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Prophylaxis of hepatitis B recurrence in post-liver transplantation patients with lamivudine-resistant ymdd mutant

Chinese Medical Journal 2007年第16期120卷 1400-1403页

作者： ZHANG Qi CAI Chang-jie LU Ming-qiang LI Xi JIANG Nan JIANG Hua XU Chi LI Hua WANG Gen-shu YI Shu-hong ZHANG Jian ZHANG Jun-feng YI Hui-min ZHANG Ying-cai CHEN Gui-hua Liver Transplant Center Third Affiliated Hospital of Sun Yat-sen University Transplantation Research Institute of Sun Yat-sen University Guangzhou 510630 China

Background The most frequently used therapy for post-transplantation recurrence of hepatitis B virus （HBV） infection is lamivudine, but this drug is associated with a high resistance rate due to ymdd mutant. In preliminary reports, adefovir dipivoxil （ADV） has been shown to have activity against lamivudine-resistant strains of HBV. However, clinical experience in treatment of HBV infection after liver transplantation （LT） is still not entirely clear. This study was aimed to evaluate the prophylactic efficacy of ADV plus hepatitis B immunoglobulin （HBIG） in patients with ymdd mutant before LT. Methods From March 2004 to March 2006, 16 patients with chronic hepatitis B had lamivudine-resistant ymdd mutants detected prior to liver transplantation and received treatment with ADV plus additional intramuscular HBIG after LT as prophylaxis against graft reinfection. Tests for liver function, serum HBsAg, anti-HBs （HBIG）, HBeAg, anti-HBc, anti-HBe, HBV-DNA, and creatinine were assessed pre- or post-liver transplantation. Results The median follow-up of these patients post-liver transplantation was 19.4 months. Fifteen patients survived and one patient died of recurrence of hepatocellular carcinoma （HCC）. There was significant difference （10.98% vs. 2.26%, P〈0.05） in ymdd mutant rate between the patients with HBV-DNA over 106 copies/ml and those with HBV-DNA less than 106 copies/mi. Fifteen patients （93.8%） had undetectable HBV-DNA at 4 weeks and 1 （6.3%） at 6 months after LT. No hepatitis B recurrence was detected by persistent testing of HBsAg, HBeAg, and HBV-DNA and no increase of serum creatinine level associated with ADV was observed in any of the patients. Conclusion ADV combined with intramuscular HBIG can effectively prevent patients with pre-transplantation ymdd mutant from HBV recurrence after LT.

关键词： liver transplantation adefovir dipivoxil ymdd mutant HBV recurrence

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Character of HBV (hepatitis B virus) polymerase gene rtM204V/I and rtL180M mutation in patients with lamivudine resistance

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2005年第7期6卷 664-667页

作者：李敏伟侯伟沃健儿刘克洲 Institute of Infectious Diseases First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China

Objectives: To investigate the relationship between HBV (hepatitis B virus) polymerase gene 180 and 204 sites mutation and lamivudine resistance. Methods: One hundred forty-one patients with lamivudine resistance after lamivudine treatment and 60 chronic hepatitis B patients without lamivudine treatment were enrolled in this study. The serum HBV DNA mutation was analyzed by sequence detection via polymerase chain reaction (PCR). The sequences of the same patient were analyzed before and after lamivudine treatment. Results: One hundred and nine lamivudine resistance patients had HBV ymdd (tyrosine-methionine-aspartate-aspartate) mutation. Among them, 45 patients had rtL 180M/M204V mutation (41.28%), 28patients had rtL180M/M204I mutation (25.70%) and 36 patients had rtM204I mutation (33.02%). There were 6 patients with rtL180M mutation in 32 lamivudine resistance patients. Sixty chronic hepatitis patients without lamivudine treatment had no mutations. Conclusions: HBV mutations, which play an important role in lamivudine resistance usually locate at polymerase gene 204 site; 180 site mutation was also observed in these patients. Evaluation of the anti-virus therapy by surveillance of the two sites mutations is of importance.

关键词： Hepatitis B virus Lamivudine ymdd mutant Sequence analysis

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