Review Article

The Prevention of Hepatitis B–Related Hepatocellular Carcinoma

C.-L. Lin; J.-H. Kao


Aliment Pharmacol Ther. 2018;48(1):5-14. 

In This Article

Abstract and Introduction


Background: Ample evidence indicates an aetiological association of persistent hepatitis B virus (HBV) infection with hepatocellular carcinoma (HCC). Several viral, host and external risk factors for the development of HBV–related HCC have been documented.

Aims: To summarise and discuss the risk stratification and the preventive strategies of HBV–related HCC.

Methods: Recent published studies identified from PubMed were comprehensively reviewed. The key words included chronic hepatitis B, HBV, hepatocellular carcinoma, prevention and antiviral therapy.

Results: The incidence of HCC is extremely high in HBV hyperendemic areas. For HBV patients left untreated, significant risk factors for HCC include male gender, aging, advanced hepatic fibrosis, persistent serum transaminase elevation, specific HBV entry receptor (NTCP) genotype, PM2.5 exposure, HBeAg positivity, HBV genotype C/D/F, high proportion of core promoter mutation, pre–S deletion, high serum levels of HBV DNA and HBsAg as well as co–infection with HCV, HDV and HIV. Primary prevention of HBV–related HCC can be achieved through universal HBV vaccination and anti–viral prophylaxis for high viraemic mothers. The goal of secondary prevention has been reached by effective anti–viral therapy to reduce the risk of HCC development in chronic hepatitis B patients. However, whether HCC is prevented or delayed deserves further examination. Finally, several studies confirmed the tertiary preventive effect of anti–viral therapy in reducing risk of HCC recurrence after curative therapies.

Conclusions: Through the strategies of three–level prevention, the global burden of HBV–related HCC should decline over time and even be eliminated in conjunction with HBV cure.


Hepatocellular carcinoma (HCC) is the fifth most common tumour worldwide and the second most common cause of cancer–related death in the world.[1] The incidence rates of HCC widely vary in different geographic areas, from the low endemicity area, such as Northern Europe and United States, to the high endemicity area, such as Far East and Southeast Asia.[2–4] The aetiologies of HCC include hepatitis B virus (HBV) or hepatitis C virus infection, the presence of cirrhosis, haemochromatosis, alpha–1 antitrypsin deficiency, aflatoxin B1 exposure, non–alcoholic fatty liver disease and alcohol liver disease.[5–9] Among these causes, persistent HBV infection is one of the most important causative agents, especially in Asia and Africa.[10,11] Previous epidemiologic studies revealed that HBsAg carriers had a higher risk of HCC compared to HBsAg–negative controls.[10,11] These findings indicated an aetiological association of persistent HBV infection with HCC development. In addition, observations concerning the natural history of chronic HBV infection showed that patients with chronic HBV infection have a high cumulative lifetime risk of adverse outcomes, including cirrhosis, end–stage liver disease, hepatic decompensation and HCC.[10]

Considering HBV infection as an aetiology of HCC, identification of risk factors for the development of HCC in HBV carriers is important for the prevention of liver cancer. In this review article, the risk stratification of HBV–related HCC and the preventive strategies of HBV–related HCC will be summarised and discussed.