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HBeAg-positive patients who continue lamivudine after HBeAg seroconversion less likely to have detectable HBV DNA levels, ALT flares, retrospective analysis reveals

Wednesday, August 26 2009 | Comments

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What's This? Among patients who are hepatitis B early antigen (HBeAg)-positive, those who continue treatment with lamivudine may be less likely to have detectable hepatitis B virus (HBV) DNA levels and alanine aminotransferase (ALT) flares during long-term follow-up, according to findings from a retrospective analysis conducted in patients treated at Queen Mary Hospital in Hong Kong. Findings also suggest that continued treatment is associated with low rates of resistance.

The study included 101 patients with lamivudine-induced HBeAg seroconversion, including 22 patients who stopped lamivudine therapy after seroconversion and 79 patients who continued treatment. All of the patients who discontinued lamivudine did so for cost reasons, the investigators noted.

In the group of patients who discontinued treatment, the median follow-up after HBeAg seroconversion was 53 months, and the median follow-up after discontinuation of lamivudine was 20 months. In the group of patients who continued lamivudine, the median follow-up after HBeAg seroconversion was 43 months.

Among those who stopped therapy, the 5-year cumulative incidence of HBeAg seroreversion was 9%.

Of the 79 patients who continued treatment, 78% had undetectable HBV DNA levels (<60 copies/mL) at last follow-up. By comparison, none of the patients who stopped therapy had undetectable HBV DNA levels (P<.001).

The 5-year cumulative incidence of ALT flares was 44% among those who stopped therapy versus 16% in those who continued treatment (P<.001). In a Cox regression model, stopping lamivudine therapy was a significant predictor of subsequent ALT flares.

Lamivudine-resistant mutations occurred in 8 patients (10%) who continued lamivudine therapy.

"Given the absence of robust biochemical or viral factors in predicting relapse after the cessation of antiviral therapy, and the relatively low incidence of lamivudine-resistant mutations after HBeAg seroconversion, long-term treatment may be a more favorable option," the authors concluded. (Fung J, et al. Am J Gastroenterol 2009;104:1940-1946.)

In an accompanying editorial, Drs. Catherine Frenette and Robert Gish with the California Pacific Medical Center in San Francisco commented on current treatment recommendations, which regard HBeAg seroconversion as the endpoint that guides decisions related to starting and stopping therapy. They suggested that the high relapse rate, the high rate of mixed infection, and the prevalence of HBeAg-negative disease indicate that HBeAg status is not the appropriate marker for when to end treatment.

"Hepatitis B surface antigen (HBsAg) loss or seroconversion is associated with a favorable prognosis in both HBeAg-positive and HBeAg-negative disease and should be considered the test result that, combined with undetectable HBV DNA, will trigger treatment cessation," the editorialists commented. (Am J Gastroenterol 2009;104:1948-1952.)

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