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Hepatitis B: Diagnosis and Treatment
THAD WILKINS, MD; DAVE ZIMMERMAN, MD; and ROBERT R. SCHADE, MD
Medical College of Georgia, Augusta, Georgia

Although an estimated 1 million persons in the United States are chronically infected with hepatitis B virus, the
prevalence of hepatitis B has declined since the implementation of a national vaccination program. Hepatitis B virus is
transmitted in blood and secretions. Acute infection may cause nonspecific symptoms, such as fatigue, poor appetite,
nausea, vomiting, abdominal pain, low-grade fever, jaundice, and dark urine; and clinical signs, such as hepatomeg-
aly and splenomegaly. Fewer than 5 percent of adults acutely infected
with hepatitis B virus progress to chronic infection. The diagnosis
of hepatitis B virus infection requires the evaluation of the patient’s
blood for hepatitis B surface antigen, hepatitis B surface antibody,
and hepatitis B core antibody. The goals of treatment for chronic
hepatitis B virus infection are to reduce inflammation of the liver and
to prevent complications by suppressing viral replication. Treatment
options include pegylated interferon alfa-2a administered subcutane-
ously or oral antiviral agents (nucleotide reverse transcriptase inhibi-

ILLUSTRATION BY JOHN KARAPELOU

tors). Persons with chronic hepatitis B virus infection should be
monitored for disease activity with liver enzyme tests and hepatitis B
virus DNA levels; considered for liver biopsy; and entered into a sur-
veillance program for hepatocellular carcinoma. (Am Fam Physician.
2010;81(8):965-972. Copyright © 2010 American Academy of Family
Physicians.)

G
Patient information: lobally, an estimated 350 million implications.5 All genotypes are present in
▲

A handout on hepatitis B is persons are chronically infected the United States, with genotypes A and C
available at http://family with hepatitis B virus (HBV), comprising 35 and 31 percent of viruses,
doctor.org/032.xml.
resulting in 600,000 deaths respectively.6 The HBV genome produces a
annually from cirrhosis, liver failure, and nucleocapsid that contains the hepatitis B
This clinical content con-
hepatocellular carcinoma.1,2 Approximately core antigen (HBcAg). This nucleocapsid is
forms to AAFP criteria for 88 percent of the world’s population live in encompassed with an outer envelope referred
evidence-based continuing regions where the prevalence of chronic HBV to as the hepatitis B surface antigen (HBsAg).
medical education (EB CME) infection among adults is more than 2 per- One segment of HBcAg results in the pro-
cent.3 The prevalence of HBV infection in duction of the hepatitis B e antigen (HBeAg),
the United States is 0.4 percent, with an esti- which is associated with viral replication and
mated 0.8 to 1.4 million persons chronically high infectivity. The DNA polymerase reverse
infected.3,4 With the implementation of vacci- transcriptase is a target for antiviral therapy.7
nation programs in 1991, the incidence of new HBV is transmitted in blood and secretions
infections in the United States has declined (e.g., semen, saliva) and is infectious outside
from 11.5 cases per 100,000 persons in 1985 the body for seven or more days.3
to 1.6 cases per 100,000 persons in 2006.3,4
Screening and Prevention
Virus Description High-risk populations should be screened
HBV is a small (diameter of 42 nm), incom- for HBV infection6 (Table 13). The Centers
pletely double-stranded DNA hepadnavi- for Disease Control and Prevention recom-
rus. Substantial genetic variations occur mends routine HBV screening in popula-
within distinct regions, globally facilitating tions in which HBsAg prevalence is at least
classification of eight distinguishable geno- 2 percent, including immigrants from these
types (A through H), which have treatment regions.1

April 15, 2010 ◆ Volume 81, Number 8 www.aafp.org/afp American Family Physician 965
Hepatitis B

Hepatitis B vaccine is part of routine

SORT: KEY RECOMMENDATIONS FOR PRACTICE
immunizations in the United States, and as
Evidence a result, the incidence of HBV has declined.8
Clinical recommendation rating References Table 2 lists hepatitis B vaccines and recom-
High-risk populations should be screened for C 6
mended dosing schedules.9-11 A Cochrane
HBV infection. review confirmed that hepatitis B vacci-
Health care professionals should receive A 12 nation decreased HBV infection in health
hepatitis B vaccination. care professionals (relative risk = 0.51; 95%
Hepatitis B vaccination and hepatitis B immune A 15 confidence interval, 0.35 to 0.73).12 Because
globulin are effective at preventing HBV infection
there is a high risk of acquiring HBV from a
in newborns of mothers infected with HBV.
All persons who meet criteria for chronic HBV C 6
needlestick injury,13 health care profession-
infection should be evaluated for treatment. als exposed to HBsAg-positive blood should
Persons with chronic HBV infection who are not C 6 be given hepatitis B immune globulin after
immune to hepatitis A should receive two doses the exposure and started on the hepatitis B
of hepatitis A vaccine at least six months apart. vaccine series if not previously vaccinated.14
Patients in the active phase of chronic HBV C 6 Hepatitis B vaccination and hepatitis B
infection should receive treatment.
immune globulin are also effective in pre-
Patients in the inactive or immune tolerant C 6
phases of chronic HBV infection should be venting HBV infection in newborns of
monitored on a regular basis (every six to mothers infected with HBV.15 Populations
12 months) for reactivation of their infection. to consider for hepatitis B vaccination are
listed in Table 3.3
HBV = hepatitis B virus.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited- Diagnosis
quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual
practice, expert opinion, or case series. For information about the SORT evidence The diagnosis of HBV infection requires the
rating system, go to http://www.aafp.org/afpsort.xml. evaluation of the patient’s blood for HBsAg,
hepatitis B surface antibody (HBsAb),
and hepatitis B core antibody (HBcAb).
Although the presence of HBsAg indicates
Table 1. Populations Recommended for HBV Screening
that the person is infectious, the presence
of HBsAb indicates recovery and immunity
Donors of blood, plasma, organs, tissue, or semen*
from HBV infection or successful immuni-
Health care professionals
zation against HBV. HBcAb appears at the
Household contacts of persons with HBV infection
onset of acute HBV infection, but may also
Infants born to mothers identified as HBsAg positive
indicate chronic HBV infection. Interpreta-
Injection drug users*
tion of HBV immunologic markers is shown
Men who have sex with men*
in Table 4.11 HBV DNA sometimes may be
Persons born in countries with HBsAg prevalence of ≥ 2 percent
the only marker present in early infections.
Persons born in the United States who were not vaccinated as infants and
whose parents were born in regions with HBsAg prevalence of ≥ 8 percent
ACUTE INFECTION
Persons infected with human immunodeficiency virus
Persons needing immunosuppressive therapy (chemotherapy and Symptoms of acute HBV infection are non-
immunosuppression for rheumatologic or gastrointestinal diseases)* specific and include fatigue, poor appe-
Persons undergoing hemodialysis* tite, nausea, vomiting, abdominal pain,
Persons with persistently elevated aspartate and alanine transaminase levels low-grade fever, jaundice, and dark urine.
Pregnant women Clinical signs include liver tenderness, hepa-
Sex partners of persons with HBV infection tomegaly, and splenomegaly. Acute HBV
Survivors of sexual assault infection typically lasts two to four months.
Approximately 30 to 50 percent of children
HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus. five years and older and most adults are
*—New recommendations from the Centers for Disease Control and Prevention. symptomatic; infants, children younger than
Information from reference 3. five years, and immunosuppressed adults are
more likely to be asymptomatic.14 In adults

966 American Family Physician www.aafp.org/afp Volume 81, Number 8 ◆ April 15, 2010
 Hepatitis B

Table 2. Hepatitis B Vaccines and Recommended Dosing Schedules

Dosing

Vaccine Children Schedule Adult Schedule

Engerix-B 10 mcg (0.5-mL vial) Birth; one to two 20 mcg (1-mL vial) Time of first injection and
Recombivax HB 5 mcg (0.5-mL vial) months, and six to 10 mcg (1-mL vial) then at one to two, and
18 months of age four to six months
Comvax (hepatitis B and 5 mcg (0.5-mL vial) Two, four, and 12 to — —
Haemophilus influenzae type b)* 15 months of age
Pediarix (hepatitis B; diphtheria 10 mcg (0.5-mL vial) Two, four, and six — —
and tetanus toxoids and acellular months of age
pertussis; and inactivated polio)*†
Twinrix (hepatitis A and B) — — 20 mcg (1-mL vial) Time of first injection and
then at one, and six to
12 months

NOTE:Other vaccination regimens can be found at http://cdc.gov/vaccines/recs/schedules/child-schedule.htm and http://cdc.gov/vaccines/recs/

schedules/adult-schedule.htm.
*—Should not be given to infants younger than six weeks.
†—Should not be given to persons older than seven years.
Information from references 9 through 11.

with healthy immune systems, approximately 95 per-

cent of acute infections are self-limited, with patients Table 3. Populations to Consider
recovering and developing immunity.6 Fewer than for Hepatitis B Vaccination
5 percent of adults acutely infected with HBV progress
to chronic infection. A small number (1 percent) develop Children and adolescents younger than 19 years who have not
acute hepatic failure and may die or require emergent been vaccinated previously
liver transplantation.16 Health care and public safety workers at risk of exposure to
blood or blood-contaminated body fluids
CHRONIC INFECTION Infants, beginning at birth
Injection drug users
HBV infection is considered chronic when it persists
longer than six months. Risk of chronic HBV infection Men who have sex with men

is inversely related to age, with chronic infection devel- Persons seeking evaluation or treatment for a sexually
transmitted infection
oping in about 90 percent of infected infants, 30 per-
Persons seeking protection from HBV infection (acknowledgment
cent of children younger than five years, and less than of a specific risk factor is not a requirement for vaccination)
5 percent in all other persons.6 Occult HBV infection
Persons with chronic liver disease; end-stage renal disease
may be reactivated by chemotherapy or other immu- (including predialysis, peritoneal dialysis, hemodialysis, and
nosuppressants. Coinfection with human immuno- home dialysis); or human immunodeficiency virus infection
deficiency virus (HIV) or hepatitis C virus can occur. Residents and staff of facilities for persons who are
All persons who meet criteria for chronic HBV infec- developmentally disabled
tion should be evaluated for treatment.6 Persons with Sexually active persons who are not in a long-term, mutually
monogamous relationship (e.g., persons with more than one
chronic HBV infection who are not immune to hepati-
sex partner during the past six months)
tis A should receive two doses of hepatitis A vaccine at
Susceptible household contacts or sex partners of persons
least six months apart.6 identified as HBsAg positive
Travelers to regions with intermediate or high rates of endemic
Goals of Therapy HBV infection
The goals for treatment of chronic HBV infection
are to reduce inflammation of the liver; prevent liver HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus.

failure and cirrhosis; and reduce the risk of hepato- Information from reference 3.
cellular carcinoma by suppressing HBV replication.

April 15, 2010 ◆ Volume 81, Number 8 www.aafp.org/afp American Family Physician 967
Hepatitis B
Table 4. Interpretation of HBV Immunologic Markers

Markers

HBsAg* HBcAb† HBsAb‡ Interpretation

It is important to distinguish between
– – – Susceptible to HBV infection (should be patients who are HBeAg positive and those
vaccinated) who are HBeAg negative because of a viral
– – + Immune because of vaccination mutation. Seroconversion (i.e., conversion
– + + Immune because of natural HBV infection from HBeAg positive to HBeAg negative, fol-
+ + – Acute or chronic HBV infection lowed by conversion from hepatitis B e anti-
– + – Interpretation unclear; four possibilities: body [HBeAb] negative to HBeAb positive)
1. Resolved HBV infection (most common) predicts long-term reduction in viral replica-
2. False-positive HBcAb, thus susceptible
tion and is used as a response marker to ther-
3. “Low-level” chronic HBV infection
apy. Genotypes affect response and guide
4. Resolving acute HBV infection
treatment choices. For example, genotype A
HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = is highly responsive to pegylated interferon
hepatitis B surface antigen; HBV = hepatitis B virus; + = positive test result; – = negative alfa-2a (Pegasys) therapy.21 Certain popula-
test result. tions (e.g., persons with renal insufficiency
*—The presence of HBsAg indicates that the person is infectious. or decompensated liver disease, liver trans-
†— HBcAb appears at the onset of acute HBV infection. Presence may also indicate
chronic HBV infection or a false-positive test.
plant recipients) require additional monitor-
‡—The presence of HBsAb indicates recovery and immunity from HBV infection or ing and expertise.
successful immunization against HBV.
Adapted from Mast EE, Margolis HS, Fiore AE, et al., for the Advisory Committee Treatment Indications and Phases
on Immunization Practices (ACIP). A comprehensive immunization strategy to elimi- of Chronic HBV Infection
nate transmission of hepatitis B virus infection in the United States: recommendations
of the Advisory Committee on Immunization Practices (ACIP) part 1: immuniza- Over time, chronic HBV infection can go
tion of infants, children, and adolescents [published corrections appear in MMWR through four phases that can affect thera-
Morb Mortal Wkly Rep. 2006;55(6):158-159, and MMWR Morb Mortal Wkly Rep.
peutic considerations (Table 5).22
2007;56(48):1267]. MMWR Recomm Rep. 2005;54(RR-16):4.

ACTIVE PHASE

During the active phase of chronic HBV

Normalization of alanine transaminase (ALT), loss of infection, ALT levels are elevated and HBV DNA levels
HBeAg (seroconversion), decrease in serum HBV DNA exceed 20,000 IU per mL (105 copies per mL).18,22 Patients
level, and improvement in liver histology indicate treat- in the active phase of chronic HBV infection should be
ment effectiveness.1,6,17,18 A recent systematic review found offered treatment.6 Liver biopsy may not be necessary.
insufficient evidence to assess treatment effectiveness on
INACTIVE PHASE
patient-oriented outcomes, such as decreased mortality
and improved quality of life.19 A disease-oriented out- During the inactive phase of chronic HBV infection, ALT
come, suppression of HBV DNA levels, is often used as an levels are normal and HBV DNA levels are low (less than
end point of treatment.20 20,000 IU per mL).18,22 Treatment and liver biopsy are

Table 5. Phases of Chronic HBV Infection

Tests Histology

Alanine Hepatitis B Hepatitis B HBV DNA

Phase transaminase level e antigen e antibody (IU per mL) Inflammation Fibrosis Treatment

Active Elevated +/– +/– > 20,000 Active Variable Indicated

Inactive Normal – + < 20,000 None Minimal Not indicated
Gray zone Elevated or normal +/– +/– Variable Variable Variable May or may not
be indicated
Immune tolerant Normal + – > 20,000 Minimal Minimal Not indicated

HBV = hepatitis B virus; + = detectable; – = undetectable; +/– = may or may not be detectable.
Information from reference 22.

968 American Family Physician www.aafp.org/afp Volume 81, Number 8 ◆ April 15, 2010
 Hepatitis B

not indicated in patients with inactive HBV infection. response to the drug must be weighed against its poten-
Patients should be monitored every six to 12 months for tial adverse effects.
reactivation of their infection.6
ORAL ANTIVIRAL AGENTS
GRAY ZONE PHASE Five oral nucleotide reverse transcriptase inhibitors are
During the gray zone phase of chronic HBV infection, a approved for the treatment of HBV infection (Table 7).1
discordance of ALT and HBV DNA levels is present.18,22 These medications require renal function monitoring. If
A liver biopsy may be helpful to determine the presence HBV DNA levels do not become undetectable within six
of other underlying concomitant liver pathology, and to to 12 months, a second antiviral agent should be used.
determine if treatment should be initiated. The incidence of seroconversion increases in a stepwise
fashion with ongoing treatment and with the duration
IMMUNE TOLERANT PHASE of undetectable HBV DNA levels. After three years of
During the immune tolerant phase of chronic HBV therapy with oral antiviral agents, the incidence of sero-
infection, HBeAg is positive, HBV DNA levels are conversion approaches that of 12 months of therapy
high (greater than 20,000 IU per mL), and ALT lev- with pegylated interferon alfa-2a. Oral therapy should
els are normal.18,22 In this phase, there is minimal be continued for at least an additional six months once
inflammation or fibrosis, and treatment is not indi- seroconversion is achieved.22 If seroconversion does
cated. Because there is a direct relationship between not occur, treatment should be continued.6 Regardless
HBV DNA levels and the risk of hepatocellular car- of patient seroconversion status, HBV DNA and liver
cinoma, patients in this phase should be monitored enzyme levels should be monitored, and therapy should
every six months with ultrasonography and serum be reinitiated if needed.6
α-fetoprotein levels.2,23 Patients should also be
RESISTANCE
monitored every six to 12 months for reactivation.6
Patients who convert to the active phase should be The primary limitation of all oral antiviral agents is
treated. development of viral resistance because of mutations
in the viral DNA during replication.18,22 Lamivudine
Treatment Options (Epivir) and telbivudine (Tyzeka) are most likely to fail
Several medications are approved in the United States because of resistance. If resistance develops to one agent,
for the treatment of HBV infection (Table 6).1 Although the effectiveness of a second agent with the same site of
interferon is approved for treatment, pegylated interferon action is reduced. The risk of resistance increases when-
alfa-2a has higher effectiveness, with a similar adverse ever patients have persistent detectable HBV DNA lev-
effect profile, and is preferred over interferon. els.18,22 The addition of a second agent with a different
site of action is vital in patients with detectable serum
PEGYLATED INTERFERON ALFA-2A HBV DNA levels after six to 12 months of therapy.18,22
Pegylated interferon alfa-2a is administered subcutane- Adding a second agent may be preferable to switching
ously in well-compensated patients once weekly for six agents.
to 12 months. More than 50 percent of patients with
HBeAg-positive genotype A infections will achieve Complications
seroconversion, whereas only 30 percent of those with Chronic HBV infection can lead to cirrhosis and its
non-A genotypes will seroconvert.1 Seroconversion may complications, including ascites, portal hypertension,
not occur for up to six months after therapy has ended. hemorrhage, and hepatocellular carcinoma. Hepatocel-
Aspartate transaminase and ALT levels should be moni- lular carcinoma surveillance in patients with chronic
tored often during treatment, and a complete blood HBV infection is often performed every six to 12 months
count should be performed regularly. An increase in using α-fetoprotein levels and abdominal ultrasonogra-
ALT levels often occurs during interferon therapy and phy 18,26 ; however, a Cochrane review found insufficient
typically precedes seroconversion. Serum HBV DNA evidence to demonstrate that hepatocellular carcinoma
level, HBeAg, and HBeAb should be measured at the end surveillance improves survival.27 A randomized trial
of treatment, and at three and six months after treat- of 18,816 persons with chronic HBV infection found a
ment.18,24,25 Pegylated interferon alfa-2a should not be mortality reduction of 37 percent at one year in those
used in patients with advanced liver disease or in those screened versus those not screened.28 A recent meta-
coinfected with HIV. The advantage of a long-term analysis of six studies including 2,984 patients found a

April 15, 2010 ◆ Volume 81, Number 8 www.aafp.org/afp American Family Physician 969
Hepatitis B
Table 6. Antiviral Therapies for Patients with Treatment-Naïve HBeAg-Positive Chronic HBV Infection

Undetectable HBeAg Durability of Histologic Estimated cost

Duration HBV DNA at seroconversion seroconversion improvement of one year of
Drug Adult dosage* (weeks) one year (%) at one year (%) at one year (%)† in one year (%) treatment‡

Injectable
Pegylated 180 mcg per week 48 25 27 82 38 $32,590
interferon
alfa-2a
(Pegasys)

Oral
Adefovir 10 mg per day ≥ 48 13 to 21 12 91 53 to 68 $11,135
(Hepsera)

Entecavir 0.5 mg per day ≥ 48 67 21 82 72 $9,195

(Baraclude)

Lamivudine 100 mg per day 48 to ≥ 52 36 to 44 16 to 21 70 to 80 49 to 62 $4,290

(Epivir)

Telbivudine 600 mg per day ≥ 52 60 22 80 65 $8,180

(Tyzeka)

Tenofovir 300 mg per day ≥ 52 80 21 NA 74 $8,320

(Viread)

HBeAg = hepatitis B e antigen; HBV = hepatitis B virus; HIV = human immunodeficiency virus; NA = not available.
*—Based on patients with normal renal function.
†— Durability of response is defined as the percentage of patients who achieved seroconversion and maintained their HBeAg-negative
status at one year after the termination of treatment.
‡—Estimated retail price of treatment based on information obtained at http://www.drugstore.com (accessed January 19, 2010).
Adapted with permission from Dienstag JL. Hepatitis B virus infection. N Engl J Med. 2008;359(14):1490.

Table 7. Antiviral Therapies for Patients with Treatment-Naïve HBeAg-Negative Chronic HBV Infection

Undetectable HBV Histologic improvement Durability of response

Drug Adult dosage* DNA at one year (%) in one year (%) at one year (%)†

Injectable
Pegylated interferon 180 mcg per week 63 48 18
alfa-2a (Pegasys)
Oral
Adefovir (Hepsera) 10 mg per day 51 to 64 64 < 10
Entecavir (Baraclude) 0.5 mg per day 90 70 NA
Lamivudine (Epivir) 100 mg per day 60 to 73 61 to 66 < 10
Telbivudine (Tyzeka) 600 mg per day 88 67 NA
Tenofovir (Viread) 300 mg per day 95 72 NA

HBeAg = hepatitis B e antigen; HBV = hepatitis B virus; NA = not available.

*—Based on patients with normal renal function.
†—Durability of response is defined as the percentage of patients who achieved undetectable serum HBV DNA levels and maintained this status
at one year after the termination of treatment.
Adapted with permission from Dienstag JL. Hepatitis B virus infection. N Engl J Med. 2008;359(14):1491.

970 American Family Physician www.aafp.org/afp Volume 81, Number 8 ◆ April 15, 2010
 Hepatitis B
Table 8. Risk Factors for Developing Hepato-
cellular Carcinoma with Chronic HBV Infection

Alcohol abuse HBV DNA viral load > 10,000 IU

Strengths Weaknesses Asian or African race per mL
Cirrhosis HBV genotype C
Coinfection with hepatitis C Longer duration of infection
No resistance; highest Not well tolerated; expensive;
sero­conversion rate subcutaneous injections; cannot use and D virus Male sex
at one year; finite in persons with decompensated liver Exposure to aflatoxin Older age
treatment time disease or HIV infection Family history of Presence of hepatitis B e antigen
hepatocellular carcinoma Smoking

Oral; well tolerated Mild effectiveness; moderate probability

HBV = hepatitis B virus.
of resistance development; need to
monitor renal function Information from references 26 and 30.

Oral; well tolerated; Not recommended in persons coin-

moderate effectiveness; fected with HIV because of possible
low probability of development of HIV resistance;
resistance development need to monitor renal function globulin within 12 hours of birth, followed by three
timed doses of hepatitis B vaccine.11,18 Because the
Oral; well tolerated Mild effectiveness; high probability
of resistance development; need to
risk of transmission is directly related to the mother’s
monitor renal function serum HBV DNA level at the time of birth, it is reason-
able to treat women with high serum HBV DNA lev-
Oral; well tolerated; High resistance; need to monitor renal
moderate effectiveness function
els (greater than 20,000 IU per mL) with oral agents
during the final trimester of pregnancy. Lamivudine,
Oral; well tolerated; Need to monitor renal function entecavir (Baraclude), and telbivudine are U.S. Food
moderate effectiveness;
low probability of and Drug Administration pregnancy category C.18
resistance development Breastfeeding is safe in women who are HBsAg posi-
tive3 ; however, women should not breastfeed while
undergoing treatment for HBV infection.

The Authors
THAD WILKINS, MD, is an associate professor in the Department of Family
Medicine at the Medical College of Georgia, Augusta.

DAVE ZIMMERMAN, MD, is a third-year resident in the Department of

Family Medicine at the Medical College of Georgia.

pooled sensitivity of 94 percent and a pooled specific- ROBERT R. SCHADE, MD, is a professor in the Department of Medicine; the
chief of the Division of Gastroenterology and Hepatology; and the medical
ity of 94 percent for screening ultrasonography, with
director of the Special Procedures/Endoscopy Unit at the Medical College
screening every six months superior to screening every of Georgia.
12 months (P = .001).29 Hepatocellular carcinoma is
Address correspondence to Thad Wilkins, MD, Medical College of Geor-
relatively uncommon in the United States (2.8 cases per gia, 1120 15th St., HB-4032, Augusta, GA 30912 (e-mail: twilkins@mcg.
100,000 white men and 6.1 cases per 100,000 black men), edu). Reprints are not available from the authors.
but the incidence has increased 71.4 percent over the past
Author disclosure: Nothing to disclose.
30 years.30 Risk factors are shown in Table 8.26,30 Treat-
ment algorithms for hepatocellular carcinoma, which
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972 American Family Physician www.aafp.org/afp Volume 81, Number 8 ◆ April 15, 2010

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