Risk of alcohol-associated liver disease in the offspring of parents with alcohol-associated liver disease: A nationwide cohort study

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.