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

BACKGROUND: 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. AIM: to determine the incidence of CFLD, identify risk factors and document the natural history of liver abnormalities in cystic fibrosis (CF). METHODS: 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) RESULTS: 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. No participant >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. CONCLUSION: 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.

The impact of liver disease on mortality in cystic fibrosis-A systematic review.

BACKGROUND: There is conflicting evidence on the impact of liver disease (CFLD) on life expectancy in CF. Therefore the aim of this systematic review was to evaluate the impact of liver disease (CFLD) on mortality in CF. METHODS: The protocol was published at (https://hrbopenresearch.org/articles/3-44/v3) using PRISPMA-P guidelines and registered in Prospero 2020 (CRD42020182885). Three databases were searched for publications (1938-2020) where the outcome was all-cause mortality (defined as death and transplantation) or CF-specific mortality in participants with CFLD. Studies with and without a comparator group were included. Studies were divided into 2 groups based on the definition of CFLD: Group 1 used 2 categories of liver disease (i) liver disease with portal hypertension (PH) (ii) non-specific abnormalities which did not meet the criteria for PH, Group 2 studies only included participants with PH. RESULTS: All 14 eligible studies were observational, with a moderate-high risk of bias, Six of the 14 studies directly compared mortality between those with CFLD and those with no liver disease, and 5/6 demonstrated that those with CFLD had at least 3 time the risk of death compared to those with no liver disease. Pulmonary complications were the primary cause of death. CONCLUSION: This SR demonstrates that liver disease shortens life expectancy in CF, and that pulmonary complications are the primary cause of death in those with CFLD. There has been no improvement in survival for persons with CFLD despite significant improvements in life expectancy for persons with CF who have no evidence of liver disease.

Repeatability of transient elastography in children.

BACKGROUND: Poorly performing diagnostic tests can impact patient safety. Clinical investigations must have good precision and diagnostic accuracy before widespread use in clinical practice. Transient elastography (TE) measures liver stiffness, a surrogate marker of liver fibrosis in adults and children. Studies to evaluate its repeatability and reproducibility (precision) in children are limited. Our aim was to determine (i) the normal range of TE measurements and (ii) the repeatability and reproducibility of TE in healthy children. METHODS: TE was performed in 257 healthy children, of whom 235 (91%, mean age 11.7 years, standard deviation (SD) 2.51, 107 were males (45.5%)) had two valid TE measurements performed, at least 24 h apart, by two operators under similar circumstances. High-quality TE images were obtained for each examination. RESULTS: The normal range of TE was 2.88-6.52 kPa. The mean difference between paired measurements was 0.044 (SD 0.4). The 95% limits of agreement ranged from -0.8 to +0.76 kPa for repeat measurements. There was a difference of >1 kPa between measurements in 61/235 (25.9%) children. The lack of precision was similar across all age groups. CONCLUSIONS: This study demonstrates that TE does not have acceptable precision in healthy children, because random measurement variation results in the lack of agreement between paired measurements. IMPACT: The precision and diagnostic accuracy of a new technology must be determined before it is deployed in children in order to ensure that appropriate clinical decisions are made, and healthcare resources are not wasted. TE is widely used to diagnose liver disease in children without adequate evaluation of the precision (repeatability) of TE either in healthy children or children with liver disease. This study demonstrates that TE does not have adequate precision in children. This study was performed in accordance with methods previously published for children. Refinements to the test protocol, such as duration of fasting or probe size, will have to be evaluated for their impact on precision and accuracy before the test is deployed in research studies or clinical practice.

The impact of liver disease on mortality in cystic fibrosis - a systematic review protocol.

Background Cystic fibrosis (CF) is a multiorgan disease affecting the lungs pancreas and gastrointestinal tract. Pulmonary complications are the most common manifestation of the disease. Recent advances in the treatment of pulmonary complications have resulted in substantial improvement in life expectancy. Less than 10% of persons with CF (PWCF) develop liver disease (CFLD). There is conflicting evidence about impact of liver disease on mortality in CF, with evidence suggesting that CFLD contributes to increased mortality in CF, while other studies suggest that the impact on mortality is limited. Understanding the contribution of liver disease to mortality in CF is essential if further improvements in life expectancy are to be achieved. Objective: To document the impact of liver disease on life expectancy for PWCF. Methods: This systematic review will be conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P 2015). PubMed, Medline and Embase will be searched for English language publications (1949-2020). Studies reporting the outcome for CFLD will be included where the definition of CFLD is outlined clearly in a CF population. Studies with and without a comparator will be evaluated. Clinical trials of ursodeoxycholic acid will be excluded as well as organ transplantation outcome studies. We will examine all-cause and specific causes of mortality.We will include transplantation in our estimates of all-cause mortality. The Axis Risk of Bias Tool for Observational Studies will be used to evaluate the quality of studies. We will provide a narrative synthesis of our findings using tabular formats to highlight any impact of liver disease on mortality in CF. Conclusion: It is anticipated that this review will bring clarity to the question of whether CFLD shortens life expectancy in PWCF and stimulate new approaches to the management of CFLD.