Risk for hepatocellular carcinoma in the course of chronic hepatitis B virus infection and the protective effect of therapy with nucleos(t)ide analogues

Abstract

Hepatocellular carcinoma (HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus (HBV) infection (CHB) is the most important etiologic factor of this tumor, accounting for the development of more than 50% of the cases in the world. Primary prevention of HCC is possible by hepatitis B vaccination conferring protection from HBV infection. However, according to the World Health Organization Hepatitis B Fact sheet N° 204 (update of July 2014) globally there exists a large pool of > 240 million people chronically infected with HBV who are at risk for development of HCC. These individuals represent a target population for secondary prevention both of cirrhosis and of HCC. Since ongoing HBV replication in CHB is linked with the progression of the underlying liver disease to cirrhosis as well as with the development of HCC, effective antiviral treatment in CHB has also been evaluated in terms of secondary prevention of HCC. Currently, most patients with active CHB are subjected to long term treatment with the first line nucleos(t)ide analogues entecavir and tenofovir. These compounds are of high antiviral potency and have a high barrier to HBV resistance compared to lamivudine, adefovir dipivoxil and even telbivudine. Many studies have shown that patients under antiviral treatment, especially those in virological remission, develop less frequently HCC compared to the untreated ones. However, the risk for development of HCC cannot be eliminated. Therefore, surveillance for the development of HCC of patients with chronic hepatitis B must be lifelong or until a time in the future when new treatments will be able to completely eradicate HBV from the liver particularly in the early stages of CHB infection. In this context, the aim of this review is to outline the magnitude of the risk for development of HCC among patients with CHB, in the various phases of the infection and in relation to virus, host and environmental factors as evaluated in the world literature. Moreover, the benefits of antiviral treatment of CHB with nucleos/tide analogs, which have changed the natural history of the disease and have reduced but not eliminated the risk of HCC are also reviewed.

Keywords: Adefovir; Chronic hepatitis B; Cirrhosis; Entecavir; Hepatitis B virus; Hepatocellular carcinoma; Interferon; Lamivudine; Nucleos(t)ide analogues; Tenofovir; Treatment; Virological remission.