Effects of Age, Sex, Body Weight, and Quantity of Alcohol Consumption on Occurrence and Severity of Alcoholic Hepatitis.
Only a minority of heavy drinking individuals develop alcoholic hepatitis (AH), for unclear reasons. We analyzed data from the Translational Research and Evolving Alcoholic Hepatitis Treatment cohort, consisting of subjects who drink heavily with normal results from liver tests (controls) and patients with AH. We examined risk factors for the development of AH including body mass index (BMI), drinking pattern and quantity, and sex.



We compared data from 145 patients with AH and 124 controls based on BMI when they joined the cohort; groups were matched for sex and race. Drinking patterns were assessed using the timeline followback method, the Alcohol Use Disorders Identification Test, and the National Institute of Alcohol Abuse and Alcoholism 6-question survey. We performed univariable and multivariable analyses to assess the effects of these factors and their interaction in increasing the risk for AH. We also explored the association between PNPLA3 variants and AH.



Cases with AH were older (47 vs 44 y; P = .03). For nearly all measures of quantity of alcohol consumed or frequency of binge drinking, controls drank more heavily than cases with AH. We did not find an association between BMI, sex, drinking patterns, and the presence of AH. Age and BMI were independent predictors for the severity of AH. When we analyzed cases and controls of European ancestry, the PNPLA3 single-nucleotide polymorphism rs738409 was associated with risk for AH (odds ratio, 1.89; P = .007).



Compared with heavy drinkers without liver disease, subjects with AH consumed lower levels of alcohol and had less binge drinking, suggesting an increased sensitivity to the toxic effects of alcohol. The risk for AH may be associated with the PNPLA3 rs738409 polymorphism.
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Medicine, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana. Electronic address: sliangpu@iupui.edu.
Suthat
S
Liangpunsakul
Division of Gastroenterology and Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia.
Puneet
P
Puri
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Vijay H
VH
Shah
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Patrick
P
Kamath
Division of Gastroenterology and Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia.
Arun
A
Sanyal
Division of Pharmacotherapy and Experimental Therapeutics, Center for Pharmacogenomics and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina.
Thomas
T
Urban
Department of Biostatistics, Richard M. Fairbanks School of Public Health, Indiana University School of Medicine, Indianapolis, Indiana.
Xiaowei
X
Ren
Department of Biostatistics, Richard M. Fairbanks School of Public Health, Indiana University School of Medicine, Indianapolis, Indiana.
Barry
B
Katz
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland.
Svetlana
S
Radaeva
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Naga
N
Chalasani
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Eskenazi Health, Indianapolis, Indiana.
David W
DW
Crabb
D000328:Adult; D000367:Age Factors; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D001835:Body Weight; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006519:Hepatitis, Alcoholic / Q000453:epidemiology* / Q000473:pathology*; D006801:Humans; D008049:Lipase / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
Alcohol Intake; Alcoholic Hepatitis; Body Weight; Gender; TLFB; TREAT