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Rescue therapy for lamivudine-resistant chronic hepatitis B: adefovir monotherapy, adefovir plus lamivudine or entecavir combination therapy.

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(10) 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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  • Authors+Show Affiliations

    ,

    Department of Infectious Diseases and Hepatology, Shanghai 7th People's Hospital, China. hmh_1021@sina.com

    , , , , , , , , ,

    Source

    Internal medicine (Tokyo, Japan) 51:12 2012 pg 1509-15

    MeSH

    Adenine
    Adult
    Antiviral Agents
    DNA, Viral
    Drug Resistance, Viral
    Drug Therapy, Combination
    Female
    Guanine
    Hepatitis B virus
    Hepatitis B, Chronic
    Humans
    Lamivudine
    Male
    Middle Aged
    Mutation
    Organophosphonates
    Time Factors

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22728482

    Citation

    TY - JOUR T1 - Rescue therapy for lamivudine-resistant chronic hepatitis B: adefovir monotherapy, adefovir plus lamivudine or entecavir combination therapy. AU - Ha,Minghao, AU - Zhang,Guotong, AU - Diao,Shu, AU - Lin,Mingfang, AU - Wu,Jianqiu, AU - Sun,Liping, AU - She,Huiyuan, AU - Shen,Lihui, AU - Huang,Chunhong, AU - Shen,Wenjuan, AU - Huang,Zhongming, Y1 - 2012/06/15/ PY - 2012/6/15/epublish PY - 2012/6/26/entrez PY - 2012/6/26/pubmed PY - 2012/11/14/medline SP - 1509 EP - 15 JF - Internal medicine (Tokyo, Japan) JO - Intern. Med. VL - 51 IS - 12 N2 - 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(10) 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. SN - 1349-7235 UR - https://www.unboundmedicine.com/medline/citation/22728482/Rescue_therapy_for_lamivudine_resistant_chronic_hepatitis_B:_adefovir_monotherapy_adefovir_plus_lamivudine_or_entecavir_combination_therapy_ L2 - http://joi.jlc.jst.go.jp/DN/JST.JSTAGE/internalmedicine/51.7329?from=PubMed ER -