Prognostic indicators of breakthrough hepatitis during lamivudine monotherapy for chronic hepatitis B virus infection

Journal of Gastroenterology
Yasuhito TanakaMasashi Mizokami

Abstract

Breakthrough hepatitis (BTH), defined as a flare of transaminases alanine aminotransferase [ALT]) can occur during lamivudine monotherapy for hepatitis B virus (HBV) infection. There have been many reports of lamivudine-resistant mutations within the C domain of the viral reverse transcriptase; however, the appearance of these mutants is not necessarily correlated with BTH during lamivudine therapy. Entire serial HBV genomic sequences before and during lamivudine therapy for 4 patients with BTH and 1 patient without BTH were analyzed and showed changes in the pre-S region. These changes may be associated with ALT flares. Further investigation in a cohort of 36 patients with a median treatment period of 25 months showed that 21 patients had a rise in HBV-DNA titer, of whom 18 had BTH. Univariate statistical analyses showed that possible prognostic indicators for the occurrence of BTH were pre-S deletions ( P = 0.03) and L180M/M204L mutations ( P = 0.04). By multivariate Cox regression analyses, significant variables were pre-S deletions (hazard ratio, 0.17; 95% confidence internal (CI), 0.044-0.66) and precore mutations (hazard ratio, 5.70; 95% CI, 1.74-18.71) prior to the commencement of lamivudine monotherapy. Interestingly, B...Continue Reading

Citations

Oct 29, 2014·Hepatitis Research and Treatment·Hamid Ullah WaniMuneera J Al-Mohannadi
Apr 20, 2006·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Etsuro OritoMasashi Mizokami
Apr 28, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tsuyoshi HatakeyamaKazuaki Chayama

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