VPB0740 - Unique Protein Profiles with Inflammatory, Complement, and Endothelial Activation Signature Identified Patients with Alcohol-Associated and Non-Alcoholic Steatohepatitis Associated Cirrhosis

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Cecily Allen, MD

Medical Resident
Yale School of Medicine
New Haven, Connecticut, United States

Co-Author(s)

AB

Ayesha Butt

Postdoctoral Research Associate
Yale School of Medicine
New Haven, Connecticut, United States
XZ

Xiwen Zhao

Biostatistician
Yale School of Medicine
New Haven, Connecticut, United States
FL

Fangyong Li

Statistician
Yale School of Medicine
New Haven, Connecticut, United States
PB

Parveen Bahel

Research Assistant Department of Laboratory Medicine
Yale School of Medicine
New Haven, Connecticut, United States
CC

C-Hong Chang

Associate Research Scientist Cardiovascular Research Center
Yale School of Medicine
New Haven, Connecticut, United States
HC

Hyung Chun

Associate Professor (Cardiology)
Yale School of Medicine
New Haven, Connecticut, United States
SG

Sean Gu

Hospital Resident
Yale School of Medicine
New Haven, Connecticut, United States
JH

John Hwa

Professor of Medicine (Cardiology)
Yale School of Medicine
New Haven, Connecticut, United States
SJ

Sofia Simona Jakab

Associate Professor of Medicine (Digestive Diseases)
Yale School of Medicine
New Haven, Connecticut, United States
MM

Matthew McConnell

Instructor (Digestive Diseases)
Yale School of Medicine
New Haven, Connecticut, United States
HR

Henry Rinder

Professor of Laboratory Medicine and of Medicine (Hematology)
Yale School of Medicine
New Haven, Connecticut, United States
UT

Uyen To

Assistant Professor of Medicine (Digestive Diseases)
Yale School of Medicine
New Haven, Connecticut, United States
AL

Alfred Lee

Associate Professor of Medicine (Hematology); Director, Hematology/Oncology Fellowship Program
Yale School of Medicine
New Haven, Connecticut, United States
AP

Alexander Pine

Assistant Professor of Medicine (Hematology)
Yale School of Medicine
New Haven, Connecticut, United States

Background: Cirrhosis-related coagulation derangements result in altered hemostasis, and hypercoagulability markers such as von Willebrand factor (VWF) antigen and the factor VIII-to-protein C ratio (FVIII/PC) have prognostic significance. We sought to use plasma proteomic profiling to characterize plasma protein signatures in alcoholic versus non-alcoholic cirrhosis, and to identify protein biomarkers of prognostic significance associated with hypercoagulability of alcohol-associated cirrhosis.

Aims: To characterize and differentiate plasma protein signatures in alcohol versus non-alcoholic cirrhosis, with a focus on VWF and FVIII/PC in alcohol-associated cirrhosis.

Methods: Thirteen patients with alcohol-associated cirrhosis (4 Child-Pugh Class A, 9 Class C), 7 with non-alcoholic steatohepatitis (NASH) cirrhosis (4 Class A, 3 Class C), and 5 controls without cirrhosis were recruited between April and June 2021 with informed consent and Institutional Review Board approval. Blood was drawn and plasma sent for proteomic profiling (Eve Technologies). Proteomic profiles were compared using pairwise t-test and Wilcoxon rank sum test, identifying proteins that best clustered groups with linear discriminant analysis using Wilk’s Lambda criteria. Boruta feature selection was performed to identify candidate proteins associated with VWF antigen or FVIII/PC in alcohol-associated cirrhosis. Statistical analysis was performed using R (v4, R Core Team); P-values < 0.05 were considered statistically significant.

Results: Of study patients, 9 were female; 17 had cardiovascular risk factors and 3 chronic kidney disease. Eleven proteins involved in inflammation, complement activation, or endothelial activation uniquely segregated alcohol-associated cirrhosis, NASH cirrhosis, and controls (Figure 1). Several plasma proteins were significantly associated with VWF antigen or FVIII/PC in alcohol-associated cirrhosis (Figure 2).

Conclusion(s): Plasma proteomic profiling identifies unique complement, inflammation, and endothelial activation signatures in alcohol-associated versus NASH cirrhosis. Endotheliopathy may contribute to the prognostic value of VWF antigen and FVIII/PC in alcohol-associated cirrhosis. Further investigations may highlight the interconnection of complement and inflammation with the endothelium in the pathogenesis and coagulopathy of cirrhosis.