Risk of Liver Cancer From Major Causes Compared to Smoking and Lung Cancer: A Systematic Review and Meta-Analysis

Liver cancer is the second leading cause of premature cancer mortality globally, whose main causes-HBV, HCV, MASH and alcohol use-are preventable. Viral hepatitis' carcinogenicity is not as well-known as the risk of lung cancer from smoking, leading to rising rates of liver cancer worldwide. The aim of this study was to compare the risk of liver cancer in HBV, HCV, HDV, MASH and alcohol consumption with the better-known risk of lung cancer associated with smoking. We extracted the relative risk of liver cancer from HBV, HCV, HDV, MASH, and alcohol use and the relative risk of lung cancer from smoking from previous studies. We included cohort, case-control and nested case-control studies published as original articles. Odds ratios for each factor were pooled globally and by region to test for significant differences. One hundred and twenty-six studies with 86,097,714 participants were included. Relative to the risk of lung cancer and currently smoking (OR 6.0), HBV (OR 15.2, p < 0.001), HCV (OR 12.8, p < 0.01) and HDV (OR 23.5, p < 0.01) were significantly associated with a higher risk of liver cancer, while MASLD (OR 2.6, p < 0.01) and alcohol use (OR 2.4, p < 0.001) were significantly associated with a lower risk of liver cancer. There was no statistically significant difference in liver cancer risk across regions. These findings highlight that viral hepatitis is a carcinogenic infectious disease. Better integration of HCC surveillance within the management of viral hepatitis is critical.