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Precore stop codon mutation of hepatitis B virus is associated with low breakthrough rate following long‐term lamivudine therapy
Author(s) -
SHIN JUNG WOO,
CHUNG YOUNGHWA,
CHOI MIN HEE,
KIM JEONG A,
RYU SOO HYUNG,
JANG MYOUNG KUK,
KIM IN SOOK,
PARK NEUNG HWA,
LEE HAN CHU,
LEE YUNG SANG,
SUH DONG JIN
Publication year - 2005
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2005.03824.x
Subject(s) - lamivudine , medicine , hbeag , hepatitis b virus , virology , gastroenterology , cirrhosis , viral load , hepatitis b , univariate analysis , virus , hbsag , multivariate analysis
Background: Frequent viral breakthroughs limit the usefulness of lamivudine in the treatment of chronic hepatitis B (CHB). The purpose of the present study was to evaluate the effects of precore stop codon mutation (G to A mutation at nucleotide 1896; A 1896 ) of hepatitis B virus (HBV) on the occurrence of viral breakthrough following lamivudine therapy. Methods: Among 260 consecutive CHB patients treated with lamivudine for >12 months, 231 patients whose pretreatment sera were available were tested for A 1896 variant of HBV using direct sequencing. Results: Between patients with A 1896 variant ( n = 74) and those without it ( n = 157), there was no difference in age, gender, serum alanine aminotransferase (ALT) level, the duration of therapy and prevalence of core promoter mutants. Serum hepatitis B e antigen (HBeAg) positivity and HBV‐DNA level were lower ( P = 0.00 and P = 0.01) and liver cirrhosis was more commonly associated in patients with A 1896 variant mutant compared with those without it. In univariate analysis, viral breakthrough was more frequent in HBeAg‐positive patients ( P = 0.03) and in those with high serum HBV‐DNA level ( P = 0.01) as well as in those without A 1896 variant ( P = 0.01). However, in multivariate analysis, the absence of A 1896 variant ( P = 0.02) and high serum HBV‐DNA level ( P = 0.03) were independent factors for viral breakthrough following lamivudine therapy. The cumulative viral breakthrough rates at 1 and 2 years were much lower in patients with A 1896 variant compared with those without it ( P = 0.01). Conclusion: The stop codon mutation at the precore region of HBV in addition to low serum HBV‐DNA level may be associated with low breakthrough rate following lamivudine therapy.