 4% per year.
Stage 3
• Patients with ascites with or without gastro-oesophageal varices (but no bleeding) have a mortality of
approximately 20% per year.
Stage 4
• Patients with gastrointestinal bleeding due to portal hypertension with or without ascites have a 1-year
mortality of 57%.
Cirrhosis Guidelines
Diagnostic guidelines
United Kingdom
Guidelines on the use of liver biopsy in clinical practice (ht tps://

www.bsg.org.uk/clinical/bsg-guidelines.html)
Published by: British Society of Gastroenterology Last published: 2020
Management of abnormal liver blood tests (ht tps://www.bsg.org.uk/clinical/

bsg-guidelines.html)
Liver disease (ht tps://www.nice.org.uk/guidance/qs152)

Published by: National Institute for Health and Care Excellence Last published: 2017
GUIDELINES
Cirrhosis in over 16s: assessment and management (ht tps://www.nice.org.uk/
guidance/ng50)
Europe
Non-invasive tests for evaluation of liver disease severity and prognosis

(ht tps://www.journal-of-hepatology.eu/article/S0168-8278(21)00398-6/fulltext)
Published by: European Association for the Study of the Liver Last published: 2021
Management of alcohol-related liver disease (ht tps://www.journal-of-

hepatology.eu/article/S0168-8278(18)30214-9/fulltext)
59
North America
Acute-on-chronic liver failure clinical guidelines (ht tps://gi.org/guidelines)

Published by: American College of Gastroenterology Last published: 2022
Adverse events associated with EGD and EGD-related techniques (ht tps://
www.asge.org/home/resources/key-resources/guidelines)
Published by: American Society for Gastrointestinal Endoscopy Last published: 2022
Informed consent for GI endoscopic procedures (ht tps://www.giejournal.org/

article/S0016-5107(21)01759-4/fulltext)
Diagnosis and treatment of alcohol‐associated liver diseases (ht tps://

www.aasld.org/publications/practice-guidelines)
GUIDELINES
Published by: American Association for the Study of Liver Diseases Last published: 2019
The role of elastography in the evaluation of liver fibrosis (ht tps://

www.gastro.org/guidelines)
Published by: American Gastroenterological Association Last published: 2017
Evaluation of abnormal liver chemistries (ht tps://gi.org/guidelines)

Asia
Evidence-based clinical practice guidelines for liver cirrhosis 2020 (ht tps://
link.springer.com/article/10.1007/s00535-021-01788-x)
Published by: Japanese Society of Gastroenterology Last published: 2021
Treatment guidelines
United Kingdom
National clinical guidelines for the treatment of HCV in adults (ht tps://
www.hps.scot.nhs.uk/guidance)
Published by: NHS National Services Scotland Last published: 2018
Liver disease (ht tps://www.nice.org.uk/guidance/qs152)

Cirrhosis in over 16s: assessment and management (ht tps://www.nice.org.uk/

guidance/ng50)
GUIDELINES
UK guidelines on the management of variceal haemorrhage in cirrhotic
patients (ht tps://www.bsg.org.uk/clinical/bsg-guidelines.html)
Europe
Clinical practice guidelines on prevention and management of bleeding and

thrombosis in patients with cirrhosis (ht tps://www.journal-of-hepatology.eu/
article/S0168-8278(21)02033-X/fulltext)
Clinical practice guidelines on the management of hepatic encephalopathy

(ht tps://www.journal-of-hepatology.eu/article/S0168-8278(22)00346-4/fulltext)
Management of alcohol-related liver disease (ht tps://www.journal-of-

hepatology.eu/article/S0168-8278(18)30214-9/fulltext)
Management of patients with decompensated cirrhosis (ht tps://www.journal-

of-hepatology.eu/article/S0168-8278(18)31966-4/fulltext)
Clinical practice guidelines on nutrition in chronic liver disease (ht tps://

www.ncbi.nlm.nih.gov/pmc/articles/PMC6657019)
61
International
Baveno VII: renewing consensus in portal hypertension (ht tps://

www.sciencedirect.com/science/article/pii/S0168827821022996)
Published by: Baveno Cooperation (endorsed by the European Last published: 2022
Association for the Study of the Liver)
Hepatic encephalopathy in chronic liver disease (ht tps://www.aasld.org/

practice-guidelines)
Published by: American Association for the Study of Liver Diseases; Last published: 2014
European Association for the Study of the Liver
GUIDELINES
North America
AGA clinical practice update on the evaluation and management of

acute kidney injury in patients with cirrhosis: expert review (ht tps://
aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/lt.26072)
Acute-on-chronic liver failure clinical guidelines (ht tps://gi.org/guidelines)

Palliative care and symptom-based management in decompensated cirrhosis

(ht tps://www.aasld.org/practice-guidelines)
Drug, herbal, and dietary supplement-induced liver injury (ht tps://

www.aasld.org/practice-guidelines)
GUIDELINES
Adverse events associated with EGD and EGD-related techniques (ht tps://
www.asge.org/home/resources/key-resources/guidelines)
Diagnosis, evaluation, and management of ascites, spontaneous bacterial

peritonitis and hepatorenal syndrome (ht tps://www.aasld.org/publications/
practice-guidelines)
Clinical practice guideline on the management of coagulation disorders in

patients with cirrhosis (ht tps://gastro.org/clinical-guidance)
Malnutrition, frailty, and sarcopenia in patients with cirrhosis (ht tps://

www.aasld.org/practice-guidelines)
Clinical practice update on palliative care management in cirrhosis: expert

review (ht tps://gastro.org/clinical-guidance)
Guidelines for the management of adult acute and acute-on-chronic liver

failure in the ICU: cardiovascular, endocrine, hematologic, pulmonary, and
renal considerations (ht tps://www.sccm.org/Clinical-Resources/Guidelines/
Guidelines)
Published by: Society of Critical Care Medicine Last published: 2020
63
North America
Diagnosis and treatment of alcohol‐associated liver diseases (ht tps://

Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and

management (ht tps://www.aasld.org/practice-guidelines)
Evaluation for liver transplantation in adults (ht tps://www.aasld.org/

publications/practice-guidelines)
American Society of Transplantation
Evaluation of the pediatric patient for liver transplantation (ht tps://

GUIDELINES
American Society of Transplantation; North American Society for Pediatric
Gastroenterology, Hepatology and Nutrition
Asia
Evidence-based clinical practice guidelines for liver cirrhosis 2020 (ht tps://
link.springer.com/article/10.1007/s00535-021-01788-x)
Published by: Japanese Society of Gastroenterology Last published: 2021
Cirrhosis References
Key articles
• de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII: renewing consensus in portal hypertension.
REFERENCES
J Hepatol. 2022 Apr;76(4):959-74. Full text (https://www.journal-of-hepatology.eu/article/
S0168-8278(21)02299-6/fulltext) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/35120736?
tool=bestpractice.bmj.com)
• National Institute for Health and Care Excellence. Cirrhosis in over 16s: assessment and
management. July 2016 [internet publication]. Full text (https://www.nice.org.uk/guidance/ng50)
• European Association for the Study of the Liver. EASL clinical practice guidelines on non-invasive tests
for evaluation of liver disease severity and prognosis: 2021 update. J Hepatol. 2021 Sep;75(3):659-89.
Full text (https://www.journal-of-hepatology.eu/article/S0168-8278(21)00398-6/fulltext) Abstract (http://
www.ncbi.nlm.nih.gov/pubmed/34166721?tool=bestpractice.bmj.com)
• European Association for the Study of the Liver. EASL clinical practice guidelines for the
management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69(2):406-60. Full
text (https://www.journal-of-hepatology.eu/article/S0168-8278(18)31966-4/fulltext) Abstract (http://
• Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis:

risk stratification, diagnosis, and management - 2016 practice guidance by the American
Association for the Study of Liver Diseases. Hepatology. 2017 Jan;65(1):310-35. Full text (https://
aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.28906) Abstract (http://www.ncbi.nlm.nih.gov/
pubmed/27786365?tool=bestpractice.bmj.com)
• Rogal SS, Hansen L, Patel A, et al. AASLD practice guidance: palliative care and symptom-based
management in decompensated cirrhosis. Hepatology. 2022 Sep;76(3):819-53. Full text (https://
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Cirrhosis Images
Images
Figure 1: Laparoscopic view of a cirrhotic liver
IMAGES
81
IMAGES Cirrhosis Images
Figure 2: Icterus or jaundice

Cirrhosis Images
IMAGES
Figure 3: Liver palms erythema of adult alcoholic
Dr P. Marazzi / Science Photo Library; used with permission
83
Figure 4: Preoperative view of a small finger flexion contracture

Cirrhosis Images
IMAGES
Figure 5: Caput medusa: dilated superficial (superior and inferior) epigastric veins radiating from a central
large venous varix
Singh NK, Cheema U, Khalil A. Caput medusae. Case Reports. 2010;2010:bcr0320102795; used with
permission
85
Figure 6: Ascites. View of the abdomen of a female patient with alcoholic liver disease and cirrhosis, showing
swelling due to ascites (accumulation of fluid in the peritoneal cavity), jaundice (yellowing of the skin), and
bruising
Science Photo Library; used with permission
Cirrhosis Images
IMAGES
Figure 7: Child-Pugh-Turcotte scoring system
87
Figure 8: Oesophageal varices in a patient with portal hypertension

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Contributors:
// Authors:
Apostolos Koffas, MD (AUTH), MRCP (UK)

Clinical Research Fellow
Barts Liver Centre, Barts and the London School of Medicine and Dentistry, London, UK
DISCLOSURES: AK declares that he has no competing interests.
Patrick T. F. Kennedy, MB, BCh, BAO, BMedSci, FRCP, MD

Professor and Consultant Hepatologist
Barts Liver Centre, Barts and the London School of Medicine and Dentistry, London, UK
DISCLOSURES: PTFK acts as an advisor for Gilead Sciences, Janssen, and Immunocore. PTFK has
received grant funding from Gilead Sciences. These roles are unrelated to the current article.
// Acknowledgements:
Dr Apostolos Koffas and Professor Patrick T. F. Kennedy would like to gratefully acknowledge Dr Grace E.
Dolman, Dr Keith D. Lindor, and Dr Flavia Mendes, previous contributors to this topic.
DISCLOSURES: GED declares that she has no competing interests. KDL is an unpaid advisor for Intercept
Pharmaceuticals and Shire Pharmaceuticals. FM declares that she has no competing interests.
// Peer Reviewers:
Nancy Reau, MD
Assistant Professor of Medicine
University of Chicago, Center for Liver Disease, Chicago, IL
DISCLOSURES: NR declares that she has no competing interests.
Cynthia Levy, MD
Clinical Assistant Professor
Division of Gastroenterology Hepatology and Nutrition, University of Florida, Gainesville, FL
DISCLOSURES: CL declares that she has no competing interests.
James Neuberger, DM, FRCP, Hon

Consultant Physician
Hon Professor in Medicine, Associate Medical Director NHSBT, Queen Elizabeth Hospital, Birmingham, UK
DISCLOSURES: JN declares that he has no competing interests.

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Cirrhosis

Straight to the point of care

Last updated: Feb 23, 2023

Laparoscopic view of a cirrhotic liver

The various causes of cirrhosis are listed below.

Laparoscopic view of a cirrhotic liver

hypoalbuminaemia, which can worsen complications of liver cirrhosis such as ascites.

Liver enzymes may show only mild abnormality, if any.

• Abdominal distension due to ascites

• A family history of haemochromatosis, Wilson's disease, or alpha-1 antitrypsin deficiency provides

Hand and nail features

• Leukonychia (white nails) secondary to hypoalbuminaemia

Liver palms erythema of adult alcoholic

Preoperative view of a small finger flexion contracture

• Parotid gland swelling

Chest wall features

Caput medusa: dilated superficial (superior and inferior)

Ascites. View of the abdomen of a female patient with alcoholic liver

Liver function tests

• Aminotransferases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) levels

• A decrease in serum albumin is a marker of hepatic synthetic dysfunction.

Full blood count and clotting

• Prolongation of the prothrombin time is a marker of hepatic synthetic dysfunction. (Although

• Presence of immunoglobulin G (IgG) antibodies to hepatitis C virus (confirmed with hepatitis C

• Serum ceruloplasmin is decreased in Wilson's disease.

• Approximately 15% of adults with alpha-1 antitrypsin deficiency develop cirrhosis.[31]

Child-Pugh-Turcotte scoring system

Model of End-Stage Liver Disease (MELD)

Imaging techniques to detect fibrosis

History and exam

abdominal distension (common)

jaundice and pruritus (common)

• Suggestive of decompensated cirrhosis secondary to reduced hepatic excretion of conjugated bilirubin

blood in vomit (haematemesis) and black stool (melaena) (common)

Preoperative view of a small finger flexion contracture

facial features (e.g., telangiectasia, spider naevi, jaundiced sclera) (common)

(yellow plaques on eyelids secondary to lipid deposition) in primary biliary cholangitis.

abdominal features (e.g., collateral circulation, hepatosplenomegaly,

altered mental status (uncommon)

Other diagnostic factors

lower extremity swelling (common)

hepatic fetor (common)

muscle wasting (common)

peripheral oedema (common)

recurrent infections (uncommon)

decreased libido (uncommon)

chest wall features (e.g., gynaecomastia) (uncommon)

chest pain (uncommon)

intravenous drug use

Other tests to consider

antimitochondrial antibody present in primary biliary

plasma alpha-1 antitrypsin reduced in alpha-1

• Baveno VII consensus guidelines conclude that patients who avoid

Oesophageal varices in a patient with portal hypertension

Condition Differentiating signs / Differentiating tests

Portal vein thrombosis • Signs and symptoms of the • Magnetic resonance

Splenic vein thrombosis • Signs and symptoms • Abdominal ultrasound and

Nodular regenerative • No differentiating signs and • Liver biopsy: small

Idiopathic portal • No differentiating signs and • Liver biopsy: no evidence of