Pre-emptive Transjugular Intrahepatic Portosystemic Shunt (TIPS) in Cystic Fibrosis Related Liver Disease

University Hospital, Ghent5 enrolled

Overview

Portal hypertension (PHT) and its sequelae are the most clinically important manifestation in cystic fibrosis related liver disease (CFLD), with end-stage liver failure as a late and rare manifestation. The aim is to evaluate the safety and efficacy of a pre-emptive Transjugular Intrahepatic Portosystemic Shunt (TIPS) for the prophylaxis of variceal bleeding in pediatric CFLD patients with subclinical non-cirrhotic portal hypertension (NCPH)

Cystic fibrosis (CF) is the most frequent autosomal recessive disorder in Caucasians caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene. Cystic Fibrosis associated Liver Disease (CFLD) is a well-known complication and includes a wide range of hepatobiliary diseases. The clinical outcome in CFLD is largely determined by PHT and its sequelae. Variceal bleeding is the most feared complication. Currently, there is no medical therapy to delay or reverse clinically established CFLD.Treatment focuses on screening for and managing the complications of portal hypertension and optimizing nutritional status. Eventually, liver transplantation (LT) is an effective therapeutic option for CF patients with end-stage liver failure, treatment resistant, and complicated portal hypertension. TIPS placement is a well-established procedure for portal vein decompression in adults. In retrospective case studies of severe CFLD cirrhosis in pediatric populations, TIPS has been proven a feasible option in acute or refractory variceal bleeding and as a bridge to LT. In CFLD patients, little data are available on the long-term outcome of treatments to mitigate PHT. In this trial, the primary aim was to evaluate the safety and efficacy of a pre-emptive TIPS for the prophylaxis of variceal bleeding in non-cirrhotic CFLD with early PHT. The secondary aim was to investigate the long-term clinical outcome of a pre-emptive TIPS and in more particular, whether TIPS might effectively postpone LT.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Eligibility

Sex: ALLMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Cystic fibrosis * Liver disease detected by an abnormal physical examination (hepatomegaly or splenomegaly, confirmed on US), abnormalities of liver function tests (increase of AST, ALT, GGT levels above the upper normal limits) or ultrasonographic evidence of liver involvement (US liver score ≥ 5). * Indirect signs of portal hypertension on Doppler US * Progressive portal hypertension / liver disease on bi-monthly follow-up, evaluated by physical examination, blood analysis and US Exclusion Criteria: * Cirrhosis on biopsy * Symptomatic portal hypertension (Portosytemic pressure gradient \> 10 mmHg)

Outcomes

Primary Outcomes

Variceal bleeding

Variceal bleeding, diagnosed on endoscopy, is regarded as the main complication of portal hypertension from cystic fibrosis liver disease

Time frame: Through study completion, an average of 10 year

Secondary Outcomes

Hypersplenism

Thrombocytopenia causes an increased bleeding tendency. Increasing splenomegaly causes earlier concerns with abdominal distension and decreased appetite by gastric compression. In symptomatic hypersplenism, a surgical splenorenal shunt or splenectomy might be indicated.