Transcriptomics of Liver and PBMCs in Alcohol-Associated Liver Disease

This study was designed to characterize the transcriptome of alcohol-associated hepatitis using RNA sequencing (RNA-seq) technology for both liver tissue biopsies and peripheral blood mononuclear cells (PBMCs) extracted from blood samples, in order to identify expressed genes that are markers of the disease. To distinguish genes that differentiate alcohol-associated hepatitis from other inflammatory liver diseases, we compared the RNA-seq data generated from participants with alcohol-associated hepatitis, alcohol-associated cirrhosis, chronic hepatitis C infection, non-alcohol-associated fatty liver disease, and healthy controls. We utilized computational approaches to demonstrate that gene expression data generated from either liver tissue or blood samples can be used to identify a small set of gene biomarkers to distinguish between these liver diseases. The raw RNA-seq data will be available through dbGaP.]]>
The full description of inclusion and exclusion criteria for this study can be found in the Supplemental materials for our publication (PMID: 36119721). Briefly, the inclusion and exclusion criteria are as follows. Alcohol-associated hepatitis (AH) Inclusion: History of chronic alcohol consumption (e.g., >40 g/day for women and >60 g/day for men). A clinical diagnosis of possible alcoholic hepatitis. Serum total bilirubin >3 mg/dL. Exclusion: Liver disease significantly caused by hemochromatosis, autoimmune liver disease, Wilson disease, non-alcoholic fatty liver disease (NAFLD), hepatitis C, or hepatitis B. Alcohol-associated cirrhosis (AC) Inclusion: History of chronic alcohol consumption (e.g., >40 g/day for women and >60 g/day for men). A clinical diagnosis of alcoholic cirrhosis. Exclusion: Liver disease significantly caused by hemochromatosis, autoimmune liver disease, Wilson disease, NAFLD, hepatitis C, or hepatitis B. Non-Alcohol-Associated Fatty Liver DiseaseInclusion: A clinical diagnosis of NAFLD. Abstinent (consumption of less than one standard drink/week) during the 6 months prior to enrollment. Exclusion: Liver disease caused by hemochromatosis, autoimmune liver disease, Wilson disease, hepatitis C, or hepatitis B. Participants currently receiving treatment for NAFLD. Chronic Hepatitis CInclusion: Chronic hepatitis C diagnosis. Evidence of cirrhosis. Abstinent (consumption of less than one standard drink/week) during the 6 months prior to enrollment. Exclusion: Clinical evidence for NAFLD or laboratory evidence of hemochromatosis, autoimmune liver disease, Wilson disease, or hepatitis B. Has received or currently receiving treatment for HCV infection. Healthy ParticipantsInclusion: AUDIT-C scores of <4 for men and <3 for women. Abstinent (consumption of less than one standard drink/week) during the 6 months prior to enrollment. Exclusion: Clinical history or laboratory evidence of liver disease. BMI>32. Any of the following laboratory values within 90 days prior to enrollment: Creatinine: >1.5 mg/dLHemoglobin: <12 g/dLTotal bilirubin: >1.5 mg/dLAspartate transferase (AST): >40 IU/mLAlanine aminotransferase (ALT): >40 IU/mL ]]>