Hepatol Int. 2025 Sep 13. doi: 10.1007/s12072-025-10906-3. Online ahead of print.
ABSTRACT
BACKGROUND: The effects of genetic predispositions and steatotic liver disease (SLD) on the outcomes of chronic hepatitis C (CHC) patients with sustained virological responses (SVRs) remain unknown.
METHODS: A 15-year prospective study of CHC patients with SVRs was conducted.
RESULTS: Among 965 SVR patients, the baseline and 24-week post-HCV therapy SLD rates were 64% and 54%, respectively; the patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M-rs738409 G allele was negatively correlated with the methylenetetrahydrofolate reductase (MTHFR) C677T Ala222Val-rs1801133 T allele (Pearson’s correlation: -0.078, p = 0.025). At baseline, body mass index (BMI) (OR: 1.18; 95% CI: 1.12-1.25), cirrhosis (0.34; 0.20-0.56) and the PNPLA3 G allele (1.28; 1.03-1.60) were associated with SLD. At 24 weeks posttherapy, BMI (1.16; 1.09-1.24), the fibrosis-4 index (0.86; 0.75-0.99), cirrhosis (0.23; 0.14-0.40), HOMA-IR (1.16; 1.04-1.30), the ALT level (1.01; 1.00-1.03) and the MTHFR T allele (0.66; 0.48-0.91) were associated with 24-week SLD in SVR patients. Longitudinally, compared with sex- and age-matched patients without 24-week SLD, patients with 24-week SLD had higher BMIs and ALT levels, poorer metabolic profiles, and greater cumulative incidences of cardiovascular events (70.9% vs. 63.7%, p = 0.026) but lower fibrosis-4 indices and cumulative incidences of cirrhosis (12.7% vs. 31.5%, p < 0.001) and HCC (4.6% vs. 12.1%, p < 0.001). A 24-week SLD was negatively associated with the cumulative incidences of cirrhosis (HR: 0.548; 95% CI HR: 0.281 ~ 0.894) and HCC (0.637; 0.32 ~ 0.99).
CONCLUSIONS: Poorer metabolic profiles and greater cardiovascular but lower hepatic event cumulative incidences were noted in patients with than in those without 24-week SLD. The paradoxical association between SLD and hepatic events might stem from the negative correlation between the PNPLA3 G allele and the MTHFR T allele, which are HCV-specific SLD factors.
PMID:40946137 | DOI:10.1007/s12072-025-10906-3
