Individualized hepatocellular carcinoma risk: the challenges for designing successful chemoprevention strategies

Abstract

Hepatocellular carcinoma (HCC) develops in the context of environmental risk factors like chronic viral hepatitis, diabetes and alcohol exposure, often associated to an increased risk of cirrhosis. Antiviral treatments that are effective to counteract hepatitis B and C may also attenuate the risk of tumor development. However, since hepatitis B-related carcinogenesis is promoted independently of the onset of cirrhosis, such antiviral treatments as nucleo(t)side analogs can promote regression of cirrhosis, prevent clinical decompensation and variceal bleeding but not HCC. This means that in successfully treated patients with cirrhosis, HCC is often the consequence of their extended survival. In hepatitis C patients, a sustained virological response to interferon-based therapies can reduce the rate of HCC development, even in patients with cirrhosis who experience histological regression of their liver disease. Future therapies aimed at this endpoint in at risk populations should take into consideration pretreatment patient stratification for host, viral and environmental risk factors. In this context the recent discovery of single nucleotide polymorphisms involved in the immune system function and tumorigenesis, might permit enrollment of populations of patients enriched with HCC risk factors for targeted chemopreventive therapies. This could finally pave the way to personalized algorithms, as already seen in the diagnosis and treatment schemes for chemoprevention.

Keywords: Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma; Human immunodeficiency virus; Nucleoside analogues; Peginterferon; Single nucleotide polymorphisms; Sustained virological response.

Figure 1

Hepatocellular carcinoma rates in nucleos(t)ide analogs-naive cirrhotic patients with long-term response. Several studies have shown that hepatitis B virus patients who achieve a virological response to lamivudine in some cases still develop hepatocellular carcinoma (HCC) as the only complication. LAM: Lamivudine; ETV: Entecavir; RCT: Randomized controlled trial.

Figure 2

Cumulative incidence of hepatocellular carcinoma in patients with cirrhosis stratified by sustained virological response. Studies in Caucasian patients as well as in patients from Asia have repeatedly shown that a sustained virological response (SVR) following interferon-based therapies can reduce the rate of hepatocellular carcinoma development in hepatitis C virus related cirrhosis. HCC: Hepatocellular carcinoma.