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Background: Parental drinking can cause harm to the offspring. A parent's diagnosis of alcohol-related liver disease (ALD) might be an opportunity to reach offspring with preventive interventions. We investigated offspring risk of adverse health outcomes throughout life, their association with their parent's educational level and diagnosis of ALD., Methods and Findings: We used nationwide health registries to identify offspring of parents diagnosed with ALD in Denmark 1996 to 2018 and age- and sex-matched comparators (20:1). We estimated the incidence rate ratios (IRRs) of hospital contacts with adverse health outcomes, overall and in socioeconomic strata. We used a self-controlled design to examine whether health outcomes were more likely to occur during the first year after the parent's ALD diagnosis. The 60,804 offspring of parents with ALD had a higher incidence rate of hospital contacts from age 15 to 60 years for psychiatric disease, poisoning, fracture or injury, alcohol-specific diagnoses, other substance abuse, and of death than comparators. Associations were stronger for offspring with low compared to high socioeconomic position: The IRR for admission due to poisoning was 2.2 versus 1.0 for offspring of an ALD parent with a primary level versus a highly educated ALD parent. Offspring had an increased risk for admission with psychiatric disease and poisoning in the year after their parent's ALD diagnosis. For example, among offspring whose first hospital contact with psychiatric disease was at age 13 to 25 years, the IRR in the first year after their parent's ALD diagnosis versus at another time was 1.29 (95% CI 1.13, 1.47). Main limitation was inability to include adverse health outcomes not involving hospital contact., Conclusions: Offspring of parents with ALD had a long-lasting higher rate of health outcomes associated with poor mental health and self-harm that increased shortly after their parent's diagnosis of ALD. Offspring of parents of low educational level were particularly vulnerable. This study highlights an opportunity to reach out to offspring in connection with their parent's hospitalization with ALD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jepsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: Offspring of patients with alcohol-associated liver disease (ALD) may have a higher risk of ALD. We examined their risk of ALD and survival with ALD., Approach and Results: We used Danish nationwide registries to identify the offspring of patients diagnosed with ALD in 1996-2018 and 20:1 matched comparators from the general population. They were followed for ALD diagnosis through 2018. We used landmark competing risk analysis to estimate the age-specific absolute and relative 10-year risks of ALD. ALD was diagnosed in 385 of 60,707 offspring and 2842 of 1,213,357 comparators during 0.7 and 14.0 million person-years of follow-up, respectively, yielding an incidence rate ratio of 2.73 (95% CI: 2.44-3.03). The risk of being diagnosed with ALD within the next 10 years peaked at age 55 years for offspring and age 57 years for comparators with 10-year risks of 1.66% (95% CI: 1.16-2.30) in offspring and 0.81% (95% CI: 0.68-0.97) in comparators at these ages. Offspring were younger at ALD diagnosis than comparators (median age of 47.4 vs. 48.9 years), yet slightly more of them had developed cirrhosis (60.3% vs. 58.7%). Survival after ALD diagnosis was similar in offspring and comparators, adjusted hazard ratio=1.03 (95% CI: 0.88-1.21), so on average offspring died younger due to their younger age at diagnosis., Conclusions: Offspring of patients with ALD had a low but increased risk of ALD. Screening offspring for chronic liver disease may be unnecessary, but other interventions to mitigate alcohol-associated harm should be considered., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Introduction: England has seen an increase in deaths due to alcohol-related liver disease (ALD) since 2001. We studied the influence of socioeconomic position on the incidence of ALD and the mortality after ALD diagnosis in England in 2001-2018., Methods: This was an observational cohort study based on health records contained within the UK Clinical Practice Research Datalink covering primary care, secondary care, cause of death registration, and deprivation of neighborhood areas in 18.8 million residents. We estimated incidence rate and incidence rate ratios of ALD and hazard ratios of mortality., Results: ALD was diagnosed in 57,784 individuals with a median age of 54 years and of whom 43% had cirrhosis. The ALD incidence rate increased by 65% between 2001 and 2018 in England to reach 56.1 per 100,000 person-years in 2018. The ALD incidence was 3-fold higher in those from the most deprived quintile vs those from the least deprived quintile (incidence rate ratio 3.30, 95% confidence interval 3.21-3.38), with reducing inequality at older than at younger ages. For 55- to 74-year-olds, there was a notable increase in the incidence rate between 2001 and 2018, from 96.1 to 158 per 100,000 person-years in the most deprived quintile and from 32.5 to 70.0 in the least deprived quintile. After ALD diagnosis, the mortality risk was higher for patients from the most deprived quintile vs those from the least deprived quintile (hazard ratio 1.22, 95% confidence interval 1.18-1.27), and this ratio did not change during 2001-2018., Discussion: The increasing ALD incidence in England is a greater burden on individuals of low economic position compared with that on those of high socioeconomic position. This finding highlights ALD as a contributor to inequality in health., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Increased knowledge of the causes of death will be essential to prevent premature death in alcohol-related liver disease. We examined cause-specific mortality, including death due to specific cancers, in the 15 years after diagnosis of alcohol-related liver disease., Methods: We used nationwide health registries to identify patients (aged ≥18 years) with a first diagnosis of alcohol-related liver disease between Jan 1, 2002, and Dec 31, 2017, in Denmark and followed up patients for their underlying cause of death up to Dec 31, 2019. We estimated the cause-specific mortality and investigated whether the cause-specific mortality differed by sex, age (<50, 50-59, and ≥60 years), alcohol-related liver disease severity at diagnosis (decompensated cirrhosis, compensated cirrhosis, alcoholic hepatitis, and steatosis or unspecified liver disease), and presence of diabetes., Findings: The study included 23 385 patients with incident alcohol-related liver disease. Patients had a median age of 58 years (IQR 51-65), 15 819 (68%) were men and 7566 (32%) were women, and 15 358 (66%) had cirrhosis. During 111 532 person-years of follow-up, 15 692 (67%) patients died. Liver disease was the leading cause of death. In the first 5 years after alcohol-related liver disease diagnosis, liver disease caused almost half of all deaths, and the 5-year risk of death due to liver disease was 25·8% (95% CI 25·3-26·4). Beyond 5 years, causes other than liver disease combined became more common; of these extrahepatic causes, cancer, cardiovascular disease, and alcohol use disorder were the most common. Hepatocellular carcinoma was the dominant cause of cancer death (10-year risk of 2·5%, 95% CI 2·3-2·7), followed by lung cancer (1·9%, 1·7-2·1). The 10-year risk of death due to liver disease (around 30%) was similar for patients in all age groups and independent of sex and diabetes but was three times higher for those with decompensated cirrhosis (46·7%, 44·8-48·4) than steatosis or unspecified liver disease (16·2%, 15·3-17·2)., Interpretation: Patients diagnosed with alcohol-related liver disease were at high risk of dying from liver disease many years after diagnosis, irrespective of age and sex. Death due to specific cancers, including hepatocellular carcinoma, each contributed minimally to the total mortality in patients with alcohol-related liver disease., Funding: TrygFonden and the Novo Nordisk Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background & Aims: Sleep disturbances are related to hepatic encephalopathy and hyperammonaemia in patients with cirrhosis. The circadian rhythm is regulated by light stimulation of the retina via melanopsin-containing ganglion cells. The study aimed to investigate whether induced hyperammonaemia affects the pupillary light response and sleep efficiency in patients with cirrhosis., Methods: The study was a single-blinded crossover trial including nine patients with cirrhosis. Sleep was evaluated by Pittsburgh Sleep Quality Index (PSQI) and monitored for twelve nights with wrist accelerometers and sleep diaries. On two experimental days, separated by one week, patients were randomized to ingest either an oral amino acid challenge (AAC) or an isocaloric glucose solution (GS). We measured pupillary light response, capillary ammonia, the Karolinska Sleepiness Scale (KSS), and two neuropsychological tests on both experimental days., Results: The patients had poor self-assessed sleep quality. The amino acid challenge led to a significant increase in capillary ammonia and KSS. The time spent in bed sleeping after AAC was longer and with a reduced movement index compared to baseline but not different from GS. We found no difference in the pupillary light response or neuropsychiatric tests when comparing the effect of AAC with GS., Conclusions: Patients with cirrhosis had impaired sleep quality. Induced hyperammonaemia led to increased sleepiness but had no acute effect on pupillary light response or the neuropsychiatric tests., Trial Registration: Registration number: NCT04771104., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The study aim was to identify predictors of motivation to reduce alcohol consumption and whether motivation predicts engagement in alcohol misuse treatment in alcohol-related liver disease (ALD)., Methods: Data from health surveys and health-care registries were combined., Results: Of 674 patients with ALD, 65% consumed alcohol. Recent hospital admission and severe alcohol problems were associated with motivation to reduce alcohol consumption. Two-year probability for engagement in misuse treatment was 29% for patients with motivation to reduce alcohol consumption versus 6.5% for patients without motivation., Discussion: ALD patients with recent hospital admission were more motivated to cut down alcohol consumption, and motivation predicted engagement in alcohol misuse treatment. This insight can help us target brief interventions., (Copyright © 2022 by The American College of Gastroenterology.)

Alcohol is the dominant cause of liver disease in Denmark. Around 1,000 persons, usually of 40 to 70 years of age, are diagnosed with alcohol-related liver disease (ALD) each year in Denmark. ALD is usually preceded by several years of heavy drinking, during which alcohol cessation could have prevented manifest ALD as argued in this review. There is a substantial inequality in ALD incidence by geography and socioeconomic status in Denmark. ALD is associated with a high mortality: The five-year mortality risk is 54%, although the prognosis for patients with ALD has improved in recent years.