Liver Disease in the young adult with cystic fibrosis

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Abbreviation

CF

cystic fibrosis.

Introduction

The rapid development of new diagnostic tests, improved therapy, and especially the success of liver transplantation has changed the outcome for young adults with cystic fibrosis (CF) liver disease, many of whom survive into adolescence and adult life with or without liver transplantation. No common mutation of this gene has been associated with liver disease, although the role of genetic modifiers such as the Serpina gene (for alpha‐I anti‐ trypsin deficiency) is being evaluated.1

Clinical Features

The main clinical manifestations are with lung or pancreatic disease, but liver disease is recognized in 4.5% to 20%, depending on age and the definition of significant liver disease. It is more common in males. It has a wide spectrum ranging from biliary problems to cryptogenic cirrhosis and portal hypertension, which is the most common form of presentation in young adults.2, 3

Diagnostic Criteria

• Increase of aspartate aminotransferase, alanine aminotransferase, and gamma‐glutamyltranspeptidase levels on three consecutive determinations over 12 months. It is important to remember to consider additional causes of liver injury such as drug-induced liver injury (DILI), alcoholic liver disease, and in young persons who have used intravenous street drugs or cocaine, newly acquired viral hepatitis.

• Ultrasonographic evidence of increased and/or heterogeneous echogenicity, irregular margins, nodularity, portal hypertension, or biliary abnormalities.4

Liver histology includes fatty infiltration, focal biliary cirrhosis, and multilobular cirrhosis. Cholestasis is rarely identified. Liver biopsy should be performed to establish the extent and severity of liver disease.5

Transient elastography (Fibroscan) measures liver stiffness and is closely related to liver fibrosis and may be useful in estimating progression of disease.5 Studies in CF patients are in progress.

Percutaneous transhepatic cholangiography and endoscopic retrograde cholangiography are invasive procedures that are not suitable for screening and diagnostic purposes and have been replaced by MRI.4

Treatment

Treatment consists of intensive nutritional support and the prevention and management of hepatic complications. Nutritional support includes: an energy intake up to 150% of average requirements by carbohydrate supplements such as glucose polymer or by increasing the percentage of fat; increasing the proportion of medium chain triglycerides to 50% of the fat content; and supplementation with fat‐soluble vitamins, including vitamin A (5‐15,000 IU/day), vitamin E (100‐500 mg/day), vitamin D (50 ng/kg), and vitamin K (1‐10 mg/day).2

The use of ursodeoxycholic acid (10‐20 mg/kg) is accepted despite the absence of clinical trials. Treatment improves the biochemistry and may prevent progression if prescribed early.6

Adolescent Issues

Adolescence is a challenging time for any young person because of the need to achieve autonomy and independence and develop a sense of identity.

Chronic illness and transplantation in adolescence or early adult life exaggerate these challenges and place the young person at risk of social isolation, delayed development of peer‐support networks, and enforced dependency on family members. These young people need a different approach to management that involves consideration of their physical and psychological stage of development.7 A focused approach to planning transition to adult care is essential for long‐term survival and quality of life. Transition of care for young liver transplant patients has been discussed in a previous CLD article.8

Management

Annual follow‐up is recommended to detect progression to cirrhosis and portal hypertension.

• Patients with portal hypertension should be screened for varices by endoscopy, as required. Prophylactic therapy with beta blockers is not recommended, but band ligation is effective if variceal hemorrhage develops. Alternatively, a transjugular intrahepatic portal systemic shunt will reduce portal pressure.4

• Hepatopulmonary syndrome is suggested by a decrease in oxygen saturation (> 5%) when moving from supine to upright and should be confirmed by a contrast‐enhanced (bubble) echocardiography.2, 4

• Thrombocytopenia and leucopenia resulting from hypersplenism do not require any specific therapy.

Indications for Transplantation

These include the development of end‐stage liver failure with jaundice, ascites, and coagulopathy or intractable portal hypertension.9

It is important to consider transplantation before the development of significant pulmonary complications (< 50% of normal function) in order to prevent the necessity for heart, lung, and liver transplantation. The use of pulmonary deoxyribonuclease preoperatively is recommended. Perioperative antibiotics should be based on the sensitivity of colonized pulmonary bacteria.

The outcome following liver transplantation is similar to that in children transplanted for other causes of liver disease. Lung function may improve or stabilize after transplantation,10 but long‐term outcome is dependent on the other manifestations of cystic fibrosis; thus, deaths from respiratory failure in adult life should be anticipated.10

Combined lung‐liver should be considered for young adults with severe lung disease (< 50% FEV1) and liver failure. Current 1‐year survival is 70% with early deaths from sepsis.11