Category: Other - Nonalcoholic fatty liver diseasae / nonalcoholic steatohepatitis (NAFLD / NASH)

Monitor: 15

15 - BASELINE CHARACTERISTICS OF PATIENTS WITH AND WITHOUT DIABETES IN TRIALS FOR ADVANCED FIBROSIS/CIRRHOSIS DUE TO NONALCOHOLIC STEATOHEPATITIS (NASH)

Thursday, Apr 25
1:00 PM – 1:30 PM

Objective : Diabetes is a major risk factor for NASH.  It is estimated that greater than 50% of patients with diabetes have NASH and 5-7% have advanced fibrosis/cirrhosis. Here, we describe the baseline characteristics of patients with and without diabetes enrolled in three randomized, placebo-controlled trials in patients with advanced fibrosis/cirrhosis due to NASH [STELLAR-3 and -4 (NCT03053050, NCT03053063) and ATLAS (NCT03449446)].


Methods : Patients recruited from over 400 sites in 24 countries underwent liver biopsy and were eligible based on presence of NASH and advanced fibrosis/cirrhosis (stage F3-F4). Enrollment was stratified by diabetes status. Patients were excluded if their screening hemoglobin A1c (HbA1c) was >9.5% or serum fructosamine >381 µmol if a hemoglobin A1c was unable to be resulted. Doses of diabetes medications were stable for at least 3 months prior to the diagnostic liver biopsy.


Results : A total of 2,070 patients were enrolled including 1,516 (73%) with diabetes (70% among F3 and 77% among F4). Median age was 59 years, 61% were female, and 76% were white (17% Hispanic). As expected, patients with diabetes had higher values of glucose (131 vs 98 mg/dL), HbA1c (6.9% vs 5.5%), and BMI (33.3 vs 31.8 kg/m2) compared to those without diabetes (all p® (16.8 vs 14.3 kPa), and greater hepatic collagen content on liver biopsy (7.1% vs 5.9%, all p<0.001). While metformin was the most commonly prescribed diabetes medication at baseline (67%), basal insulin (23%), GLP-1 agonists (17%), SGLT-2 inhibitors (16%), and thiazolidinediones (2.8%) were also utilized.


Discussion : Over 70% of patients enrolled in these trials for NASH and advanced fibrosis/cirrhosis have diabetes, the majority of which are well-controlled based on their HbA1c. The proportion of patients with diabetes is higher in those with cirrhosis. While serum ALT was not significantly different between groups, patients with diabetes had higher values of GGT, liver stiffness, and hepatic collagen content.


Conclusion : Advanced fibrosis/cirrhosis is an important complication of NASH in patients with diabetes. Compared to patients without diabetes, those with diabetes have more severe disease based on laboratory and histologic features, including those whose diabetes is controlled with lifestyle or medications.

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Zobair Younossi

Principal Investigator
Inova Fairfax Hospital

A principal investigator of clinical trials for advanced fibrosis due to NASH.

Eric Lawitz

Principal Investigator
Texas Liver Institute, University of Texas Health San Antonio

A principal investigator of clinical trials for advanced fibrosis due to NASH.

Vincent Wong

Principal Investigator
Department of Medicine and Therapeutics, The Chinese University of Hong Kong

A principal investigator of clinical trials for advanced fibrosis due to NASH.

Manuel Romero-Gomez

Principal Investigator
Hospital Universitario Virgen del Rocio

A principal investigator of clinical trials for advanced fibrosis due to NASH.

Takeshi Okanoue

Principal Investigator
Saiseikai Suita Hospital
Suita, Osaka564-0013, Japan

A principal investigator of clinical trials for advanced fibrosis due to NASH.

Michael Trauner

Principal Investigator
Division of Gastroenterology and Hepatology, Medical University of Vienna

A principal investigator of clinical trials for advanced fibrosis due to NASH.

Bryan J. McColgan

Senior Director of Clinical Research
Gilead Sciences, Inc.
San Francisco, California

A director of clinical research for advanced fibrosis due to NASH.

Stephen Harrison

Principal Investigator
Pinnacle Clinical Research

A principal investigator of clinical trials for advanced fibrosis due to NASH.

Zachary Goodman

Pathologist
Inova Fairfax Hospital

Central reader for clinical trials for advanced fibrosis due to NASH.

Quentin Anstee

Principal Investigator
Institute of Cellular Medicine, Newcastle University

A principal investigator of clinical trials for advanced fibrosis due to NASH.

Takeshi Okanoue

Principal Investigator
Saiseikai Suita Hospital
Suita, Osaka564-0013, Japan

A principal investigator of clinical trials for advanced fibrosis due to NASH.

Takeshi Okanoue

Principal Investigator
Saiseikai Suita Hospital
Suita, Osaka564-0013, Japan

A principal investigator of clinical trials for advanced fibrosis due to NASH.