Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis - PubMed (original) (raw)

Meta-Analysis

Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis

Yun-Jian Sheng et al. Virol J. 2011.

Abstract

Background: Chronic hepatitis B virus (HBV) infection represents a serious global health problem and resistance to lamivudine (LAM) has become a serious clinical challenge. Previous rescue therapy for the treatment of chronic LAM-resistant hepatitis B infected patients included switching to entecavir (ETV) and adding adefovir (ADV) or tenofovir (TFV). At present, switching to ETV is not recommended for rescue therapy for LAM-resistant chronic hepatitis B (CHB). The aim of this report was to determine whether add-on ADV was a superior rescue strategy in the treatment of CHB patients with LAM resistance.

Methods: We searched Medline/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library. Relative risks (RRs) of virologic response, virologic breakthrough, normalization of serum alanine aminotransferase (ALT) levels and HBeAg seroconversion rates were studied. Factors predicting virologic response, standardized mean differences (SMD) in HBV DNA levels and safety were reviewed.

Results: Six eligible trials (451 patients in total) were included in the analysis. The rate of virologic breakthrough in the ETV group was higher than that in the LAM plus ADV group. There were no statistical differences in virologic response, ALT normalization and HBeAg seroconversion in either group 48 weeks post treatment. LAM plus ADV combination therapy produced faster and greater HBV DNA reduction rates 24 weeks post therapy compared to ETV monotherapy. HBV DNA baseline levels and the initial virologic response (IVR) were predictive of the virologic response. Additionally, combination therapy or monotherapy were both well tolerated.

Conclusions: LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. However, considering the practical benefits and limitations of ADV, individualized therapy will be needed in patients with prior history of LAM resistant infections.

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Figures

Figure 1

Figure 1

Map of the literature search and selection process.

Figure 2

Figure 2

Effect of LAM + ADV vs. ETV on virologic response 48 weeks post treatment.

Figure 3

Figure 3

Effect of LAM + ADV vs. ETV on the mean reduction of HBV DNA 12 weeks post treatment.

Figure 4

Figure 4

Effect of LAM + ADV vs. ETV on the mean reduction of HBV DNA 48 weeks post treatment.

Figure 5

Figure 5

Effect of LAM + ADV vs. ETV on the mean reduction of HBV DNA 24 weeks post treatment.

Figure 6

Figure 6

Effect of LAM + ADV vs. ETV on ALT normalization 48 weeks post treatment.

Figure 7

Figure 7

Effect of LAM + ADV vs. ETV on virologic breakthrough 48 weeks post treatment.

Figure 8

Figure 8

Effect of LAM + ADV vs. ETV on HBeAg seroconversion 48 weeks post treatment.

References

    1. Cao GW. Clinical relevance and public health significance of hepatitis B virus genomic variations. World J Gastroenterol. 2009;15(46):5761–5769. doi: 10.3748/wjg.15.5761. - DOI - PMC - PubMed
    1. Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350(11):1118–1129. doi: 10.1056/NEJMra031087. - DOI - PubMed
    1. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65–73. doi: 10.1001/jama.295.1.65. - DOI - PubMed
    1. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130(3):678–686. doi: 10.1053/j.gastro.2005.11.016. - DOI - PubMed
    1. Pawlotsky JM, Dusheiko G, Hatzakis A, Lau D, Lau G, Liang TJ, Locarnini S, Martin P, Richman DD, Zoulim F. Virologic monitoring of hepatitis B virus therapy in clinical trials and practice: recommendations for a standardized approach. Gastroenterology. 2008;134(2):405–415. doi: 10.1053/j.gastro.2007.11.036. - DOI - PMC - PubMed

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