Congenital porto systemic shunts

Area of hepatology: background and rationale

Absence of portal flow or incomplete portal flow is known to lead to a number of systemic complications in portal hypertension secondary to cirrhosis, in pre-hepatic portal hypertension secondary to obstruction of the portal vein with cavernous transformation, and in the rare setting of congenital porto-systemic shunts (cPSS). Although its prevalence is not known, cPSS is believed to be a relatively rare condition in humans. cPSS are associated with severe systemic complications at all ages, which is why developing a registry to understand their prevalence, clinical and pathological presentation, and natural history is of considerable clinical importance.

The potential implications of abnormal porto-venous shunting and decreased hepatic portal flow are numerous and potentially serious. In children, cPSS are increasingly sought in patients presenting with unexplained neurological or psychiatric abnormalities, severe cardiopulmonary complications such as hepatopulmonary syndrome, portopulmonary hypertension and neonatal hight-output heart failure, as well as in primary liver tumours [1]. Other less well described associations include growth retardation or overgrowth, nephropathy and coagulation abnormalities. In adults, cPSS have been reported at all ages, and are often interpreted as incidental findings, although in referral centers they are now sought as part of the work up of pulmonary hypertension [2].

Although cPSS are increasingly suspected and sought in specialized centers, much is still unknown clinically, histologically and biologically. They have been studied in some detail in other mammals including dogs, cats[3], and mice [4]. Although these models are valuable, understanding the pathophysiology and natural history in human subjects is paramount for two reasons: first, to identify patients at risk of developing complications, and second to determine the timing and type of management according to clinical presentation.

At present, this rare clinical problem affecting both children and adults is managed and studied in a few specialized centers thereby lending itself well to the creation of a collaborative registry with the goals to a) characterize the natural history of cPSS b) develop a clear, consensual nomenclature c) identify subjects at risk of developing complications and d) standardize care of patients with cPSS.

Registry project set up: collaborations and recruitment 

Set up

The overall concept is to collect data at each participating center by a research coordinator. The data will be stored centrally in a registry and images in a repository, both based at the University of Geneva/University Hospital Geneva.

Collaborations and organization within the group 

The registry will be led by the Scientific Committee (SC) which includes at least one representative of each subspeciality. In its current form the SC includes: Pediatric hepatology: Dr Mc Lin, the applicant, (University Hospitals Geneva,Switzerland), Dr Gonzales (Hôpital Bicêtre, APHP, Paris XI University France), Dr Debray (Hôpital Necker, Paris V University APHP, France), Paediatric Radiology Dr Franchi-Abella and Dr Pariente (Bicêtre), Pediatric Surgery : Dr Guérin (Bicêtre), France Pathology : Dr Fabre (Necker), Dr Rougemont and Prof Rubbia-Brandt (Geneva), Pediatric Cardiology : Pr Beghetti (Geneva), Pulmonology: Dr Savale (Bicêtre) Prenatal Diagnosis/Obstetrics Pr Sénat and Dr Franchi-Abella (Bicêtre). A charter will establish authorship rules and respective duties and responsibilities. The SC will meet at regular intervals. Minutes of each meeting will be kept by the Secretary. The role of each SC member will be to liaise within their respective communities to develop a network of centers interested in participating in the registry or willing to refer cases for enrolment. The basic principle is that each participating center has a designated participant for each sub-specialty-in other words participating centers offer comprehensive multidisciplinary management of cPSS. 

The project as it stands today is the product of several collaborations within each sub-specialty. For each discipline (surgery, radiology, hepatology, cardiology, histopathology, pulmonary, neurology, obstetrics) a member of the SC has overseen the collaborative development of an electronic case-report-form (CRF) by consulting multiple specialists throughout Europe. The SC is now working on avoiding overlap between CRFs.


Patients will be eligible for enrolment once they have been screened for causes of secondary porto-systemic shunting (liver disease and other causes of portal hypertension). Patients will be enrolled at the time of diagnosis upon informed consent from the parents or the subjects themselves. Since the aim of the registry is to understand the full spectrum of cPSS, we aim to include neonates, children, and adults and to follow subjects longitudinally. The data of neonates diagnosed before delivery will be entered restrospectively at the time of enrolment. Patient recruitment will be both retrospective and prospective, as nearly 100 cases are currently followed by the participating centers whose data is important to include. Owing to the rarity of the condition, it is important to emphasize the importance of recording both prevalent and incident cases. As such, there will be limitations to the retrospective data of prevalent cases. It is anticipated that complete datasets will only be available for incident cases entered prospectively.

Patients can withdraw from the registry at any time. Deaths related to cPSS or other causes will be recorded. Once the registry is operational, our long term goal is to expand the registry to all of Europe, identifying one national data center per country.

Description of group/consortia set up to support the project and relevant track record

Description of group

As of the time of writing, the international, consortium includes the following European centers for their multidisciplinary expertise in the diagnosis and management of cPSS.  Switzerland: University Hospitals Geneva. France: Hôpital Bicêtre, Hôpital Necker Enfants Malades, Hôpital Beaujon. Italy: Ospedale Bambino Gesù  England: King’s College London. Germany: Germany: Universitätsklinikum Essen

Projected participants for future projects: Imunology: Dr Falk, (Hanover Medical School, Germany), Genetics and Molecular Biology: Dr Girard (Hôpital Necker, Paris V University APHP, France), Dr Makrythanasis (University of Geneva, Switzerland), Pathophysiology of pulmonary vascular diseases Dr Savale, INSERM U999

Relevant track record:

All participating centers are recognized national and international centers for liver disease in children and adults. Publications relevant to the present project by members of the group are outlined below and serve as proof of their individual track record. Contributors from the centers outlined above are highlighted in bold font.

Shunt management- pediatric and adult

Blanc T, Guerin F, Franchi-Abella S, Jacquemin E, Pariente D, Soubrane O, Branchereau S, Gauthier F.

Congenital portosystemic shunts in children: a new anatomical classification correlated with surgical strategy. Ann Surg. 2014 Jul;260(1):188-98

Franchi-Abella S, Branchereau S, Lambert V, Fabre M, Steimberg C, Losay J, Riou JY, Pariente D, Gauthier F, Jacquemin E, Bernard O. Complications of congenital portosystemic shunts in children: therapeutic options and outcomes.J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):322-30

Guérin F, Porras J, Fabre M, Guettier C, Pariente D, Bernard O, Gauthier F.Liver nodules after portal systemic shunt surgery for extrahepatic portal vein obstruction in children.J Pediatr Surg. 2009 Jul;44(7):1337-43

Pupulim LF, Vullierme MP, Paradis V, Valla D, Terraz S, Vilgrain V. Congenital portosystemic shunts associated with liver tumours. Clin Radiol. 2013 Jul;68(7):e362-9

M. Anooshiravani-Dumont, A. Kanavaki, B. Wildhaber, V. McLin, S. Hanquinet, S. Terraz; Imaging and interventional radiology in congenital porto-systemic shunts. SS230 99ème Congrès Annuel de la SSR 

Cardiopulmonary complications

Berger RM1, Beghetti M, Humpl T, Raskob GE, Ivy DD, Jing ZC, Bonnet D, Schulze-Neick I, Barst RJ. Clinical features of paediatric pulmonary hypertension: a registry study. Lancet. 2012 Feb 11;379(9815):537-46. doi: 10.1016/S0140-6736(11)61621-8.

Beghetti M, Hoeper MM, Kiely DG, Carlsen J, Schwierin B, Segal ES, Humbert M. Safety experience with bosentan in 146 children 2-11 years old with pulmonary arterial hypertension: results from the European Postmarketing Surveillance program. Pediatr Res. 2008 Aug;64(2):200-4

Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaïci A, Hajji L, O'Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011 Jul 7;365(1):44-53


Zucman-Rossi J, Jeannot E, Nhieu JT, Scoazec JY, Guettier C, Rebouissou S, Bacq Y, Leteurtre E, Paradis V, Michalak S, Wendum D, Chiche L, Fabre M, Mellottee L, Laurent C, Partensky C, Castaing D, Zafrani ES, Laurent-Puig P, Balabaud C, Bioulac-Sage P. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC.Hepatology. 2006 Mar;43(3):515-24

Animal models

Cudalbu C, McLin VA, Lei H, Duarte JM, Rougemont AL, Oldani G, Terraz S, Toso C, Gruetter R. The C57BL/6J mouse exhibits sporadic congenital portosystemic shunts. PloS One, vol. 8 (2013), No 7, p. e69782 (8 p.) 

IT system /software to be used to collect, record, update data

The registry will be build using SecuTrial©, an up-to-date web-based interface which meets the most demanding international security standards ( Database design and maintenance will be performed by Khaled Mostaguir, PhD, of the Clinical Research Center, University Hospitals Geneva (HUG). Dr Mostaguir is an expert in the use of SecuTrial© for the design and maintenance of databases and clinical trials. Confidentiality: SecuTrial generates automatic personal identification numbers (PIN) to ensure that the data is anonymous according to international standards.

The image repository will be housed on an Osirix-based research plateform based at the University of Geneva with the purpose of allowing researchers to share images in a confidential fashion. The SecuTrial PIN will be used to link the images in the repository with the clinical and biological data in the registry.

Length of the project

It is estimated that the creation of the registry and inclusion of retrospective cases will take two years. Once up and running, the registry will not be limited in time. Here we seek funding for personnel for the first two years, and support for registry and repository maintenance for five. 

Key milestones will be

  1. First publication with retrospective data
  2. Development of universal nomenclature/classification
  3. Identification of predisposing factors to complications of cPSS
  4. Proposed algorithm for standardization of care

Key questions the registry will answer

The main goals of the registry are to a) characterize the natural history of cPSS b) develop a clear, consensual nomenclature c) identify subjects at risk of developing complications and d) standardize care of patients with cPSS diagnosis, follow-up and treatment. It ensues that in fulfilling these goals, subsidiary questions of clinical relevance may be elucidated. These include the epidemiology of the different anatomical forms, clinical presentation, and syndromic associations. Further, by analyzing serum biochemistries, the investigators will try to identify a laboratory parameter/biomarker (or series of parameters) which might facilitate the early detection of patients with cPSS. 

Utilisation of research outputs

Publications and communications in differents subspecialities will ensure diffusion of knowledge. Publications will facilitate the search for additional grant support. Importantly, a long term goal of the consortium is to link the registry to a biobank, but the development of the latter is beyond the scope of the present proposal. Collaborators for these ancillary projects are identified and listed in the ‘group’ section above. ESPGHAN support will be acknowledged in all publications and presentations.

In summary, the present project aims to characterize cPSS, a rare congenital malformation, with the goal to offer optimal care to patients of all ages from birth to adulthood. It brings together a multidisciplinary and complementary existing consortium of experts all of whom have a track record in the field. In the long term, this European project will expand to include a biobank. 


  1. Franchi-Abella, S., et al., Complications of congenital portosystemic shunts in children: therapeutic options and outcomes. J Pediatr Gastroenterol Nutr, 2010. 51(3): p. 322-30.
  2. Savale, L., et al., Current management approaches to portopulmonary hypertension. Int J Clin Pract Suppl, 2011(169): p. 11-8.
  3. van Steenbeek, F.G., et al., Inherited liver shunts in dogs elucidate pathways regulating embryonic development and clinical disorders of the portal vein. Mamm Genome, 2012. 23(1-2): p. 76-84.
  4. Cudalbu, C., et al., The C57BL/6J mouse exhibits sporadic congenital portosystemic shunts. PLoS One, 2013. 8(7): p. e69782