Subclones of drug-resistant hepatitis B virus mutants and the outcome of breakthrough hepatitis in patients treated with lamivudine.
Breakthroughs during lamivudine therapy were assessed according to hepatitis flares and mutational polymorphism of hepatitis B virus (HBV) infecting patients. Of 42 patients with chronic hepatitis B and positive for hepatitis B e antigen in serum, 13 (30%) harbored HBV mutants with lamivudine resistance after a mean duration of 29 months on lamivudine. The virological breakthrough occurred 14.5 months after the start of lamivudine treatment, and all the patients with it developed breakthrough hepatitis 3 months later. The clinical course of breakthrough hepatitis was self-limited except in one patient who had already developed cirrhosis at the baseline. One year after breakthrough hepatitis, serum ALT, albumin, prothrombin time and platelet counts were maintained well on conventional treatments without resorting to interferon. Major HBV mutants during breakthrough hepatitis were those with M552I in the YMDD motif of viral DNA polymerase/reverse transcriptase in 7 patients (54%), M552I/L528M in 4 patients (31%) and M552V/L528M in 2 patients (15%). There were no patients in whom mutations at nucleotide 529 occurred including the 2 who later developed hepatocellular carcinoma. There was no clear relationship between distinct mutational patterns and clinical courses. Further studies are needed for making out the effects of lamivudine-resistant mutants on clinical outcomes, taking into considerations genotypes of HBV.
Kumashiro
Ryukichi
R
Second Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, 830-0011, Japan. kuma@med.kurume-u.ac.jp
Kuwahara
Reiichiro
R
Ide
Tatsuya
T
Koga
Yuriko
Y
Arinaga
Teruko
T
Hisamochi
Akiko
A
Ogata
Kei
K
Tanaka
Kazuo
K
Sata
Michio
M
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D024882:Drug Resistance, Viral / Q000235:genetics; D006509:Hepatitis B / Q000188:drug therapy* / Q000503:physiopathology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology; D019694:Hepatitis B, Chronic / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009154:Mutation / Q000235:genetics*; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase