The natural history of cystic fibrosis liver disease a prospective cohort study

•Liver disease with portal hypertension developed almost always in children under 10 years of age.•Children who had no evidence of liver disease by 10 years of age did not develop CFLD during follow up.•Most children with nonspecific liver abnormalities will not progress to advanced liver disease.•CFLD was associated with increased mortality rates and shortened life expectancy. Our understanding of the natural history of cystic fibrosis liver disease (CFLD) is limited, leading to uncertainty for patients their families and clinicians when liver abnormalities are identified. to determine the incidence of CFLD, identify risk factors and document the natural history of liver abnormalities in cystic fibrosis (CF). The Irish longitudinal study of CFLD (ILSCFLD) prospectively enrolled 95% of children with CF in 2007. Their liver disease status was classified as (i) advanced liver disease with portal hypertension (CFLD). (ii) nonspecific cystic fibrosis liver disease (NSCFLD) (iii) no liver disease (NoLD) 480/522 (91.9%) children were followed for a median 8.53 years IQR 1.28, of whom 35 (7.29%) had CFLD, 110 (22.9%) NSCFLD and 335 (69.79%) had NoLD. At follow-up 28/445 (6.29%) participants without CFLD at baseline, progressed to CFLD (Incidence 7.51/1000 person years (Pyrs) (95%CI 4.99–10.86). Of these 25/28(89.28%) were 10 years of age without clinical or radiological evidence of liver disease at baseline progressed to CFLD. During follow-up 18/35(51.43%) participants with CFLD died or received a transplant, MTx rate 7.75/100 Pyrs (95%CI 4.59–12.25) compared to NSCFLD 2.33/100 Pyrs (95%CI 1.44–3.56) and NoLD 1.13/100 Pyrs (95%CI 0.77–1.59). CFLD was an independent risk factor for mortality in CF. Children with CFLD also had a shorter life expectancy. The incidence of CFLD was highest in children under10 years. Children over10 years, with normal hepatic function did not develop CFLD. Research to identify the cause and improve outcome should focus on young children. [Display omitted]