Entecavir: A potent new antiviral drug for hepatitis B
ABSTRACT Entecavir, a new deoxyguanine nucleoside analogue, is a selective inhibitor of the replication of the hepatitis B virus. In vitro this compound has proven to be far more effective than other nucleoside analogues. In animal models, an impressive reduction of serum viral DNA has been observed with covalently closed circular DNA and hepatitis B viral core antigen negativity in liver biopsy specimens. In clinical studies, entecavir revealed excellent suppression of hepatitis B virus replication without significant side effects or evidence of mitochondrial toxicity. Until now, no entecavir-resistant viral mutants have been described. Prolonged therapy as well as prophylactic therapy, for example, in liver transplant recipients, is feasible and not limited by breakthrough infections. Data on entecavir therapy for treatment of nucleoside-naive, wild-type hepatitis B virus is being generated in Phase III clinical trials worldwide for both hepatitis B envelope antigen-positive and -negative subpopulations, as well as in lamivudine-resistant patients. Based on mechanism and potency of interferon and entecavir, clinical trials with combination therapy are eagerly awaited.
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ABSTRACT: Chronic hepatitis B remains a public health problem of global importance despite the availability of an effective vaccine. Between 350 and 400 million people, approximately 6% of the world's population, suffer from chronic hepatitis B and face a 30% likelihood of developing cirrhotic liver disease or hepatocellular carcinoma. Current treatment options include three monotherapies of subcutaneous interferon, oral nucleoside lamivudine and oral nucleotide adefovir dipivoxil. Unfortunately, these agents have not effectively and frequently been able to attain a 'cure' or complete eradication of the virus. Consequently, the expectation of current therapies is confined to the achievement of clinically beneficial and durable responses defined by lasting suppression of virus replication, histological improvement and increased survival for patients with decompensated liver diseases. Other disadvantages include the undesirable tolerability of interferon, the rapid resistance to lamivudine and the compromise between efficacy and toxicity that led to the development of the 10 mg dose of adefovir dipivoxil. Clearly, better therapeutics and treatment strategies are needed. Increased potency, activity against current treatment-refractory viruses, as well as efficacy in difficult-to-treat populations will be critical to meeting the therapeutic challenge of chronic hepatitis B.Expert Opinion on Investigational Drugs 09/2003; 12(8):1281-95. DOI:10.1517/135437188.8.131.521 · 5.43 Impact Factor
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ABSTRACT: Redistribution of virions from extrahepatic reservoirs with resultant reinfection of the graft is a serious complication after liver transplantation for hepatitis B-related liver disease. Prophylaxis of hepatitis B virus recurrence is a major issue in these patients. With the introduction of passive immunoprophylaxis and the development of antiviral drugs, liver transplantation has evolved as an established therapy of hepatitis B-induced end-stage liver failure. However, even under indefinite monoprophylaxis, a significant percentage of patients develop reinfection due to a high mutation rate of the hepatitis B virus. Progress, especially in the field of antiviral therapy, has opened new strategies, including combination prophylaxis and therapy, which further improve outcome. On the other hand, the broad use of antiviral drugs brings about new problems such as resistance formation prior to liver transplantation. In addition, due to the high costs of hepatitis B immunoglobulin alternatives such as prophylaxis with nucleoside analogs or vaccination are increasingly being investigated.Expert Review of Anticancer Therapy 09/2003; 1(2):307-18. DOI:10.1586/14787184.108.40.2067 · 3.06 Impact Factor