Decreasing Incidence of Alcohol-Related Liver Disease in Denmark: A 25-Year Nationwide Study.

PurposeAlcohol consumption has decreased in Denmark in recent years. We aimed to illustrate and investigate the developments in the incidence, hospital care, and mortality of alcohol-related liver disease (ALD) in Denmark during the last 25 years.Patients and methodsThrough nationwide healthcare registries, we identified all Danish patients with incident ALD in 1994-2018. We computed standardized incidence rates by sex, age, and geography, age-specific incidence rates by birth cohort, and standardized prevalence. We enumerated inpatient admissions, days of admission, outpatient visits, and emergency room visits. Lastly, we estimated relative risks of mortality, standardized mortality rates, and the proportion of deaths caused by ALD.ResultsThe standardized incidence rate decreased from its peak at 357 per 1,000,000 in 2009 to 240 per 1,000,000 in 2018, and the decrease was evident for both sexes and all age groups below 70 years. The standardized prevalence was stable around 0.22% from 2011 onwards. There was an almost fivefold geographic variation in standardized incidence by municipalities, and age-specific incidence rates decreased sequentially with each 5-year birth cohort after 1960. The number of inpatient admissions, days of admission, and emergency room visits decreased during the study period, while the number of outpatient visits was stable. For patients diagnosed in 2014-2018 compared to 1994-1998, the relative risk of 1-year mortality was 0.83 (95% confidence interval: 0.78-0.87), and the standardized mortality along with the proportion of deaths caused by ALD decreased during the study period.ConclusionThe incidence of ALD decreased from 357 to 240 per 1,000,000 over the last 10 years in Denmark. During the same period, the prevalence remained stable around 0.22% and mortality decreased. Additionally, the burden of ALD on hospital care decreased significantly between 1994 and 2018. We anticipate a further decrease in the incidence of ALD in the future

Risk of hepatocellular carcinoma in Danish outpatients with alcohol-related cirrhosis

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

Effects of statins and aspirin on HCC risk in alcohol-related cirrhosis: nationwide emulated trials

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

Socioeconomic inequalities in the incidence of alcohol-related liver disease: A nationwide Danish study.

BackgroundThere 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.MethodsWe 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.FindingsOf 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.InterpretationThis study showed substantial socioeconomic inequalities in ALD incidence for people aged 30-69 years.FundingThe study was supported by grants from the Novo Nordisk Foundation (NNF18OC0054612) and the Research Fund of Bispebjerg Hospital

Population-based study of alcohol-related liver disease in England 2001-2018: Influence of socioeconomic position

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

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

Background and aims: Offspring of patients with alcohol-related liver disease (ALD) may have higher risk of ALD. We examined their risk of ALD and survival with ALD.Approach & Results: We used Danish nationwide registries to identify 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 2,842 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-related harm should be considered.Funding: Novo Nordisk Foundation and the ‘Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat’ foundation