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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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DECEMBER 2005
Entecavir dose-ranging study. Chang and colleagues conducted a
dose-ranging phase II study of entecavir, a nucleoside analog with potent in vitro activity against hepatitis B
virus (HBV), including lamivudine-resistant HBV. In this study, 182 patients
with lamivudine-resistant HBV were randomized to receive entecavir 0.1, 0.5, or
1.0 mg/day orally or to continue lamivudine 100 mg/day for up to 76 weeks. At week 24, a greater percentage of
patients treated with entecavir 0.5 or 1.0 mg/day achieved undetectable serum
HBV DNA levels than did patients treated with lamivudine (51% and 79% vs 13%). Moreover,
the difference between the proportion of entecavir 0.5 mg/day–treated patients
and entecavir 1.0 mg/day–treated patients achieving undetectable HBV DNA levels
was significant. After 48 weeks of therapy, the mean reductions in serum HBV DNA levels
attained in all three entecavir groups were significantly greater than that in the
lamivudine group. In addition, 47%, 59%, and 68% of patients treated with
entecavir 0.1, 0.5, and 1.0 mg/day, respectively, achieved normalization of alanine
aminotransferase (ALT) levels compared with only 6% of patients in the
lamivudine group. Viral rebound was observed in two, three, and no patients,
respectively. These results suggest that entecavir may be clinically beneficial
for lamivudine-refractory HBV infection. (Chang TT, et al. Gastroenterology. 2005;129:1198–1209.)
Relation of HBV flares to treatment
response. Flares of
inflammatory activity commonly occur during therapy for chronic hepatitis B;
however, little is known about their effect on response to treatment. Flink and
others analyzed data from 266 patients with hepatitis B e antigen (HBeAg)-positive
chronic hepatitis B who received peginterferon alfa-2b therapy in an
international study to clarify the role of flares. A total of 67 patients (25%)
experienced 75 flares. In 24 patients (36%) the flare was followed by a
decrease in serum HBV DNA level (host-induced flare), while in 25 patients (37%)
the flare was preceded by an increase in HBV DNA level (virus-induced flare). The
response rate was 58% among patients with host-induced flares and 20% in
patients with virus-induced flares (P
= 0.008). Multivariate logistic analysis identified host-induced flares to be
an independent predictor of response. Overall, 30% of patients with flares,
compared with 38% of patients without flares, responded to peginterferon
therapy (P = 0.25). These data show
that although flares do not occur more commonly in responders, host-induced
flares are highly associated with treatment response. (Flink HJ, et al. Gut 2005;54:1604–1609.)
HBV reactivation following
lamivudine withdrawal in patients who completed cytotoxic chemotherapy. Hui and associates examined the
occurrence of hepatitis B reactivation in 46 consecutive hepatitis B surface
antigen (HBsAg)-positive patients who underwent treatment with cytotoxic
chemotherapy for hematologic malignancy. Preemptive lamivudine therapy was
initiated 1 week prior to the start of chemotherapy and was stopped at a median of 3.1
months after its completion. Following the withdrawal of lamivudine, patients
were followed for a median of 25.7 months (range, 5.7 to 75.7 months). Eleven patients
(23.9%) developed HBV reactivation during follow-up. These hepatic flares were
associated with high pre-chemotherapy HBV DNA levels (≥104
copies/mL) and HBeAg positivity. These data suggest that a more prolonged
course of antiviral therapy may be necessary for chemotherapy-treated patients
at high risk for HBV reactivation. (Hui C-K, et al. Gut. 2005;54:1597–1603.)
Prognostic determinants in Asian
patients with chronic HBV. Yuen and colleagues report data from 3,233 Chinese patients with HBV followed
at the Queen Mary Hospital, Hong Kong, from January 1976 to December 2000.
All patients were HBsAg-positive for ≥6 months, and patients who had
already experienced cirrhosis-related complications (eg, ascites, spontaneous
bacterial peritonitis, esophageal varices, encephalopathy, hepatocellular
carcinoma) prior to presentation were excluded. Liver biochemistry, viral
serology, and HBV DNA levels were checked every 3 to 6 months. Median follow-up
was only 30 months; 30% and 10% of patients were followed for 5 and 10 years,
respectively. Peak ALT levels during acute exacerbations, the number of hepatic
flare episodes, and HBeAg status were not associated with the development of
complications. However, patients with ALT levels 0.5 to 2 times the upper limit
of normal during follow-up had an increased risk for complications (P <0.0001). In addition, the Cox
proportional hazards model identified male gender, presence of stigmata of
chronic liver disease, increasing age, low albumin level, and high
alpha-fetoprotein level to be independent factors associated with the
development of complications. Male gender, hepatitis symptoms, increasing age,
and low albumin level were associated with shorter actuarial survival. These
data indicate that continuous liver damage, as reflected by elevated ALT
levels, leads to complications of chronic hepatitis B in Asians. Longer
prospective studies are needed. (Yuen M-F, et al. Gut. 2005;54:1610–1614.)
Maternal HBsAg carrier status and
pregnancy outcomes.
Tse and colleagues performed a retrospective case-control study to examine the
impact of maternal HBsAg carrier status on pregnancy outcomes. A total of 253
maternal HBsAg carriers were compared with 253 controls matched for age,
parity, and year of delivery. Infants born to HBsAg carriers had lower Apgar
scores and an increased incidence of intraventricular hemorrhage. Mothers who
were HBsAg carriers had higher incidences of gestational diabetes mellitus,
antepartum hemorrhage, and threatened preterm labor. Thus, HBsAg carrier status
may be a risk factor for maternal and neonatal well-being. Further studies are
warranted. (Tse KY, et al. J Hepatol.
2005;43:771–775.)
HBV DNA levels in serum, saliva, and
urine. van der Eijk
and coworkers discovered a high correlation between serum HBV DNA levels and levels of
HBV DNA in saliva and urine, thus suggesting that these body fluids may be
sources of horizontal HBV transmission. (van der
Eijk AA, et al. Eur J Gastroenterol
Hepatol. 2005;17:1173–1179.)
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