期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 107, 期 4, 页码 E1356-E1366出版社
ENDOCRINE SOC
DOI: 10.1210/clinem/dgab897
关键词
Nonalcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH); obesity; adipose tissue; biomarker; collagen
资金
- Programme hospitalier de Recherche Clinique is French Ministry of Health and Solidarities [AOM10285/P100111]
- Aviesan Alliance Nationale pour les Sciences de la Vie et de la Sante and ITMO Sante Publique
- Institut Appert and Nestle Research. Nongovernmental entities had no role in the design implementation
- EPoS (Elucidating Pathways of Steatohepatitis) consortium - Horizon 2020 Framework Program of the European Comission [634413]
- French national program Investissement d'Avenir FORCE
- LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis) consortium - European Union [777377]
The study found that PRO-C3 is associated with advanced liver fibrosis in patients with severe obesity and decreased after bariatric surgery, without being affected by adipose tissue fibrosis. These data suggest that bariatric surgery prominently eliminates drivers of hepatic fibrogenesis in nonalcoholic fatty liver disease.
Context: Serum propeptides of type III and type VI collagen (PRO-C3 and PRO-C6) are elevated in advanced nonalcoholic fatty liver disease (NAFLD), but their value in patients with severe obesity and their evolution after bariatric surgery (BS) is unknown. It is unclear if these markers of fibrogenesis are affected by adipose tissue fibrosis (ATF). Objective: We studied the association of PRO-C3 and PRO-C6 with liver fibrosis before BS, examined their evolution after BS, and evaluated how much patients' ATF contribute to their levels. Methods: Serum PRO-C3 and PRO-C6 were measured in 158 BS patients and compared with liver, subcutaneous, and omental adipose tissue histology obtained during surgery. PRO-C3 and PRO-C6 levels of 63 patients were determined in follow-up at 3 and 12 months post-BS. Results: Patients in the highest quartile of PRO-C3 had a higher risk of advanced liver fibrosis (stage F3-4; odds ratio 5.8; 95% CI [1.5-29.9]; P = 0.017) vs the lowest quartile (adjustment for age, gender, and BMI). PRO-C3 was positively correlated with markers of insulin resistance and liver enzymes. After BS, PRO-C3 levels decreased in patients with high baseline liver fibrosis. This decrease correlated with improvement of metabolic and liver parameters. PRO-C6 was not related to stage of liver fibrosis. ATF did not correlate with PRO-C3 or PRO-C6 levels at baseline or after BS. Conclusion: PRO-C3 was associated with advanced liver fibrosis in patients with severe obesity, and decreased after BS, without being affected by ATF. These data suggest that BS prominently eliminates drivers of hepatic fibrogenesis in NAFLD.
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