These authors contributed equally to this work.
Steatohepatitis/Metabolic Liver Disease
Article first published online: 4 DEC 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 6, pages 2142–2153, December 2012
How to Cite
Nobili, V., Carpino, G., Alisi, A., Franchitto, A., Alpini, G., De Vito, R., Onori, P., Alvaro, D. and Gaudio, E. (2012), Hepatic progenitor cells activation, fibrosis, and adipokines production in pediatric nonalcoholic fatty liver disease. Hepatology, 56: 2142–2153. doi: 10.1002/hep.25742
Potential conflict of interest: Nothing to report.
E.G. was supported by a research project grant from the University “Sapienza” of Rome (Rome, Italy) (Fondo per gli Investimenti della Ricerca di Base [FIRB] grant no. RBAP10Z7FS_001 and by Research Program for the Development of Research of National Interest [PRIN] grant no. 2009X84L84_001). D.A. was supported by FIRB grant no. RBAP10Z7FS_004 and by PRIN grant no. 2009X84L84_002).
- Issue published online: 4 DEC 2012
- Article first published online: 4 DEC 2012
- Accepted manuscript online: 29 MAR 2012 06:16AM EST
- Manuscript Accepted: 19 MAR 2012
- Manuscript Received: 22 NOV 2011
- University “Sapienza” of Rome (Rome, Italy)
- Fondo per gli Investimenti della Ricerca di Base [FIRB]. Grant Number: RBAP10Z7FS_001
- Development of Research of National Interest [PRIN]. Grant Number: 2009X84L84_001
- FIRB. Grant Number: RBAP10Z7FS_004
- PRIN. Grant Number: 2009X84L84_002
Hepatic progenitor cells (HPCs) play a major role in liver repair and regeneration. We evaluated HPC involvement in pediatric nonalcoholic fatty liver disease (pNAFLD). Thirty biopsies of consecutive children and adolescents with untreated NAFLD (19 with nonalcoholic steatohepatitis [NASH] and 11 without NASH) were studied using immunohistochemistry and immunofluorescence. HPCs and HPC-expressing adipokines (e.g., adiponectin, resistin, and glucagon-like peptide 1 [GLP-1]) were counted and correlated with steatosis, inflammation, hepatocyte ballooning, fibrosis, and NAFLD activity score (NAS). The HPC compartment was expanded in pNAFLD, especially in children with NASH, and was independently associated with degree of fibrosis (r = 0.303; P = 0.033). NASH livers were also characterized by increased hepatocyte apoptosis, cell-cycle arrest, and an expanded pool of intermediate hepatocytes. Adiponectin expression in HPCs of pNAFLD patients was down-regulated with respect to the healthy liver, and this expression was inversely correlated with NAS score (r = −0.792; P < 0.001) and steatosis (r = −0.769; P < 0.001). Resistin expression in HPCs increased in pNAFLD and was related to degree of fibrosis (r = 0.432; P < 0.05). GLP-1 was overexpressed in HPCs of pNAFLD patients, and GLP-1 expression was related to degree of steatosis (r = 0.577; P < 0.05) and NAS (r = 0.594; P < 0.01). Conclusions: HPC activation is involved in the response of the liver to oxidative stress in pNAFLD and is correlated with fibrosis and the progression toward NASH. HPCs express adiponectin, resistin, and GLP-1, which become available to resident liver cells and are strongly associated with the severity of NAFLD. These results may have important pathophysiological implications in the modulation of hepatic insulin resistance and the progression of liver injury. (HEPATOLOGY 2012;56:2142–2153)