Long-term prognosis by lamivudine monotherapy for severe acute exacerbation in chronic hepatitis B infection: emergence of YMDD motif mutant and risk of breakthrough hepatitis – an open-cohort study

Background/Aims: Comparison of long-term prognosis in patients with chronic hepatitis B treated with lamivudine, with or without severe acute exacerbation (SAE). Methods: In chronic hepatitis B HBeAg-positive patients on lamivudine monotherapy, 21 patients with SAE were retrospectively compared with 63 patients without SAE. Both groups were matched for age and sex. We investigated the efficacy and problems associated with monotherapy with respect to SAE. Results: In SAE and non-SAE, HBeAg seroconversion rates were 21.1 vs. 27.6%, 20.0 vs. 50.0%, and 14.3 vs. 66.7% at 1, 2, and 3 years, respectively. YMDD mutant emerged later in SAE than in non-SAE, but the emergence rates in SAE almost exceeded those of non-SAE from 2 years (rates of about 35%). DNA breakthrough (hepatitis B virus DNA becoming detectable after a period of negativity, accompanied by emergence of YMDD mutant) and breakthrough hepatitis (alanine aminotransferase becoming abnormal after a period of normalization, accompanied by DNA breakthrough) also appeared later in SAE than in non-SAE, but the rates in SAE exceeded those of non-SAE at 3 years. Conclusions: Our results suggest that Japanese genotype C-dominant hepatitis B patients with SAE seem to be at greater risk of re-exacerbation after temporary relief of the initial SAE by long-term lamivudine monotherapy, compared with those without SAE.