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Clinical Question:
Is lamivudine a safe and effective for the treatment of hepatitis B in
patients with advanced liver disease?
Bottom Line:
Continuous treatment with lamivudine delays clinical progression in patients
with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly
reducing the incidence of hepatic decompensation and the risk of
hepatocellular carcinoma.
Reference:
Liaw Y-F, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic
hepatitis B and advanced liver disease. N Engl J Med 2004; 351:1521-31.
Study Design:
Randomized controlled trial (double-blinded)
Funding:
Industry
Setting:
Outpatient (specialty)
Allocation:
Uncertain
Synopsis:
The effectiveness of antiviral therapy in preventing disease progression in
patients with chronic hepatitis B and advanced fibrosis or cirrhosis is
unknown. Patients with chronic hepatitis B who had histologically confirmed
cirrhosis or advanced fibrosis were randomly assigned in a 2:1 ratio to
receive lamivudine (100 mg per day) or placebo for a maximum of five years.
Of 651 patients, 436 were assigned to receive lamivudine and 215 to receive
placebo. The primary end point was time to disease progression, defined by
hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial
peritonitis, bleeding gastroesophageal varices, or death related to liver
disease. An independent data and safety monitoring board monitored the
progress of the study and performed interim analyses of the data. We
randomly assigned 651 patients (98 percent Asian and 85 percent male) to
receive lamivudine or placebo. The study was terminated after a median
duration of treatment of 32.4 months (range, 0 to 42) owing to a significant
difference between treatment groups in the number of end points reached. End
points were reached by 7.8 percent of the patients receiving lamivudine and
17.7 percent of those receiving placebo (hazard ratio for disease
progression, 0.45; P=0.001). The Child-Pugh score increased in 3.4 percent
of the patients receiving lamivudine and 8.8 percent of those receiving
placebo (hazard ratio, 0.45; P=0.02), whereas hepatocellular carcinoma
occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of
those in the placebo group (hazard ratio, 0.49; P=0.047). Genotypic
resistance YMDD mutations developed in 49 percent of the patients treated
with lamivudine, and the Child-Pugh score was more likely to increase in
patients with these mutations than in the other patients treated with
lamivudine (7 percent vs. <1 percent). Overall, 12 percent of the patients
in the lamivudine group and 18 percent of the patients in the placebo group
reported serious adverse events. |