Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Payam, E.
Hereditary Cholestasis Syndromes and Their Clinical Appearance – Review of the literature and cases at the Medical University Graz
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2025. pp. 59
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Wagner Martin
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- Abstract:
- Background: Hereditary cholestasis syndromes are a heterogeneous group of rare liver diseases that are caused by genetic defects in genes related with bile acid transport or metabolism. Although they are rare, these diseases are clinically important as affected patients can present with severe clinical symptoms like jaundice, pruritus as well as further complications like chronic liver disease, potentially requiring a liver transplant as ultimate therapy. Cholestatic pruritus can greatly reduce quality of life. With new treatments like ASBT inhibitors now available, it’s important to know how common this condition is in order to understand how many patients could benefit from these new options. Throughout this wide group of syndromes, clinical presentation can vary between types of genetic mutations, age groups, and triggering events such as infections, pregnancy or drug medications, possibly triggering the manifestation of symptoms in patients with a genetic predisposition. Methods: We retrospectively analyzed patients with a suspected hereditary cause of cholestasis who underwent genetic testing at our university hospital throughout the last 20 years. Clinical data, laboratory findings, and genetic variants (e.g. mutations, SNPs) were reviewed to evaluate genotype-phenotype correlations, clinical presentation by age, and potential disease triggers. Results: From medical records, we identified 88 patients, 64 children and 24 adults, with a possible hereditary cause of cholestasis. Only 53 patients presented with a clear cholestatic phenotype (such as PFIC, BRIC, ICP or LPAC). The remaining 35 patients had evidence of cholestasis or mutations but without a final clinical classification at the time of research. Genetic variants were identified in 50 out of 88 patients, most frequently in the ABCB11 and ABCB4 gene. 38 patients had mutations without a clear clinical diagnosis. The clinical presentation varied by age. Pediatric cases (predominantly male (44 out of 64)) were more often associated with ABCB11 variants and presented with jaundice, whereas adult patients (predominantly female (16 out of 24)) more often carried ABCB4 variants and presented with biliary symptoms or gallstone disease. Simply determination of zygosity status of a variant (i.e. homo- or heterozygote variants) cannot predict clinical appearance since remaining function of the protein a critical contributing factor. Pruritus was documented in only approximately 6% of cases at the time of diagnosis but in around 22% during disease course, clustering with ABCB11 variants in children and ABCB4 or ATP8B1 variants in adults. Treatment was mainly symptomatic, with UDCA prescribed in 32 patients and in only two cases a specific antipruritic therapy was documented. An unexpected finding was the occurrence of EBV infections as a potential trigger for cholestatic episodes in eight patients, five of whom had mutations in ABCB11.