Etiologic fractions in patients of hepatocellular carcinoma in India with and without a background of cirrhosis: a multi-centric study

BackgroundHepatocellular cancer (HCC) typically arises in the background of cirrhosis. The epidemiology of HCC has changed in recent years due to availability of newer antivirals, changing life-styles and greater possibility for early detection. We undertook a multicentric national sentinel surveillance for liver cirrhosis and HCC to assess the attributable risk factors for the development of HCC, both with and without a background of cirrhosis.MethodsData from January 2017 till August 2022 from hospital-based records of eleven participating centers were included. Diagnosed cases of cirrhosis [radiological (multiphase and/or histopathological] and HCC [as per AASLD 2018] were included. History of significant alcohol intake was elicited by AUDIT-C questionnaire.ResultsAltogether 5798 enrolled patients were assessed, of which 2664 patients had HCC. The mean age was 58.2 +/- 11.7 years and 84.3% (n = 2247) were males. Diabetes was found in over a third of those with HCC (n = 1032;39.5%). The most common etiology of HCC was NAFLD (n = 927;35.5%) followed by viral hepatitis B and C and harmful levels of alcohol. Among those with HCC, 27.9% (n = 744) had no cirrhosis. Higher proportion of cirrhotic HCC patients had alcohol as an etiological factor as compared to non-cirrhotic (17.5 vs. 4.7%, p <= 0.001). NAFLD was an etiological factor for a higher proportion of non-cirrhotic HCC patients as compared to cirrhotic HCC (48.2 vs. 30.6%, p <= 0.001). Diabetics more commonly had non-cirrhotic HCC (50.5 vs. 35.2%). The following factors were associated with an occurrence of cirrhotic HCC: male gender (OR 1.372 and 95% CI 1.070-1.759), age above 60 years (OR 1.409 and 95% CI 1.176-1.689), HBV (OR 1.164 and 95% CI 0.928-1.460), HCV (OR 1.228 and 95 CI 0.964-1.565) and harmful consumption of alcohol (OR 3.472 and 95% CI 2.388-5.047). The adjusted odds of non-cirrhotic patients having NAFLD was 1.553 (95% CI 1.290-1.869).ConclusionThis large multi-centric study demonstrates that NAFLD is the most important risk factor for development of both cirrhotic and non-cirrhotic HCC in India and has overtaken viral hepatitis. Awareness campaigns and large-scale screening are required to reduce the high burden of NAFLD-related HCC in India.