Tenofovir in the treatment of chronic hepatitis B

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Authors: Derek Yu and Jenny Heathcote
Date: Sept. 2011
From: Therapy(Vol. 8, Issue 5)
Publisher: Future Medicine Ltd.
Document Type: Report
Length: 10,921 words
Lexile Measure: 1600L

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Author(s): Derek Yu 1 , Jenny Heathcote [[dagger]] 2



adverse drug reaction; chronic hepatitis B; drug interactions; hepatitis B virus; nephrotoxicity; osteomalacia; tenofovir disoproxil fumarate

An estimated 350 million individuals worldwide are chronically infected with hepatitis B virus (HBV) [1] . Prevalence rates of hepatitis B surface antigen (HBsAg) in cross-sectional studies range from 0.3-1.5% in North America and Western Europe [2,3] to as high as 9-12% in some regions of Asia and Africa [2,4] . Although most patients chronically infected with HBV do not develop clinically significant liver disease, serious sequelae such as, cirrhosis, and hepatocellular carcinoma (HCC) will develop in 15-40% during their lifetime [5] .

A large population-based study of predominantely males with chronic hepatitis B (CHB), conducted in Taiwan, showed that persistence of HBeAg (+) status over the age of 30 years was associated with a high 9-year risk of HCC [6] . The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL) study indicated that an elevated serum baseline HBV DNA level in middle-aged men was a strong risk predictor for subsequent HCC [7] . These observations may suggest that effective control of viral replication after antiviral therapy may help reduce the complications of CHB, at the very least in older Asian men. Early randomized control trials (RCT) have indicated that continued viral suppression in those who had active advanced CHB prior to the onset of therapy does lead to improved biochemical, viral, histologic and survival outcomes and suggest a decrease in rate of HCC [8,9] .

A total of seven drugs have been evaluated and licensed to treat CHB, including standard and PEGylated IFN-[alpha], lamivudine (LAM), adefovir (ADV), entecavir (ETV), telbivudine and tenofovir disoproxil fumurate (TDF). Before initiating any oral antiviral medication, the advantages and disadvantages of therapy need to be discussed with the patient. It is especially hard for young men and women to comprehend the long-term benefit of intervening with treatment when they feel reasonably well. The disadvantages of treatment include the risk of drug resistance over time, the risk of sudden flare if their medications are stopped at an inappropriate time, and side effects. The ideal drug needs to be potent, possess a high barrier to resistance, lack significant toxicity and have minimal side effects. The most recently licensed drugs for treatment of CHB, tenofovir and entacavir, go a long way to fulfilling most of these characteristics and are the preferable first-line agents in the treatment of CHB [10] . This article will focus on specific aspects of the published clinical trials, which have evaluated both efficacy and safety of TDF in the treatment of CHB and include a discussion on the comparative effectiveness of TDF with other treatments for CHB.

Pharmacology of TDF

* Mechanism of action

Tenofovir disoproxil fumurate, an oral prodrug, is an acyclic nucleotide phosphonate diester analogue of adenosine 5´-monophosphate. During absorption from the gastrointestinal tract, TDF is hydrolyzed to tenofovir, which is phosphorylated to the active drug tenofovir diphosphate once taken up by hepatocytes. TDF inhibits the activity of HBV DNA polymerase by competing...

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Gale Document Number: GALE|A268609816