Sobrevida de pacientes com doença hepática associada à fibrose cística

Abstract

The life expectancy of patients with cystic fibrosis has been significantly increased with improvements in nutritional care and pulmonary therapies. Cystic fibrosis associated liver disease (CFLD) is emerging as a cause of morbidity and mortality. However, the impact of CFLD on patient survival remains to be further studied. The aim of this study is to determine the association between severity of liver disease and survival in patients with cystic fibrosis. Patients at the Queensland Children’s Hospital Cystic Fibrosis Service (Brisbane, Australia) were evaluated in a 27-year clinical cohort study. Annual registry data from 1991 to 2018 was used to estimate the probabilities of survival. Cystic fibrosis patients under 19 years of age were followed until the occurrence of liver transplantation, death, or end of follow-up. CFLD was diagnosed using clinical, biochemical and imaging best-practice guidelines. Severe CFLD was established by the presence of cirrhosis, portal hypertension, or esophageal varices. A directed acyclic graph was used to assess possible predictors of survival in cystic fibrosis patients. To estimate the total effect of liver disease on survival, the causal diagram indicated the variables sex, diabetes, genotype, and ursodeoxycholic acid therapy for the adjusted model. The Kaplan-Meier method and Cox's proportional hazards model were used for data analysis. 290 patients were followed up with an observation time of 2,101 person-years. The median overall survival was 23 years (95% CI, 21.0 to 25.0). Severe CFLD was a predictor of reduced survival when adjusted for sex, diabetes and ursodeoxycholic acid therapy (HR 5.02, 95% CI 1.53 to 16.46, p = 0.008). The study shows evidence that severe CFLD may be associated with an increased risk of death in patients with cystic fibrosis when adjusted for sex, diabetes and ursodeoxycholic acid therapy. Further studies are needed to assess this effect with greater accuracy.