Chronic hepatitis B infection can l...

Chronic hepatitis B infection can lead to cirrhosis, hepatic failure, and hepatocellular carcinoma. present therapies are successful in a minority of patients. Approximately 19 percent of patients answer to interferon alfa, and 10 to 15 percent rejoin to lamivudine (Epivir). The long-term efficacy of general agents may be worse. For lamivudine, viral resistance is reported in more than single in kind half of patients within three years. Janssen and colleagues reasoned that the combination of interferon alfa and lamivudine in a long-term treatment regimen could improve sustained answer rates in chronic hepatitis B infection.

The authors mannersed a randomized, double-blind controlled trial at 42 center in 15 countries to compare the safety and effectiveness of interferon alfa monotherapy with combination therapy using interferon alfa plus lamivudine. Participants were at least 16 years of age and had been positive for hepatitis B surface antigen for at least six month In the eight weeks before randomization, participants were required to be positive for hepatitis B e antigen (HBeAg) in succession at least two occasions and to have sum of two units documented measurements of alanine transaminase on a levels that were at least twice the upper limit of the normal range. Patients were exclud from the application of mind if they had antibodies against hepatitis C or D viruses or if they were positive for human immunodeficiency virus. Patients with a history of antiviral or immunosuppressive therapy within the previous six months; pregnancy or inadequate contraception in women; substance abuse; liver, thyroid, psychiatric, or serious medical conditions; and inadequate leucocyte granulocyte, or platelet casts also were excluded. After screening, patients were randomly assigned to therapy with 100 mcg pegylated interferon alfa-2b one time per week plus 100 mg lamivudine (combination therapy), or to monotherapy using 100 mcg pegylated alfa-2b weekly plus a daily placebo. After 32 weeks, the interferon dose in the two groups was lowered to 50 mcg by week. Patients were monitored at outpatient clinics each four weeks during the 52 weeks of the subject of attention and for 26 weeks after treatment. In addition to monitoring of laboratory markers and reported adverse forces participants underwent liver biopsy at the beginning of the thought and were offered repeat biopsy after treatment.

Of the 307 patients randomized, 266 (87 percent) were included in the analysis. Reasons for exclusion included nonadherence with medication or follow-up visits, clearance of HBeAg before starting therapy, and moot points in data verification from united study center. The patients in the brace treatment groups were comparable at recruitment and at conclusion of the inquiry By the end of the 52 weeks, significantly more patients using combination therapy corresponded with loss of HBeAg (44 percent compared with 29 percent) However, on the end of the follow-up period (at 78 weeks), 35 percent of the combination therapy assign places to and 36 percent of the monotherapy assemblage had sustained response. This pattern was shown in couple other markers of hepatitis B infection. Fibrosis scores improved in 33 percent of the 52 combination therapy patients who agreed to brace biopsies, compared with 22 percent of the 58 patients assigned to monotherapy. Biopsies revealed deteriorating fibrosis scores in 38 percent of available patients in as well-as; not only-but also; not only-but; not alone-but treatment groups. Regardless of treatment assemblage the sustained response rate was significantly influenced by means of the hepatitis B virus genotype. For genotypes A and B the sustained answer rates were 47 and 44 percent respectively. For genotypes C and D the comparable rates were 28 and 25 percent Side purports were common, especially influenza-like syndrome which affected 62 to 74 percent of patients. Thirty-two serious adverse weights were reported, of which common half were attributed to therapy. Despite adverse imports 91 percent of patients remained upon therapy after the study.

The authors bring to an end that combination therapy was superior to monotherapy through the whole extent of 52 weeks, but this advantage was not sustained during follow-up They emphasize that long-term use of lamivudine is contraindicated because of put drugs into resistance, and that the virus genotype is a tonic predictor of response to antiviral therapy.

ANNE D WALLING, MD Janssen HLA, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet January 8 2005;365:123-9

COPYRIGHT 2005 American Academy of Family Physicians

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