Interaction between the patatin‐like phospholipase domain‐containing protein 3 genotype and coffee drinking and the risk for acute alcoholic hepatitis

Abstract

Only a subset of subjects with excessive alcohol consumption develops alcoholic liver disease (ALD). One of the major risk factors for ALD is the genetic variant of the patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) gene. Coffee is one of the most commonly consumed beverages, and coffee consumption has been associated with lower levels of serum alanine aminotransferase. The aim of this study was to investigate the role of coffee drinking and PNPLA3 rs738409 and their association with alcoholic hepatitis (AH) in a well‐characterized cohort of subjects from the Translational Research and Evolving Alcoholic Hepatitis Treatment consortium. AH subjects and heavy drinking controls without a history of liver disease who were enrolled between May 2013 and May 2016 were included (n = 339), and the details of alcohol and coffee consumption were assessed. The PNPLA3 variant was determined among participants of European ancestry (n = 183). Relationships between baseline data and AH status were determined, and multivariable logistic regression modeling was performed. During the study period, 189 cases with AH and 150 heavy drinking controls were prospectively enrolled. The prevalence of regular coffee consumption was significantly lower in patients with AH compared to controls (20% versus 43%; P < 0.0001). The overall minor allele frequency of the PNPLA3 variant was higher in AH cases. Multivariable logistic regression revealed that coffee consumption and PNPLA3 were significantly associated with AH status at baseline after adjusting for relevant patient characteristics. Conclusion: We found a higher prevalence of AH among heavy drinkers with PNPLA3 G/G and G/C genotypes regardless of coffee consumption status and a higher prevalence of AH among heavy drinkers who were not regular coffee drinkers. These findings remained after considering relevant baseline patient characteristics. Further studies are needed to confirm our observation. (Hepatology Communications 2018;2:29–34)

Clinical characteristics and outcomes of mild to moderate alcoholic hepatitis

“…We have previously shown an interaction between PNPLA3 genotype and coffee drinking and the risk for AH among heavy drinkers. 8 The current study suggests a similar interaction between coffee drinking and PNPLA3 genotype in modifying the AH severity. Coffee consumption in high-risk PNPLA3 allele carriers reduced the proportion of individuals presenting with severe AH to that seen in low-risk PNPLA3 allele carriers who were not coffee consumers.…”

“…7 We also saw a lower prevalence of regular coffee consumption among heavy alcohol drinkers who develop AH. 8 We wanted to determine the clinical features, environmental risk factors such as coffee consumption and genetic risk factors such as PNPLA3 of individuals with AH who present with M-AH compared to severe AH. In this study, we report the risk factors, clinical characteristics and outcomes of patients presenting with M-AH who are enrolled into a prospective study and followed up for 12 months following their enrolment.…”

Diagnosis and Treatment of Alcohol‐Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases

“…There is evidence that binge drinking increases the risk of ALD . Coffee consumption protects against cirrhosis of many causes, including ALD as well as AH …”

“…(92) Coffee consumption protects against cirrhosis of many causes, including ALD as well as AH. (93)(94)(95)(96)(97) Studies of monozygotic versus dizygotic twins suggest a heritability of about 50% for AUD, and subsequent genome-wide studies show this to be a complex polygenic disorder. (98,99) Polymorphisms in the alcohol-metabolizing genes alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) have been strongly linked to risk of AUDs, but not with risk of liver disease.…”

Assessing Interactions between PNPLA3 and Dietary Intake on Liver Steatosis in Mexican-Origin Adults

“…PNPLA3 genotype status has also been found to significantly modify the association between total carbohydrate, as well as total sugar intake, and levels of liver fat in a sample of 153 Hispanic children and adolescents [ 19 ]. To date, few studies have attempted to characterize the interactions between PNPLA3 genotype status and dietary intake in adult populations (for exceptions see Scorletti et al, 2015 [ 24 ], Stojkovic et al, 2014 [ 25 ], and Liangpunsakul et al, 2017 [ 26 ]); however, to our knowledge, interactions have yet to be investigated in MO adults specifically, despite their higher risk for NAFLD. Additionally, to our knowledge, no studies have attempted to explore interactions between this variant and dietary intake in relation to levels of hepatic steatosis as assessed by non-invasive transient elastography (Fibroscan ® ), an assessment method widely used for its high-accuracy and utility in guiding clinical management strategies in patients with liver disease [ 27 ].…”