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Abstract and Introduction
Abstract
Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are potent nucleos(t)ide analogues (NUCs) recommended as first-line monotherapies for chronic hepatitis B. In Phase III trials, ETV and TDF demonstrated superior efficacy, and comparable safety compared with other NUCs. In long-term clinical studies, both drugs achieved virologic response rates of around 95%, with very low rates of resistance development and good safety profiles. Clinical trials are conducted under standardized conditions with strict enrolment criteria that limit the heterogeneity of study populations. 'Real-life' populations tend to be composed of a wider range of patients, often older and with different morbidities, comorbidities that may impact treatment efficacy and co-factors, such as smoking and alcohol intake, which can have a direct impact on disease progression. Real-life studies provide better representations of everyday clinical practice and are important to confirm the results reported in clinical studies and to identify rare or late-emerging adverse events. In five 'real-life' studies of ETV in more than 1000 patients, up to 4 years of treatment resulted in virologic responses in 76–96% of patients. Two real-life studies of TDF reported response rates of 71–92% after up to 21 months of treatment. Low incidences of drug resistance and favourable tolerabilities were reported for both drugs, thus confirming the results from registration trials.
Introduction
It is estimated that one-third of the world's population has serologic evidence of a past or present hepatitis B virus (HBV) infection, with around 370 million being chronically infected. HBV-related liver failure, cirrhosis and hepatocellular carcinoma (HCC) currently account for over 1 million deaths annually. The goal of chronic hepatitis B (CHB) treatment is to improve survival by preventing disease progression to decompensated cirrhosis and HCC. It is now well established that the risk of disease progression is reduced through the sustained reduction in HBV DNA to undetectable levels. The effective and sustained suppression of HBV replication can result in regression of liver fibrosis and can even reverse liver cirrhosis. Furthermore, maintaining undetectable levels of HBV DNA also increases the rate of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion, which are also desired endpoints of CHB therapy. However, HBV is not completely eradicated by treatment, even if HBsAg loss occurs. This is because of the persistence of nuclear covalently closed circular DNA and HBV DNA integrated into the host genome, which may trigger HBV reactivation or direct viral hepatocarcinogenesis, respectively. Long-term therapy is required in HBeAg(−) and in HBeAg(+) patients who cannot maintain virologic suppression off-treatment and for those with advanced liver disease. One barrier to the success of long-term therapy is the emergence of drug-resistant mutants, which are frequently observed during treatment of CHB with lamivudine (LVD), adefovir (ADV) or telbivudine as monotherapies. Current guidelines, therefore, recommend that the most potent drugs with optimal resistance profiles (i.e. entecavir [ETV] and tenofovir disoproxil fumarate [TDF]) should be used as first-line monotherapies in CHB. These two agents were approved by the US Food and Drug Administration (FDA) for the treatment of CHB on the basis of Phase III clinical study results in 2005 (ETV) and 2008 (TDF). Since that time, accumulating data from observational 'real-life' cohort studies have added considerably to our understanding of the efficacy and safety profiles of these two drugs. This review aims to summarize the currently available clinical practice or 'real-life' data for ETV and TDF as first-line treatments for CHB.
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