Pro-fibrotic polymorphisms predictive of advanced liver fibrosis in the severely obese

Dixon, JB, Bhathal, PS, Jonsson, JR, Dixon, AF, Powell, EE and O'Brien, PE (2003) Pro-fibrotic polymorphisms predictive of advanced liver fibrosis in the severely obese. Journal of Hepatology, 39 6: 967-971.


Author Dixon, JB
Bhathal, PS
Jonsson, JR
Dixon, AF
Powell, EE
O'Brien, PE
Title Pro-fibrotic polymorphisms predictive of advanced liver fibrosis in the severely obese
Journal name Journal of Hepatology   Check publisher's open access policy
ISSN 0168-8278
Publication date 2003
Sub-type Article (original research)
DOI 10.1016/S0168-8278(03)00459-8
Volume 39
Issue 6
Start page 967
End page 971
Total pages 5
Editor Juan Rodes
Place of publication Netherlands
Publisher Elsevier
Collection year 2003
Language eng
Subject C1
321006 Gastroenterology and Hepatology
730109 Surgical methods and procedures
Abstract Background/Aims: Insulin resistance and systemic hypertension are predictors of advanced fibrosis in obese patients with non-alcoholic fatty liver disease (NAFLD). Genetic factors may also be important. We hypothesize that high angiotensinogen (AT) and transforming growth factor-beta1 (TGF-beta1) producing genotypes increase the risk of liver fibrosis in obese subjects with NAFLD. Methods: One hundred and five of 130 consecutive severely obese patients having a liver biopsy at the time of laparoscopic obesity surgery agreed to have genotype analysis. Influence of specific genotype or combination of genotypes on the stage of hepatic fibrosis was assessed after controlling for known risk factors. Results: There was no fibrosis in 70 (67%), stages 1-2 in 21 (20%) and stages 3-4 fibrosis in 14 (13%) of subjects. There was no relationship between either high AT or TGF-beta1 producing genotypes alone and hepatic fibrosis after controlling for confounding factors. However, advanced hepatic fibrosis occurred in five of 13 subjects (odds ratio 5.7, 95% confidence interval 1.5-21.2, P = 0.005) who inherited both high AT and TGF-beta1 producing polymorphisms. Conclusions: The combination of high AT and TGF-beta1 producing polymorphisms is associated with advanced hepatic fibrosis in obese patients with NAFLD. These findings support the hypothesis that angiotensin II stimulated TGF-beta1 production may promote hepatic fibrosis. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Keyword Gastroenterology & Hepatology
Fibrosis
Obese Patients
Non-alcoholic Fatty Liver Disease
Transforming Growth-factor-beta-1 Gene
Homeostasis Model Assessment
Rat Hepatic-fibrosis
Growth-factor-beta
Angiotensin-ii
Nonalcoholic Steatohepatitis
Insulin-resistance
Blood-pressure
Tgf-beta
Disease
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2004 Higher Education Research Data Collection
School of Medicine Publications
 
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