Exposure to poly- and perfluoroalkyl substances and risk of hepatocellular carcinoma in male patients with cirrhosis related to HCV infection

Background: Prior studies suggest that per- and polyfluoroalkyl substances (PFAS) may increase risk of liver disease including hepatocellular carcinoma (HCC) via changes in hepatic lipid, amino acid, and glucose metabolism. However, whether PFAS promotes HCC among individuals with cirrhosis has not been examined. We examined associations of PFAS exposure and risk of HCC among patients with cirrhosis. Methods: In this nested case-control study, prediagnostic serum PFAS concentrations were measured using liquid chromatography-tandem mass spectrometry in 47 male patients with cirrhosis who developed incident HCC (cases) and 47 sex and race/ethnicity matched male cirrhosis patients who did not progress to HCC (controls). We estimated odds ratios (OR) and 95% confidence intervals (95% CI) using conditional logistic regression. Results: All cases and controls were male, and there were no differences in the distributions of age and race/ethnicity between matched cases and controls. Most cases and controls (81%) had HCV, and 85% were overweight/obese. Higher levels of perfluorooctanoic acid (PFOA)-type compounds, including L-perfluorooctanoic acid (OR, 1.63; 95% CI 1.00-2.74), perfluorodecanoic acid (OR, 2.16; 95% CI 1.00-5.12), perfluorononanoic acid (OR, 4.26; 95% CI 1.84-11.9) and perfluoroundecanoic acid (OR, 3.18; 95% CI 1.27-8.77), were associated with increased risk of HCC. Similarly, higher levels of perfluorooctane sulfonate (PFOS) were associated with higher HCC risk but only in patients with HCV (total PFOS, OR, 1.81; 95% CI 1.08-4.00). Conversely, higher perfluorobutanesulfonic acid were associated with lower risk of HCC and there was no significant association between perfluoroethylcyclohexanesulfonate level and HCC risk. Conclusions: Exposure to higher PFAS levels were associated with increased risk of HCC among patients with cirrhosis. These preliminary findings need to be confirmed in large studies and may provide a new insight into the mechanisms of environmental-associated HCC.