CF Guidelines - Liver Disease

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CF Guidelines - Liver Disease

Liver Disease in Cystic Fibrosis:
		This guideline describes the range of liver disease in CF, how to screen for it and how to treat it. Including the management of bleeding varices (the form(ref) for which should be completed for all patients with portal hypertension, placed in the notes and copied to the patient/carer.
		Reports of the prevalence of liver disease in CF vary but focal biliary cirrhosis has been reported in 70% of CF adults in their third decade. Symptomatic liver disease is uncommon, being reported as a cause of death in only 2% of CF patients. incidence does not rise progressively and peaks in the second decade. Modifier genes may influence the severity of liver disease - e.g. ATT deficiency. It is more common in males (3:1). There is no known genotype-phenotype correlation but there is a high familial concordance. The characteristic pathology arises from a diffuse intra-hepatic biliary abnormality leading to focul biliary cirrhosis. In infancy, presentation may be with cholesasis due to inspissated bile or fatty change that may cause hepatomegaly, abdominal distension and sometimes hypoglycaemia. Gallstones and cholecystitis may develop in later childhood. Jaundice, ascites and encephalopathy are late manifestations. Compensated liver cirrhosis is not a contraindiction to lung transplantation.

Detection of liver disease:
		Palpation of an enlarged liver, often the left lobe is more easily felt. An abdominal examination should be performed at every clinical review.

Blood Tests:
		Liver function test should be done on an annual basis - not a reliable indicator of liver disease, with poor specificity although reasonable sensitivity - alkaline phosphatise, y-glutamine transpeptidase more so than transaminases. If persistently elevated 3 - 4 times above normal then biliary disease is more likely. They can be influenced by infection, hypoxia and drugs. More advanced disease may be associated with a raised pro-thrombin time and hypersplenism - low platelets, leucopenia. Late manifestations include a low serum albumin and increased bilirubin. Some patients with established cirrhosis have normal liver function results.

Imaging:
	-	Abdominal Ultrasound - to include echogenicity (normal, coarse or irregular) of liver parenchyma, contour of the liver edge (smooth or nodular), peri-portal fibrosis (none, moderate or severe), spleen size, doppler portal venous blood flow measures, detection of collateral vessels and detection of gallstones.
	-	Request USS in infants with MI or abnormal liver function.
	-	Otherwise create a baseline during pre school years, then at 7 and 10 years old, followed by a scan every 1 or 2 years through adolescence.
	-	Beyond this, request additional scan if liver function is abnormal and perform annually if any abnormalities are detected. Once mature every 5 years or if clinically detected. USS should take the opportunity to check structural health of other abdominal organs.

		MRI and MRCP - Magnetic Resonance CholangioPancreatography - can produce high definition images of cirrhotic liver disease, collateral vessels and the biliary tree. They are useful in detecting small gallstones in the bile duct. May be useful in patients with rapid clinical progression, pancreatitis and obstructive jaundice. Preferred to the more invasive ERCP.
		Radio-nucleotide Imaging. Technetium-99 IDA. Delay in hepatocyte uptake and excretion is observed early on in CF liver disease.

Liver Biopsy:
		Due to the patchy nature of CF liver disease, histology from a biopsy may not reflect the overall pattern of the disease. Ultrasound guided biopsy may reduce the chance of missing the affected areas. Risk of bleeding and pneumothorax. This investigation is best left to tertiary liver centers to consider and is usually reserved for cases where aetiology is a question.

Referral to Hepatologist:
		Local gastroenterologists may provide an early opinion, otherwise CF hepatology requires liaison with a tertiary hepatology center. In the peninsula, Plymouth now have three adult hepatologists who undertake assessments and follow up of patients for transplantation in conjunction with the King's College London Liver Team.

		Derriford Team - Dr Cramp, Dr Mitchell and Dr Cross		01752 792434
		King's College Hospital		020 7346 3214 020 7737 4000
		London or Birmingham Children's Hospital		0121 333 9999

		Refer patients with complications including:
		-	Sudden changes in liver function test.
		-	Progressive changes on imaging.
		-	Jaundice.
		-	Varices/Bleeding.
		-	Ascites.
		-	Atypical abdominal pain.
		-	Abdominal sepsis.

Treatment:
	-	Ursodeoxycholic Acid - UDCA. A bile acid, increases bile flow and protects hepatocytes from toxic the toxic effects of hydrophobic bile acids. A dose of 10mg - 15mg/kg bd. The main side effect is diarrhoea, if this occurs, reduce the dosage accordingly.
	-	Taurine. Can be used with UDCA as a taurine deficiency is associated with fat malabsorption and faecal loss of taurine-conjugated bile salts. Deficiency may increase hepatoxic glycol-conjugated bile acids. A dose of 500mg daily should be sufficient. Studies are limited, with no proof of improvement in liver function. However, there is a possible nutritional benefit.
	-	Vitamin K. if prothrombin time prolonged. Ideally in a water soluble form, Menadiol 5mg daily in those under 8 years, 10mg for those over 8 years. If PTT corrects then continue with daily oral vitamin K. Occasionally 2 IV stat doses are required.
	-	Nutrition. Maximise energy intake. Do not restrict protein intake, unless there is decompensated liver failure with hepatic encephalopathy.
	-	Careful Prescribing - Avoid Aspirin, NSAID's and beware of hepatotoxicity with other medications e.g. flucloxacillin, augmentin, meropenem, itraconazole and TPN - additional monitoring will be required.
	-	Avoid contact sports when the patient has splenomegly.

Complications - Liaise with Liver Centre:
	-	Gallstones in as man as 25% of CF patients. The gallbladder may be shrunken and non functional. Gallstones biliary sludge are common but not always symptomatic in CF. most are cholesterol and are radio lucent. Standard treatment given, laproscopic cholecystectomy can be considered. UDCA should be considered in those with biliary sludge.
	-	Varices can occur in compensated liver disease. Emergency management of bleeding outlined in the form provided - PDF File. Fill this form in and place it at the front of their patient notes and then copied to the patient as a medi-alert document. Transjugular intrahepatic porto-systemic shunts (TIPSS) or surgical shunts may be an option. Patients presenting with variceal bleeding should have treatment with broad-spectrum IV antibiotics.
	-	Ascites always appear with other features of decompensation. Treatment is sodium restriction and diuretics.
	-	Encaphalopathy is rare in CF liver disease. It is triggered by sepsis, bleeding and severe constipation. Treatment is as per advanced disease/portal hypertension form. Protein restriction is not usually required.
	-	Jaundice. this is uncommon, usually appears in advanced disease. Exclude all other causes - sepsis, drug reaction and haemolysis.
	-	Gross splenomegaly can impair diaphragmatic function.
	-	Hepatobiliary malignancy - gallbladder presenting with colic and hepatocellular carcinoma have been described.

		Dowloadable PDF File - PDF File
				Document approved - 2011
				Document due for review - December 2013

		Acknowledgements: The Peninsula CF team acknowledges the use of guidelines produced by The CF Trust, Manchester, Papworth, Leeds and Brompton CF teams during development of these local Peninsula protocols and guidelines.

Disclaimer: While efforts have been made to ensure that all the information published on this web site is correct, the authors take no responsibility for the accuracy of information, or for harm arising as a consequence of errors contained within this web site. If you have concerns regarding treatment, drugs or doses then consult your local CF consultant.