Acute on chronic liver failure, NASH

Non-alcoholic fatty liver disease

Non-alcoholic liver failure (NAFLD) is the most common cause of abnormal liver blood tests and has an increasing prevalence in the community. Complications of this disease and ultimately the need for liver transplantation are increasingly seen. Our research is aimed at noninvasive identification of and improving treatment of patients with NAFLD at high risk of complications. Current projects include 1) studies within the NEO study (Dutch Epidemiology of Obesity Study) in collaboration with the Departments of Epidemiology and Radiology LUMC and 2) RADIcAL study, aimed at cost-effectiveness and accuracy of noninvasive diagnostics of NAFLD/NASH in patients suspected of NAFLD and patients after liver transplantation, funded by a Horizon2020 grant and executed in a European consortium. Moreover, we participate in several phase II and III pharmaceutical studies, in collaboration with the Centre for Human Drug Research, the Dutch Donor Feces Bank and the Department of Microbiology of the LUMC.

Risk stratification in complications of end-stage liver disease: Acute on chronic liver failure, hepatocellular carcinoma (PI M.J. Coenraad)

Acute on chronic liver failure

Our projects focus on determination of risk factors of acute decompensation of cirrhosis and organ failure in decompensated cirrhosis, so-called acute on chronic liver failure (ACLF) with a focus on how hemodynamic factors and inflammation are involved in acute decompensation of cirrhosis and the development of ACLF. This research is embedded in the medical research profile Immunity, infectious diseases and tolerance and encompasses clinical and translational studies.

Since 2012, the LUMC is an active member of the European Foundation for the study of Chronic liver failure (EF Clif). As such, we participate in European multicenter studies of the EF Clif and several research projects within the EF Clif are initiated and executed by the LUMC. Recently, the Dutch Working Group Portal Hypertension was founded, and this will serve as a platform for ongoing studies on portal hypertension and research collaboration between Dutch centers.  Our work is supported by LUMC research fund and EF Clif.

    

Ongoing PhD projects

Jelte Schaapman, M.D. – Chronic liver disease, ACLF and MRI

 

Gabrielle Alblas, M.D.– NAFLD

 

 

Completed PhD projects

Annarein Kerbert, M.D., Ph.D. – Invasive and noninvasive prognostic markers in cirrhotic portal hypertension and acute on chronic liver failure. (2017), Unversity of Leiden.

Grant support: LUMC ’vrije beleidsruimte’.

Promotor: prof. dr. B. van Hoek, copromotor: dr. M.J. Coenraad.

 

Biosketch Minneke Coenraad

Minneke Coenraad MD PhD is gastroenterologist –hepatologist since 2007 at the Leiden University Medical Center, Leiden, The Netherlands. After graduating cum laude as medical doctor, she completed her specialization in Internal Medicine (2004) and subsequently in Gastroenterology-Hepatology (2007). She obtained her PhD in 2009. Her clinical focus is on cirrhosis, hepatocellular carcinoma and liver transplantation.

She is actively involved in scientific research in the field of complications of end-stage liver disease, specifically acute on chronic liver failure (ACLF) and hepatocellular carcinoma (HCC). Her main focus in ACLF is on hemodynamics and the interrelationship with inflammation. In HCC her research is focused on determination of factors associated with aggressive biologic behaviour of tumors and optimizing treatment. She is study director of an ongoing European multicentre study on the cost-effectiveness of hemodynamic monitoring of nonselective betablockers in patients with cirrhosis and principal investigator of an EU-funded European multicentre study on MRI imaging in patients after liver transplantation.

Coenraad is chairman of the Dutch Flemish Liver Week and board member of the Netherlands Association for the Study of the Liver from 2012-2018. She is chairman of the national biobank working group of the Dutch Hepatocellular & Cholangiocarcinoma Group. She is board member of the Dutch Portal Hypertension working group. She is member of the European Foundation for the study of Chronic liver failure.

 

Grants awarded:

2013 LUMC research grant for European multicentre study on the cost-effectiveness of hemodynamic monitoring of nonselective betablockers in cirrhosis.

2016 participant in Horizon2020 grant for non-invasive rapid assessment of chronic liver disease using multiparametric Magnetic Resonance Imaging.

2017 Dutch Cancer Society grant for the development of a Dutch Hepatocellular & Cholangiocarcinoma Group national biobank and database for hepatocellular carcinoma.

 

Selected publications Coenraad

 

1.         Karkampouna S, van der Helm D, Gray PC, Chen L, Klima I, Grosjean J, Burgmans MC, Farina-Sarasqueta A, Snaar-Jagalska EB, Stroka DM, Terracciano L, van Hoek B, Schaapherder AF, Osanto S, Thalmann GN, Verspaget HW, Coenraad MJ, Kruithof-de Julio M. CRIPTO promotes an aggressive tumour phenotype and resistance to treatment in hepatocellular carcinoma.  J Pathol. 2018 Mar 31. doi: 10.1002/path.5083.

 

2.         Coenraad MJ, Porcher R, Bendtsen F. Hepatic and cardiac hemodynamics and systemic inflammation in cirrhosis: It takes three to tango.  J Hepatol. 2018 May;68(5):887-889. doi: 10.1016/j.jhep.2018.02.007.

 

3.         Solà E*, Kerbert AJ*, Verspaget HW, Moreira R, Pose E, Ruiz P, Cela R, Morales-Ruiz M, López E, Graupera I, Solé C, Huelin P, Navarro AA, Ariza X, Jalan R, Fabrellas N, Benten D, de Prada G, Durand F, Jimenez W, van der Reijden JJ, Fernandez J, van Hoek B, Coenraad MJ*, Ginès P*. Plasma copeptin as biomarker of disease progression and prognosis in cirrhosis.  J Hepatol. 2016 Nov;65(5):914-920. doi: 10.1016/j.jhep.2016.07.003. * contributed equally.

 

4.         Clària J, Stauber RE, Coenraad MJ, Moreau R, Jalan R, Pavesi M, Amorós À, Titos E, Alcaraz-Quiles J, Oettl K, Morales-Ruiz M, Angeli P, Domenicali M, Alessandria C, Gerbes A, Wendon J, Nevens F, Trebicka J, Laleman W, Saliba F, Welzel TM, Albillos A, Gustot T, Benten D, Durand F, Ginès P, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure (EF-CLIF). Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure.  Hepatology. 2016 Oct;64(4):1249-64.