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Advances in Primary Sclerosing Cholangitis: Pathogenesis, Diagnosis and Emerging Therapies
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Advances in Primary Sclerosing Cholangitis: Pathogenesis, Diagnosis and Emerging Therapies

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: 25 April 2026 | Viewed by 2128

Special Issue Editors

Dr. Konstantinos H. Katsanos

E-Mail Website
Guest Editor
Department of Gastroenterology, University Hospital of Ioannina, 455 00 Ioannina, Greece
Interests: inflammatory bowel disease; ulcerative colitis; gastroenterology; endoscopy; colorectal cancer; gastrointestinal diseases; hepatology
Special Issues, Collections and Topics in MDPI journals
Dr. Fotios S. Fousekis

E-Mail Website
Guest Editor
Department of Gastroenterology and Hepatology, University of Ioannina, Ioannina, Greece
Interests: inflammatory bowel disease; endoscopy; ulcerative colitis; Crohn’s disease; mucosal immunology

Special Issue Information

Dear Colleagues,

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts, leading to biliary cirrhosis, liver failure, and an increased risk of cholangiocarcinoma. Despite extensive research, the pathogenesis of PSC remains incompletely understood, and effective therapies are lacking.

This Special Issue aims to explore recent advances in the understanding of PSC, including genetic and immunological mechanisms, microbiome interactions, and novel diagnostic biomarkers. We also welcome studies on emerging therapeutic strategies.

Contributions may include original research and reviews that provide new insights into disease mechanisms, innovative imaging techniques, and patient management strategies. This Special Issue aims to improve our understanding of PSC and support the development of better treatments.

We encourage you to submit your work and contribute to the ongoing efforts to improve outcomes for patients with PSC.

Dr. Konstantinos H. Katsanos
Dr. Fotios S. Fousekis
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cholangiocarcinoma
  • primary sclerosing cholangitis
  • cholestatic
  • inflammatory bowel disease
  • liver

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Published Papers (2 papers)

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11 pages, 613 KB  
Article
Impact of Metabolic Dysfunction-Associated Steatotic Liver Disease on Fatigue and Pruritus in Primary Sclerosing Cholangitis: A U.S. Single-Center Study
by Natalia Rojas-Amaris, Ana Marenco-Flores, Carmen Lara-Romero, Romelia Barba, Denisse Rubio-Cruz, Ximena Parraga, Daniela Goyes, John Esli Medina-Morales, Leandro Sierra, Manuel Romero-Gomez, Michelle Lai, Behnam Saberi, Vilas Patwardhan and Alan Bonder
J. Clin. Med. 2025, 14(22), 8083; https://doi.org/10.3390/jcm14228083 - 14 Nov 2025
Viewed by 489
Abstract
Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of liver disease in the United States and frequently coexists with other liver diseases. Despite growing interest, the presence of MASLD in patients with primary sclerosing cholangitis (PSC) remains [...] Read more.
Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of liver disease in the United States and frequently coexists with other liver diseases. Despite growing interest, the presence of MASLD in patients with primary sclerosing cholangitis (PSC) remains underexplored. This study aimed to assess the prevalence and characteristics of the MASLD-PSC overlap syndrome, with a specific focus on patient-reported outcomes such as pruritus and fatigue. Methods: A cross-sectional analysis was performed within a prospective cohort of patients with PSC enrolled in the Autoimmune Liver Diseases Registry at a United States tertiary medical center (2018–2024). MASLD overlap was established based on evidence of hepatic steatosis on liver imaging or biopsy, combined with at least one cardiometabolic risk factor. Fatigue and pruritus were assessed using the Chronic Liver Disease Questionnaire (CLDQ) and the 5D Itch Scale. Ordinal logistic regression models were used to explore the potential impact of MASLD overlap on fatigue and pruritus severity. Results: Among 103 PSC patients, 33% had MASLD overlap. These patients were older (55 vs. 46 years, p = 0.006), had a higher BMI (30 vs. 25 kg/m2, p < 0.001), and were more likely to have small bile duct involvement (43% vs. 12%, p = 0.002). A history of liver transplantation (LT) was noted in 18% of PSC-only patients, compared to 3% of those with PSC/MASLD (p = 0.055). MASLD overlap was significantly associated with higher pruritus intensity (OR 3.09, 95% CI 1.02–9.28, p = 0.044), but was paradoxically linked to lower fatigue levels (OR 0.37, 95% CI 0.16–0.85, p = 0.020). Conclusions: Patients with PSC/MASLD exhibit distinct clinical features. MASLD overlap was found to significantly impact patient-reported outcomes, with lower fatigue intensity but increased pruritus severity, suggesting a role for metabolic or inflammatory pathways, warranting further investigation. Full article
(This article belongs to the Special Issue Advances in Primary Sclerosing Cholangitis: Pathogenesis, Diagnosis and Emerging Therapies)
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Review

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16 pages, 931 KB  
Review
Gut–Liver Axis, Microbiota, Bile Acids, and Immune Response in Pathogenesis of Primary Sclerosing Cholangitis: An Overview
by Fotios S. Fousekis, Konstantinos Mpakogiannis, Georgios D. Lianos, Elisabetta Antonelli, Gabrio Bassotti and Konstantinos H. Katsanos
J. Clin. Med. 2025, 14(21), 7817; https://doi.org/10.3390/jcm14217817 - 3 Nov 2025
Viewed by 1290
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive bile duct inflammation and fibrosis. Its strong association with inflammatory bowel disease (IBD) highlights the possible role of the gut–liver axis in disease pathogenesis. Here, we review the mechanisms [...] Read more.
Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive bile duct inflammation and fibrosis. Its strong association with inflammatory bowel disease (IBD) highlights the possible role of the gut–liver axis in disease pathogenesis. Here, we review the mechanisms that may contribute to the disruption of the gut–liver axis, leading to liver injury and the development of PSC. In particular, disruption of the intestinal barrier allows microbial products to enter the portal circulation, stimulating hepatic immune cells and triggering biliary inflammation. Concurrently, gut-primed lymphocytes expressing mucosal homing receptors migrate aberrantly to the liver, where they may contribute to biliary epithelial cell injury. Dysbiosis, characterized by reduced microbial diversity and the expansion of bile-tolerant and pro-inflammatory taxa, amplifies this immune activation and disturbs gut–liver homeostasis. Moreover, bile acids act as signaling molecules, regulating metabolism and immune responses through receptors such as FXR and TGR5. Dysregulation of these pathways may promote cholestasis, inflammation, and fibrosis. By understanding these interactions, we may identify novel therapeutic targets for PSC. Full article
(This article belongs to the Special Issue Advances in Primary Sclerosing Cholangitis: Pathogenesis, Diagnosis and Emerging Therapies)
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