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.
"Entecavir is a carboxylic analogue of guanosine and is the most recently FDA approved drug for the treatment of chronic Hepatitis B. Like Adefovir, it has been shown to be a potent antiviral agent for the wild type and LAM-resistant forms of chronic HBV. [84-86] It is expected that Entecavir will be efficacious in the prevention and treatment of recurrent HBV following liver transplantation. The first reports of Entecavir's use in this setting are now being reported. "
[Show abstract][Hide abstract] ABSTRACT: The Hepatitis B virus (HBV) is a DNA virus that can cause both acute and chronic liver disease in humans. Approximately 350-400 million people are affected worldwide and up to one million deaths occur annually from cirrhosis and hepatocellular carcinoma. When cirrhosis and liver failure develop, the definitive treatment of choice remains orthotopic liver transplantation (OLT). In the past, an unacceptable HBV recurrence rate with a high rate of graft loss was noted. The use of Hepatitis B immunoglobulin (HBIG) has resulted in improved patient and graft survival rates. The addition of the nucleoside analog Lamivudine (LAM) to HBIG has improved these survival curves to an even greater degree. Prolonged use of LAM will almost invariably lead to the development of viral mutations resistant to the drug. There are now several other nucleoside and nucleotide analogs (Adefovir, Entecavir, Tenofovir, and Truvada) available for the clinician to utilize against these resistant strains. It should be possible to prevent recurrence in most, if not all, post-transplant patients and also to significantly reduce viral loads with normalization of transaminases in those who have developed recurrent infection. The antiviral regimen should be robust and minimize the risk of breakthrough mutations. A prudent approach may be the implication of combination antiviral therapy. This review summarizes the efficacy of previous regimens utilized to prevent and treat recurrent HBV following OLT. Particular attention will be paid to the newer nucleoside and nucleotide analogs and the direction for future strategies to treat HBV in the post transplant setting.
Annals of Clinical Microbiology and Antimicrobials 02/2006; 5(1):8. DOI:10.1186/1476-0711-5-8 · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AIM: To investigate the resistance profiles of chronic hepatitis B patients with entecavir (ETV) refractory treatment. METHODS: Twenty serum samples of patients who failed treatment with ETV were assigned into non-complete virological group and virological breakthrough group in accordance with response action. Direct sequencing of PCR products was used to determine ETV resistance. NCBI HBV genotyping tool was used to identify HBV genotype. RESULTS: ETV resistance was detected from 11 out of 20 ETV-refractory patients, all of which was in virological breakthrough group, and rtM204V + rtL180M + rtT184L was common in Chinese ETV resistance patients. There was remarkably statistical difference between the two groups (P = 0.0022). Three in 6 patients with genotype B were detected to have ETV resistance, meanwhile 11 in 14 with genotype C. There was no statistical difference in resistance among genotype B and C patients. CONCLUSION: rtM204V + rtL180M + rtT184L mutations are common in genotype B and C ETV resistance patients. Patients with virological breakthrough experienced more ETV resistance than non-complete virological group. There is no statistical difference in resistance between genotype B and C patients.
World Chinese Journal of Digestology 04/2009; 17(12).
[Show abstract][Hide abstract] 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.
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