Polymerase domain B mutation is associated with hepatitis relapse during long-term lamivudine therapy for chronic hepatitis B.
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.
Nakanishi
Hiroyuki
H
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Kurosaki
Masayuki
M
Asahina
Yasuhiro
Y
Onuki
Yuko
Y
Ueda
Ken
K
Nishimura
Yuki
Y
Tsuchiya
Kaoru
K
Kitamura
Takatoshi
T
Uchihara
Masakatsu
M
Miyake
Shozo
S
Enomoto
Nobuyuki
N
Izumi
Namiki
N
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
D000998:Antiviral Agents; D004279:DNA, Viral; D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase