Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study

Daniel Q Huang; Laura A Wilson; Cynthia Behling; David E Kleiner; Kris V Kowdley; Srinivasan Dasarathy; Maral Amangurbanova; Norah A Terrault; Anna Mae Diehl; Naga Chalasani; Brent A Neuschwander-Tetri; Arun J Sanyal; James Tonascia; NASH Clinical Research Network; Rohit Loomba

doi:10.1053/j.gastro.2023.04.025

Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study

Gastroenterology. 2023 Aug;165(2):463-472.e5. doi: 10.1053/j.gastro.2023.04.025. Epub 2023 Apr 29.

Authors

Collaborators

NASH Clinical Research Network:
Daniela Allende¹³, Annette Bellar¹³, Jaividhya Dasarathy¹³, Srinivasan Dasarathy¹³, Nicole Welch¹³, Rahul Yerrapothu¹³, Mustafa Bashir¹⁴, Anna Mae Diehl¹⁴, Cynthia Guy¹⁴, Mariko Kopping¹⁴, Dawn Piercy¹⁴, Ayako Suzuki¹⁴, Naglaa Tawadrou¹⁴, Naga Chalasani¹⁰, Mandy Cruz¹⁰, Oscar W Cummings¹⁰, Lisa Garrison¹⁰, Samer Gawrieh¹⁰, Niharika Samala¹⁰, Raj Vuppalanchi¹⁰, Danielle Carpenter¹¹, Theresa Cattoor¹¹, Janet Freebersyser¹¹, Brent A Neuschwander-Tetri¹¹, Pannapat Angkanaworakul⁵, Achashman Berihun⁵, Andrew Buysse⁵, Theresa Dorrian⁵, Breanna Gulati⁵, Kris V Kowdley⁵, Kevin Liu⁵, Sandra Misic⁵, Adam Sohal⁵, Joseph Vuong⁵, Veeral Ajmera¹⁵, Cynthia Behling¹⁵, Rohit Loomba¹⁵, Egbert Madamba¹⁵, Michael S Middleton¹⁵, Lisa Richards¹⁵, Seema Singh¹⁵, Claude Sirlin¹⁵, Ryan Gill¹⁶, Bilal Hameed¹⁶, Remilekun Awe¹⁶, Daisy Olvera¹⁷, Norah Terrault¹⁷, Liyun Yuan¹⁷, Matthew Yeh¹⁸, Somaya Albhaisi¹⁹, Amon Asgharpour¹⁹, Sherry Boyett¹⁹, Melissa J Contos¹⁹, Velimir A C Luketic¹⁹, Arun J Sanyal¹⁹, Jolene Schlosser¹⁹, Mohammad S Siddiqui¹⁹, David E Kleiner²⁰, Peggy Adamo²¹, Patricia Belt²¹, Jeanne M Clark²¹, Jennifer M DeSanto²¹, Jill Meinert²¹, Laura Miriel²¹, Emily P Mitchell²¹, Carrie Shade²¹, Jacqueline Smith²¹, Michael Smith²¹, Alice Sternberg²¹, James Tonascia²¹, Mark L Van Natta²¹, Annette Wagoner²¹, Laura A Wilson²¹, Tinsay Woreta²¹, Katherine P Yates²¹

Affiliations

¹ Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore.
² Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
³ University of California San Diego School of Medicine, San Diego, California.
⁴ Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
⁵ Liver Institute Northwest, Seattle, Washington.
⁶ Cleveland Clinic, Cleveland, Ohio.
⁷ Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California.
⁸ Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California.
⁹ Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina.
¹⁰ Indiana University School of Medicine, Indianapolis, Indiana.
¹¹ Saint Louis University, St Louis, Missouri.
¹² Virginia Commonwealth University School of Medicine, Richmond, Virginia.
¹³ Cleveland Clinic Foundation, Cleveland, Ohio.
¹⁴ Duke University Medical Center, Durham, North Carolina.
¹⁵ University of California San Diego, San Diego, California.
¹⁶ University of California San Francisco, San Francisco, California.
¹⁷ University of Southern California, Los Angeles, California.
¹⁸ University of Washington Medical Center, Seattle, Washington.
¹⁹ Virginia Commonwealth University, Richmond, Virginia.
²⁰ National Cancer Institute, Bethesda, Maryland.
²¹ Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland.
²² Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California; Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, California. Electronic address: roloomba@ucsd.edu.

PMID: 37127100
PMCID: PMC10699569 (available on 2024-08-01)
DOI: 10.1053/j.gastro.2023.04.025

Abstract

Background & aims: There are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD) in people with type 2 diabetes mellitus (T2DM) compared with people without T2DM. We assessed the time to fibrosis progression in people with T2DM compared with people without T2DM in a large, multicenter, study of people with NAFLD who had paired liver biopsies.

Methods: This study included 447 adult participants (64% were female) with NAFLD who had paired liver biopsies more than 1 year apart. Liver histology was systematically assessed by a central pathology committee blinded to clinical data. The primary outcome was the cumulative incidence of a ≥1-stage increase in fibrosis in participants with T2DM compared with participants without T2DM.

Results: The mean (SD) age and body mass index (calculated as weight in kilograms divided by the square of the height in meters) were 50.9 (11.5) years and 34.7 (6.3), respectively. The median time between biopsies was 3.3 years (interquartile range, 1.8-6.1 years). Participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at 4 years (24% vs 20%), 8 years (60% vs 50%), and 12 years (93% vs 76%) (P = .005). Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio, 1.69; 95% CI, 1.17-2.43; P = .005). The cumulative incidence of fibrosis regression by ≥1 stage was similar in participants with T2DM compared with participants without T2DM (P = .24).

Conclusions: In this large, multicenter cohort study of well-characterized participants with NAFLD and paired liver biopsies, we found that fibrosis progressed faster in participants with T2DM compared with participants without T2DM. These data have important implications for clinical practice and trial design.

Keywords: Cirrhosis; NAFLD; Nonalcoholic Steatohepatitis; Type 2 Diabetes Mellitus.

Publication types

Multicenter Study
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Adult
Biopsy
Cohort Studies
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / diagnosis
Diabetes Mellitus, Type 2* / epidemiology
Female
Humans
Liver Cirrhosis / diagnosis
Liver Cirrhosis / epidemiology
Liver Cirrhosis / pathology
Male
Non-alcoholic Fatty Liver Disease* / diagnosis
Non-alcoholic Fatty Liver Disease* / epidemiology
Non-alcoholic Fatty Liver Disease* / pathology

Abstract

Publication types

MeSH terms

Grants and funding