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Case Reports
. 2025 Apr 27;17(4):92426.
doi: 10.4254/wjh.v17.i4.92426.

Hepatitis E virus infection-triggered intrahepatic cholestasis: A case report

Stephan Drexler  1 , Frederic Haedge  2 , Susanne N Weber  3 , Marcin Krawczyk  3   4 , Matthias S Matter  5 , Carol I Geppert  6   7 , Achim Weber  8 , Bruno Stieger  9 , Christian Trautwein  10 , Andreas E Kremer  9   11
Affiliations
Case Reports

Hepatitis E virus infection-triggered intrahepatic cholestasis: A case report

Stephan Drexler et al. World J Hepatol. .

Abstract

Background: Genetic disorders affecting hepatobiliary transporters can be triggered by various factors, resulting in marked cholestasis.

Case summary: We report two patients who experienced a severe episode of intrahepatic cholestasis triggered by an acute hepatitis E virus infection. Following an extensive clinical examination that ruled out common causes of cholestatic liver damage, we conducted next-generation sequencing to determine the genetic profiles of the patients. The analysis revealed several known and unknown variants in genes associated with hepatobiliary transporters and bile salt regulation, including ATP8B1, ABCB11, ABCB4, MYO5B, and FXR. For a comprehensive understanding of the pathophysiology, we performed ClinVar analysis and utilized PolyPhen for bioinformatic prediction of functional impact. Both patients exhibited rapid symptom improvement and a decrease in hyperbilirubinemia when treated with either rifampicin or bezafibrate.

Conclusion: Our findings introduce hepatitis E viral infection as a novel trigger for intrahepatic cholestasis, and we categorize the significance of the various genetic variants based on the current state of research.

Keywords: ATP8B1; Case report; Hepatitis E; Intrahepatic cholestasis; Next generation sequencing.

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Conflict of interest statement

Conflict-of-interest statement: Kremer AE has served as a consultant for AbbVie, Bayer, Beiersdorf, CymaBay Therapeutics, Escient, Dr. Falk, FMC, Gilead, GlaxoSmithKline, Guidepoint, Intercept Pharma, Medscape, Mirum, MSD, Myr, Roche, and Viofor, and received speaker’s honoraria from AbbVie, AOP Orphan, Bayer, Bristol Myers Squibb, CMS, CymaBay Therapeutics, Dr. Falk, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Intercept, Janssen, MSD, Newbridge, Novartis, and Zambon. M.S.M. has served as a consultant for ThermoFisher, Merck, GlaxoSmithKline, Janssen-Cilag, Roche, and Novartis and received speaker’s honoraria from Incyte Biosciences. Trautwein C: Grant support: DFG, BMBF, EU; Lectures: Falk, MSD, Sanofi, GSK, Ipsen; Advisory: Ipsen, MSD, GSK; Travel Support: Gilead, Abbvie. Apart from the declared conflicts of interest, the other authors assured that they do not have any disclosures to report.

Figures

Figure 1
Figure 1
Longitudinal course of liver tests and genetic variants. A: Clinical course of Patient 1 and Patient 2 showing bilirubin levels (black line) and gamma-glutamyltransferase (GGT) levels (gray line) over time (in days). B: Genetic variants determined by next-generation sequencing and genotyping. Variants are annotated with corresponding minor allele frequencies (MAFs), obtained from ensembl.org, and linked to previously published references (Supplementary Table 1). GGT, gamma-glutamyl transferase; MAF, minor allele frequency; ABCB4: ATP-binding cassette 4; ABCB11: ATP-binding cassette, sub-family B member 11; ATPB1: ATPase phospholipid transporting 8B1; MYO5B: Myosin VB; FXR, farnesoid X receptor; n/a: Not available.
Figure 2
Figure 2
Histology of liver biopsies. Representative histological staining of liver biopsy samples from both patients. The following stainings were performed: BSEP: Bile salt export pump; CK7: Cytokeratin 7; HE: Hematoxylin and eosin; MAS: Masson’s trichrome; MDR3: Multidrug resistance protein 3. Long scale bar: 100 µm; Short scale bar in inlay: 40 µm (BSEP and MDR3 staining).
See this image and copyright information in PMC

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