Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: A meta-analysis q Sara Raimondi 1, * , Savino Bruno 2 , Mario U. Mondelli 3 , Patrick Maisonneuve 1 1 Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy 2 Department of Medicine, Liver Unit, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milan, Italy 3 Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy Background/ Aims: Hepatitis C virus (HCV) is a known risk factor for hepatocellular carcinoma (HCC), but whether the risk varies among patients infected with different HCV genotypes is still controversial. We performed a meta-analysis to clarify whether the genotype 1b is associated with a higher risk of HCC than other genotypes. Methods: We identified 57 relevant papers through a literature search to December 2007 but, since age could represent a major confounder, we focused the meta-analysis on the 21 studies presenting age-adjusted risk estimates for HCV geno- type 1b vs. other genotypes. We used random-effects models with the DerSimonian–Laird method and assessed heteroge- neity between studies and publication bias. Results: Patients infected with HCV genotype 1b have almost double the risk to develop HCC than those infected with other genotypes (Relative Risk (95% Confidence Intervals) = 1.78(1.36–2.32)). The pooled risk estimate was somewhat lower when we restricted the analysis to the eight studies conducted in patients with liver cirrhosis (1.60;1.07–2.39) or con- sidering the 36 studies presenting only crude data (1.63;1.30–2.06). In seven studies excluding patients with liver cirrhosis, the RR (95% CI) increased to 2.46(1.69–3.59). Conclusions: This meta-analysis suggests that HCV genotype 1b plays an important role in HCC development, espe- cially in patients with early stage liver disease. Ó 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Keywords: Epidemiology; Liver cancer; Virology 1. Introduction Approximately 20% of patients with HCV infection will develop cirrhosis after a mean period of 20 years, and 1–4% of them will eventually develop hepatocellular carcinoma (HCC) on average 30 years after infection [1,2]. HCC represents the most serious complication of Chronic Liver Disease (CLD) and the most frequent cause of death in patients with compensated liver cirrho- sis (LC) [3]. Besides HCV infection, other well known risk factors for HCC include infection with hepatitis B virus (HBV), high ethanol intake, older age, male gen- der, tobacco smoking, LC, advanced fibrosis stage, high histological activity score and elevated alanine amino- transferase serum levels [4–9]. In this setting, the impact of HCV genotypes has also been evaluated in several studies. Despite some of them reported that patients infected with HCV genotype 1b have a higher risk of developing HCC than those infected with other genotypes, [10–14] other studies did not confirm this result [15–18]. As a consequence, no 0168-8278/$36.00 Ó 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jhep.2009.01.019 Received 10 November 2008; received in revised form 13 January 2009; accepted 26 January 2009; available online 20 March 2009 Associate Editor: J.M. Llovet q The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. * Corresponding author. Tel.: +39 02 57489377; fax: +39 02 57489922. E-mail address: sara.raimondi@ieo.it (S. Raimondi). www.elsevier.com/locate/jhep Journal of Hepatology 50 (2009) 1142–1154