HEPATOLOGY WATCH®
Timely
Information for Practicing Physicians
august
2001
Hepatitis C Virus (HCV)
Asymptomatic
carriers. K Tsuji and
coworkers report that 27.4% of 120 asymptomatic HCV RNA-positive carriers with
normal alanine aminotransferase (ALT) levels developed a flare of serum ALT
during a 10-year follow-up period. All
ALT flares occurred within the first 5 years, and multivariate analysis showed
that the presence of either C100-3 antibody or anti-human T-cell leukemia virus
(HTLV)-I antibody were independent predictors of an ALT flare-up (P=0.04
and 0.03, respectively). No histologic
feature was found to be associated with flares. (Tsuji K, et al. J
Gastroenterol Hepatol 2001;16:536-540)
Studies
of viral clearance. SE Bassett et al investigated chimpanzees that had
previously cleared a primary HCV infection.
These chimpanzees were observed to rapidly clear virus following a
rechallenge with HCV. Some of these
animals had not been exposed to HCV for over 16 years. An early and strong in vitro recall response to HCV nonstructural proteins by
peripheral blood mononuclear cells appeared to be associated with viral
clearance. This subgroup of animals
developed strong and durable cellular immunity against HCV, which may provide
clues to future therapies or vaccines.
(Bassett SE, et al. Hepatology
2001;33:1479-1487)
Association
of steatosis with progressive fibrosis. Luigi Adinolfi and colleagues studied 180 consecutive patients
with chronic hepatitis C to investigate the role of steatosis in the
progression of liver damage. Within the
study population, 86 patients were found to have steatosis by liver
biopsy. There was a higher prevalence
of steatosis in patients infected with genotype 3a (P<0.01) or having
visceral obesity (P<0.001).
Higher grades of steatosis were correlated with the development of fibrosis
(P<0.001), a worsening histological activity index (P<0.007),
and higher ALT levels (P<0.001).
These data indicate that obesity and genotype 3a are associated with
steatosis, which is a cofactor in progression of liver damage. (Adinolfi L, et al. Hepatology 2001;33:1358-1364)
Cigarette
smoking and hepatic lesions.
Fabienne Pessione and coworkers performed a cross-sectional study
consisting of 310 patients with chronic hepatitis C and observed an increased
severity of hepatic lesions (increased fibrosis and worse Knodell activity
scores) in those patients who smoked cigarettes. (Pessione F, et al. Hepatology
2001;34:121-125)
Hepatocellular Carcinoma (HCC)
Alpha-fetoprotein
(AFP). Serum AFP has
traditionally been utilized as a diagnostic test for HCC. However, advanced abdominal imaging
techniques have shown that many HCCs identified radiographically do not secrete
diagnostic levels of AFP. In light of
these findings, F Trevisani and associates conducted a retrospective
case-control study in 340 patients (170 with HCC and 170 with chronic liver
disease [CLD]) that were matched for age, sex, CLD, and HBsAg/anti-HCV status
to evaluate AFP as a marker for HCC among patients with CLD. They observed an AFP value of 20 ng/mL to
have a sensitivity of only 62.4%.
Moreover, the data showed that AFP monitoring missed several HCCs and
inappropriately raised a suspicion of malignancy in patients without HCC. The authors concluded that AFP is not an
accurate diagnostic test to detect HCC.
This paper is accompanied by an editorial by Morris Sherman, which
concisely and critically summarizes the history of the use of AFP as a tool for
the diagnosis of HCC. (Trevisani F, et
al. J Hepatol 2001;34:570-575 and
Sherman M. J Hepatol 2001;34:603-605)
Cholangiocarcinoma
Increasing
incidence of mortality. An analysis by
Tushar Patel of the Surveillance, Epidemiology, and End Results (SEER) and
United States Vital Statistics databases from the years 1973 to 1997 revealed
increases in the incidence and mortality rate of patients with
cholangiocarcinoma of 9.11% and 9.44% annually, respectively. The age-adjusted mortality rate per 100,000
persons for cholangiocarcinoma was 0.65 from 1993 to 1997 but only 0.14 from
1975 to 1979. These data emphasize the
extremely poor prognosis that continues to be associated with
cholangiocarcinoma. (Patel T. Hepatology 2001;33:1353-1357)
Nonalcoholic Fatty Liver Disease (NAFLD)
Predictors
of nonalcoholic steatohepatitis (NASH) and liver fibrosis. John Dixon and colleagues reviewed liver biopsies obtained from
105 consecutive patients during obesity surgery and found 26 patients (25%)
with NASH. Eleven patients (42%) had
advanced fibrosis. An analysis of
clinical and biochemical variables demonstrated that a raised index of insulin
resistance, systemic hypertension, and an elevated serum ALT level were
independent predictors for NASH. In
addition, moderate alcohol consumption was observed to be associated with a
reduction in the risk for NASH and diabetes.
Thus, insulin resistance and systemic hypertension in obese patients is
associated with advanced NAFLD. (Dixon JB, et al. Gastrenterology 2001;121:91-100)
Reviews of the Month
Primary biliary cirrhosis (PBC). Akiyoshi
Nishio and colleagues review the natural history and manifestations of PBC from
"induction to destruction" and treatment options that are
available. (Nishio A, et al. Semin Gastrointest Dis 2001;12:89-102)
Management of hepatitis B. Anna Lok et al summarize a 3-day
workshop sponsored by the NIH and AGA on the prevention and treatment of
hepatitis B virus infection. (Lok AS,
et al. Gastroenterology
2001;120:1828-1853)
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