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Editorial
Board:
Emmet B. Keeffe, MD (Chair);
Anna
Lok, MD; Brian McMahon, MD; Albert Min, MD; Myron Tong, MD; Naoky Tsai, MD;
Bruce Tung, MD
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HBV Watch™
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Timely Information for Practicing Physicians
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Hepatocellular Carcinoma
(HCC) in Taiwanese Children
Prospective study of Taiwanese children with chronic
HBV infection. A strong association between HBV
infection and HCC has been shown by epidemiologic studies. HCC usually occurs after decades of HBV
infection, but the incidence of childhood HCC is high in Taiwan, a region hyperendemic for
HBV. The nearly 100% seropositive rate
of HBsAg in Taiwanese children with HCC indicates the important role of HBV
infection in childhood HCC. Wan-Hun Wen and
colleagues prospectively followed 426 children with chronic HBV infection in Taiwan recruited from the years 1974 to
1995 (6,250 person-years). The median
age at study entry was 6.3 years (range, 3 days to 14.8 years), and the median
duration of observation was 14.9 years (range, 5.1 to 27.2 years). Three patients progressed to cirrhosis and 2
of these patients developed HCC (incidence, 32 per 100,000 person-years). The 2 patients who developed HCC were among
only 8 children who had seroconverted from HBeAg-positivity to anti-HBe before
the age of 3 years. The authors
speculated that the extremely young age of HBeAg seroconversion and preceding
hepatocyte necrosis may explain the vulnerability of the liver to fibrosis and
early malignant transformation. These
data need to be confirmed as HBeAg seroconversion in adults is associated with
reduced incidence of HCC. (Wen W-H, et
al. J Pediatr 2004;144:397-399)
Treatment with
Alpha-Interferon (IFN)
Long-term follow-up. The aim of treatment for chronic HBV
is inactivation of liver disease as indicated by the disappearance of serum HBV
DNA and HBeAg seroconversion. IFN has
been reported to be associated with an HBeAg seroconversion rate as high as
33%. To further evaluate the long-term
effects of IFN therapy, Monika van Zonneveld and others from the Erasmus Medical Center (Rotterdam, The Netherlands) performed a
retrospective cohort study of all HBeAg-positive patients treated with
IFN-based therapy in their liver unit between 1978 and 2002. The study population consisted of 165
patients (133 patients were treated in trials and 32 patients were treated
electively). In addition, 62 of these
patients (38%) had received nucleoside analogues in combination with IFN. The median duration of therapy was 16 weeks
(range, 1 - 92 weeks) and the median follow-up time was 8.8 years (range, 0.3 -
24 years). A response (HBeAg
seroconversion within 12 months after the end of IFN therapy) was achieved by
54 patients (33%). HBeAg reactivation
occurred in 7 (13%) of the responders.
HBsAg seroconversion developed in 52% of responders compared to 9% of
nonresponders. Decreased
necroinflammatory activity and decreased progression of fibrosis were observed
in liver biopsy specimens of responders.
HCC developed in 8 patients (6 of these patients were
nonresponders). Multivariate analysis
identified response to IFN-based therapy as an independent predictor of
survival and reduced risk for HCC. These
findings demonstrated that response to IFN-based therapy was associated with
prolonged clinical remission and improved clinical and histopathological
outcomes. (van Zonneveld M, et al. Hepatology 2004;39:804-810)
Epidemiology
Changes in a US community. The incidence of newly acquired HBV infection in the US has declined steadily since the
mid-1980s. This trend is thought to be
due to a number of public health interventions such as the screening of
pregnant women, the vaccination of infants and adolescents, and the use of safe
injection practices. In the current
study, W. Ray Kim and coworkers at the Mayo Clinic analyzed the demographic and
clinical characteristics of subjects with chronic HBV infection in Olmsted County, Minnesota.
There were 191 county residents identified with chronic HBV infection
from The Rochester Epidemiology Project records. The ethnic origins of these residents with
HBV infection were 53% Asian, 29% African, 13% Caucasian, and 5% other. The
overall age- and sex-adjusted prevalence of HBV infection in this community was
0.15%. The prevalence was highest among
Asians (2.1%) and African-Americans (1.9%).
The prevalence among Caucasians was 0.02%. A large majority of the 191 county residents
with HBV infection had been born outside of the US (86%). Among 131 HBsAg-positive residents tested for
HBV replicative status, 27% had viral replication as defined by the presence of
HBeAg or HBV DNA. Among 184 residents
tested for ALT levels, 28% had an abnormal value at least once. These findings demonstrated that most
residents with chronic HBV infection in this Midwestern community were
immigrants from other parts of the world endemic for HBV and underscore the
importance of screening immigrants for HBV infection. (Kim WR, et al. Hepatology 2004;39:811-816)
Treatment Guidelines
Recommendation updates. Based on new developments in the diagnosis and treatment of
chronic HBV infection, two treatment guidelines were recently published. The first guideline (Anna Lok and Brian
McMahon) was developed under the auspices of the Practice Guideline Committee
of the AASLD and published in the March 2004 issue of Hepatology. A complete version, including a review of
recently published literature, can be found at the AASLD web site. The recommendations were based on literature
review and the experience of the authors, and reviewed and approved by the
AASLD Governing Board. The second
guideline is a treatment algorithm for chronic HBV infection developed by a
panel of US hepatologists and published in the February 2004 issue of Clinical Gastroenterology and Hepatology.
The algorithm was based on available
evidence and also clinical experience and expert opinion. The recommendations of the two guidelines are
generally similar but there are differences in some areas (e.g., consideration
of treatment of patients with serum HBV DNA levels <105
copies/mL, possible use of combination therapy). (Lok ASF and McMahon BJ. Hepatology
2004;39: 857-861 and Keeffe EB, et al. Clin
Gastroenterol Hepatol 2004;2:87-106)
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