Successful therapy of hepatitis B with tenofovir in HIV-infected patients failing previous adefovir and lamivudine treatment
Institut für Medizinische Mikrobiologie und Immunologie, Universität Bonn, 53105 Bonn, Germany. AIDS
(Impact Factor: 5.55).
Three HIV-infected patients with chronic hepatitis B (genotype A) were switched to adefovir therapy after unsuccessful lamivudine treatment. Surprisingly, adefovir therapy failed, although none of the virus isolates displayed mutations known to be associated with adefovir resistance (A181V, N236T). In two isolates we identified hepatitis B virus DNA polymerase mutation L217R, in one case we found multiple frameshifts in the same region. In all cases adefovir was replaced by tenofovir, resulting in a significant drop in the viral load.
Available from: Jürgen Rockstroh
Available from: Joan Figueras
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ABSTRACT: Antiviral treatment can be complex in decompensated hepatitis B virus (HBV) cirrhosis because of potential emergence of lamivudine-resistant mutants and worsening liver function, and to multifactorial nephrotoxicity. Negative HBV-DNA status by hybridization before liver transplantation is a favorable prognostic factor. We present the case of a 54-year-old HBV+ liver transplantation candidate who, after testing negative for HBV-DNA, developed YMDD lamivudine-resistant mutants resulting in a deteriorated clinical condition. After 8 months of adefovir plus lamivudine double therapy, only partial response was achieved. Tenofovir was added to this regimen, and an early decline of HBV-DNA was seen at 4 weeks without adverse events. The patient underwent transplantation. At 21-month postoperative follow-up, the patient's outcome was excellent. Post-transplantation HBV prophylaxis, taking into account the prior development of mutants, consists of hepatitis B immunoglobulin plus lamivudine and adefovir. Tenofovir was well tolerated and produced a fast antiviral response, suggesting its potential value in combined antiviral treatment for liver transplantation candidates.
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ABSTRACT: Chronic liver disease due to hepatitis B virus or hepatitis C virus infection results in cirrhosis and hepatocellular carcinoma. Successful eradication or suppression of viral replication may lead to clinical improvement and better prognosis. Important discoveries have been made in recent years on the management of these diseases. This article aims at reviewing important publications of the past year that contribute to better understanding and treatment of chronic viral hepatitis.
The effect of virus genotype on the natural history continued to be an important topic of research. Landmark studies on the use of pegylated interferon in chronic hepatitis B and benefit of antiviral treatment in patients with advanced fibrosis or cirrhosis have been published. New antiviral agents were evaluated with encouraging results. In chronic hepatitis C, several treatment trials using pegylated interferon on HIV-coinfected patients have been published. Treatment in specific groups of patients, including those with normal alanine transaminase or posttransplantation recurrence, has also been investigated.
Major progress has been made in the treatment of chronic hepatitis B and pegylated interferon is likely to become one of the first-line therapeutic options in the near future. Combined pegylated interferon and ribavirin will be the standard treatment regimen for hepatitis C and HIV coinfection. Future challenges include treatment of hepatitis B and HIV coinfection and discovery of more potent antiviral agents.
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