Association of Genetic Polymorphisms with Clinical Characteristics and Survival of Hepatocellular Carcinoma Patients with or without Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)

The influence of single-nucleotide polymorphisms (SNPs) on hepatocellular carcinoma (HCC) in terms of etiological factors remains to be explored. This study evaluated the distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs6834314 and overall survival of HCC patients with metabolic dysfunction-associated steatotic liver disease (MASLD-HCC) and viral-related HCC (VIRAL-HCC). In this study, 564 patients with HCC were included: 254 with MASLD-HCC and 310 with VIRAL-HCC. The SNPs were determined by real-time PCR using TaqMan assays. Results: The mean ages of patients with MASLD-HCC and VIRAL-HCC were 68.4 vs. 60.9 years (p < 0.001), with a significant difference between groups. The prevalence of PNPLA3 genotype GG in MASLD-HCC was significantly higher in MASLD-HCC than in VIRAL-HCC (24.0 % vs. 15.5%; OR = 1.86; 95% CI = 1.14–3.05; p = 0.009). Similarly, the prevalence of TM6SF2 genotype TT in MASLD-HCC and VIRAL-HCC was 7.1% vs. 2.6% (OR = 3.39; 95% CI = 1.36–9.21; p = 0.003), while HSD17B13 genotype GG in the corresponding groups was 7.1% vs. 12.6% (OR = 0.53; 95 % CI = 0.27–1.01; p = 0.039). The overall median survival of MASLD-HCC was significantly shorter than the VIRAL-HCC group (42 vs. 66 months; p = 0.035). In Cox regression hazard analysis, HSD17B13 GG genotype was significantly associated with a lower mortality rate in MASLD-HCC (HR = 0.38 ; 95% CI = 0.18–0.81; p = 0.011). In contrast, PNPLA3 and TM6SF2 were not associated with overall survival in patients with MASLD-HCC or VIRAL-HCC. Conclusions: These data demonstrated that the prevalence of the studied SNPs significantly differed between MASLD-HCC and VIRAL-HCC. The HSD176B13 GG genotype was also associated with a survival benefit in Thai patients with MASLD-HCC.