1876-P: Impact of Diabetes on Liver Disease Progression in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis (NASH)
Authors: SANYAL ARUN J. , ABDELMALEK MANAL F. , CALDWELL STEPHEN , SHIFFMAN MITCHELL L. , GHALIB REEM , LAWITZ ERIC , JIANG DEYUAN , AGUILAR SCHALL RAUL E. , MCCOLGAN BRYAN J. , MYERS ROB , DJEDJOS STEPHEN , MUIR ANDREW , RATZIU VLAD , AFDHAL NEZAM , GOODMAN ZACHARY , BOSCH JAIME , HARRISON STEPHEN A. 
Published: June 2019

Background: Diabetes is a risk factor for advanced fibrosis due to NASH, but the effect of diabetes on disease progression is not well-characterized. Here, we describe clinical outcomes for patients with and without diabetes in two negative, randomized, placebo-controlled trials of simtuzumab.

Methods: 217 patients with bridging fibrosis (F3) and 258 subjects with compensated cirrhosis (F4) were enrolled. Liver biopsies were reviewed by a central pathologist at screening and weeks 48 and 96. Patients were stratified based on the presence or absence of diabetes. Adjudicated clinical outcomes included: esophageal varices, variceal bleeding, ascites, hepatic encephalopathy, ≥2 point increase in Child-Pugh-Turcotte score, MELD &gt;15, or death.

Results: 145 (67%) of patients with F3 and 179 (69%) of patients with F4 had diabetes at baseline. Median age was 56 years. By week 96, 25% (31/129) of F3 patients with diabetes had progressed to cirrhosis, compared to 18% (11/67) of patients without diabetes [p=0.27]. Cirrhotic (F4) patients with diabetes had a higher rate of clinical events (Figure).

Conclusion: Diabetes is common in patients with advanced fibrosis due to NASH and associated with numerically higher rates of progression. Larger studies are needed to confirm these findings. Patients with diabetes have a high unmet need for therapies that target advanced fibrosis due to NASH.

Disclosure

A.J. Sanyal: Consultant; Self; Ardelyx, Boehringer Ingelheim Pharmaceuticals, Inc., Exhalenz, Gilead Sciences, Inc., Hemoshear, Intercept Pharmaceuticals, Inc., Lilly, Mallinckrodt Pharmaceuticals, Nimbus Therapeutics, Nitto Denko, Novartis Pharmaceuticals Corporation, Pfizer Inc. Employee; Self; Sanyal Bio. Research Support; Self; Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Echosens, Galectin Therapeutics Inc., Immuron Ltd, Merck & Co., Inc., Salix Pharmaceuticals, Sequanna. Stock/Shareholder; Self; Akarna Therapeutics, GENFIT, Natural Shield, NewCo LLC, Tiziana. Other Relationship; Self; Elsevier, UpToDate. M.F. Abdelmalek: Advisory Panel; Self; Allergan, Bristol-Myers Squibb Company, Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Prometic Life Sciences Inc. Consultant; Self; TaiwanJ Pharmaceuticals Co., Ltd. Research Support; Self; Akcea Therapeutics, Allergan, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Galectin Therapeutics Inc., GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Prometheus, Shire, TaiwanJ Pharmaceuticals Co., Ltd. Speaker's Bureau; Self; Alexion Pharmaceuticals, Inc. S. Caldwell: Research Support; Self; Conatus Pharmaceuticals Inc., Galmed Pharmaceuticals Ltd., GENFIT, Gilead Sciences, Inc., Halyard, Mallinckrodt Pharmaceuticals, TARGET PharmaSolutions, Vital Therapy, Zydus Pharmaceuticals, Inc. Other Relationship; Self; Dova. M.L. Shiffman: Advisory Panel; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. Research Support; Self; Allergan, Conatus, Enanta Pharmaceuticals, Inc., Exhalenz, GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Novartis AG, Shire. Speaker's Bureau; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. R. Ghalib: None. E. Lawitz: Research Support; Self; birdrock bio, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Durect Corporation, Enanta Pharmaceuticals, Inc., Galmed Pharmaceuticals Ltd., GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., madrigal, Novartis AG, octeta, Zydus Cadila. D. Jiang: Employee; Self; Gilead Sciences, Inc. R.E. Aguilar Schall: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. B.J. McColgan: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. R. Myers: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. S. Djedjos: Employee; Self; Gilead Sciences, Inc. A. Muir: Advisory Panel; Self; AbbVie Inc., Gilead Sciences, Inc. Research Support; Self; AbbVie Inc., Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., NGM Biopharmaceuticals. V. Ratziu: Other Relationship; Self; Gilead Sciences, Inc. N. Afdhal: Advisory Panel; Self; Gilead Sciences, Inc., Ligand Pharmaceuticals, Inc. Consultant; Self; Echosens. Employee; Self; Spring bank Pharmaceuticals. Z. Goodman: None. J. Bosch: Advisory Panel; Self; Actelion Pharmaceuticals US, Inc., Conatus Pharmaceuticals Inc., Exhalenz. S.A. Harrison: Advisory Panel; Self; Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.