Elevated ALT Predicts HBeAg Loss with Epivir-HBV Treatment

liver411

By Brian Boyle, MD

Research efforts are currently underway in both hepatitis C virus (HCV) and hepatitis B virus (HBV) infection to determine with more accuracy the predictors of successful therapy.

Several studies have shown that elevated alanine transaminase (ALT) levels and low HBV viral loads are somewhat predictive of successful therapy with interferon as indicated by a higher likelihood of hepatitis B e antigen (HBeAg) clearance. HBeAg clearance is considered an important marker of HBV replication and the clearance of HBeAg is an indicator of a lower level of HBV replication, which may be associated with an improvement in long-term outcomes. At this point, however, predictors of HBeAg clearance in patients treated with Epivir-HBV (lamivudine, 3TC) are not known.

In a study published in Hepatology, investigators reviewed the results of 4 Phase III clinical trials involving Epivir-HBV and interferon in the treatment of chronic HBV to determine if there were any factors that were predictive of clearance of HBeAg. In these studies, which involved a total of 805 adults with chronic HBV, the subjects were randomized to be treated with either Epivir-HBV, Interferon, the combination of the 2 or a placebo.

The investigators found that HBeAg loss was related to pretreatment ALT levels in all of the groups studied. The rate of HBeAg clearance was highest in patients with pretreatment ALT levels greater than 5 times the upper limit of normal (ULN) and was most pronounced in the patients treated with Epivir-HBV. Using a multivariate analysis, the investigators found that an elevated baseline ALT level and histologic activity index score were significant predictors of HBeAg clearance in response to treatment with Epivir-HBV.

The authors conclude, "analyses of a large series of patients with chronic hepatitis B treated for 1 year revealed that pretreatment ALT level was a significant predictor of HBeAg loss secondary to lamivudine treatment. As pretreatment ALT levels increased, HBeAg loss became more frequent and the rate of HBeAg loss was markedly higher among patients with pretreatment ALT levels greater than 5 times the ULN.

"The rates of HBeAg loss appeared similar for Asians and Caucasians treated with lamivudine across all ALT groups. Analyses using both univariate and multivariate techniques suggested that the patients most likely to experience HBeAg loss in response to treatment with lamivudine were patients with active liver disease as evidenced by elevated pretreatment levels of ALT and/or a significant level of necroinflammatory activity on pretreatment liver biopsy.

"Taken together, the association of baseline ALT level with response and high baseline HAI activity reaffirm the importance of the immune response to HBV in affecting a sustained suppression of viral replication."

07/03/02

Reference
R Perrillo and others. Predictors of HBeAg Loss After Lamivudine Treatment for Chronic Hepatitis B. Hepatology 2002; 36:186-194.

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