Predictive Factors and Clinical Outcome of Viral Breakthrough during Lamivudine Treatment for Chronic Hepatitis B Infection / 대한간학회지

BACKGROUND/AIMS: Long-term treatment with lamivudine causes breakthrough, but the clinical course after lamivudine breakthrough is not well known. The aims of this study were to evaluate the clinical course in lamivudine after breakthrough, and to identify predictive factors of breakthrough. METHODS: 124 patients with chronic hepatitis B infection, who represented viral breakthrough during lamivudine therapy, were included. The mean duration of lamivudine therapy and additional lamivudine therapy after breakthrough was 30.5 months and 12.5 months, respectively. RESULTS: The cumulative breakthrough rates at 12, 18, 24 and 36 months were 8, 24, 36 and 52%, respectively. After viral breakthrough, only 4 patients maintained normal ALT levels. 120 patients showed ALT elevation. The number of patients with ALT levels greater than 5 times, and greater than 10 times, the upper normal limit were 67 (56%) and 29 (24%), respectively. While still on lamivudine therapy after breakthrough, 98 patients presented ALT elevation. Only 22 had normalized ALT levels. Hepatic decompensation developed in 2 patients. HBeAg seroconversion after breakthrough occurred in 10 patients. The changing pattern of quantitative HBeAg levels during lamivudine therapy was the only predictive factor associated with viral breakthrough. The mean time of turning points in decrescendo-crescendo patterns of HBeAg levels during lamivudine therapy was earlier than viral breakthrough (9 months vs. 17 months). CONCLUSIONS: These results suggested that deterioration of hepatic function can usually be observed after breakthrough. The serial monitoring of serum quantitative HBeAg levels may allow an early recognition of viral breakthrough.

Clinical Evaluation of HBeAg Quantitation Using Enzyme Immunoassay in the Follow-Up of Patients with Chronic Hepatitis B / 대한진단검사의학회지

BACKGROUND: The quantitative measurement of HBV DNA is useful in the follow-up of patients with chronic hepatitis B. However, the disappearance of HBV DNA, which is not always followed by HBeAg seroconversion, may not predict the outcome of the treatment. We evaluated the usefulness of HBeAg quantitation in comparison with HBV DNA quantitation. METHODS: A total number of 89 blood samples from 34 patients who were diagnosed with chronic hepatitis B were evaluated for HBeAg quantitation by the Murex HBeAg Standard and the Murex HBeAg/anti-HBe (Murex Biotech, Dartford, England). HBV DNA levels were measured by the Hybrid Capture System (Digene Corp., Beltsville, MD, USA). RESULTS: Among the total of 34 patients, the changes in the HBeAg level in 19 patients were parallel to those of the HBV DNA level in serial monitoring. In 5 patients, whose results showed discrepancy in the levels of HBeAg and DNA, the HBV DNA became undetectable earlier than did the HBeAg. Their HBeAg levels were less than 100 U/mL and were followed by HBeAg seroconversion after 1-4 months. And, in 1 patient, a progressive increase in HBeAg quantitation was not followed by HBeAg seroconversion after 8 months, even though HBV DNA was persistently undetectable. The concor-dance rate between quantitative HBeAg and HBV DNA results was 78.7%. CONCLUSIONS: This study suggests that HBeAg quantitation can be helpful in predicting seroconver-sion, especially when HBeAg is positive and HBV DNA is negative.