3 years ago

Growth differentiation factor 15 predicts advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease

Jeong Hwan Park, Sae Kyung Joo, Dong Soo Seo, Won Kim, Bo Kyung Koo, Mee Soo Chang, Jieun Lee, Jung Ho Kim, Jeong Mo Bae, Won-Il Jeong, Sung Hee Um
Background & Aims We explored whether growth differentiation factor 15 (GDF15) affects the histological severity of non-alcoholic fatty liver disease (NAFLD) independent of insulin resistance. Methods In a biopsy-proven NAFLD cohort, we measured serum GDF15 levels using enzyme-linked immunosorbent assays. Results Among 190 subjects (mean age, 53±14 years; men, 52.1%), 72 (men, 65.3%) and 78 (men, 44.9%) were diagnosed with biopsy-proven non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), respectively. GDF15 levels were significantly higher in NASH patients than in controls (P = 0.010) or NAFL patients (P = 0.001). Subjects with advanced fibrosis (≥F3) also showed higher GDF15 levels compared to the others (F0–2; P <0.001). Among NAFLD patients, the highest quartile of GDF15 levels was significantly associated with a risk of advanced fibrosis even after adjustment for age, gender, body mass index, smoking status, hypertension, diabetes, aspartate aminotransferase, platelet, albumin, insulin resistance, and low skeletal muscle mass (odds ratio, 4.27; 95% confidence interval, 1.04–17.63), but not with NASH risk. GDF15 levels showed a significant positive correlation with liver stiffness (Spearman's ρ, 0.525; P < 0.001). Palmitate treatment increased the GDF15 mRNA expression level significantly in Kupffer cells, but not in hepatocytes. In LX-2 cells, GDF15 treatment resulted in enhanced expression of α-smooth muscle actin and collagen I, as well as phosphorylation of SMAD2 and SMAD3. Conclusions Our findings suggest that GDF15 may serve as a novel biomarker of advanced fibrosis in NAFLD, thereby indicating the need for urgent anti-fibrotic pharmacotherapy. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/liv.13587

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.