Glycemic Control Predicts Severity of Hepatocyte Ballooning and Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease.

Abstract

Background and aims

Whether glycemic control, as opposed to diabetes status, is associated with the severity of nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to evaluate whether degree of glycemic control in the years preceding liver biopsy predicts the histologic severity of nonalcoholic steatohepatitis (NASH).

Methods & results

Using the Duke NAFLD Clinical Database we examined patients with biopsy-proven NAFLD/NASH (n=713) and the association of liver injury with glycemic control as measured by hemoglobin A1c (HbA1c). The study cohort was predominantly female (59%), Caucasian (84%) with median (IQR) age of 50 (42, 58) years; 49% had diabetes (n=348). Generalized linear regression models adjusted for age, sex, race, diabetes, body mass index, and hyperlipidemia were used to assess the association between mean HbA1c over the year preceding liver biopsy and severity of histologic features of NAFLD/NASH. Histologic features were graded and staged according to NASH Clinical Research Network system. Group-based trajectory analysis was used to examine patients with ≥3 HbA1c (n=298) measures over 5 years preceding clinically indicated liver biopsy. Higher mean HbA1c was associated with higher grade of steatosis and ballooned hepatocytes, but not lobular inflammation. Every 1% increase in mean HbA1c was associated with 15% higher odds of increased fibrosis stage (OR 1.15, 95% CI 1.01, 1.31). As compared with good glycemic control, moderate control was significantly associated with increased severity of ballooned hepatocytes (OR 1.74, 95% CI 1.01, 3.01, p=0.048) and hepatic fibrosis (OR 4.59, 95% CI 2.33, 9.06, p<0.01).

Conclusions

Glycemic control predicts severity of ballooned hepatocytes and hepatic fibrosis in NAFLD/NASH, and thus optimizing glycemic control may be a means of modifying risk of NASH-related fibrosis progression.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1002/hep.31806

Publication Info

Alexopoulos, Anastasia-Stefania, Matthew J Crowley, Ying Wang, Cynthia A Moylan, Cynthia D Guy, Ricardo Henao, Dawn L Piercy, Keri A Seymour, et al. (2021). Glycemic Control Predicts Severity of Hepatocyte Ballooning and Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease. Hepatology (Baltimore, Md.). 10.1002/hep.31806 Retrieved from https://hdl.handle.net/10161/22505.

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Scholars@Duke

Alexopoulos

Anastasia Stefania Alexopoulos

Assistant Professor of Medicine
Crowley

Matthew Janik Crowley

Associate Professor of Medicine

Diabetes, Hypertension, Health Services Research

Moylan

Cynthia Ann Moylan

Associate Professor of Medicine

My research interests focus on the study of chronic liver disease and primary liver cancer, particularly from metabolic dysfunction associated steatotic liver disease (MASLD), formerly called nonalcoholic fatty liver disease (NAFLD).  As part of the MASLD Research Team at Duke, we are investigating the role of environmental contaminants, epigenetics, and genetics on the development of advanced fibrosis and liver cancer from MASLD and other chronic liver diseases.  We are also interested in understanding risks for progressive liver disease including developmental programming and in utero exposures and have been investigating these risks through studies of the Newborn Epigenetics Study (NEST).  The long term goal of our research is to develop non-invasive biomarkers to identify those patients at increased risk for cirrhosis and end stage liver disease in order to risk stratify patients as well as to develop better preventative and therapeutic strategies.

Guy

Cynthia Dianne Guy

Professor of Pathology

My research interests include:
Fine Needle Aspiration of Liver, Gastrointestinal Tract, and Pancreatic Lesions
Biliary Duct Brushings
Nonalcoholic Fatty Liver Disease/NASH
Liver Fibrogenesis

Henao

Ricardo Henao

Associate Professor of Biostatistics & Bioinformatics
Seymour

Keri Anne Seymour

Associate Professor of Surgery
Sudan

Ranjan Sudan

Professor of Surgery
Portenier

Dana Dale Portenier

Associate Professor of Surgery

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