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Patients with alcohol-related liver disease (ALD) frequently have risk factors for cardiovascular disease (CVD), but their long-term risk of CVD is not well-known, especially considering the competing risk of death from liver-related causes. It is further unknown if any excess risk varies across histological subgroups.We investigated the risk of CVD outcomes in 3488 persons with ALD and an available liver biopsy in Sweden between 1969 and 2016, compared with a matched reference population (n = 15,461). Administrative coding from national diagnostic and histopathology registers were used to define exposures and outcomes. Competing risk regression, taking non-CVD death into account and adjusting for potential confounders, was used to estimate subdistribution hazard ratios for incident CVD up until Dec 31, 2019.At baseline, patients with ALD had a median age of 58 years, 64% were men, and 2039 (58%) had cirrhosis on histology. The incidence rate of CVD was 35.6 per 1000 person-years in ALD compared with 19.0 per 1000 person-years in reference individuals. ALD was associated with a 2-fold increased short-term risk for CVD compared with matched reference individuals (subdistribution hazard ratio during the first year after diagnosis, 2.29; 95% confidence interval, 1.79-2.95), but this risk decreased with time. Incidence rates of CVD were comparable across histological subgroups (ranging from 27.4 CVD cases per 1000 person-years in those with normal histology to 39.2 cases per 1000 person-years in those with cirrhosis).Persons with biopsy-proven ALD have increased rates of CVD across histological subgroups compared with matched reference individuals, particularly just after ALD diagnosis. Active surveillance of modifiable CVD risk factors should be considered by clinicians treating patients with ALD.

Background & Aims Prolonged colon transit times may increase the contact time between potential carcinogens in the stool and the colonic mucosa. Nonetheless, previous studies have yielded conflicting results connecting chronic constipation with the risk of colorectal cancer (CRC). We examined the association between chronic constipation and later CRC. Methods In this nationwide case-control study, we identified 41,299 CRC cases by colorectal biopsy in Sweden between July 2007 and December 2016 and matched them to 203,181 age- and sex-matched controls from the general population. We compared odds of earlier chronic constipation (defined as ≥2 laxative prescriptions in the Prescribed Drug Register with ≥6 months between the first and last prescription) between CRC cases and controls using logistic regression. In separate analyses, we compared odds of earlier constipation between CRC cases and sibling comparators, but also examined earlier risk of having an inpatient/outpatient specialty diagnosis of chronic constipation before CRC. Results Overall, 3943 patients with CRC met our criteria for chronic constipation before CRC. The crude proportion of chronic constipation in CRC patients was 9.5% compared with 8.8% in controls. After multivariable adjustment, there was a modest association between chronic constipation and later CRC (odds ratio [OR], 1.10; 95% CI, 1.06–1.14) that vanished using sibling comparators to control for residual confounding (OR, 1.04; 95% CI, 0.97–1.13). In a sensitivity analysis of 126,650 CRC patients diagnosed from 1989 to 2016, we found no association with earlier chronic constipation diagnosed in inpatient/outpatient specialty clinics (OR, 0.88; 95% CI, 0.75–1.04). Conclusions In a nationwide case-control study, chronic constipation was not associated with later CRC.

Background & Aims Celiac disease (CD) is associated with increased mortality, in part due to cancer. Most studies investigating this cancer risk involved patients diagnosed before widespread increases in CD diagnosis rates and access to gluten-free food. We performed a population-based study of the risk of cancer in CD. Methods We identified all patients in Sweden with CD as defined as duodenal/jejunal villus atrophy, using the Epidemiology Strengthened by histoPathology Reports in Sweden cohort. Each patient was matched to ≤5 controls by age, sex, and county. We used stratified Cox proportional hazards model, following patients from diagnosis until first cancer, or by December 31, 2016. Results Among 47,241 patients with CD, 30,080 (64%) were diagnosed since 2000. After a median follow-up of 11.5 years, the incidence of cancer was 6.5 and 5.7 per 1000 person-years in CD patients and controls, respectively. The overall risk of cancer was increased (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.07–1.15), but it was only significantly elevated in the first year after CD diagnosis (HR, 2.47; 95% CI, 2.22–2.74) and not subsequently (HR, 1.01; 95% CI, 0.97–1.05), although the risks of hematologic, lymphoproliferative, hepatobiliary, and pancreatic cancers persisted. The overall risk was highest in those diagnosed with CD after age 60 years (HR, 1.22; 95% CI, 1.16–1.29) and was not increased in those diagnosed before age 40. The cancer risk was similar among those diagnosed with CD before or after the year 2000. Conclusions There is an increased risk of cancer in CD even in recent years, but this risk increase is confined to those diagnosed with CD after age 40 and is primarily present within the first year of diagnosis.

Background and Aims Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that may lead to cirrhosis and liver failure, but data on overall mortality in AIH are conflicting. Methods This was a nationwide population-based cohort study in Sweden from 1969-2017 of 6,016 adults with AIH and 28,146 matched general population reference individuals. AIH was defined by a combination of a medical diagnosis of AIH plus a liver biopsy from any of Sweden’s 28 pathology departments. Through Cox regression, we estimated hazard ratios (HRs) for overall and cause-specific death. Liver transplant was included in our main outcome of death. Results During follow-up, 3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years). The 10-year cumulative incidence of death was 32.3% (95%CI = 31.1-33.6) for AIH individuals and 14.1% (95%CI = 13.7-14.5) for reference individuals. This corresponded to an adjusted HR of 2.29 (95%CI = 2.17-2.41), which remained elevated ≥ 20 years follow-up. AIH individuals with cirrhosis on biopsy had a high risk of death (HR = 4.55; 95%CI = 3.95-5.25), while mortality in patients with fibrosis, inflammation without fibrosis, or necrosis did not differ. Portal hypertension and overlap with cholestatic liver diseases were also associated with death. AIH was associated with an increased risk of death from cardiovascular disease (HR = 1.27; 95%CI = 1.15-1.40), liver disease (HR = 66.24; 95%CI = 48.19-91.03) and extrahepatic malignancy (HR = 1.69; 95%CI = 1.51-1.89). In a sibling comparison, AIH individuals remained at increased risk of death. Conclusion AIH is associated with a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension, and overlap with cholestatic liver disease.