Fibrotic disease co-occurrence and associated risk of subsequent organ failure: a nationwide matched cohort study

Abstract Objectives Shared pathophysiologic features of fibrotic diseases, irrespective of anatomical site, have been suggested from epidemiologic, genetic, and mechanistic studies. Improvement in diagnostic capabilities and emergence of antifibrotic medications warrants identification of trajectories of fibrotic diseases and earlier identification of patients at risk of organ failure. Methods We used Danish nationwide health registries to identify all adults with a first-time diagnosis of any of nine major fibrotic diseases from 1998 to 2024. Co-occurrence between fibrotic diseases was assessed using logistic regression, adjusted for sex, birth year, time-at-risk, educational level, and ethnicity. Next, we used multivariable Cox proportional hazard models to evaluate the risk of developing an organ failure in all individuals with a fibrotic disease relative to matched controls. Results We identified 328 344 individuals with at least one fibrotic disease. Median age at first fibrotic diagnosis was 57 years (interquartile range 48–67), with 54% being female. Most fibrotic diseases were associated with an increased risk of co-occurring fibrosis, with the highest rate between carpal tunnel syndrome and trigger finger (odds ratio 6.05, 95% confidence interval (CI) 5.94–6.15). Compared with 985 032 controls, individuals with a fibrotic disease had a higher risk of organ failure over 10 years of follow-up (hazard ratio: 1.20, 95% CI 1.18–1.22). Conclusion Fibrotic diseases frequently co-occur and are associated with an increased risk of organ failure, which support the concept of a partially shared systemic fibrotic hypothesis, pointing towards the potential of using early onset fibrotic diseases as prognostic markers for system-wide fibrosis susceptibility.