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.