Liver Steatosis-Related Polygenic Risk Score Predicts Hepatocellular Carcinoma Risk After Hepatitis C Virus...

Area of Science:

• Hepatology
• Genetics
• Oncology

Background:

• Genetic predisposition to hepatic steatosis may influence hepatocellular carcinoma (HCC) risk post-hepatitis C virus (HCV) eradication.
• The impact of steatosis-related genetic risk on broader patient populations after direct-acting antiviral (DAA) therapy is not well understood.

Purpose of the Study:

• To evaluate the association between a steatosis-polygenic risk score (PRS-5) and the risk of developing HCC.
• To investigate the predictive value of PRS-5 in patients undergoing DAA therapy for HCV.

Main Methods:

• Retrospective cohort study using data from the Taiwan Precision Medicine Initiative.
• Genotyping was performed, and PRS-5 was calculated to quantify genetic risk.
• Cox proportional hazards models and restricted cubic spline analysis were used to assess the association between PRS-5 and incident HCC.

Main Results:

• A PRS-5 of ≥0.66 was associated with a significantly higher 5-year cumulative incidence of HCC (23.97%) compared to PRS-5 <0.66 (8.89%).
• Higher PRS-5, elevated body weight index (>24 kg/m²), and high Fibrosis-4 index (>3.25) were independently associated with increased HCC risk.
• PRS-5 demonstrated predictive value across various patient subgroups, including those with lower fibrosis scores and without cirrhosis.

Conclusions:

• The PRS-5 is an independent predictor of increased HCC risk following HCV eradication with DAAs.
• These findings support the integration of PRS-5 into personalized HCC surveillance strategies for treated HCV patients.