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Lamivudine plus adefovir or entecavir for patients with chronic hepatitis B resistant to lamivudine and adefovir.

Abstract

BACKGROUND & AIMS

Little is known about the optimal management of patients with chronic hepatitis B (CHB) who developed multiple-drug resistance.

METHODS

We assessed 91 patients with compensated CHB who developed adefovir-resistant mutations during adefovir monotherapy for lamivudine-resistant CHB. Of these, 41 were treated with a combination of lamivudine plus adefovir (LAM+ADV group) and 50 were treated with entecavir monotherapy (ETV group).

RESULTS

There were no significant differences between the two groups in baseline characteristics, including serum HBV DNA levels (p>0.05). The rate of virologic non-response (HBV DNA reduction <1 log(10) IU/ml at 6 months) was significantly greater in the LAM+ADV than in the ETV group (51.2% vs. 16.0%, p<0.01). At 12 months, HBV DNA declined less in the LAM+ADV than in the ETV group (-1.49+/-1.78 vs. -3.47+/-2.13 log(10) IU/ml, p<0.01). Only 12.2% and 22.0% of patients in the LAM+ADV and ETV groups, respectively, achieved complete virologic response (HBV DNA <60 IU/ml) at 12 months. Multivariable analysis showed that LAM+ADV group (OR=0.08, CI=0.02-0.28) and the presence of the rtA181V/T mutation (OR=0.21, CI=0.05-0.91) were independently associated with a decreased rate of virologic response (HBV DNA <2000 IU/ml) at 12 months.

CONCLUSIONS

In patients with CHB resistant to lamivudine and adefovir, combination therapy with these two drugs was not effective and was inferior to entecavir monotherapy in suppressing HBV DNA. However, the response to entecavir monotherapy was also not optimal. These results emphasize the importance of preventing the development of multidrug-resistant HBV and of exploration for adequate combination therapy in treatment of multidrug-resistant CHB.

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  • Authors+Show Affiliations

    ,

    Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

    , , , ,

    Source

    Journal of hepatology 53:3 2010 Sep pg 449-54

    MeSH

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

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    20646776