Fibrosis progression rate in biopsy-proven nonalcoholic fatty liver disease among people with diabetes versus people without diabetes: a multicenter study
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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.
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In a study of 447 adults with MASLD and paired liver biopsies more than 1 year apart, individuals with T2D 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%), with an adjusted HR of 1.69 (95% CI 1.17-2.43).
“in a study on 447 adult participants with MASLD and paired liver biopsies > 1 year apart, individuals with T2D had a signi fi cantly higher cumulative incidence of fi brosis progression at 4 years (24% vs. 20%), 8 years (60% vs. 50%), and 12 years (93% vs. 76%) ( p < 0.005), with an adjusted HR of 1.69 (95% con fi dence interval [CI], 1.17 -2.43; p < 0.005) on multivariate analysis.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [53]
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Research works printed but not linked: 13
- Daniel Q. Huang, MBBS, FRCP (Conceptualization: Supporting; Formal analysis: Supporting; Investigation: Lead; Methodology: Equal; Writing - original draft: Lead; Writing -review & editing: Lead).
- Cynthia Behling, MD (Data curation: Supporting; Writing -review & editing: Supporting).
- David E. Kleiner, MD (Data curation: Supporting; Writing -review & editing: Supporting).
- Kris V. Kowdley, MD (Writing -review & editing: Supporting).
- Srinivasan Dasarathy, MD (Writing -review & editing: Supporting).
- Maral Amangurbanova, MD (Writing -review & editing: Supporting).
- Norah A. Terrault, MD (Writing -review & editing: Supporting).
- Anna Mae Diehl, MD (Writing -review & editing: Supporting).
- Naga Chalasani, MD (Writing -review & editing: Supporting).
- Brent A. Neuschwander-Tetri, MD (Writing -review & editing: Supporting).
- Arun J. Sanyal, MD (Writing -review & editing: Supporting).
- James Tonascia, PhD (Methodology: Supporting; Writing -review & editing: Supporting).
- Rohit Loomba, MD, MHSc (Conceptualization: Lead; Formal analysis: Supporting; Funding acquisition: Lead; Investigation: Equal; Methodology: Lead; Project administration: Lead; Resources: Lead; Supervision: Lead; Visualization: Lead; Writing -review & editing: Supporting).
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- Authors
- Huang, D. Q., Wilson, L. A., Behling, C., Kleiner, D. E., Kowdley, K. V., Dasarathy, S., Amangurbanova, M., Terrault, N. A., Diehl, A. M., Chalasani, N., Neuschwander-Tetri, B. A., Sanyal, A. J., Tonascia, J., Allende, D., Bellar, A., Dasarathy, J., Dasarathy, S., Welch, N., Yerrapothu, R., Bashir, M., Diehl, A. M., Guy, C., Kopping, M., Piercy, D., Suzuki, A., Tawadrou, N., Chalasani, N., Cruz, M., Cummings, O. W., Garrison, L., Gawrieh, S., Samala, N., Vuppalanchi, R., Carpenter, D., Cattoor, T., Freebersyser, J., Neuschwander-Tetri, B. A., Angkanaworakul, P., Berihun, A., Buysse, A., Dorrian, T., Gulati, B., Kowdley, K. V., Liu, K., Misic, S., Sohal, A., Vuong, J., Ajmera, V., Behling, C., Loomba, R., Madamba, E., Middleton, M. S., Richards, L., Singh, S., Sirlin, C., Gill, R., Hameed, B., Awe, R., Olvera, D., Terrault, N., Yuan, L., Yeh, M., Albhaisi, S., Asgharpour, A., Boyett, S., Contos, M. J., Luketic, V. A. C., Sanyal, A. J., Schlosser, J., Siddiqui, M. S., Kleiner, D. E., Adamo, P., Belt, P., Clark, J. M., DeSanto, J. M., Meinert, J., Miriel, L., Mitchell, E. P., Shade, C., Smith, J., Smith, M., Sternberg, A., Tonascia, J., Van Natta, M. L., Wagoner, A., Wilson, L. A., Woreta, T., Yates, K. P., & Loomba, R.
- Affiliations
- National University of Singapore (SG)
- University of California San Diego (US)
- Cleveland Clinic (US)
- Duke Medical Center (US)
- Indiana University School of Medicine (US)
- Saint Louis University (US)
- Liver Institute Northwest (US)
- University of California, San Francisco (US)
- University of Southern California (US)
- University of Washington Medical Center (US)
- Virginia Commonwealth University (US)
- Johns Hopkins University (US)
- ORCID
- Huang, Daniel Q.
- Amangurbanova, Maral
- Allende, Daniela
- Bellar, Annette
- Welch, Nicole
- Bashir, Mustafa
- Guy, Cynthia
- Piercy, Dawn
- Suzuki, Ayako
- Cummings, Oscar W.
- Gawrieh, Samer
- Samala, Niharika
- Vuppalanchi, Raj
- Carpenter, Danielle
- Liu, Kevin
- Ajmera, Veeral
- Madamba, Egbert
- Middleton, Michael S.
- Singh, Seema
- Sirlin, Claude
- Gill, Ryan
- Hameed, Bilal
- Yuan, Liyun
- Yeh, Matthew
- Albhaisi, Somaya
- Asgharpour, Amon
- Luketic, Velimir A.C.
- Siddiqui, Mohammad S.
- Clark, Jeanne M.
- DeSanto, Jennifer M.
- Miriel, Laura
- Smith, Michael
- Woreta, Tinsay
- Yates, Katherine P.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2023-08
- Volume
- 165
- Issue
- 2
- Pages
- 463-472.e5
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC10699569
- OpenAlex
- W4367397089
- Cited by
- 190
- References
- 40
- Citations by year
- 2026: 50 · 2025: 64 · 2024: 55 · 2023: 20
- FWCI
- 37.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Gastroenterology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Center for Advancing Translational Sciences (U01AA029019, UL1TR000436, UL1TR000439, UL1TR002649, UL1TR000004, UL1TR000100, UL1TR000448, UL1TR000423, UL1TR000006)
- Takeda Pharmaceuticals North America
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK061732, U01DK061737, U01DK061738, U01DK061713, U24DK061730, R01DK121378, R01DK106419, P30DK120515, U01DK061718, R01DK124318, U01DK061734, U01DK130190, U01DK061728)
- National Institutes of Health
- Ministry of Health -Singapore
- National Institute on Alcohol Abuse and Alcoholism
- National Medical Research Council (MOH-000595-01)
- National Cancer Institute (NCT00063622)
- National Heart, Lung, and Blood Institute (P01HL147835)
- National Institute of Environmental Health Sciences (5P42ES010337, 5UL1TR001442)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- non-alcoholic fatty liver disease, type 2 diabetes, liver fibrosis progression, fibrosis regression, liver histopathology, cumulative incidence, diabetes as risk factor
- MeSH terms
- Adult, Biopsy, Diabetes Mellitus, Type 2, Female, Humans, Liver Cirrhosis, Male, Cohort Studies, Non-alcoholic Fatty Liver Disease
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