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Background <p>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.</p> Methods <p>A 15-year prospective study of CHC patients with SVRs was conducted.</p> Results <p>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, <i>p</i> = 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&#xa0;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%, <i>p</i> = 0.026) but lower fibrosis-4 indices and cumulative incidences of cirrhosis (12.7% vs. 31.5%,<i> p</i> &lt; 0.001) and HCC (4.6% vs. 12.1%, <i>p</i> &lt; 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).</p> Conclusions <p>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.</p>

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Paradoxical association between steatotic liver disease and favorable hepatic outcomes in HCV patients with SVRs

  • 期刊论文

  • 发表日期：

    2025年9月13日

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  • Ming-Ling Chang,
  • Jur-Shan Cheng,
  • Jennifer Tai,
  • Wei-Ting Chen,
  • Sien-Sing Yang,
  • Cheng-Hsun Chiu,
  • Rong-Nan Chien,
  • Chia-Lin Hsu,
  • Shang-Jung Wu,
  • Cathy SJ Fann

摘要

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.