Masteronderzoek Maag-, darm- en leverziekte

Title
Real-life experience with Transjugular Intrahepatic Portosystemic Shunt (TIPS): an international, multicenter cohort study
Korte titel: TIPS Outcome Cohort (TOC) study 

Department
Gastroenterology and Hepatology 

Supervisor
Dr. Raoel Maan, Hepatologist

Contact details 
r.maan@erasmusmc.nl 

Background 
Cirrhosis is the end stage of any chronic liver disease and can eventually lead to an increase in portal pressure, resulting in portal hypertension (1,2). Portal hypertension is associated with the development of ascites, hepatic encephalopathy, and variceal bleeding, which leads to high morbidity and mortality in these patients (3,4). A Transjugular Intrahepatic Portosystemic Shunt (TIPS) is a stent placed between the portal vein and one of the hepatic veins through a radiological intervention, thereby reducing the
high portal pressure (5). This intervention has proven to be successful in various studies for the treatment of persistent ascites and (bleeding) varices (6-8). However, these studies were conducted with strictly selected patient groups, and often these patients were followed up for only a short time after TIPS placement. Long-term complications such as TIPS thrombosis or the development of hepatic encephalopathy are still insufficiently known, especially in real-life settings (9). At Erasmus MC, TIPS
have been placed for more than 20 years, and many of these patients are still being followed up in the outpatient clinic. Through an unique collaboration with international hospitals, we can gain insights into the (long-term) outcomes after the placement of a TIPS.

Aim  
With this study, we aim to map patients who received a TIPS or a revision of their TIPS between 2007 and 2022. We will examine the long-term outcome of these patients after TIPS placement and the occurrence of TIPS-related and non-TIPS-related complications. With this cohort, we can potentially identify some risk factors associated with the development of TIPS failure and/or TIPS-related complications.

Research questions

1. What were the indications for TIPS placement?
2. What is the prevalence of liver-related complications? (How successful was the TIPS placement?)
3. How does a TIPS affect the liver function (biochemistry) over time?
4. What is the prevalence of TIPS-related complications, how often was a new intervention needed, and what are the risk factors?
5. How were the liver and non-liver-related complications treated and how successful was this?

Methods  
We are looking for one or two dedicated students to collect clinical data from all patients who received a TIPS or a revision of their TIPS between 2007 and 2022. Currently, data of patients in Erasmus MC has already been collected and only needs to be extended. Both patient characteristics and laboratory values will be collected at baseline and during follow-up. Patient characteristics will include gender, age, underlying liver disease, medication use, the presence of liver-related complications such as ascites or
varices (at baseline and during follow-up), the presence of TIPS-related complications (during follow- up), TIPS-specific data such as the measured pressure before and after placement, the type of stent used, the diameter, and which radiologist placed it. Laboratory results will include Alkaline Phosphatase (AP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transpeptidase (GGT), Bilirubin, Albumin, Platelets, INR, Creatinine, Urea, and GFR.

The clinical data will be collected using an electronic data collection system (Castor) and will be analyzed using R.

Output  
With this study, we expect to obtain important information about the prognosis of patients with a TIPS and gain insights into the success rate of this treatment as well as the occurrence of complications. We hope to identify some risk factors for the failure of a TIPS or the development of complications so that we can apply even better patient selection. Depending on the results, we expect to be able to publish at least one, but probably several, highly regarded articles with the data from this cohort.

Referenties 

1. Ripoll, C., et al., Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology, 2007. 133(2): p. 481-8. 
2. D'Amico, G., et al., Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther, 2014. 39(10): p. 1180-93. 
3. Arroyo, V. and J. Colmenero, Ascites and hepatorenal syndrome in cirrhosis: pathophysiological basis of therapy and current management. J Hepatol, 2003. 38 Suppl 1: p. S69-89. 
4. European Association for the Study of the Liver. Electronic address, e.e.e. and L. European Association for the Study of the, EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol, 2018. 69(2): p. 406-460. 
5. Ochs, A., et al., The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites. N Engl J Med, 1995. 332(18): p. 1192-7. 
6. Narahara, Y., et al., Transjugular intrahepatic portosystemic shunt versus paracentesis plus albumin in patients with refractory ascites who have good hepatic and renal function: a prospective randomized trial. J Gastroenterol, 2011. 46(1): p. 78-85. 
7. Garcia-Pagan, J.C., et al., Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med, 2010. 362(25): p. 2370-9. 
8. Bureau, C., et al., Transjugular Intrahepatic Portosystemic Shunts With Covered Stents Increase Transplant-Free Survival of Patients With Cirrhosis and Recurrent Ascites. Gastroenterology, 2017. 152(1): p. 157-163. 
9. Garcia-Pagan, J.C., et al., Where does TIPS fit in the management of patients with cirrhosis? JHEP Rep, 2020. 2(4): p. 100122. 

Tasks  
Data collection in Castor, data analysis in R, summary of the main analyses and results in a thesis.
Depending on the student’s preference, they can (co)-author the articles that result from this.

Startdate
January 2025

Requirements 
Accurate data collection forms the basis of the research. Without a reliable database, there is no study. We are looking for an enthusiastic and dedicated student who is willing to commit to this project. Experience with Castor or R is a plus but not necessary