Clinical Question: Is lamivudine sa...

Clinical Question: Is lamivudine safe and effective for the treatment of hepatitis B infection in patients with advanced liver disease?

Setting: Outpatient (specialty)

contemplation Design: Randomized controlled trial (double-blinded)

Allocation: Uncertain

Synopsis: The authors identified adults with chronic hepatitis B infection who were hepatitis B e antigen (HBeAg) positive or HBeAg negative with detectable hepatitis B virus DNA and who had histologic evidence of advanced liver fibrosis (i.e., an Ishak fibrosis score of 4 or more forward a scale of 0 to 6) Exclusion criteria included hepatocellular carcinoma, a serum alanine transaminase flat more than 10 times the upper limit of normal, hepatic failure, autoimmune hepatitis, co-infection with hepatitis C or human immunodeficiency virus, anemia, leukopenia, and thrombocy-topenia. Allocation appeared to have been concealed between the walls of a central randomization process (although no details were given), and analysis was by dint of intention to treat. Outcomes were assessed by means of a committee masked to treatment assignment. greatest in quantity of the patients were men (85 percent) and almost all were Asian.

Participants were randomized to receive lamivudine in a dosage of 100 mg for day (n = 436) or placebo (n = 215) and were suppos to be followed for five years. However, the thought ended prematurely once the benefit of lamivudine become apparent. The primary cessation point was a combined issue called "time to disease progression," and included an increase in the Child-Pugh score of pair or more points, spontaneous bacterial peritonitis with sepsis, renal insufficiency, variceal bleeding, hepatocellular carcinoma, or death caused according to liver disease.

After a median treatment duration of 32 month 34 patients in the lamivudine dispose and 38 patients in the placebo clump had reached the primary combined cessation point (7.8 versus 17.7 percent; P = 001; absolute risk reduction = 99 percent; number emergencyed to treat [NNT] = 10) chiefly of the benefit was attributed to fewer patients with an increased Child-Pugh score (34 versus 88 percent; P = 02; NNT = 18) and fewer cases of hepatocellular carcinoma (39 versus 74 percent; P = 05; NNT = 29) After reaching an period point, patients had the option of receiving lamivudine during an open-label continuation phase of the study

During the double-blind phase, brace deaths occurred in the lamivudine dispose compared with none in the placebo clump Serious adverse events were similar between arranges (12 percent for lamivudine versus 18 percent for placebo; P = 09) However, when the open-label phase of the trial is included, more deaths occurr in the lamivudine cluster (12 versus four; statistical significance not reported). Approximately single half of the patients in the lamivudine dispose developed the YMDD mutation during treatment, speculation to be caused by lamivudine. These patients were more likely to reach the primary period point than those who remained negative (11 versus 4 percent) and were more likely to die of hepatocellular carcinoma, however they still did better than patients receiving placebo.

Bottom Line: For each 10 patients with chronic hepatitis B infection and advanced liver disease who take lamivudine instead of placebo for 25 years, undivided fewer patient experiences progression of liver disease. Long-term use of lamivudine repeatedly triggers the YMDD mutation, and the benefit is attenuated in these patients. (Level of Evidence: 1b)

consideration Reference: Liaw YF, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J M October 7 2004;351:1521-31

Used with permission from Ebell M Lamivudine graduals progression in Hep B with advanced fibrosis. Accessed online November 24 2004 at: http://www.InfoPOEMs.com.

COPYRIGHT 2005 American Academy of Family Physicians

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