title: 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.
authors.affiliation: AM Migliavacca Center for Liver Diseases, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, 20122 Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Della Corte
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
mesh_terms: D064829:Alcohol Abstinence; D000428:Alcohol Drinking / Q000009:adverse effects; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D018890:Chemoprevention / Q000379:methods*; D020022:Genetic Predisposition to Disease; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D024821:Metabolic Syndrome / Q000150:complications / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D018570:Risk Assessment; D012307:Risk Factors; D040242:Risk Reduction Behavior
chemical_list: D000998:Antiviral Agents
keywords: Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma; Human immunodeficiency virus; Nucleoside analogues; Peginterferon; Single nucleotide polymorphisms; Sustained virological response
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