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Prevalence and Clinical Correlates of YMDD Variants during Lamivudine Therapy for Patients with Chronic Hepatitis B

Ching‐Lung Lai, Jules L. Dienstag, Eugene R. Schiff, Nancy Leung, Mark Atkins, Christine M. Hunt, Nathaniel Brown, Mary Woessner, Richard Boehme, Lynn D. Condreay

Clinical Infectious Diseases · 2003 · 637 citations · 36 references

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TL;DR

Lamivudine therapy for chronic hepatitis B can select for YMDD variants of HBV. In 794 patients across four controlled studies, YMDD variants were identified by PCR and restriction fragment‑length polymorphism assays, and their long‑term effects were followed for up to four years. After one year, 24 % of patients developed YMDD variants, yet their HBV DNA, ALT, and histology improved; over four years, similar improvements were seen, and emergence was linked to sex, BMI, and baseline HBV DNA, suggesting that patients with rising viral load and ALT may need additional treatment.

Abstract

YMDD variants of hepatitis B virus (HBV) emerge in some patients with chronic hepatitis B who receive lamivudine. YMDD variants were examined in 794 patients in 4 controlled studies of 1 year's duration. The long-term effects of YMDD variants were examined in a subset of patients treated up to 4 years. YMDD variants were detected by polymerase chain reaction (PCR) and restriction fragment-length polymorphism assays. After 1 year, YMDD variants were detected in 81 (24%) of 335 patients. In these patients, the median serum HBV DNA concentration at 1 year was <20% of the baseline level, and serum alanine transaminase (ALT) levels and liver histologic findings had significantly improved. In patients with YMDD variants who were treated for up to 4 years, median HBV DNA and ALT levels showed improvements. Sex, baseline body mass index, and HBV DNA level were associated with emergence of YMDD variants. Patients with YMDD variants losing clinical response with a significant increase in the HBV DNA and ALT levels may require additional therapy.