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Original Article | Open Access

Glycemic control predicts the risk of hepatic fibrosis in biopsy-proven NAFLD: a possible mediating role for leukemia inhibitory factor?

Feng Gonga, Kenneth I. Zhengb, Liang-Jie Tangb, Gang Lib, Rafael S. Riosb, Ou-Yang Huangb, Yang-Yang Lic, Christopher D. Byrned, Giovanni Targhere, Man Mia, Na Hef, Hong-Lei Mab, Ming-Hua Zhengb,g,h( )
Xi'an Medical University, China
NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
The First Affiliated Hospital of Xi'an Medical University, Xi'an, China
Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
Show Author Information

Abstract

Background

Despite the clear link between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus, little is understood about how glycemic control impacts histological severity. We aimed to investigate the deeper association between hemoglobin A1c (HbA1c) and the histologic severity of liver fibrosis.

Methods

A total of 568 adults with biopsy-proven NAFLD from the PERSONS cohort in Wenzhou were enrolled. The association between mean HbA1c and hepatic histological features was investigated with ordinal logistic regression. Generalized additive models were used to identify the non-linear relationship between HbA1c and increased fibrosis stage (stage F ​≥ ​3). Causal mediation analysis was performed to calculate the indirect effect of the relationship between HbA1c and hepatic fibrosis mediated by cytokines.

Results

Every 1% increase in mean HbA1c was associated with 16% higher odds of increased fibrosis stage (odds ratio 1.16, 95%CI 1.04-1.30), even after adjustment for confounding factors. There was a non-linear association between HbA1c and increased fibrosis stage (stage F ​≥ ​3), and the HbA1c inflection point was 9.2%. In particular, the ORs on the left and right sides of this inflection point were 2.1 (95%CI 1.4-3.3) and 0.1 (95%CI 0-4.8), respectively. 7% of the association (OR 1.07, 95%CI 1.01-1.12) between HbA1c and liver fibrosis was mediated by leukemia inhibitory factor.

Conclusions

Glycemic control predicts severity of hepatic fibrosis and leukemia inhibitory factor plays an intermediary role between them, and thus optimizing glycemic control may be a means of modifying the risk of fibrosis progression in NAFLD.

Keywords

NAFLDLeukemia inhibitory factorHepatic fibrosis

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iLIVER
Volume 1 Issue 1,
March 2022
Pages 30-34
DOI: 10.1016/j.iliver.2022.02.001
Cite this article:
Gong F, Zheng KI, Tang L-J, et al. Glycemic control predicts the risk of hepatic fibrosis in biopsy-proven NAFLD: a possible mediating role for leukemia inhibitory factor?. iLIVER, 2022, 1(1): 30-34. https://doi.org/10.1016/j.iliver.2022.02.001

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Published: 07 March 2022
© 2022 The Author(s). Published by Elsevier Ltd on behalf of Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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