Comparison of clinical outcome between patients continuing and discontinuing lamivudine therapy after biochemical breakthrough of YMDD mutants

Background/Aims The aim of this study was to compare the clinical outcome between patients continuing and discontinuing lamivudine therapy after the biochemical breakthrough of hepatitis B virus tyrosine-methionine-aspartate- aspartate (YMDD) mutant. Methods YMDD mutants were detected in 51 chronic hepatitis B patients who experienced a flare-up of alanine aminotransferase (ALT) during lamivudine treatment. Twenty-seven of them discontinued lamivudine therapy (group A), and 24 continued therapy (group B) after biochemical breakthrough. The follow-up period was 12 months in both the groups. Results There was no significant difference between groups A and B in the incidence and severity of ALT peaks and hepatic decompensation within the first 3 months after biochemical breakthrough. After the fourth month of biochemical breakthrough, however, group A experienced acute exacerbation more frequently [20/26 (77%) vs. 7/23 (30%); P=0.002] and higher ALT peaks than group B. The same result was found when the patients were divided into naïve and retreated or cirrhotic and non-cirrhotic groups. Hepatic decompensation at the onset of biochemical breakthrough was associated with higher mortality (OR=70, 95% CI=6.06-807.75). Conclusions Patients who discontinued lamivudine therapy increased the frequency of flare-ups and higher ALT peaks than those who continued therapy after 4 months post-breakthrough.