Changing etiological spectrum of hepatocellular carcinoma in India – A systematic review and meta-analysis

Background Recent studies from both India and outside India have shown a change in the etiological profile of hepatocellular carcinoma (HCC). We aimed to analyze the etiological spectrum and changing trends of HCC etiology in India using a systematic review of current literature and meta-analysis. Methods Electronic databases of Pubmed/Medline, Scopus, and Embase were searched from inception to July 2023 for studies reporting the data on the etiology of HCC from India. The pooled proportions with 95% confidence interval were calculated using summative statistics. Results A total of 60 studies (n = 12327) were included in the final analysis. The pooled proportions of HCC cases with at least one positive and negative viral marker were 56.0 (49.5 – 62.6) and 43.1% (36.5 – 49.8), respectively. The pooled proportion of HCC cases with positive hepatitis B virus (HBV) markers was 41.0 (35.8 – 46.1), while those with positive markers for hepatitis C virus (HCV) were 20.3 (17.0 – 23.6). The pooled proportion of cases with HCC with significant alcohol intake was 19.0% (15.6 – 22.4), and those related to non-alcoholic fatty liver disease (NAFLD) were 16.9% (12.1 – 21.7). Around 7.9% (5.8 – 10.0) of the cases had HCC with multiple etiologies. Subgroup analysis showed a significant variation with the location of the study based on zone. Meta-regression analysis based on publication year (1990-2023) showed a significant reduction in the proportion of cases with HBV and an increase in cases with NAFLD. In contrast, the proportion of cases with HCV and alcohol did not change significantly. Conclusion Viral hepatitis is the most common etiology of HCC in India, predominantly HBV. The proportions of cases with HCC related to NAFLD are increasing, and those related to HBV are declining.