Absence of fatty liver is associated with higher risk of hepatocellular carcinoma in chronic hepatitis B infection

Abstract

Introduction: Concomitant chronic hepatitis B infection (CHB) and non-alcoholic fatty liver disease (NAFLD) is common, but the implications of NAFLD on clinical outcomes of CHB, including hepatocellular carcinoma (HCC), are not well-investigated. Methods: CHB patients [both treatment-naïve and treated with nucleos(t)ide analogues (NA)] were recruited for transient elastography assessment for liver stiffness, and controlled attenuation parameter (CAP), a non-invasive quantification of hepatic steatosis, and were prospectively followed up for development of HCC. Steatosis and severe steatosis were diagnosed by CAP ≥248 dB/m and ≥280 dB/m respectively, and advanced fibrosis/ cirrhosis was diagnosed by liver stiffness ≥9 kPa. Results: Among 2403 CHB patients (55.6% male, median age 55.6 years, 57.1% NA-treated, median ALT 26 U/L), 48 patients developed HCC during a median follow-up of 46.4 months. Multivariate analysis showed increased CAP to be inversely associated with HCC development (OR 0.994, 95%CI 0.988-0.999). The cumulative probability of HCC was 2.88%, 1.56% and 0.71%, respectively for patients with no steatosis, mild-to-moderate steatosis, and severe steatosis, respectively (p=0.01). Subgroup analysis among patients without advanced fibrosis/cirrhosis and NA-treated patients showed increased CAP remaining to be inversely associated with HCC (OR 0.991, 95%CI 0.983-0.999; and OR 0.993, 95%CI 0.987-0.999 respectively). The risk of HCC increased from 1.56% to 8.89% in patients without severe steatosis if advanced fibrosis/cirrhosis were present (p<0.001). Conclusion: Reduced hepatic steatosis was significantly associated with a higher risk of incident HCC in CHB patients. Routine CAP and liver stiffness measurements can be important for risk stratification, especially in on-treatment patients.