Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B

Abstract

Concurrent fatty liver in hepatitis B virus (HBV)-infected patients without significant alcohol intake is a frequent and increasingly alarming problem due to the non-alcoholic fatty liver disease (NAFLD) pandemic. Concomitant obesity and diabetes increase the risk of HBV-related hepatocellular carcinoma (HCC) development. Direct evidence of the hepatocarcinogenic effect of fatty liver in chronic HBV remains elusive. We aimed to evaluate the risk of concurrent histologically-proven fatty liver in HBV hepatocarcinogenesis. We conducted a retrospective cohort study on a liver biopsy cohort of HBV-infected patients without significant alcohol intake to evaluate the prevalence of concurrent histologically-proven fatty liver and its association with subsequent HCC development. We also examined 9 polymorphisms on 6 NAFLD-related candidate genes (ADIPOQ, APOC3, GCKR, LEPR, PNPLA3 and PPARG). Among 270 HBV-infected patients, concurrent fatty liver was found in 107 patients (39.6%) and was associated with metabolic risks, cirrhosis (P = 0.016) and PNPLA3 rs738409 CG/GG genotype (P = 0.002). At a median follow-up of 79.9 months, 11 patients (4.1%) developed HCC and 9 of them had concurrent fatty liver. By multivariable Cox analysis, concurrent fatty liver (hazard ratio 7.27,95% CI:1.52-34.76;P = 0.013), age, cirrhosis and APOC3 rs2854116 TC/CC genotype (hazard ratio 3.93,95% CI:1.30-11.84;P = 0.013) were independent factors predicting HCC development. Concurrent fatty liver is common in HBV-infected patients and an independent risk factor potentiating HBV-associated HCC development by 7.3-folds. APOC3 gene polymorphism also increases risk of HBV-related HCC and its role requires further characterization.