Critical reappraisal of risk factors for occurrence of hepatocellular carcinoma in patients with hepatitis C virus

Savino Bruno1, Daniela Savojardo1, Piero L Almasio2, Mario U Mondelli31Liver Unit, Department of Medicine, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milan, Italy; 2Unità Complessa di Gastroenterologia ed Epatologia, University of Palermo, Palermo, Italy; 3Struttura Complessa Laboratori di Infettivologia, Dipartimento di Malattie Infettive, Fondazione IRCCS Policlinico San Matteo e Università di Pavia, Pavia, ItalyAbstract: More than one and half of current cases of hepatocellular carcinoma in the US, Europe, and Japan are attributable to hepatitis C virus (HCV) infection. HCV is also the primary cause of death in patients with HCV-related cirrhosis, with annual incidences of 0.5%–5% in Europe and 4%–10% in Asia. Screening is based on serum alpha-fetoprotein determination and liver ultrasound scan, but the sensitivity of the former is far less than optimal, and screening intervals are still poorly defined for the latter. Risk factors related to the host or environment, or both, appear to be more relevant than viral factors, such as HCV genotype, in determining disease progression to cirrhosis and cancer, and include age, male gender, severity of liver disease at presentation, coinfection with hepatitis B virus or human immunodeficiency virus, and alcohol abuse. Early liver transplantation in selected cases can be curative, but most patients are not eligible for liver grafting and are treated with locoregional ablative therapies, after which recurrence is common. Recently, orally available inhibitors of the vascular endothelial growth factor receptor have shown a significant, albeit modest, increment of survival in patients with advanced hepatocellular carcinoma, thus paving the way for modern molecular approaches to treatment of this highly malignant tumor.Keywords: hepatocellular carcinoma, hepatitis C virus