Pulmonary function, genetic predisposition, and the risk of cirrhosis: A prospective cohort study

Abstract Background Pulmonary function is known to be associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis modifies these associations. Methods A total of 308,678 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk. Results During a median follow-up of 12.0 years, 2,725 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.30 [1.16, 1.45]) and airflow obstruction (HR [95%CI]: 1.19 [1.08, 1.32]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.68 [1.41, 2.00]). Conclusion Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition.