Serum ferritin and the risk of hepatocellular carcinoma in chronic liver disease of viral etiology: A case-control study

Background: The worldwide incidence rates of hepatocellular carcinoma (HCC) vary widely. Some countries like India have a low incidence despite having a large burden of chronic hepatitis B (HBV) and C virus (HCV) infection. We hypothesized that long-term iron deficiency could attenuate the hepatic inflammation and lead to a lower incidence of HCC in India than expected. Methods: We evaluated the association of serum ferritin levels and HCC in Indian patients with HBV- or HCV-related chronic liver disease (CLD) using a case-control study design. We enrolled 141 patients with HCC (cases) and 240 patients having chronic HBV or HCV infection-related CLD (controls). Study participants were grouped on the basis of ferritin values into low-normal, high-normal, and high subgroups. Results: Mean ferritin values were higher in cases as compared to controls (425.8 vs. 135.6 ng/mL, p = 0.000). A significant dose-response effect for serum ferritin levels and HCC was seen with an odds ratio (95 % confidence interval) of 3.0 (1.6-5.9, p = 0.001) for subjects with high-normal ferritin levels and 8.2 (4.1-16.5, p = 0.000) for subjects with high ferritin levels in a multivariate model. Other significant independent risk factors in the multivariate model included older age, male gender, alcohol and tobacco use, elevated alanine aminotransferase, higher family income, and coffee drinking. Conclusion: We found an independent association between serum ferritin levels and HCC in patients with CLD of viral etiology. Further prospective studies are needed to confirm the hypothesis that iron deficiency protects against HCC in CLD. © 2013 Indian Society of Gastroenterology.