The 2017 Royal Society Of Medicine Cystic Fibrosis Symposium
Assessment of liver disease in cystic fibrosis

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Abstract

Liver disease in cystic fibrosis has many causes, with biliary fibrosis due to abnormal CFTR protein predominating. Assessment requires aetiology to be defined. Biliary fibrosis may progress to cirrhosis and portal hypertension, which although initially asymptomatic, may cause varices and splenomegaly. Monitoring progression includes clinical and ultrasound assessment with endoscopic assessment of varices for those at risk. Extrapolated primarily from longitudinal assessment of viral hepatitis in adults, non-invasive elastography has a potential role. Evidence is lacking to support intervention strategies, but ursodeoxycholic acid and ligation of varices are widely applied. Indication and timing of liver transplantation are not clearly defined. Multidisciplinary approach is needed to tailor assessment and guide management.

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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