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Intern Med. <#> 2012;51(12):1509-15. Epub 2012 Jun 15.
Rescue Therapy for Lamivudine-resistant Chronic Hepatitis B: Adefovir Monotherapy, Adefovir Plus Lamivudine or Entecavir Combination Therapy.
Ha M , Zhang G, Diao S, Lin M, Wu J , Sun L, She H , Shen L, Huang C, Shen W, Huang Z.
Source
Department of Infectious Diseases and Hepatology, Shanghai 7th People's Hospital, China.
Abstract
Objective We aimed to compare the cumulative efficacy and resistance of ADV monotherapy, ADV add-on LAM (ADV + LAM), ADV and ETV (ADV + ETV) combination therapy in LAM-resistant patients. Methods Ninety-one adult CHB patients with LAM-resistance mutations (YMDD) were identified. Of these 91, 29 patients were treated with ADV monotherapy, 30 were treated with ADV + LAM and 32 were treated with ADV + ETV combination therapy, for at least 24 months. Results The mean serum HBV-DNA decreases from baseline at 3, 6, 12, and 24 months were -3.23, -4.41, -5.32, and -5.58 log<inf>10</inf>IU/mL in the ADV + ETV combination therapy groups, respectively; the most significant among the three treatment groups (p<0.01). The rate of HBV-DNA PCR undetectability (<60 IU/mL) at 6 months in ADV + ETV combination therapy was 78.1%; also the most significant among the three treatment groups (p=0.024). Viral breakthrough and genotypic mutations were detected in 8 (27.6%) and 4 (13.3%) patients in the ADV monotherapy and ADV+LAM therapy groups, respectively; whereas no case of viral breakthrough and genotypic resistance was detected in the ADV+ETV combination therapy group after 24 months (p<0.05).
Conclusion
ADV + ETV combination therapy demonstrated faster and significantly greater suppression of HBV DNA compared with ADV add-on LAM combination therapy for patients with LAM-resistance mutations. ADV + ETV was superior to ADV + LAM in achieving initial virological response and long- term suppression activity against HBV. ADV + ETV combination therapy was the most effective to refrain from selecting HBV strains with cross- resistance to three NAs (LAM, ADV and ETV) for LAM-resistance patients.
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