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

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

Pre-emptive Transjugular Intrahepatic Portosystemic Shunt (TIPS) in Pediatric Patients With Cystic Fibrosis Related Liver Disease and Non-cirrhotic Portal Hypertension

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.

Cystic Fibrosis Liver Disease, Portal Hypertension Due to Cystic Fibrosis (Disorder), Portal Hypertension, Noncirrhotic

Patients with CFLD without cirrhosis were eligible for a pre-emptive TIPS, when early (asymptomatic) signs of portal hypertension. All procedures were performed under general anaesthesia by an experienced interventional radiologist. Depending on the patient's age and physiognomy, TIPS was created following a conventional transjugular technique as for adults or by a dedicated combined percutaneous transhepatic-transjugular (PIPS) approach for small children. Routinely, an expanded polytetrafluoroethylene-covered endoprosthesis was used for shunt creation. If the sheath could not be negotiated into the main portal vein, a self-expandable, non-covered stent was placed. We did not pursue a minimum gradient reduction. Percutaneous liver biopsy was performed during TIPS procedure to confirm the diagnosis of fibrosis or cirrhosis.

Transjugular Intrahepatic Portosystemic Shunt is performed to prevent / treat symptomatic portal hypertension

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

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.

Transplant/splenectomy-free survival time was calculated from date of TIPS to the following event: transplant, splenectomy and death from any cause.

The Model for End-Stage Liver Disease, or MELD, is a scoring system for assessing the severity of chronic liver disease.

BMI-for age Z-scores are measures of relative weight adjusted for child age and sex defined by the Flemish growth charts

Length-for age Z-scores are measures of relative length adjusted for child age and sex defined by the Flemish growth charts

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)