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Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: A case–control study of 213 hepatocellular carcinoma patients from India


Dr Shiv Kumar Sarin, Director Professor and Head, Room no. 201, Academic Block, Department of Gastroenterology, GB Pant Hospital, Affiliated to the University of Delhi, New Delhi 110002, India. Email:


Aim:  To assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol intake as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis in Indian population.

Methods:  A total of 213 patients with HCC and 254 control subjects not affected with hepatic diseases or neoplasm were recruited. Odds ratios (ORs) were estimated for each risk factor and synergism among various risk factors was also studied.

Results:  The ORs and 95% confidence intervals (CI) of HCC were 48.02 (25.06–91.98) for any HBV marker, 38.98 (19.55–77.71) for HBsAg positivity, 12.34 (2.84–53.61) for HBsAg negative and antibody positive (either of anti-HBe or total anti-HBc), 5.45 (2.02–14.71) for anti-HCV positive and HCV RNA positive, and 2.83 (1.51–5.28) for heavy alcohol use. No significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA negative. Synergism between alcohol and HCV infection in causing HCC was found, but not between alcohol and HBV. Overall, conclusive evidence of the presence or absence of cirrhosis was reached in 189 (88.73%) HCC patients; cirrhosis was present in 137 (72.48%) of them. ORs with 95% CI of HCC in the presence and absence of cirrhosis, respectively, for HBV were as follows: (i) 48.90 (24.61–97.19) and 35.03 (15.59–78.66) for any HBV marker; (ii) 39.88 (19.41–81.97) and 24.40 (10.60–56.18) for HBsAg positivity; and (iii) 12.10 (2.67–54.88) and 19.60 (3.94–97.39) for HBsAg negativity and antibody positivity. Significantly increased risk was found among cirrhotic patients for anti-HCV positivity and HCV RNA positivity [OR = 7.53 (2.73–20.78)] and for heavy alcohol use [OR = 3.32 (1.70–6.47)]; however, in the absence of cirrhosis, no significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA positive [OR = 0.97 (0.11–8.54)], or who had history of heavy alcohol use [OR = 1.58 (0.55–4.53)].

Conclusions:  Infection with HBV and HCV are the major risk factors for the development of HCC in Indian patients. Presence of HBV antibodies even in the absence of HBsAg conferred increased risk for HCC in the presence or absence of cirrhosis. Anti-HCV positivity in the absence of HCV RNA conferred no increased risk. HCV RNA positivity and heavy alcohol use significantly increased the risk of HCC among cirrhotic patients, but not non-cirrhotic patients.