Research for Rare - Research for rare diseases

HiChol - German Network for Hereditary Intrahepatic Cholestasis

What is hereditary intrahepatic cholestasis?

Defective bile handling is referred to as cholestasis and can be caused by mutations in several genes important for bile formation or transport in the liver. Cholestasis as result of genetic variants is referred to as hereditary intrahepatic cholestasis and comprises a heterogeneous group of rare disorders characterized by progressive liver disease often necessitating liver transplantation. The incidence of these disorders is estimated at 1:50.000 births, however, they account for 10-15% of neonatal cholestasis.

The clinical presentation is highly variable consequently to the different genes and mutation subtypes involved. A subgroup of these patients has an increased risk for liver cancer, however, the frequency and the underlying mechanism of this complication are unknown.

Joint research in the HiChol network

Aim of this translational network is the characterization of genetic defects in patients with severe intrahepatic cholestasis as well as the analysis of the biological consequences of novel mutations. This will be addressed by in silico modeling, the use of induced pluripotent stem cell-derived liver cells, and biopsy-derived liver organoids. Thus, consequences of mutations on one or more genes on the function of the mutated proteins, on bile formation and on adaptive mechanisms will be studied and may help to identify future therapeutic targets. Beyond the liver, microbiome changes induced both by the underlying cholestatic disease and IBAT inhibitor treatment will be traced. The network includes a clinical registry establishing genotype-phenotype relationships.

Results will not only provide a better understanding of this rare disease group but also generate clinical evidence, which will affect diagnosis, surveillance and treatment of these rare disorders in the future.


Prof. Dr. med. Verena Keitel-Anselmino
Klinik für Gastroenterologie, Hepatologie und Infektiologie
Universitätsklinikum Magdeburg
Leipziger Str. 44
39120 Magdeburg

Tel.: +49 391 67-13100



Patient leaflet progressive familial intrahepatic cholestasis (PFIC), University Hospital Tübingen, 2020

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