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  • Title: Precore stop codon mutation of hepatitis B virus is associated with low breakthrough rate following long-term lamivudine therapy.
    Author: Shin JW, Chung YH, Choi MH, Kim JA, Ryu SH, Jang MK, Kim IS, Park NH, Lee HC, Lee YS, Suh DJ.
    Journal: J Gastroenterol Hepatol; 2005 Jun; 20(6):844-9. PubMed ID: 15946130.
    Abstract:
    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.
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