Liver Disease in Cystic Fibrosis: an Update

Abstract

ContextCystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF.Evidence AcquisitionA literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library.ResultsCF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease.ConclusionsLiver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of fibrosis prevention and to avoid its progression prior to development its related complications.

Aspartate aminotransferase to platelet ratio and fibrosis‐4 as biomarkers in biopsy‐validated pediatric cystic fibrosis liver disease

“…A well‐characterized consequence of cystic fibrosis (CF) is CF‐related liver disease (CFLD). Within the first decade of life, up to 10% of CF patients will have progressed from nonuniform, portal tract focal biliary cirrhosis to multilobular cirrhosis and portal hypertension (PH) with significant morbidity . Liver biopsy is generally accepted as the gold standard for assessment of histological staging of fibrosis, which, in turn, is a strong predictor of outcome of CFLD .…”

“…Within the first decade of life, up to 10% of CF patients will have progressed from nonuniform, portal tract focal biliary cirrhosis to multilobular cirrhosis and portal hypertension (PH) with significant morbidity. 1 Liver biopsy is generally accepted as the gold standard for assessment of histological staging of fibrosis, 2 which, in turn, is a strong predictor of outcome of CFLD. [3][4][5] However, liver biopsy is not without risks and limitations in children, including discomfort, sedation complications, hemorrhage/infection, sampling error, and interobserver variability.…”

Guía de Práctica Clínica para el manejo nutricional de personas con Fibrosis Quística (GPC-FQ)

“…El 33% de las personas con FQ presentan enfermedad hepatobiliar significativa 41 , pudiéndose observar evidencias bioquímicas, ultrasónicas o clínicas de enfermedad hepática 42 . Aproximadamente el 5-10% de las personas con FQ padecen cirrosis multilobular durante la primera década de la vida 43 .…”

“…Hasta el 50% de las personas con FQ pueden presentar una elevación intermitente de transaminasas o GGT 44 . La presencia de esteatosis puede ser detectada por la elevación de las transaminasas con concentraciones de GGT y fosfatasa alcalina y ALT y GGT por encima de los límites superiores normales al menos en tres determinaciones consecutivas, tras más de 12 meses después de la exclusión de otras causas de enfermedades del hígado 42 . Asimismo, pueden padecer serias alteraciones nutricionales relacionadas con macronutrientes específicos y vitaminas liposolubles.…”

The role of conventional ultrasound in pediatric chronic liver diseases

“…A significantly abnormal US has been shown to be a good predictor of advanced CFLD, with a specificity of approximately 84%. Due to all these facts, annual US should be performed in all patients with CF as a valuable marker for detecting liver disease, assessing the severity and development of complications ( 38,39,40,41).…”