title: Polymerase domain B mutation is associated with hepatitis relapse during long-term lamivudine therapy for chronic hepatitis B.
abstract: Breakthrough hepatitis remains the major issue in long-term lamivudine therapy for chronic hepatitis B. However, the emergence of drug-resistant hepatitis B virus (HBV) is not always accompanied by a relapse of hepatitis. To elucidate factors predictive of breakthrough hepatitis, 53 patients with genotype C of HBV on long-term lamivudine therapy were analyzed. HBV reappeared during therapy in 19 patients with a cumulative incidence of 15% at 1 year, 34% at 2 years, and 60% at 3 years. Within this group, breakthrough hepatitis developed in 12 patients (63%). A polymerase gene domain B mutation (rt180M) emerged in 13 patients, and domain C mutations (rt204I, rt204V) were found in 19 patients. The rt180M mutation was associated with breakthrough hepatitis (p < 0.05) with a positive predictive value of 85% and a negative predictive value of 83%. Patients with the rt180M mutation had higher HBV-DNA levels during viral breakthrough compared to patients with rt180wt (p < 0.05). The mutational pattern of rt204 was not associated with breakthrough hepatitis. In conclusion, genotypic assays for the rt180M mutation after viral breakthrough may be useful in predicting the risk of breakthrough hepatitis and in deciding when to initiate alternative or additive nucleoside analogue therapy.
authors: Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Nakanishi
authors: Masayuki
authors: M
authors: Kurosaki
authors: Yasuhiro
authors: Y
authors: Asahina
authors: Yuko
authors: Y
authors: Onuki
authors: Ken
authors: K
authors: Ueda
authors: Yuki
authors: Y
authors: Nishimura
authors: Kaoru
authors: K
authors: Tsuchiya
authors: Takatoshi
authors: T
authors: Kitamura
authors: Masakatsu
authors: M
authors: Uchihara
authors: Shozo
authors: S
authors: Miyake
authors: Nobuyuki
authors: N
authors: Enomoto
authors: Namiki
authors: N
authors: Izumi
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015684:Gene Products, pol / Q000235:genetics*; D006515:Hepatitis B virus / Q000201:enzymology / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology*; D006801:Humans; D007564:Japan; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011237:Predictive Value of Tests; D017434:Protein Structure, Tertiary / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D012008:Recurrence
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase