Background and aims: Accurate estimates of the risk of hepatocellular carcinoma (HCC) in patients with cirrhosis are important for clinical decisions about HCC surveillance. We described HCC risk among outpatients with alcoholic cirrhosis and contrasted the risk of death from HCC with the risk of death from variceal bleeding or trauma.Methods: This was a nationwide, registry-based historical cohort study between 2006 and 2018.We included all Danish outpatients with a hospital diagnosis of alcoholic cirrhosis, except those with cancer, those with chronic viral hepatitis or autoimmune liver disease, and those older than 80 years. We followed them through 2018 and described the cumulative risk of HCC and the cumulative risk of death from HCC, variceal bleeding, or trauma.Results: Of the 4553 included patients, 181 developed HCC and 2274 died. The cumulative risk of HCC was 0.9% (95% confidence interval [CI] 0.7 to 1.3) after 1 year, 3.6% (95% CI 3.0 to 4.2) after 5 years, and 6.0% (95% CI 5.1 to 7.0) after 10 years, or approximately 0.7% per year. Male gender, older age, and decompensated cirrhosis predicted a higher HCC risk. After 10 years, 6.9% of deaths in the cohort could be attributed to HCC, whereas 6.5% could be attributed to variceal bleeding, and 5.0% to trauma. Conclusions:In 2006-2018, Danish outpatients with alcoholic cirrhosis had an HCC risk of 0.7% per year, and they were nearly as likely to die from variceal bleeding or from trauma as from HCC.The implications are that many potentially harmful examinations are required for every HCC found through surveillance, so interventions targeting the prevention of other causes of death might be more cost-effective.

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Summary Background There is socio-economic inequality in total alcohol-related harm, but knowledge of inequality in the incidence of specific alcohol-related diseases would be beneficial for prevention. Registry-based studies with nationwide coverage may reveal the full burden of socioeconomic inequality compared to what can be captured in questionnaire-based studies. We examined the incidence of alcohol-related liver disease (ALD) according to socioeconomic status and age. Methods We used national registries to identify patients with an incident diagnosis of ALD and their socioeconomic status in 2009–2018 in Denmark. We computed ALD incidence rates by socioeconomic status (education and employment status) and age-group (30–39, 40–49, 50–59, 60–69 years) and quantified the inequalities as the absolute and relative difference in incidence rates between low and high socioeconomic status. Findings Of 17,473 patients with newly diagnosed ALD, 78% of whom had cirrhosis, 86% had a low or medium-low educational level and only 20% were employed. ALD patients were less likely to be employed in the 10 years prior to diagnosis than controls. The incidence rate of ALD correlated inversely with educational level, from 181 (95% CI, 167–197) to 910 (95% CI, 764–1086) per million person-years from the highest to the lowest educational level. By employment status, the incidence rate per million person-years was 211 (95% CI, 189–236) for employed and 3449 (95% CI, 2785–4271) for unemployed. Incidence rates increased gradually with age leading to larger inequalities in absolute numbers for older age-groups. Although ALD was rare in the younger age-groups, the relative differences in incidence rates between high and low socioeconomic status were large for these ages. The pattern of socioeconomic inequality in ALD incidence was similar for men and women. Interpretation This study showed substantial socioeconomic inequalities in ALD incidence for people aged 30–69 years. Funding The study was supported by grants from the Novo Nordisk Foundation (NNF18OC0054612) and the Research Fund of Bispebjerg Hospital.

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Background and Aims: Observational studies have shown an association between statin or aspirin use and a decreased risk of HCC, but the effects of a well-defined treatment strategy remain unknown. We emulated trials of the effects of continuous statin or aspirin use on HCC risk in patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis). Approach and Results: We specified target trials for statins and, separately, aspirin and emulated them using Danish health care registries. All eligible patients with ALD cirrhosis diagnosed in 2000–2018 were included in either an exposed or an unexposed arm. Patients were followed until HCC or death without HCC. The 5-year risk of HCC was estimated using marginal structural models with inverse probability weighting. Using statins continuously for 5 years compared with not using statins resulted in a relative risk (RR) of HCC of 0.67 (95% CI: 0.45–0.91). The RR of death without HCC was 0.69 (95% CI: 0.65–0.77). For aspirin, the RR was 1.05 (95% CI: 0.60–1.42) for HCC and 1.02 (95% CI: 0.95–1.09) for death without HCC. Conclusions: In patients with ALD cirrhosis, 5 years of continuous statin use resulted in a 33% RR reduction of HCC (number needed to treat = 94) and a 31% RR reduction of death without HCC (number needed to treat = 7). Such strong causal effects are implausible and best explained by uncontrollable confounding, highlighting the need for randomized trials. Aspirin use likely does not affect the risk of HCC or death without HCC.