HEPATOLOGY WATCH®
SPECIAL
ISSUE: VIRAL HEPATITIS IN ASIAN AMERICANS
Overview and rationale for therapy. According to the year 2000 census, there are approximately 12.6 million
Asians and Pacific Islanders living in the U.S. One in ten of these individuals
is chronically infected with hepatitis B virus (HBV). The prevalence of
hepatitis C virus (HCV) infection among Asian American blood donors is 0.5%.
The prevalence of HCV among recent immigrants and those with lower
socioeconomic status is not known, but is expected to be higher. For example,
the prevalence of anti-HCV in the general population in China is 3%. The epidemiology, natural history, and treatment of viral hepatitis in
Asian Americans differ significantly from that in non-Asians. Perinatal and
childhood transmission account for the vast majority of HBV and HCV infection
in Asians. Thus, most Asians with chronic hepatitis were infected early in
life. Cirrhosis and
hepatocellular carcinoma (HCC) are the two major complications of chronic viral
hepatitis. Approximately 20% of patients with HBV and 15% to 20% of patients
with HCV will eventually develop cirrhosis. HBV-infected patients with or
without cirrhosis have a high risk of HCC. The relative risk for HCC is 9.6 and
60.2 among HBsAg-positive/HBeAg-negative and HBsAg-positive/HBeAg-positive
Asian patients, respectively. While the risk of HCC in HCV-infected patients
without cirrhosis is minimal, the annual incidence of HCC in those with
cirrhosis is 8% in Asians (vs. 3% in non-Asians). The goal of antiviral therapy
is to prevent progression to cirrhosis, liver failure, and HCC. As part of
general management, screening for HCC with twice-yearly ultrasound and serum
alpha-fetoprotein is recommended for patients with HBV who are older than 35
years of age or have a family history of HCC, and patients with cirrhosis of
any cause. In addition, alcohol should be avoided or used only occasionally in
small amounts.
Chronic hepatitis B. The treatment endpoints for chronic HBV are normalization
of alanine aminotransferase (ALT), loss of HBV DNA, and seroconversion from
HBeAg to anti-HBe. Interferon-a (IFN) and lamivudine (LAM) are the
only two drugs approved by the U.S. Food and Drug Administration (FDA) for the
treatment for chronic HBV infection. IFN is effective in inducing long-lasting
HBeAg seroconversion (37% vs. 7% for placebo). Factors that predict a favorable
response to IFN include pretreatment HBV DNA <200 pg/mL, ALT >100 U/L,
and evidence of necroinflammatory activity in the liver. Unfortunately, side
effects including significant depression in up to 15% have limited the
tolerability and clinical use of IFN. LAM induces HBeAg seroconversion at a
rate of 17% (vs. 6% for placebo), 27%, and 47% after 1, 2, and 4 years of
therapy, respectively. Pretreatment ALT level is the strongest predictor of
response; patients with ALT less than 2 times normal have HBeAg seroconversion
rates of less than 10% after one year of treatment. While IFN is
contraindicated in patients with decompensated cirrhosis, LAM may be beneficial
in these patients. LAM is very well tolerated with side effects no different
from placebo. Limitations of LAM therapy include a high relapse rate (49% two
years after HBeAg seroconversion and discontinuation of therapy in Asians), and
the emergence of YMDD mutation (32%, 38%, 57%, and 67% at 1, 2, 3, and 4 years,
respectively), which has been associated with a few cases of severe hepatitis.
Adefovir (ADV) is a nucleotide analog that induces HBeAg seroconversion in 12%
of patients after 48 weeks of therapy. No evidence of ADV resistance has been
identified during treatment, and ADV can suppress the replication of
LAM-resistant HBV. ADV is scheduled for FDA review soon. Virological response
to IFN, LAM, and ADV are associated with histological improvement. Agents that
are under investigation for treatment of chronic HBV include pegylated IFN (PEG
IFN), entecavir, emtricitabine (FTC), other nucleoside analogs as well as
therapeutic vaccines. Various combination regimens are also being investigated.
Chronic hepatitis C. The treatment endpoints for chronic HCV are normalization
of ALT and sustained virological response (SVR), defined as loss of HCV RNA 6
months after the end of treatment. Combination therapy with PEG IFN and
ribavirin (RBV) is currently the standard of care for eligible patients. The
side effects with PEG IFN are similar to that of IFN; the main side effect of
RBV is hemolytic anemia. The strongest predictors for treatment response are
viral genotype other than genotype 1, viral load < 2 million copies/mL, and
no advanced fibrosis. Minor predictors of response include female gender, Asian
or Caucasian race, shorter duration of infection, and age less than 40 years.
The expected SVR is 45% for genotype 1 and 80% for genotype non-1. SVR is also
associated with improved histology and a lower incidence of HCC on follow-up. A
20% reduction in HCC incidence is seen in Asian patients treated with IFN-based
therapy for chronic HCV, compared to only a 10% reduction in non-Asian
patients.
Liver transplantation.
HBV recurrence and
late HBV-mortality in Asians and non-Asians are similar after liver
transplantation for HBV. The rate of posttransplant HBV infection is 20% to 30%
with hepatitis B immune globulin (HBIg) and less than 10% with HBIg and LAM.
There is no differential survival or rate of HCV recurrence among Asians and
non-Asians following liver transplantation for HCV. Recurrence of HCV is
universal, and treatment with IFN + RBV or PEG IFN ± RBV is
under investigation.
Vaccination for hepatitis A and hepatitis B. Preventing
primary infection by vaccination is an important strategy to decrease the risk
of chronic HBV and its subsequent complications. HBV vaccine is highly
effective, and over 95% of patients develop anti-HBs. Universal vaccination
programs for HBV in children have dramatically reduced the prevalence of HCC in
endemic areas. Unfortunately, vaccination for HBV among Asian American children
varies from 55% to 90%. Vaccination for hepatitis A virus (HAV) reduces
mortality of acute hepatitis A in patients with chronic liver disease and
should be given to all such patients. Seroprevalence for HAV is high in Asians;
therefore, testing for anti-HAV should be performed prior to vaccination. A
combined HAV and HBV vaccine (Twinrix) is now available. There is no
prophylactic vaccine for HCV; therapeutic vaccines for HCV are under
development.
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