Chronic hepatitis

We quantified hepatitis C virus (HCV) RNA at different times in plasma and peripheral blood mononuclear cells (PBMC) in 51 patients with chronic hepatitis C undergoing inter-feron-α2a (IFN-α2a) therapy. HCV RNA loads in plasma correlated with those in PBMC before and ...

Staging fibrosis accurately has always been a challenge in viral hepatitis and other liver diseases. Liver biopsy is an imperfect gold standard due to its intra and interobserver agreement limitations and additional characteristics such as its safety and cost. Hence, non-invasive tests have been developed to stage liver fibrosis. In addition to serological biomarkers, physical tests with reasonable accuracy are available and adopted in the daily clinic regarding viral hepatitis fibrosis staging. In this review, we discuss the published data regarding the staging of liver fibrosis in chronic hepatitis B and C, emphasizing non-invasive markers of fibrosis, both serological and physical. Moreover, we also discuss a persistent central gap, the evaluation of liver fibrosis after HCV cure.

A six-year-old boy presented with cough, cyanosis and clubbing. Investigations revealed hypoxia (PaO2 53 mm Hg on room air) which was only partially correctable (PaO2 73 mm Hg) with 100% oxygen administered through a non re breathing face mask. Liver function tests showed elevated total bilirubin, and transaminases, liver biopsy confirmed chronic hepatitis and endoscopy showed grade three varices. A contrast enhanced echocardiography (bubble study) revealed pulmonary arterio-venous communication. A diagnosis of hepatopulmonary syndrome was made based on the triad of hypoxemia, liver disease and intra pulmonary vascular communications.

Mutations that prevent the expression of the hepatitis B e antigen frequently emerge in the immunoreactive phase of infection. The predominant mutation, the precore G→A-1896 mutation, is restricted by the variability at position 1858 and is rare in strains with cytosine at nucleotide 1858. The C-1858 variant is characteristic of genotype A. It also occurs in genotypes C and F, but not in B, D, or E, explaining the geographical variation in the prevalence of precore mutants. C-1858 strains have been frequently observed in southeast Asia, but have not been phylogenetically characterized. By sequencing eight complete hepatitis B virus genomes, C-1858 variants of east Asian origin were found to constitute a phylogenetic entity within genotype C that probably diverged several hundred years ago. Further study of the distribution of this variant is warranted.

Altered cell cycle regulatory genes expression contributes to HCV-associated liver disease. We sought to assess the role of cyclins and cyclin dependent kinases (CDKs) in HCV-associated CH and HCC.Aberrant expression of cyclins A, E, D1, CDK2 and CDK4 was assessed by immunohistochemistry and differential PCR in HCV-associated CH and HCC with pericarcinomatous foci (PCF). S phase fraction (SPF) was determined

Liver chronic diseases constitute an important public health issue. When diagnosing diffuse hepatopathies, ultrasonography is a simple method bringing useful information but not safe enough when determining the difference between certain diseases (steatosis, chronic hepatitis or early cirrhosis) or quantifying their severity. Present study is focused on examining pure fibrosis tissues in order to get a clear overview on how the presence of the fibrosis affects the ultrasonographic aspect of liver. We tried to assess the usefulness of the computerized texture image analysis in noninvasive fibrosis grade quantification. From over 350 with biopsies we’ve selected 58 chronic hepatitis C patients, which have pure fibrosis without any steatosis. On each image we established a Region of Interest and we extracted 166 features using 4

An increasing frequency of hepatic granulomas, up to 10%, in chronic hepatitis C patients is reported, and their presence is considered to be a predictor of treatment success. However, there is only one prevalence study on granuloma in chronic hepatitis B, and its significance for ...

A 37-year-old splenectomized man affected by -thalassemia and chronic hepatitis, recently treated with pegylated interferon- (Peg-IFN), was admitted because of elevated fever lasting 3 months and unresponsiveness to broad-spectrum antibiotics. Laboratory studies showed white blood cell and platelet counts within the normal range but lower than observed before Peg-IFN treatment and an elevated erythrocyte sedimentation rate. The blood transfusion rate

Hepatitis G virus (HGV) has been recently identified as a new transfusion-transmissible agent. This study was performed to evaluate the role of HGV infection in patients with acute posttransfusion hepatitis in Taiwan. Sera from 63 patients with acute posttransfusion hepatitis and 61 patients with normal serum aminotransferase levels after transfusion were tested for HGV RNA by reverse-transcription polymerase chain reaction. Six of the 63 patients (9.5%) with acute posttransfusion hepatitis were positive for HGV RNA in pretransfusion sera; 4 were superinfected with hepatitis C virus (HCV) after transfusion and 3 developed chronic hepatitis. Seven (12.3%) of the remaining 57 patients had acute posttransfusion HGV infection; 5 were coinfected with HCV and 2 infected with HGV alone. None with acute HGV infection alone developed chronic hepatitis, whereas 4 of 5 patients (80%) with acute HGV and HCV coinfection developed chronic hepatitis. The clinical course of acute HGV and HCV coinfection was similar to that of acute HCV infection alone. Four of 61 subjects (6.6%) with normal serum aminotransferase levels after transfusion were subclinically infected with HGV. HGV infection accounted for 12.3% of acute posttransfusion hepatitis in Taiwan before anti-HCV screening of blood donors. The clinical course of acute posttransfusion HGV infection alone was relatively benign.

The putative core protein of hepatitis C virus (HCV) regulates cellular growth and a number of cellular promoters. To further understand its effect, we investigated the role of the core protein in the endogenous regulation of two distinct transcription factors, nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1), and the related mitogen-activated protein kinase kinase (MAPKK) and c-Jun N-terminal kinase (JNK). Stable cell transfectants expressing the HCV core protein suppressed tumor necrosis factor (TNF)-induced NF-kappaB activation. Supershift analysis revealed that NF-kappaB consists of p50 and p65 subunits. This correlated with inhibition of the degradation of IkappaBalpha, the inhibitory subunit of NF-kappaB. The effect was not specific to TNF, as suppression in core protein-expressing cells was also observed in response to a number of other inflammatory agents known to activate NF-kappaB. In contrast to the effect on NF-kappaB, the HCV core protein constitutively...

Although in vitro replication of the hepatitis C virus (HCV) JFH1 clone of genotype 2a (HCVcc) has been developed, a robust cell culture system for the 1a and 1b genotypes, which are the most prevalent viruses in the world and resistant to interferon therapy, has not yet been established. As a surrogate virus system, pseudotype viruses transiently bearing HCV envelope proteins based on the vesicular stomatitis virus (VSV) and retrovirus have been developed. Here, we have developed a replication-competent recombinant VSV with a genome encoding unmodified HCV E1 and E2 proteins in place of the VSV envelope protein (HCVrv) in human cell lines. HCVrv and a pseudotype VSV bearing the unmodified HCV envelope proteins (HCVpv) generated in 293T or Huh7 cells exhibited high infectivity in Huh7 cells. Generation of infectious HCVrv was limited in some cell lines examined. Furthermore, HCVrv but not HCVpv was able to propagate and form foci in Huh7 cells. The infection of Huh7 cells with HCVpv...

Although in vitro replication of the hepatitis C virus (HCV) JFH1 clone of genotype 2a (HCVcc) has been developed, a robust cell culture system for the 1a and 1b genotypes, which are the most prevalent viruses in the world and resistant to interferon therapy, has not yet ...

Autoimmune hepatitis (AIH) has been reported to show considerable geographical variation in frequency and clinical manifestations. It is considered a rare cause of liver disease in India. The present study was undertaken to determine the incidence, clinical, biochemical and histological profile of AIH in this part of the world. Patients presenting with acute or chronic liver disease between January 1999 and June 2002 were evaluated prospectively. AIH was diagnosed using the international autoimmune hepatitis group criteria. Workup included clinical, biochemical, USG, viral markers, UGI endoscopy, AI markers (ANA, SMA, Anti-LKM, AMA, RF, p-ANCA) using indirect immunofluorescence and liver biopsy if possible. Forty-one of 2401 (1.70%) patients were diagnosed to have autoimmune liver disease. Out of these, 38 had autoimmune hepatitis and the rest 3 had primary biliary cirrhosis. The mean age of the patients of autoimmune hepatitis was 36.2 (15.9) years, 34 (89.4%) were females, and the...

AT-61, a member of a novel class of phenylpropenamide derivatives, was found to be a highly selective and potent inhibitor of human hepatitis B virus (HBV) replication in four different human hepatoblastoma cell lines which support the replication of HBV (i.e., HepAD38, HepAD79, 2.2.15, and transiently transfected HepG2 cells). This compound was equally effective at inhibiting both the formation of intracellular immature core particles and the release of extracellular virions, with 50% effective concentrations ranging from 0.6 to 5.7 microM. AT-61 (27 microM) was able to reduce the amount of HBV covalently closed circular DNA found in the nuclei of HepAD38 cells by >99%. AT-61 at concentrations of >27 microM had little effect on the amount of viral RNA found within the cytoplasms of induced HepAD38 cells but reduced the number of immature virions which contained pregenomic RNA by >99%. The potency of AT-61 was not affected by one of the mutations responsible for (-)-beta-L-...

Paraoxonase 1 (PON1) is an ester hydrolase present in serum and in the liver. The aims of the present study were to investigate the following: (a) the relationship between serum PON1 activity alterations and the degree of liver damage in patients with chronic liver disease; (b) the influence of genetic variability on serum PON1 activity; and (c) the efficacy of serum PON1 activity measurement, alone and in combination with standard liver function tests, in the assessment of liver damage. We studied 68 patients with liver cirrhosis, 107 patients with chronic hepatitis, and 368 apparently healthy volunteers. Baseline and salt-stimulated PON1 activities were measured by the hydrolysis of paraoxon. PON1 genotyping at positions 55 and 192 was analyzed by PCR and restriction isotyping. Baseline and stimulated PON1 activities were decreased (P <0.001) in chronic hepatitis and in liver cirrhosis. PON1 activity was significantly correlated with serum total proteins, albumin, and bilirubin...

Liver is the main organ that plays an important role in the biotransformation of medicine in human body. Therefore, drug-induced liver injuries are much more common than official medical statistics show in different countries and on different continents. This circumstance is associated with many factors: the latent course of drug-induced liver injuries, inadequate interpretation of clinical symptoms and clinical laboratory parameters, insufficiently careful investigation of anamnesis, different frequency of use of various medicine in different countries.

Drug-induced liver injuries are lesions that are associated with the use of medicine. Drug-induced liver injuries must be diagnosed as early as possible, as the continued administration of medicine can repeatedly exacerbate the severity of clinical manifestations and significantly affect the outcome of the disease as a whole. In addition, legal aspects are also important in this regard, since an unrecognized drug-induced liver injury with continued use of this medicine that allegedly caused this injury is a matter of a frequent professional investigations.

The reaction of the liver on medicine depends on many factors: the initial state of liver function (already existing liver disease), heredity, gender, age, alcohol intake and other medicine. Presence of these factors in patients significantly increases the risk of development of liver injuries associated with taking medications, and if the drug-induced liver injury develops, the prognosis of its course will be heavier. Statistically-valid are frequent drug-induced liver injuries in women. The same type of medicine can cause different types of liver injuries in terms of clinical and morphological manifestations. Diagnostics of drug-induced liver injury is often difficult and requires from a specialist certain skills not only the necessity to carefully collect an anamnesis of a patient with a developed disease, but also a good orientation in his clinical and morphological manifestations.