Steatotic Liver Disease-Related Polygenetic Risk Score Prediction of Hepatocellular Carcinoma in Nucleotide/Nucleoside Analog-Treated Chronic Hepatitis B.

[BACKGROUND AND AIMS] We aimed to investigate the association between steatotic liver disease-related genetic risk and hepatocellular carcinoma (HCC) in Taiwanese patients with chronic hepatitis B (CHB) treated with nucleotide/nucleoside analogs (NAs).

[METHODS] We enrolled 745 Taiwanese patients with CHB treated with NAs and analyzed the incidence and risk factors for HCC. Steatotic liver disease (SLD)-related single nucleotide polymorphisms (SNPs) were tested, and a polygenetic risk score (PRS) for hepatocellular carcinoma was created.

[RESULTS] The annual incidence of HCC was 1.7/100 person-years after a follow-up of > 3346.9 person-years. Factors with the strongest association with HCC were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 4.51/2.12-9.62; p < 0.001), followed by male sex (4.20/1.64-10.79; p = 0.003), a sSLD-related PRS > 0.062 (2.24/1.09-4.58; p = 0.03), body mass index (BMI) (1.15/1.07-1.24; p < 0.001), and age (1.06/1.03-1.10; p < 0.001). Among patients without cirrhosis, the HCC-associated factors were male sex (HR/CI: 1.17/1.10-1.24; p < 0.001) and BMI (1.16/1.03-1.30; p = 0.01). In contrast, a high PRS (HR/CI: 2.57/1.19-5.57; p = 0.02) was the only HCC-associated factor in patients with cirrhosis.

[CONCLUSIONS] The SLD-related gPRS predicted HCC development in CHB patients treated with NAs. The genetic effects were particularly enhanced in patients with cirrhosis.