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HEPATOLOGY WATCH® |
Editorial Board: Emmet B. Keeffe, MD
(Chair); John L. Gollan, MD, PhD; Kris V. Kowdley, MD; Paul
Martin, MD; Marion G. Peters, MD |
AUGUST 2005
CHRONIC HEPATITIS C VIRUS (HCV) INFECTION
Performance of endoscopy is not a risk factor for HCV transmission. Alessia Ciancio and colleagues
investigated the role of gastrointestinal endoscopy in transmitting HCV
infection by retesting 8,260 anti-HCV–negative patients for anti-HCV 6 months
after undergoing an endoscopic procedure in 3 endoscopic units in
Peginterferon alfa-2b and ribavirin treatment for 12 vs 24 weeks in HCV
genotype 2 or 3. Alessandra
Mangia and others conducted a randomized study in which 283 patients with
genotype 2 or 3 HCV infection received peginterferon alfa-2b 1 µg/kg weekly
plus ribavirin 1,000 to 1,200 mg/day. Among these patients, 70 were treated
with peginterferon and ribavirin for 24 weeks (standard-duration group), while
the remaining 213 patients were assigned to a variable-duration group in which
patients who were HCV RNA–negative at week 4 received therapy for 12 weeks and
patients who were HCV RNA–positive at week 4 received therapy for 24 weeks. At
week 4, 64% and 62% of patients in the standard- and variable-duration groups,
respectively, were HCV RNA–negative. A sustained virologic response was
achieved in 76% of patients in the standard-duration group and 77% of patients
in the variable-duration group. The rate of relapse was similar in the
standard- and variable-duration groups (3.6% and 8.9%, respectively). Among
patients in the variable-duration group, fewer patients receiving 12 weeks than
24 weeks of therapy experienced adverse events and withdrew from treatment. These
results show that 12 weeks of peginterferon alfa-2b plus ribavirin is as
effective as a 24-week course of therapy in patients with HCV genotype 2 or 3
infection who have undetectable serum HCV RNA at 4 weeks of treatment. (Mangia
A, et al. N Engl J Med. 2005;352:2607–2617)
CHRONIC HEPATITIS B VIRUS (HBV) INFECTION
Long-term adefovir dipivoxil therapy for hepatitis B e antigen (HBeAg)-negative
patients. Stephanos
Hadziyannis and associates randomized 185 HBeAg-negative patients with chronic
HBV to receive adefovir dipivoxil 10 mg or placebo (2:1) once daily for 48
weeks. After week 48, controls were switched to adefovir dipivoxil treatment
and patients in the original adefovir dipivoxil group were randomized to
receive an additional 48 weeks of that drug (continued adefovir group) or
placebo (adefovir-placebo group). A rapid reduction in serum HBV DNA levels was
observed in the patients treated with adefovir dipivoxil. However, serum HBV
DNA levels at week 96 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). Moreover, at
week 144, serum HBV DNA levels were <1,000 copies/mL in 79% of patients in
the continued adefovir group. The safety profile was similar between patients
receiving 48 and 96 weeks of adefovir dipivoxil, and mutations were identified
in only 5.9% of patients after 144 weeks. These findings demonstrated that
continuation of adefovir dipivoxil therapy beyond week 48 is required to
maintain virologic response in patients with HBeAg-negative chronic hepatitis B.
(Hadziyannis SJ, et al.
Adefovir resistance during 4 years of treatment. Lamivudine-resistant HBV has been
reported to emerge in 70% of HBV patients by 4 years of lamivudine therapy. In
the current preliminary report, Stephen Locarnini and others analyzed 5 studies
in which patients were treated with adefovir dipivoxil for 48 to 192 weeks. The
cumulative probability of adefovir resistance was 0%, 2%, 7%, and 15% at 48,
96, 144, and 192 weeks of therapy. No adefovir-resistant mutations were
identified in patients who received lamivudine plus adefovir therapy. Logistic
regression analyses identified only higher serum HBV DNA levels at week 48 to
predict adefovir resistance. These data indicate that the chance of developing
resistance by 4 years of treatment is 4-fold lower with adefovir than with lamivudine
therapy. (Locarnini S, et al. J Hepatol. 2005;42[suppl 2]:17)
Peginterferon alfa-2a vs lamivudine. George Lau and associates conducted a partially
double-blind study in which 814 patients with HBeAg-positive chronic HBV were
randomized to receive (1) 48 weeks of peginterferon alfa-2a 180 µg subcutaneously
once weekly 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 seroconversion (P = 0.001), and serum HBV DNA levels <100,000 copies/mL (P = 0.01). No efficacy differences 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 groups, respectively. This
study showed that peginterferon therapy in patients with HBeAg-positive chronic
hepatitis B results in superior outcomes compared with lamivudine monotherapy. (Lau
GKK, et al. N Engl J Med.
2005;352:2682–2695)
The maze of treatments for hepatitis B. In an editorial,
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