The 2017 Royal Society Of Medicine Cystic Fibrosis SymposiumAssessment of liver disease in cystic fibrosis
Introduction
Liver disease may affect children and adults with cystic fibrosis (CF), although its significance, progression and impact on health may vary. Prevalence is reported to be between 10% and 30%, with onset of liver disease typically evident in the first decade, and prevalence of cirrhosis in children is suggested to be 5–10%. The Annual Report of UK Cystic Fibrosis Registry 2016 reports 1.3% prevalence of cirrhosis in those age <16 and 3.7% age >16 [1]. However, epidemiological data are impacted on by the lack of consensus definition of liver disease, both relating to diagnostic criteria and also aetiology.
Section snippets
Aetiology
Liver disease in CF is most frequently a consequence of the loss of function of the Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) protein. CFTR is located in the apical membrane of the biliary epithelial cells or cholangiocytes, and its loss of function leads to impaired bile composition and excretion. Abnormally viscous bile is retained in the biliary tree and triggers inflammation and fibrosis by hepatic stellate cell activation. Although initially focal, biliary fibrosis may
Clinical manifestations
Defining liver disease must not only take into account this spectrum of aetiologies, but also their differing clinical manifestations. Biliary fibrosis may occur without elevation of bilirubin and liver enzymes (alanine aminotransferase (ALT) and gamma glutamyl-transferase (GGT)) and liver enlargement may not be palpable. Ultrasonography (US) may identify irregular echotexture and be the most reliable indicator of early disease, but has limited sensitivity [3]. Gallstones may be asymptomatic if
Initial assessment
Once liver disease is suspected by any modality, full investigation of possible aetiology should occur. Guided by the type and pattern of abnormality detected, detailed history and laboratory investigations should be performed. Basic blood investigations are proposed in Fig. 1: more detailed assessment of individual diagnoses should be tailored according to clinical suspicion. Assessment of liver histology from tissue obtained by percutaneous liver biopsy is rarely needed and seldom diagnostic.
Assessment of progression
Accurate diagnosis is crucial to guiding prognosis, management and counselling. Acute viral hepatitis may be self-limiting, fatty liver should lead to optimisation of glycaemic control and diet, and drug toxicity addressed. Non-related CF chronic disease such as autoimmune liver disease should be referred for appropriate management. In the majority whose liver disease is due to CFTR related biliary fibrosis, there will be few if any symptoms or signs, normal blood biochemical values but still
Management of liver disease
Assessment of liver disease should allow timely intervention. The importance of early detection would be reinforced if management could reverse or at least halt progression.
Ursodeoxycholic acid (UDCA) is a hydrophilic and choleretic bile acid, which may improve bile flow, reduce the hepatotoxicity of retained bile and also confer hepatocyte cytoprotection. This mechanism of action would suggest that it may have all the properties needed to reduce the progression of biliary inflammation in CF at
Liver transplantation
The role and timing of liver transplant (LT) has been proposed as a key research direction in 2017 [6]. Initial concerns about the risks of LT, including immuno-suppression causing increased respiratory infections, have been allayed, and benefits including stabilisation or improvement of respiratory function and nutrition apparent. With reversal of all manifestations of portal hypertension, early benefits which may be sustained for at least five years are well documented. In the USA, a large
Summary and future
Assessment of liver disease encompasses identification of cause and detection of progression. Clinical judgement and experience is then applied in considering the role of UDCA, a management strategy for varices and indication for LT. It is crucial, however, that liver disease is not assessed in isolation. The multitude of co-factors: nutrition, diabetes, drugs, pathogens, rate of deterioration or stability: directly impact on decision making. It will be difficult if not impossible to define
Disclosures
I have received consultancy fees and lecture fees from Gilead Science, Inc.
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2019, Clinics in Liver DiseaseCitation Excerpt :In patients with high risk varices (ie, grade 2 or 3), band ligation is preferred to non-selective beta-blockers given the increased risk of pulmonary complications in these patients. Patients with esophageal varices can then be placed in a banding protocol that consists of endoscopies at regular intervals until the varices are successfully eradicated.9,38 However, given their concomitant underlying pulmonary disease, patients with CF are at increased risk for endoscopic procedures and anesthesia, and the risks of general anesthesia should be weighed against the risks of bleeding.
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