Hepatitis C virus genotype 1b as a major risk factor... : Hepatology (original) (raw)

Viral Hepatitis

Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: A seventeen-year prospective cohort study

Bruno, Savino1*; Crosignani, Andrea2; Maisonneuve, Patrick3; Rossi, Sonia1; Silini, Enrico4; Mondelli, Mario U.5†

1_Liver Unit, Department of Medicine, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milan, Italy_

2_Department of Medicine, Azienda Ospedaliera San Paolo, University of Milan, Milan, Italy_

3_Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy_

4_Department of Pathology and Laboratory Medicine, Azienda Ospedaliera and University of Parma, Parma, Italy_

5_Centre for Hepatology and Infectious Diseases, Fondazione Istitut di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy_

*Address reprint requests to: Internal Medicine and Liver Unit, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Corso di Porta Nuova 23, 20121 Milan, Italy

†Address reprint requests to: Centre for Hepatology, Department of Infectious Diseases, Fondazione Istitut di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Via Taramelli 5, 27100, Pavia, Italy

Email:[email protected]

Received 30 March 2007; Accepted 22 May 2007

Published online 6 August 2007 in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: Italian Ministry of University and Research (Progetti di Ricerca di Interesse Nazionale); Grant sponsor: Italian Association for Cancer Research; Grant sponsor: Research Funds of the Italian Ministry of Health (Ricerca Corrente, Fondazione Istitut di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo); Grant sponsor: Donation from CANTEL, SpA. (Fino Mornasco, Italy).

Potential conflict of interest: Nothing to report.

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Abstract

Hepatocellular carcinoma (HCC) is the most frequent cause of death in patients with hepatitis C virus (HCV)–induced cirrhosis. Despite a number of studies in different populations worldwide suggesting an association between HCV genotype 1 and the risk of HCC, no consensus has emerged yet on this matter, which is still controversial. In an attempt to clarify this issue, a prospective study of 163 consecutive HCV-positive patients with cirrhosis, who were enrolled between January 1989 and December 1990, was carried out. HCC occurrence was detected by ultrasound surveillance every 6 months. Independent predictors of HCC were assessed with a Cox regression analysis. After a median follow-up of 10.7 years, 44 [4.26/100/year, confidence interval (CI) = 3.11–5.68/100/year] of 104 patients infected with genotype 1b developed HCC versus 10 (1.69/100/year, CI = 0.82–3.09/100/year) of 52 patients infected with genotype 2a/c ( P = 0.0001). Multivariate analysis showed that HCV genotype 1b was independently associated with HCC development [hazard ratio (HR) = 3.02, 95% CI = 1.40–6.53]. Other predictors of HCC were esophageal varices (HR = 2.15, 95% CI = 1.03–4.47), male gender (HR = 2.12, 95% CI = 1.10–4.11), and age over 60 years (HR = 5.96, 95% CI = 1.23–28.8).

Conclusion:

HCV genotype 1b is associated with a statistically significant higher risk of developing HCC. Patients with cirrhosis that are infected with this genotype require more intensive surveillance for the early detection and aggressive management of neoplasia.

Abbreviations: CI, confidence interval; HB, hepatitis B; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HR, hazard ratio; IFN, interferon; PT, prothrombin time; RBV, ribavirin; SVR, sustained virological response.