Effects of Age, Sex, Body Weight, and Quantity of Alcohol Consumption on Occurrence and Severity of Alcoholic Hepatitis

Abstract

Background & Aims 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: 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. Methods We compared data from 145 patients with AH cases and 124 controls, based on BMI when they joined the cohort; groups were matched for sex and race. Drinking patterns were assessed using the time line follow back method, the Alcohol Use Disorders Identification Test, and National Institute of Alcohol Abuse and Alcoholism 6-question survey. We performed univariable and multivariable analyses we to assess effects of these factors and their interaction in increasing the risk for AH. We also explored the association between PNPLA3 variants and AH. Results Cases with AH were older (47 vs 44 years; 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 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). Conclusion 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.

Alcohol, Diet and Drug Use Preceding Alcoholic Hepatitis

“…Importantly, our data refutes previous assertions about possible precipitants of AH, in particular, that binge drinking precipitates the disease, and also that paracetamol use may cause it [10]. Other papers describe risk factors – for example, BMI [9, 11] – without addressing precipitants.…”

“…The TREAT consortium recently reported on characteristics of patients with AH and a control group of patients with ArLD [9]. Interestingly, patients with AH tended to drink less than the control group: approximately 10 standard drinks per day.…”

“…Clearly alcohol use is one triggering factor; however, Liangpunsakul et al [9] found that individuals with AH drank less than heavy drinking controls without AH, both in the month before admission with AH and over the preceding year. It has been suggested that acetaminophen use in alcoholics can trigger AH [10].…”

Challenges in Patient Enrollment and Retention in Clinical Studies for Alcoholic Hepatitis: Experience of the TREAT Consortium

“…The clinical characteristics of the patients recruited into the TREAT001 study have been previously reported (Liangpunsakul et al, 2016). The patients were mainly middle-aged white men who were very heavy drinkers.…”

“…Language barriers with Spanish-speaking patients also hinder recruitment. Hispanic patients may have an increased risk of AH (the PNLPA3 variant, common in Hispanics, which confers risk of non-alcoholic steatohepatitis (Romeo et al, 2008) and alcoholic cirrhosis (Stickel et al, 2011; Buch et al 2015) also increases risk for AH (Liangpunsakul, et al, 2016). Future studies could incorporate validated and IRB-approved Spanish translations of consent documents, surveys, and other data collection instruments (e.g., the Time Line Follow-Back survey, and instruments used to detect concomitant mental health disorders).…”