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Editorial Board: Emmet B. Keeffe, MD (Chair); |
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HBV
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Timely Information for Practicing Physicians |
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AUGUST 2005
HBeAg-negative CHRONIC HEPATITIS B
Long-term lamivudine therapy. George Papatheodoridis and
colleagues reviewed the clinical outcomes of 201 patients with hepatitis B e
antigen (HBeAg)-negative chronic hepatitis B who had received long-term therapy
with the nucleoside analog lamivudine. The results were compared with those of
2 historical cohorts: the first cohort (n = 209) was treated with
interferon-alpha and the second cohort (n = 195) was untreated. Virologic and
biochemical responses at 48 months of lamivudine therapy occurred in 34% and
36% of patients, respectively. The 5-year overall and event-free survival rates
were 96% and 93%, respectively, and were independently associated with response
to treatment. Furthermore, overall and event-free survival were improved significantly
in patients who were treated with long-term lamivudine therapy or were
sustained responders to interferon compared with patients who were untreated or
were not sustained responders to interferon. These data show that long-term
nucleoside analog therapy improves survival and reduces the incidence of major
complications in patients with HBeAg-negative chronic hepatitis B. However, the
benefit is observed mostly among patients without lamivudine resistance. (Papatheodoridis
G, et al. Hepatology. 2005;42:121–129)
Long-term adefovir dipivoxil therapy.
Stephanos
Hadziyannis and others randomized 185 HBeAg-negative patients with chronic
hepatitis B to receive adefovir dipivoxil 10 mg or placebo once daily for 48
weeks (2:1). After week 48, controls were switched to adefovir dipivoxil and
patients in the original adefovir dipivoxil group received an additional 48
weeks of the drug (continued adefovir group) or placebo (adefovir-placebo
group). Week 96 serum HBV DNA levels were <1,000 log copies/mL in 71% of
patients in the continued adefovir group compared with only 8% of patients in
the adefovir-placebo group (P
<0.001). At week 144, serum HBV DNA levels were <1,000 copies/mL in 79%
of patients in the continued adefovir group. Adefovir-resistant mutations were
identified in only 5.9% of patients, and an increase in serum creatinine was
observed in 3 patients after 144 weeks. These findings demonstrate that
continuation of adefovir dipivoxil therapy beyond week 48 is required to
maintain virologic responses in HBeAg-negative patients with chronic hepatitis
B. However, long-term therapy is associated with a small but increasing risk of
resistance and nephrotoxicity. (Hadziyannis SJ, et al. N Engl J Med. 2005;352:2673–2681)
HBeAg-positive CHRONIC
HEPATITIS B
Peginterferon
alfa-2a vs lamivudine. George Lau and associates conducted a partially double-blind
study in which 814 patients with HBeAg-positive chronic hepatitis B were
randomized to receive 48 weeks of (1) peginterferon alfa-2a 180 µg once weekly
subcutaneously plus oral placebo, (2) peginterferon alfa-2a plus oral
lamivudine 100 mg/day, or (3) lamivudine alone. At week 72, more patients who
received peginterferon-containing therapy than patients who received lamivudine
monotherapy achieved HBeAg seroconversion (P
<0.001), hepatitis B surface antigen (HBsAg) seroconversion (P = 0.001), or serum HBV DNA levels <100,000
copies/mL (P = 0.01). No differences in
efficacy were observed between the 2 peginterferon-containing groups. Serious
adverse events occurred in 4%, 6%, and 2% of patients in the peginterferon
alfa-2a plus placebo, combination therapy, and lamivudine monotherapy treatment
groups, respectively. This study showed that peginterferon treatment of patients
with HBeAg-positive chronic hepatitis B results in superior outcomes compared
with lamivudine monotherapy and that the addition of lamivudine to
peginterferon does not increase the rate of off-treatment response. (Lau GKK,
et al. N Engl J Med. 2005;352:2682–2695)
Experimental
Therapy
Phase II dose-finding study of
emtricitabine. Emtricitabine
(FTC) is a pyrimidine analog that has demonstrated antiviral activity against hepatitis
B virus (HBV) in early studies. The current study conducted by Robert Gish and
co-workers was a double-blind trial in which 98 patients with chronic HBV
infection were randomized to receive emtricitabine 25, 100, or 200 mg/day for
48 weeks. Patients were then given emtricitabine 200 mg for an additional 48
weeks. During the first 48 weeks antiviral responses were observed to be
proportional to the dose. After 2 years, serum HBV DNA levels were ≤4,700
copies/mL in 53% of patients, HBeAg seroconversion to anti-HBe occurred in 33%
of patients, and serum alanine aminotransferase levels normalized in 85% of
patients. Resistant mutations identical to those that confer resistance to
lamivudine developed in 18% of patients treated with emtricitabine 200 mg/day
for 2 years. Emtricitabine was well tolerated. The high rate of drug resistance
precludes further development of emtricitabine monotherapy. (Gish RG, et al. J Hepatol. 2005;43:60–66)
Editorial
The maze of treatments for hepatitis
B. In an
editorial,
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