Abstract
Background: The long-term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma.
Aim: To review the current treatment of chronic hepatitis B, with a focus on diagnosis and management of resistance and active management of suboptimal responses.
Methods: A systematic review of the literature, with a focus on recent guidelines, was undertaken.
Results: Among the six drugs licensed for the treatment of chronic hepatitis B in the US, the preferred agents in 2008 will include entecavir, peginterferon alfa-2a, possibly telbivudine, and tenofovir following licensure. When using an oral agent, a major focus of management is on the selection of a drug with high potency and low rate of resistance, and active on-treatment management to optimize therapy. Preventing the sequelae of antiviral drug resistance and appropriate management when resistance is initially detected are also the major focus of current management. The addition of an antiviral agent that is not cross-resistant is critical to restore suppression of viral replication.
Conclusions: Newer agents and modified treatment strategies, especially using combination therapy, hold promise to optimize the management of patients with chronic hepatitis B by achieving the high potency and the lowest rate of resistance.
Introduction
Chronic hepatitis B virus (HBV) infection is a major global cause of morbidity and mortality. Of 350 million people chronically infected with HBV worldwide, at least 1.25 million individuals live in the US.[1,2] The prevalence of chronic hepatitis B (CHB) in the US is under-reported, as epidemiological studies do not include the prison population or take into consideration the continuous influx of immigrants from endemic areas with a high prevalence rate of HBV infection. Individuals with CHB are at risk of premature death from cirrhosis with liver failure or hepatocellular carcinoma (HCC).[2,3] Recent studies have shown that the level of serum HBV DNA correlates over more than a decade with the risk of developing cirrhosis[4] and HCC (Figure 1).[5] For this reason, early diagnosis of chronic HBV infection and treatment to reduce serum HBV DNA to low or undetectable levels are important in preventing progression of HBV infection to advanced disease with these complications.
The arsenal of medications to treat CHB continues to increase.[3] Compared to two medications licensed by the US Food and Drug Administration (FDA) in the 1990s (interferon alfa-2b and lamivudine), four additional agents have now been licensed: adefovir dipivoxil, entecavir, peginterferon alfa-2a and telbivudine, with tenofovir likely to be licensed in the third quarter of 2008. The future management of CHB appears to be more promising than ever before, with many treatment options currently available, new drugs in development, and different on-treatment strategies for optimizing the use of current agents undergoing investigation
