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Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease.

ABSTRACT: Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), with higher genetic predisposition further amplifying the risk. Further, we demonstrate a pronounced interaction between heavy binge drinking and high PRS, resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevates ARC risk across all drinking and PRS categories, and showed significant interaction with both binge patterns and genetic risk. Overall, we demonstrate synergistic effects of binge drinking, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions.

SUBMITTER: Ding C

PROVIDER: S-EPMC10721893 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease.

Ding Chengyi C Ng Fat Linda L Britton Annie A Im Pek Kei PK Lin Kuang K Topiwala Anya A Li Liming L Chen Zhengming Z Millwood Iona Y IY Bell Steven S Mehta Gautam G

Nature communications 20231214 1

Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), ...[more]

PMID: 38097541

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Project description:Binge alcohol consumption elicits acute and robust increases of muscle sympathetic nerve activity (MSNA), yet the impact of evening binge drinking on morning-after MSNA is unknown. The present study examined the effects of evening binge alcohol consumption on polysomnographic sleep and morning-after MSNA. We hypothesized that evening binge drinking (i.e. 4-5 drink equivalent in <2 h) would reduce sleep quality and increase morning-after blood pressure (BP) and MSNA. Following a familiarization night within the sleep laboratory, 22 participants (12 men, 10 women; 25 ± 1 yr) were examined after simulated binge drinking or fluid control (randomized, crossover design). Morning MSNA was successfully recorded across both conditions in 16 participants (8 men, 8 women) during a 10-min baseline and three Valsalva's maneuvers (VM). Binge drinking reduced rapid eye movement (REM) sleep (15 ± 1 vs. 20 ± 1%, P = 0.003), increased stage II sleep (54 ± 1 vs. 51 ± 1%, P = 0.002), and increased total urine output (2.9 ± 0.2 vs. 2.1 ± 0.1 liters, P < 0.001) but did not alter morning-after urine specific gravity. Binge drinking increased morning-after heart rate [65 (54-72) vs. 58 (51-67) beats/min, P = 0.013] but not resting BP or MSNA. Binge drinking elicited greater sympathoexcitation during VM (38 ± 3 vs. 43 ± 3 bursts/min, P = 0.036). Binge drinking augmented heart rate (P = 0.002), systolic BP (P = 0.022), and diastolic BP (P = 0.037) reactivity to VM phase IV and blunted cardiovagal baroreflex sensitivity during VM phases II (P = 0.028) and IV (P = 0.043). In conclusion, evening binge alcohol consumption disrupted REM sleep and morning-after autonomic function. These findings provide new mechanistic insight into the potential role of binge drinking on cardiovascular risk.NEW & NOTEWORTHY Chronic binge alcohol consumption is associated with future cardiovascular disease (CVD) risk in both men and women. In addition, binge alcohol consumption is known to disrupt normal sleep quality during the early morning hours, coinciding with the morning sympathetic surge. In the present study, an evening of binge alcohol consumption increased baseline morning heart rate and cardiovascular reactivity during the Valsalva maneuver (VM) strain. Specifically, muscle sympathetic nerve activity and phase IV hemodynamic responses increased during VM the morning after binge alcohol consumption. The autonomic dysfunction and increased cardiovascular reactivity during VM suggests a contributing mechanism to CVD risk present in individuals who binge drink.

Project description:IntroductionAlthough most patients with alcohol-related liver disease (ALD) have a history of prolonged and heavy drinking, there is no clear threshold defining the level of alcohol consumption that leads to ALD. We aimed to evaluate the correlation between average alcohol consumption and the risk of liver disease and to determine the threshold for clinically significant alcohol consumption.Materials and methodsUsing the Korean National Health Insurance database, we identified participants who underwent a health-screening program in 2010 and 2011 and retrospectively analyzed their data until 2019. To diagnose and categorize the extracted participants, we used the International Classification of Diseases version 10 and Fatty Liver Index. The primary outcome was to determine the incidence of newly diagnosed liver-related diseases during the observation period and compare the incidence of liver-related diseases among non-drinkers and drinkers based on the amount of alcohol consumption.ResultsA total of 53,006 patients were enrolled and followed-up for a median of 8.4 years, during which 1,509 cases of liver-related diseases occurred. The participants were divided into five groups: no alcohol consumption (n = 31,359), 1st quartile (n = 5,242), 2nd quartile (n = 5,704), 3rd quartile (n = 5,337), and 4th quartile (n = 5,364). The corresponding number of glasses of alcohol consumed per week for each quantile (Q1, Q2, Q3, and Q4) was labeled 2.5 ± 1.1 standard units (1 standard unit = 8 g alcohol), 5.4 ± 1.9 standard units, 11.5 ± 3.3 standard units, and 27.9 ± 18.2 standard units, respectively. Compared with non-drinkers, the risk of liver-related disease was found to be higher in Q1 drinkers (adjusted hazard ratio [aHR], 1.09; 95% CI, 0.90-1.33), Q2 drinkers (aHR, 1. 10; 95% CI, 0.91-1.32), Q3 drinkers (aHR, 1.33; 95% CI, 1.11-1.59), and Q4 drinkers (aHR, 1.47; 95% CI, 1.24-1.75).ConclusionWe report that our study has shown that drinking more than 11.5 ± 3.3 standard units/week (92 ± 26.4 g/week) significantly increases the risk of developing liver-related diseases. Therefore, as a preventive measure to reduce the risk of developing liver disease, alcohol consumption should be limited beyond traditionally recommended levels.

Project description:BackgroundBinge drinking (BD) refers to a pattern of alcohol consumption characterized by the consumption of large amounts of alcohol in a short period of time followed by periods of abstinence. This drinking pattern is prevalent worldwide, mainly among young people. Excessive alcohol consumption is the spectrum of consumption patterns that may have or have had health consequences, and includes the concepts of risky alcohol use, harmful alcohol use and alcohol dependence according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), the latter two are currently grouped into alcohol use disorder (AUD) according to the fifth edition of the DSM (DSM-5). Due to the high prevalence of BD among young people, especially university students, as well as the important consequences of its practice, a study was conducted to evaluate excessive alcohol consumption and its relationship with the practice of BD in university students.MethodsA cross-sectional study was conducted among students (aged 18-30 years) enrolled in the academic year 2018-2019 at the Faculty of Nursing at a university in northern Spain. Data collection included sociodemographic information, and alcohol use information, collected using a semi-structured questionnaire. To measure the excessive alcohol consumption, this study used the Alcohol Use Disorders Identification Test (AUDIT).ResultsA total of 142 participants were included, of which 88.03% were women. Up to 38.03% were classified as BD. Up to 14.77% of non-BD participants and 66.67% of BD participants were classified as risky drinkers (AUDIT Total geq 8 in men or geq 6 in women) (p < 0.001). Up to 3.41% of the non-BD and 24.07% of the BD were drinkers with harmful alcohol use and probable alcohol dependence (AUDIT Total geq 13) (p < 0.001). A total of 5.68% of non-BD and 42.59% of BD were AUD drinkers (AUDIT Total geq 9 in males or geq 8 in females) (p < 0.001). In addition, statistically significant differences were found between the BD and non-BD groups in the responses to each of the AUDIT items, as well as in the total score and also in the scores of the three domains of the questionnaire.ConclusionsExcessive alcohol consumption is frequent among university students, especially among those who practice BD.

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Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease.

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Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease.

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