{"title":"HCV合并SVRs患者脂肪变性肝病与肝脏预后之间的矛盾关联","authors":"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","doi":"10.1007/s12072-025-10906-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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><p><strong>Methods: </strong>A 15-year prospective study of CHC patients with SVRs was conducted.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":6.1000,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Paradoxical association between steatotic liver disease and favorable hepatic outcomes in HCV patients with SVRs.\",\"authors\":\"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\",\"doi\":\"10.1007/s12072-025-10906-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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><p><strong>Methods: </strong>A 15-year prospective study of CHC patients with SVRs was conducted.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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>\",\"PeriodicalId\":12901,\"journal\":{\"name\":\"Hepatology International\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2025-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatology International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12072-025-10906-3\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12072-025-10906-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Paradoxical association between steatotic liver disease and favorable hepatic outcomes in HCV patients with SVRs.
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.
期刊介绍：
Hepatology International is the official journal of the Asian Pacific Association for the Study of the Liver (APASL). This is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal will focus mainly on new and emerging technologies, cutting-edge science and advances in liver and biliary disorders.
Types of articles published:
-Original Research Articles related to clinical care and basic research
-Review Articles
-Consensus guidelines for diagnosis and treatment
-Clinical cases, images
-Selected Author Summaries
-Video Submissions
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