Population-Based Study of Alcohol-Related Liver Disease in England in 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.

Primary liver cancer risk and mortality in patients with alcohol-related cirrhosis in England and Denmark: observational cohort studies.

BACKGROUND AIMS: Patients with alcohol-related cirrhosis (ALD cirrhosis) have an increased risk of primary liver cancer (hepatocellular carcinoma [HCC] or intrahepatic cholangiocarcinoma [iCCA]). England recommends surveillance for HCC in these patients, while Denmark does not. METHODS: We performed an observational cohort study using the English Clinical Practice Research Datalink and the nationwide Danish healthcare registries to identify 17,110 English (2000-2016) and 22,122 Danish (1994-2022) patients with diagnosis codes of ALD cirrhosis. We computed and compared incidence rates and cumulative incidence of primary liver cancer, annual ultrasound scan rates, and mortality following diagnosis of primary liver cancer. RESULTS: The overall risk of primary liver cancer was similar in England and Denmark: 5-year risk was 2.24% (95% CI 2.00-2.49) in England (iCCA 0.07%, HCC 2.16%) and 2.36% (2.15-2.57) in Denmark (iCCA 0.05%, HCC 2.30%). The annual rate of ultrasound scans per person was 0.65 (0.63-0.67) in England and 0.44 (0.42-0.46) in Denmark. The 1-year mortality after a diagnosis of primary liver cancer was 59.2% (54.4-64.0) in England and 60.9% (57.4-64.4) in Denmark. The 3-year risks of HCC in those on vs. off surveillance in England were 2.3% (1.0-4.6) vs. 1.5% (1.0-2.2). CONCLUSION: The risk of primary liver cancer was the same in English and Danish patients with ALD cirrhosis, and HCCs constituted 97% of primary liver cancers. Mortality with primary liver cancer was equally high in both countries. Notably, in England, where guidance recommends biannual HCC surveillance with ultrasound, patients with ALD cirrhosis were undergoing fewer than 1 ultrasound scan per year.

Non-Selective Beta-Blockers and Risk of Sepsis in Patients with Cirrhosis and Ascites: Results from a Large Observational Study.

Background and Aims: Previous studies have not been able to determine whether non-selective beta-blockers (NSBB) reduce the risk of sepsis in cirrhosis. We aimed to examine this question with data from 1198 patients with cirrhosis and ascites included in clinical studies of satavaptan, a vasopressin receptor antagonist with no effect on infection risk. Methods: Risk of sepsis was estimated for NSBB users vs nonusers. Patients were examined every four weeks, or in relation to hospitalization, for the one-year duration of the trials. We computed the cumulative risk of sepsis for patients who did vs did not use NSBB at baseline. We used Cox regression to compare hazard rates of sepsis between current users and nonusers, accounting for changes in NSBB use over time. We adjusted for patient sex and age, MELD-Na score, albumin, use of antibiotics, use of proton pump inhibitors, cirrhosis etiology, history of variceal bleeding or SBP, severity of ascites and HE, HCC, other cancers, and diabetes, while stratifying on geographical region. Results: Of the 1198 patients, 54% used NSBB at some time. There were 56 sepsis episodes. The 1-year risk of sepsis was reduced to 5.7% (95% confidence interval [CI] 2.8-8.6) in baseline NSBB users vs 11.6% (95% CI 7.0-15.9) in baseline nonusers. The hazard ratio of sepsis for current NSBB users vs current nonusers was reduced to 0.5 (95% CI 0.3-0.8) and after adjustment to 0.7 (95% CI 0.4-1.3). Conclusion: NSBB use may reduce the risk of sepsis in patients with cirrhosis and ascites, but the precision of the estimate was limited by the number of episodes of sepsis.

Alanine Aminotransferase and 20-Year Risk of Major Chronic Diseases and Death in a Healthy Cohort Aged 30 to 49 Years.

PURPOSE: Alanine aminotransferase is the most frequently used marker of liver cell injury. We examined the association between alanine aminotransferase levels and long-term absolute risks of morbidity and mortality in healthy Danish people aged 30-49 years. PATIENTS AND METHODS: We divided 671 healthy participants from the Ebeltoft Health Promotion Project into four categories based on their baseline alanine aminotransferase values: low (≤10U/l), medium-low (men: 11-34U/l, women: 11-22U/l), medium-high (men: 35-69U/l, women: 23-44U/l) and high (men: ≥70U/l, women: ≥45U/l), and followed them through Danish healthcare registries for up to 20 years. We examined mortality and absolute risks of liver disease, overall cancer, ischemic heart disease, and diabetes. RESULTS: The risk of any cancer was highest for participants with "low alanine aminotransferase" or "high alanine aminotransferase" (20-year risk: 17.2% [95% confidence interval (CI): 6.3-32.7%] and 18.2% [95% CI: 5.7-36.3%], respectively). The risk of diabetes was highest for participants with "medium-high alanine aminotransferase" or "high alanine aminotransferase" (20-year risk: 12.1% [95% CI: 7.3-18.3%] and 9.1% [95% CI: 1.6-25.1%], respectively). Participants with "high alanine aminotransferase" had the highest 20-year risk of liver disease (20-year risk: 13.6% [95% CI: 3.4-30.9%], while it was 1.0% or less in the other groups). The chance of being alive after 20 years without having been diagnosed with liver disease, cancer, ischemic heart disease, or diabetes was lowest in the "high alanine aminotransferase" group (50% [95% CI: 28-68%]) and 72-79% in the other groups. CONCLUSION: Our findings suggest that persons with high or abnormally low alanine aminotransferase measurements are at increased long-term risk of several chronic diseases.