|
1
|
Manns MP, Bergquist A, Karlsen TH, Levy C, Muir AJ, Ponsioen C, Trauner M, Wong G, Younossi ZM. Primary sclerosing cholangitis. Nat Rev Dis Primers 2025; 11:17. [PMID: 40082445 DOI: 10.1038/s41572-025-00600-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/07/2025] [Indexed: 03/16/2025]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic biliary inflammation associated with periductular fibrosis of the intrahepatic and extrahepatic bile ducts leading to strictures, bacterial cholangitis, decompensated liver disease and need for liver transplantation. This rare focal liver disease affects all races and ages, with a predominance of young males. There is an up to 88% association with inflammatory bowel disease. Although the aetiology is unknown and the pathophysiology is poorly understood, PSC is regarded as an autoimmune liver disease based on a strong immunogenetic background. Further, the associated risk for various malignancies, particularly cholangiocellular carcinoma, is also poorly understood. No medical therapy has been approved so far nor has been shown to improve transplant-free survival. However, ursodeoxycholic acid is widely used since it improves the biochemical parameters of cholestasis and is safe at low doses. MRI of the biliary tract is the primary imaging technology for diagnosis. Endoscopic interventions of the bile ducts should be limited to clinically relevant strictures for balloon dilatation, biopsy and brush cytology. End-stage liver disease with decompensation is an indication for liver transplantation with recurrent PSC in up to 38% of patients. Several novel therapeutic strategies are in various stages of development, including apical sodium-dependent bile acid transporter and ileal bile acid transporter inhibitors, integrin inhibitors, peroxisome proliferator-activated receptor agonists, CCL24 blockers, recombinant FGF19, CCR2/CCR5 inhibitors, farnesoid X receptor bile acid receptor agonists, and nor-ursodeoxycholic acid. Manipulation of the gut microbiome includes faecal microbiota transplantation. This article summarizes present knowledge and defines unmet medical needs to improve quality of life and survival.
Collapse
Affiliation(s)
- Michael P Manns
- Hannover Medical School (MHH) and Centre for Individualised Infection Medicine (CiiM), Hannover, Germany.
| | - Annika Bergquist
- Division of Hepatology, Department of Upper Gastrointestinal Disease, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Tom H Karlsen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Clinic of Surgery and Specialized medicine, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Cynthia Levy
- Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, Miami, FL, USA
| | - Andrew J Muir
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA
| | - Cyriel Ponsioen
- Department of Gastroenterology & Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Grace Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Union Hospital, Hong Kong SAR, China
| | | |
Collapse
|
|
2
|
Sathiaseelan M, Grammatikopoulos T. Utility of endoscopy in paediatric gastroenterology and hepatology-Review and updates. Dig Liver Dis 2025:S1590-8658(25)00211-7. [PMID: 40024816 DOI: 10.1016/j.dld.2025.01.199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 01/16/2025] [Accepted: 01/27/2025] [Indexed: 03/04/2025]
Abstract
Paediatric endoscopy has been an integral part of the diagnostic evaluation and management of gastroenterology and hepatology diseases in children. This area of clinical medicine has made meteoric advancements since it was first introduced conserving it's traditional roles of gastroscopy and colonoscopy but broadening significantly it's clinical utility and diagnostic accuracy with new and emerging technology. This article aims to explore and review the current utility and emerging applications of diagnostic and therapeutic endoscopy for the practicing paediatric gastroenterologist and hepatologist.
Collapse
Affiliation(s)
- Mohana Sathiaseelan
- Paediatric Liver, GI & Nutrition Centre and MowatLabs, King's College Hospital, London, United Kingdom.
| | - Tassos Grammatikopoulos
- Paediatric Liver, GI & Nutrition Centre and MowatLabs, King's College Hospital, London, United Kingdom; Institute of Liver Studies, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom
| |
Collapse
|
|
3
|
van Rheenen PF, Kolho K, Russell RK, Aloi M, Deganello A, Hussey S, Junge N, De Laffolie J, Deneau MR, Fitzpatrick E, Griffiths AM, Hojsak I, Nicastro E, Nita A, Pakarinen M, Ricciuto A, de Ridder L, Sonzogni A, Tenca A, Samyn M, Indolfi G. Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group. J Pediatr Gastroenterol Nutr 2025; 80:374-393. [PMID: 39741383 PMCID: PMC11788976 DOI: 10.1002/jpn3.12378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 07/31/2024] [Accepted: 08/21/2024] [Indexed: 01/03/2025]
Abstract
OBJECTIVE We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC). METHODS The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE. Core messages from the literature were phrased as position statements and then circulated to a sounding board composed of international experts in pediatric gastroenterology and hepatology, histopathology, adult gastroenterology and hepatology, radiology, and surgery. Statements reaching at least 80% agreement were considered as final. The other statements were refined and then subjected to a second online vote or rejection. RESULTS Regular screening for gamma-glutamyltransferase (GGT) is essential for detecting possible biliary disease in children with IBD. MR cholangiopancreatography is the radiological modality of choice for establishing the diagnosis of PSC. Liver biopsy is relevant in the evaluation of small duct PSC or autoimmune hepatitis. Children who do not have known IBD at the time of PSC diagnosis should undergo initial screening with fecal calprotectin for asymptomatic colitis, and then at least once yearly thereafter. Children with a cholestatic liver enzyme profile can be considered for treatment with ursodeoxycholic acid and can continue if there is a meaningful reduction or normalization in GGT. Oral vancomycin may have a beneficial effect on GGT and intestinal inflammation, but judicious use is recommended due to the lack of long-term studies. Children with PSC-IBD combined with convincing features of autoimmune hepatitis may benefit from corticosteroids and antimetabolites. CONCLUSIONS We present state-of-the-art guidance on the diagnostic criteria, follow-up strategies, and therapeutic strategies and point out research gaps in children and adolescents with PSC-IBD.
Collapse
Affiliation(s)
- Patrick F. van Rheenen
- Department of Paediatric Gastroenterology, Hepatology, and NutritionUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| | | | - Richard K. Russell
- Department of Paediatric Gastroenterology, and NutritionRoyal Hospital for Children and Young PeopleEdinburghUK
| | - Marina Aloi
- Sapienza University of Rome ‐ Umberto I HospitalRomeItaly
| | - Annamaria Deganello
- Department of RadiologyKing's College Hospital, School of Biomedical Engineering and Imaging Sciences, King's College LondonLondonUK
| | - Séamus Hussey
- Children's Health Ireland and University College DublinDublinIreland
| | - Norman Junge
- Division for Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver, and Metabolic DiseasesHannover Medical SchoolHannoverGermany
| | - Jan De Laffolie
- General Paediatrics and Neonatology, GastroenterologyJustus Liebig University GiessenGiessenGermany
| | - Mark R. Deneau
- University of Utah and Intermountain Healthcare Primary Children's HospitalSalt Lake CityUtahUSA
| | - Emer Fitzpatrick
- Children's Health Ireland and University College DublinDublinIreland
| | - Anne M. Griffiths
- Faculty of Medicine, IBD Centre, SickKids HospitalUniversity of TorontoTorontoOntarioCanada
| | - Iva Hojsak
- Children's Hospital ZagrebUniversity of Zagreb Medical SchoolZagrebCroatia
| | - Emanuele Nicastro
- Pediatric HepatologyGastroenterology and Transplantation, Hospital Papa Giovanni XXIIIBergamoItaly
| | - Andreia Nita
- Department of Paediatric GastroenterologyGreat Ormond Street HospitalLondonUK
| | - Mikko Pakarinen
- Department of Pediatric SurgeryThe New Children's HospitalUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Amanda Ricciuto
- Faculty of Medicine, IBD Centre, SickKids HospitalUniversity of TorontoTorontoOntarioCanada
| | - Lissy de Ridder
- Department of Paediatric GastroenterologyErasmus University Medical Center Sophia Children's HospitalRotterdamThe Netherlands
| | | | - Andrea Tenca
- Helsinki University and Helsinki University Hospital HUS, Abdominal CenterHelsinkiFinland
| | - Marianne Samyn
- Paediatric Liver, GI and Nutrition ServiceKing's College HospitalLondonUK
| | | |
Collapse
|
|
4
|
Waldthaler A, Warnqvist A, Waldthaler J, Vujasinovic M, Ghorbani P, von Seth E, Arnelo U, Lohr M, Bergquist A. Predicting ERCP procedure time - the SWedish Estimation of ERCP Time (SWEET) tool. Endoscopy 2025; 57:31-40. [PMID: 39111738 DOI: 10.1055/a-2371-1367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2024]
Abstract
BACKGROUND The duration of an endoscopic retrograde cholangiopancreatography (ERCP) is influenced by a multitude of factors. The aim of this study was to describe the factors influencing ERCP time and to create a tool for preintervention estimation of ERCP time. METHODS Data from 74 248 ERCPs performed from 2010 to 2019 were extracted from the Swedish National Quality Registry (GallRiks) to identify variables predictive for ERCP time using linear regression analyses and root mean squared error (RMSE) as a loss function. Ten variables were combined to create an estimation tool for ERCP duration. The tool was externally validated using 9472 ERCPs from 2020 to 2021. RESULTS Mean (SD) ERCP time was 36.8 (25.3) minutes. Indications with the strongest influence on ERCP time were primary sclerosing cholangitis and chronic pancreatitis. Hilar and intrahepatic biliary strictures and interventions on the pancreatic duct were the anatomic features that most strongly affected ERCP time. The procedure steps with most influence were intraductal endoscopy, lithotripsy, dilation, and papillectomy. Based on these results, we built and validated the SW: edish E: stimation of E: RCP T: ime (SWEET) tool, which is based on a 10-factor scoring system (e.g. 5 minutes for bile duct cannulation and 15 minutes for pancreatic duct cannulation) and predicted ERCP time with an average difference between actual and predicted duration of 17.5 minutes during external validation. CONCLUSIONS Based on new insights into the factors affecting ERCP time, we created the SWEET tool, the first specific tool for preintervention estimation of ERCP time, which is easy-to-apply in everyday clinical practice, to guide efficient ERCP scheduling.
Collapse
Affiliation(s)
- Alexander Waldthaler
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine Huddinge (MedH), Karolinska Institutet, Stockholm, Sweden
| | - Anna Warnqvist
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Josefine Waldthaler
- Department of Clinical Neuroscience (CNS), Karolinska Institutet, Stockholm, Sweden
| | - Miroslav Vujasinovic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine Huddinge (MedH), Karolinska Institutet, Stockholm, Sweden
| | - Poya Ghorbani
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Erik von Seth
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine Huddinge (MedH), Karolinska Institutet, Stockholm, Sweden
| | - Urban Arnelo
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- Department of Diagnostics and Intervention (DDI), Surgery, Umeå Universitet, Umea, Sweden
| | - Mathias Lohr
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Annika Bergquist
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine Huddinge (MedH), Karolinska Institutet, Stockholm, Sweden
| |
Collapse
|
|
5
|
Tayyub MU, Joshi D. PSC patient with jaundice - should we ERCP? Expert Rev Gastroenterol Hepatol 2025; 19:1-3. [PMID: 39758040 DOI: 10.1080/17474124.2025.2450723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 12/14/2024] [Accepted: 01/03/2025] [Indexed: 01/07/2025]
Affiliation(s)
- Muhammad Umair Tayyub
- Institute of Liver Studies, Kings College Hospital NHS Foundation Trust London, London, UK
| | - Deepak Joshi
- Institute of Liver Studies, Kings College Hospital NHS Foundation Trust London, London, UK
| |
Collapse
|
|
6
|
Cançado GGL, Hirschfield GM. Management of primary sclerosing cholangitis: Current state-of-the-art. Hepatol Commun 2024; 8:e0590. [PMID: 39774274 PMCID: PMC11567710 DOI: 10.1097/hc9.0000000000000590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 10/08/2024] [Indexed: 01/11/2025] Open
Abstract
Primary sclerosing cholangitis is a chronic liver disease characterized by progressive inflammation and fibrosis of medium-large bile ducts, most commonly in association with inflammatory bowel disease. Most patients have a progressive disease course, alongside a heightened risk of hepatobiliary and colorectal cancer. Medical therapies are lacking, and this, in part, reflects a poor grasp of disease biology. As a result, current management is largely supportive, with liver transplantation an effective life-prolonging intervention when needed, but not one that cures disease. Emerging therapies targeting disease progression, as well as symptoms such as pruritus, continue to be explored. The trial design is increasingly cognizant of the application of thoughtful inclusion criteria, as well as better endpoints aimed at using surrogates of disease that can identify treatment benefits early. This is hoped to facilitate much-needed advances toward developing safe and effective interventions for patients.
Collapse
|
|
7
|
Thylin M, Färkkilä M, Kautiainen H, Barner-Rasmussen N, Jokelainen K, Puustinen L, Boyd S, Arola J, Tenca A. The new definition of dominant stricture in primary sclerosing cholangitis: Prevalence and clinical significance. Liver Int 2024; 44:2351-2358. [PMID: 38842451 DOI: 10.1111/liv.15985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 04/17/2024] [Accepted: 05/13/2024] [Indexed: 06/07/2024]
Abstract
BACKGROUND AND AIMS A new definition of dominant stricture (NDS) has recently been defined for patients with primary sclerosing cholangitis (PSC). Prevalence and clinical features of this, compared to traditional dominant stricture (TDS), have not been reported. METHODS In this single-centre longitudinal prospective cohort study, all PSC patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between October 2021 and 2022 were recruited. Symptoms of cholestasis, laboratory values (P-alkaline phosphatase, P-Bilirubin), Helsinki PSC-score, brush cytology findings and need for endoscopic therapy (i.e. dilation, stenting) were prospectively collected. RESULTS Overall, 228 patients with PSC underwent 248 ERCPs. NDS was detected in 43 (17%; 36 patients) and TDS without NDS (TDS group) was detected in 62 (25%; 58 patients) ERCPs, respectively; in the remaining 143 ERCPs, neither TDS nor NDS was seen (no dominant stricture [NoDS] group). PSC duration (median 8 years) and patient's age did not differ between the three groups; males presented more often with NDS. Patients with NDS were more often symptomatic, had higher cholestatic liver enzymes, advanced bile duct disease and markers of biliary inflammation (p < .001). Patients with NDS needed dilation (81%) and stenting (21%) more often than the TDS group (60% and 5%, respectively). Dysplasia in brush cytology was more common in TDS (5%) and NDS (9%) than in NoDS (3%) groups (p = .04), but did not differ between TDS and NDS groups. CONCLUSIONS Dominant stricture according to the new definition developed in 17% of PSC patients in our cohort and identifies patients with more advanced disease, biliary inflammation and need of endo-therapy.
Collapse
Affiliation(s)
- Mathias Thylin
- Abdominal Center, Helsinki University and Helsinki University Hospital HUS, Helsinki, Finland
| | - Martti Färkkilä
- Abdominal Center, Helsinki University and Helsinki University Hospital HUS, Helsinki, Finland
| | - Hannu Kautiainen
- Department of Public Health, Kuopio University Hospital, Kuopio, Finland
| | - Nina Barner-Rasmussen
- Abdominal Center, Helsinki University and Helsinki University Hospital HUS, Helsinki, Finland
| | - Kalle Jokelainen
- Abdominal Center, Helsinki University and Helsinki University Hospital HUS, Helsinki, Finland
| | - Lauri Puustinen
- Abdominal Center, Helsinki University and Helsinki University Hospital HUS, Helsinki, Finland
| | - Sonja Boyd
- Department of Pathology, Helsinki University and Helsinki University Hospital HUS, Helsinki, Finland
| | - Johanna Arola
- Department of Pathology, Helsinki University and Helsinki University Hospital HUS, Helsinki, Finland
| | - Andrea Tenca
- Abdominal Center, Helsinki University and Helsinki University Hospital HUS, Helsinki, Finland
| |
Collapse
|
|
8
|
Tenca A, Kolho K, Consonni D, Jokelainen K, Färkkilä M. Dominant stricture in paediatric-onset primary sclerosing cholangitis is associated with impaired prognosis in a long-term follow-up. United European Gastroenterol J 2024; 12:717-725. [PMID: 38733616 PMCID: PMC11249836 DOI: 10.1002/ueg2.12583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 04/08/2024] [Indexed: 05/13/2024] Open
Abstract
BACKGROUND AND OBJECTIVES The impact of dominant stricture (DS) on the outcomes of paediatric-onset primary sclerosing cholangitis (PSC) is unknown. This study was aimed at investigating the impact of DS on the clinical course and prognosis of patients with paediatric-onset PSC. METHODS Patients with paediatric-onset PSC diagnosed between January 1993 and May 2017 were identified from hospital records or our PSC registry. Data including clinical, laboratory, cholangiography, and cytology at diagnosis and during follow-up (until July 2023) were reviewed. We graphed the Kaplan-Meier failure function and fitted crude and multivariable Cox model to calculate hazard ratios (HR) and 95% confidence intervals (CI) for selected variables. In these analyses, DS was treated as a time-varying variable. RESULTS We identified 68 patients (42 males) with paediatric-onset PSC (median age at diagnosis 15 years). The median follow-up was 13 years and the median age at the last follow-up was 27 years. In total, 35 (51%) had concomitant autoimmune hepatitis. DS was diagnosed in 33 patients (48%): in eight at the time of PSC diagnosis (12%) and in 25 (37%) by the end of follow-up. In patients with DS, two developed cirrhosis, seven were transplanted and one patient was operated for a biliary mass with low-grade dysplasia. In patients without a DS, two developed cirrhosis, and four were transplanted; one female was excluded from survival analysis because she already had cirrhosis at the time of PSC diagnosis. Cirrhosis or biliary dysplasia or needing liver transplantation for these indications were more frequent after the development of DS (10/33, adjusted HR 4.26, 95%CI: 1.26-14.4). No cholangiocarcinomas or deaths occurred during the follow-up. CONCLUSIONS DS was present at diagnosis or developed during follow-up in about half of the patients with paediatric-onset PSC and was associated with impaired outcome.
Collapse
Affiliation(s)
- Andrea Tenca
- Abdominal CenterHelsinki University and Helsinki University Hospital HUSHelsinkiFinland
| | - Kaija‐Leena Kolho
- Department of Paediatric GastroenterologyHelsinki University and Children's HospitalHelsinki University Hospital HUSHelsinkiFinland
| | - Dario Consonni
- Epidemiology UnitFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Kalle Jokelainen
- Abdominal CenterHelsinki University and Helsinki University Hospital HUSHelsinkiFinland
| | - Martti Färkkilä
- Abdominal CenterHelsinki University and Helsinki University Hospital HUSHelsinkiFinland
| |
Collapse
|
|
9
|
Laleman W, Peiffer KH, Tischendorf M, Ullerich HJ, Praktiknjo M, Trebicka J. Role of endoscopy in hepatology. Dig Liver Dis 2024; 56:1185-1195. [PMID: 38151452 DOI: 10.1016/j.dld.2023.11.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 11/27/2023] [Indexed: 12/29/2023]
Abstract
The growing and evolving field of EUS and advanced hepatobiliary endoscopy has amplified traditional upper gastrointestinal endoscopy and unveiled novel options for remaining unsolved hepatobiliary issues, both diagnostically and therapeutically. This conceptually appealing and fascinating integration of endoscopy within the practice of hepatology is referred to as 'endo-hepatology'. Endo-hepatology focuses on the one hand on disorders of the liver parenchyma and liver vasculature and of the hepatobiliary tract on the other hand. Applications hanging under the umbrella of endohepatology involve amongst others EUS-guided liver biopsy, EUS-guided portal pressure measurement, EUS-guided portal venous blood sampling, EUS-guided coil & glue embolization of gastric varices and spontaneous portosystemic shunts as well as ERCP in the challenging context of (decompensated cirrhosis) and intraductal cholangioscopy for primary sclerosing cholangitis. Although endoscopic proficiency however does not necessarily equal in an actual straightforward end-solution for currently persisting (complex) hepatobiliary situations. Therefore, endohepatology continues to generate high-quality data to validate and standardize procedures against currently considered (best available) "golden standards" while continuing to search and trying to provide novel minimally invasive solutions for persisting hepatological stalemate situations. In the current review, we aim to critically appraise the status and potential future directions of endo-hepatology.
Collapse
Affiliation(s)
- Wim Laleman
- Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic disorders, University Hospitals Leuven, KU Leuven, Leuven, Belgium; Department of Medicine B (Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology), University Hospital Muenster, Muenster, Germany.
| | - Kai-Henrik Peiffer
- Department of Medicine B (Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology), University Hospital Muenster, Muenster, Germany
| | - Michael Tischendorf
- Department of Medicine B (Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology), University Hospital Muenster, Muenster, Germany
| | - Hans-Joerg Ullerich
- Department of Medicine B (Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology), University Hospital Muenster, Muenster, Germany
| | - Michael Praktiknjo
- Department of Medicine B (Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology), University Hospital Muenster, Muenster, Germany
| | - Jonel Trebicka
- Department of Medicine B (Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology), University Hospital Muenster, Muenster, Germany; European Foundation of Chronic Liver Failure, EFCLIF, Barcelona, Spain
| |
Collapse
|
|
10
|
Li M, Jin M, Yang H. Remodelers of the vascular microenvironment: The effect of biopolymeric hydrogels on vascular diseases. Int J Biol Macromol 2024; 264:130764. [PMID: 38462100 DOI: 10.1016/j.ijbiomac.2024.130764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/31/2024] [Accepted: 03/07/2024] [Indexed: 03/12/2024]
Abstract
Vascular disease is the leading health problem worldwide. Vascular microenvironment encompasses diverse cell types, including those within the vascular wall, blood cells, stromal cells, and immune cells. Initiation of the inflammatory state of the vascular microenvironment and changes in its mechanics can profoundly affect vascular homeostasis. Biomedical materials play a crucial role in modern medicine, hydrogels, characterized by their high-water content, have been increasingly utilized as a three-dimensional interaction network. In recent times, the remarkable progress in utilizing hydrogels and understanding vascular microenvironment have enabled the treatment of vascular diseases. In this review, we give an emphasis on the utilization of hydrogels and their advantages in the various vascular diseases including atherosclerosis, aneurysm, vascular ulcers of the lower limbs and myocardial infarction. Further, we highlight the importance and advantages of hydrogels as artificial microenvironments.
Collapse
Affiliation(s)
- Minhao Li
- School of Intelligent Medicine, China Medical University, No.77, Puhe Road, Shenyang 110122, Liaoning Province, China
| | - Meiqi Jin
- School of Intelligent Medicine, China Medical University, No.77, Puhe Road, Shenyang 110122, Liaoning Province, China
| | - Huazhe Yang
- School of Intelligent Medicine, China Medical University, No.77, Puhe Road, Shenyang 110122, Liaoning Province, China.
| |
Collapse
|
|
11
|
Trauner M, Halilbasic E, Tatscher E, Fickert P. [Primary sclerosing cholangitis-Diagnosis and treatment 2024]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2024; 65:347-356. [PMID: 38498179 PMCID: PMC10959807 DOI: 10.1007/s00108-024-01697-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 03/05/2024] [Indexed: 03/20/2024]
Abstract
The etiology of primary sclerosing cholangitis (PSC) remains unclear, which explains in part the lack of a causal treatment. The differential diagnostic distinction from the even rarer immunoglobulin 4 (IgG4)-associated cholangitis (IAC) is becoming increasingly more successful. Advances in the understanding of different clinical courses, improvements in noninvasive diagnostics through modern magnetic resonance imaging (MRI) and the introduction of liver elastography have led to the development of improved prognostic models. The evidence for recommendations on medicinal (e.g., ursodeoxycholic acid) or endoscopic treatment (e.g., balloon dilatation and/or stent insertion) for PSC is still low. In contrast, the long-term results of liver transplantation in PSC patients are constantly improving. Due to the lack of highly sensitive and specific screening methods the early recognition of cholangiocellular carcinoma (CCC) as the most important complication is rarely successful. The continuous improvement of endoscopic retrograde cholangiopancreatography (ERCP) and direct cholangioscopy in combination with molecular biological and fluorescence in situ hybridization (FISH) analyses of bile duct tissue samples are promising for refined diagnostics. Due to the significantly increased risk of colorectal cancer, an annual colonoscopy is recommended in the presence of inflammatory bowel disease. Improvement of the early diagnostics of PSC and successful testing of new treatment strategies raise hope for a continuous improvement in the medical support of these complex patients.
Collapse
Affiliation(s)
- Michael Trauner
- Klinische Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich.
| | - Emina Halilbasic
- Klinische Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich
| | - Elisabeth Tatscher
- Klinische Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Auenbruggerplatz 15, 8036, Graz, Österreich
| | - Peter Fickert
- Klinische Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Auenbruggerplatz 15, 8036, Graz, Österreich.
| |
Collapse
|
|
12
|
Ahmed W, Joshi D, Huggett MT, Everett SM, James M, Menon S, Oppong KW, On W, Paranandi B, Trivedi P, Webster G, Hegade VS. Update on the optimisation of endoscopic retrograde cholangiography (ERC) in patients with primary sclerosing cholangitis. Frontline Gastroenterol 2024; 15:74-83. [PMID: 38487565 PMCID: PMC10935540 DOI: 10.1136/flgastro-2023-102491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 08/28/2023] [Indexed: 03/17/2024] Open
Affiliation(s)
- Wafaa Ahmed
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Deepak Joshi
- Gastroenterology, King's College Hospital Liver Unit, London, UK
| | - Matthew T Huggett
- Gastroenterology, St James's University Hospital, The Leeds Teaching Hospitals NHS Foundation Trust, Leeds, UK
| | - Simon M Everett
- Gastroenterology, St James's University Hospital NHS Trust, Leeds, UK
| | - Martin James
- Gastroenterology, Nottingham University, Nottingham, UK
| | - Shyam Menon
- Department of Hepatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - Wei On
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Bharat Paranandi
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Palak Trivedi
- National Institute for Health Research, Centre for Liver Research, University Hospitals Birmingham, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - George Webster
- Department of Gastroenterology, University College London Hospital NHS Foundation Trust, London, UK
| | - Vinod S Hegade
- Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| |
Collapse
|
|
13
|
Cocca S, Carloni L, Marocchi M, Grande G, Bianchini M, Colecchia A, Conigliaro R, Bertani H. Post-trans-arterial chemoembolization hepatic necrosis and biliary stenosis: Clinical charateristics and endoscopic approach. World J Clin Cases 2023; 11:8434-8439. [PMID: 38188216 PMCID: PMC10768501 DOI: 10.12998/wjcc.v11.i36.8434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/01/2023] [Accepted: 12/06/2023] [Indexed: 12/22/2023] Open
Abstract
Liver cancer is the fifth most common tumor and the second highest death-related cancer in the world. Hepatocarcinoma (HCC) represents 90% of liver cancers. According to the Barcelona Clinic Liver Cancer group, different treatment options could be offered to patients in consideration of tumor burden, liver function, patient performance status and biochemical marker serum concentration such as alpha-fetoprotein. Trans-arterial chemoembolization (TACE) is the treatment of choice in patients with diagnosis of unresectable HCC not eligible for liver transplantation, and preserved arterial supply. TACE is known to be safe and its complications are generally mild such as post-TACE syndrome, a self-resolving adverse event that occurs in about 90% of patients after the procedure. However, albeit rarely, more severe adverse events such as biloma, sepsis, hepatic failure, chemoagents induced toxicities, and post-TACE liver necrosis can occur. A prompt diagnosis of these clinical conditions is fundamental to prevent further complications. As a result, biliary stenosis could be a rare post-TACE necrosis complication and can be difficult to manage. Complications from untreated biliary strictures include recurring infections, jaundice, chronic cholestasis, and secondary biliary cirrhosis.
Collapse
Affiliation(s)
- Silvia Cocca
- Gastroenterology and Endoscopy Unit, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena 41121, Italy
| | - Lorenzo Carloni
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 00100, Italy
| | - Margherita Marocchi
- Gastroenterology and Endoscopy Unit, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena 41121, Italy
| | - Giuseppe Grande
- Gastroenterology and Endoscopy Unit, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena 41121, Italy
| | - Marcello Bianchini
- Department of Internal Medicine, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena 41121, Italy
| | - Antonio Colecchia
- Department of Internal Medicine, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena 41121, Italy
| | - Rita Conigliaro
- Gastroenterology and Endoscopy Unit, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena 41121, Italy
| | - Helga Bertani
- Gastroenterology and Endoscopy Unit, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena 41121, Italy
| |
Collapse
|
|
14
|
Colombo M, Forcignanò E, Da Rio L, Spadaccini M, Andreozzi M, Giacchetto CM, Carrara S, Maselli R, Galtieri PA, Pellegatta G, Capogreco A, Massimi D, Khalaf K, Hassan C, Anderloni A, Repici A, Fugazza A. Endoscopic management of benign biliary strictures: Looking for the best stent to place. World J Clin Cases 2023; 11:7521-7529. [DOI: 10.12998/wjcc.v11.i31.7521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/10/2023] [Accepted: 10/17/2023] [Indexed: 11/06/2023] Open
Abstract
Benign biliary strictures (BBS) might occur due to different pancreaticobiliary conditions. The etiology and location of biliary strictures are responsible of a wide array of clinical manifestations. The endoscopic approach endoscopic retrograde cholangiopancreatography represents the first-line treatment for BBS, considering interventional radiology and surgery when endoscopic treatment fails or it is not suitable. The purpose of this review is to provide an overview of possible endoscopic treatments for the optimal management of this subset of patients.
Collapse
Affiliation(s)
- Matteo Colombo
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| | - Edoardo Forcignanò
- Department of Surgical Sciences, University of Turin, Torino 10124, Piemonte, Italy
| | - Leonardo Da Rio
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| | - Marco Spadaccini
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20089, Milan, Italy
| | - Marta Andreozzi
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| | - Carmelo Marco Giacchetto
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| | - Silvia Carrara
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| | - Roberta Maselli
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20089, Milan, Italy
| | - Piera Alessia Galtieri
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| | - Gaia Pellegatta
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| | - Antonio Capogreco
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| | - Davide Massimi
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| | - Kareem Khalaf
- Division of Gastroenterology, St. Michael’s Hospital, University of Toronto, Toronto M5B1T8, Ontario, Canada
| | - Cesare Hassan
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20089, Milan, Italy
| | - Andrea Anderloni
- Endoscopy Unit, First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia 27100, Italy
| | - Alessandro Repici
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20089, Milan, Italy
| | - Alessandro Fugazza
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Milan, Italy
| |
Collapse
|
|
15
|
Tan N, Lubel J, Kemp W, Roberts S, Majeed A. Current Therapeutics in Primary Sclerosing Cholangitis. J Clin Transl Hepatol 2023; 11:1267-1281. [PMID: 37577219 PMCID: PMC10412694 DOI: 10.14218/jcth.2022.00068s] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 01/01/2023] [Accepted: 01/20/2023] [Indexed: 07/03/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is an orphan, cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease. Its pathophysiology is poorly understood. Chronic biliary inflammation is likely driven by immune dysregulation, gut dysbiosis, and environmental exposures resulting in gut-liver crosstalk and bile acid metabolism disturbances. There is no proven medical therapy that alters disease progression in PSC, with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses (15-23 mg/kg/day) but not alter transplant-free survival or liver-related outcomes. Liver transplantation is the only option for patients who develop end-stage liver disease or refractory complications of PSC. Immunosuppressive and antifibrotic agents have not proven to be effective, but there is promise for manipulation of the gut microbiome with fecal microbiota transplantation and antibiotics. Bile acid manipulation via alternate synthetic bile acids such as norursodeoxycholic acid, or interaction at a transcriptional level via nuclear receptor agonists and fibrates have shown potential in phase II trials in PSC with several leading to larger phase III trials. In view of the enhanced malignancy risk, statins, and aspirin show potential for reducing the risk of colorectal cancer and cholangiocarcinoma in PSC patients. For patients who develop clinically relevant strictures with cholestatic symptoms and worsening liver function, balloon dilatation is safer compared with biliary stent insertion with equivalent clinical efficacy.
Collapse
Affiliation(s)
- Natassia Tan
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
| | - John Lubel
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
| | - William Kemp
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
| | - Stuart Roberts
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
| | - Ammar Majeed
- Department of Gastroenterology and Hepatology, Alfred Health; Central Clinical School, Monash University, Melbourne, Australia
| |
Collapse
|
|
16
|
Carbone M, Della Penna A, Mazzarelli C, De Martin E, Villard C, Bergquist A, Line PD, Neuberger JM, Al-Shakhshir S, Trivedi PJ, Baumann U, Cristoferi L, Hov J, Fischler B, Hadzic NH, Debray D, D’Antiga L, Selzner N, Belli LS, Nadalin S. Liver Transplantation for Primary Sclerosing Cholangitis (PSC) With or Without Inflammatory Bowel Disease (IBD)-A European Society of Organ Transplantation (ESOT) Consensus Statement. Transpl Int 2023; 36:11729. [PMID: 37841645 PMCID: PMC10570452 DOI: 10.3389/ti.2023.11729] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 09/14/2023] [Indexed: 10/17/2023]
Abstract
Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines' Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.
Collapse
Affiliation(s)
- M. Carbone
- Centre for Autoimmune Liver Diseases, Department of Medicina and Surgery, University of Milano-Bicocca, Milan, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), IRCCS San Gerardo dei Tintori, Monza, Italy
| | - A. Della Penna
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - C. Mazzarelli
- Hepatology and Gastroenterology Unit, ASST GOM Niguarda, Milan, Italy
| | - E. De Martin
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-Immunes, Villejuif, France
| | - C. Villard
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), IRCCS San Gerardo dei Tintori, Monza, Italy
- Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - A. Bergquist
- Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - P. D. Line
- Norwegian PSC Research Center and Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - J. M. Neuberger
- Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - S. Al-Shakhshir
- National Institute for Health and Care Research (NIHR) Birmingham Liver Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - P. J. Trivedi
- National Institute for Health and Care Research (NIHR) Birmingham Liver Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - U. Baumann
- Division of Pediatric Gastroenterology, Hepatology and Liver Transplantation, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - L. Cristoferi
- Centre for Autoimmune Liver Diseases, Department of Medicina and Surgery, University of Milano-Bicocca, Milan, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), IRCCS San Gerardo dei Tintori, Monza, Italy
| | - J. Hov
- Norwegian PSC Research Center and Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - B. Fischler
- Department of Pediatrics, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - N. H. Hadzic
- Paediatric Centre for Hepatology, Gastroenterology and Nutrition, King’s College, London, United Kingdom
| | - D. Debray
- Unité d’Hépatologie Pédiatrique, Hôpital Necker-Enfants Malades, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-Immunes, Filfoie, Paris, France
| | - L. D’Antiga
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - N. Selzner
- Multiorgan Transplant Program, University of Toronto, Toronto, ON, Canada
| | - L. S. Belli
- Hepatology and Gastroenterology Unit, ASST GOM Niguarda, Milan, Italy
| | - S. Nadalin
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| |
Collapse
|
|
17
|
Assis DN, Bowlus CL. Recent Advances in the Management of Primary Sclerosing Cholangitis. Clin Gastroenterol Hepatol 2023; 21:2065-2075. [PMID: 37084929 DOI: 10.1016/j.cgh.2023.04.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 04/05/2023] [Accepted: 04/10/2023] [Indexed: 04/23/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by fibroinflammatory damage to the biliary tree, typically in the setting of inflammatory bowel disease, with an increased risk of liver failure and cholangiocarcinoma. A complex pathophysiology, heterogeneity in clinical features, and the rare nature of the disease have contributed to the lack of effective therapy to date. However, recent innovations in the characterization and prognostication of patients with PSC, in addition to new tools for medical management and emerging pharmacologic agents, give rise to the potential for meaningful progress in the next several years. This review summarizes current concepts in PSC and highlights particular areas in need of further study.
Collapse
|
|
18
|
Zhang CC, Sauer P. Response. Gastrointest Endosc 2023; 97:1172. [PMID: 37208047 DOI: 10.1016/j.gie.2023.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 02/10/2023] [Indexed: 05/21/2023]
Affiliation(s)
| | - Peter Sauer
- Interdisciplinary Center of Endoscopy, University Hospital Heidelberg, Heidelberg, Germany
| |
Collapse
|
|
19
|
Han S, Obando JV, Bhatt A, Bucobo JC, Chen D, Copland AP, Das KK, Girotra M, Kahn A, Krishnan K, Sakaria SS, Saumoy M, Trikudanathan G, Trindade AJ, Yang J, Law RJ, Lichtenstein DR. Biliary and pancreatic stents. IGIE 2023; 2:240-253. [DOI: 10.1016/j.igie.2023.04.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/19/2025]
|
|
20
|
Bowlus CL, Arrivé L, Bergquist A, Deneau M, Forman L, Ilyas SI, Lunsford KE, Martinez M, Sapisochin G, Shroff R, Tabibian JH, Assis DN. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023; 77:659-702. [PMID: 36083140 DOI: 10.1002/hep.32771] [Citation(s) in RCA: 141] [Impact Index Per Article: 70.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 01/28/2023]
Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology , University of California Davis Health , Sacramento , California , USA
| | | | - Annika Bergquist
- Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden
| | - Mark Deneau
- University of Utah , Salt Lake City , Utah , USA
| | - Lisa Forman
- University of Colorado , Aurora , Colorado , USA
| | - Sumera I Ilyas
- Mayo Clinic College of Medicine and Science , Rochester , Minnesota , USA
| | - Keri E Lunsford
- Rutgers University-New Jersey Medical School , Newark , New Jersey , USA
| | - Mercedes Martinez
- Vagelos College of Physicians and Surgeons , Columbia University , New York , New York , USA
| | | | | | - James H Tabibian
- David Geffen School of Medicine at UCLA , Los Angeles , California , USA
| | - David N Assis
- Yale School of Medicine , New Haven , Connecticut , USA
| |
Collapse
|
|
21
|
Bogatic D, Bryant RV, Lynch KD, Costello SP. Systematic review: microbial manipulation as therapy for primary sclerosing cholangitis. Aliment Pharmacol Ther 2023; 57:23-36. [PMID: 36324251 PMCID: PMC10092549 DOI: 10.1111/apt.17251] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/06/2022] [Accepted: 10/01/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested. AIM To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis. METHODS We conducted a comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC. RESULTS A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking. CONCLUSIONS The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease.
Collapse
Affiliation(s)
- Damjana Bogatic
- Department of GastroenterologyThe Queen Elizabeth HospitalWoodvilleSouth AustraliaAustralia
- Faculty of Health SciencesSchool of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
| | - Robert V. Bryant
- Department of GastroenterologyThe Queen Elizabeth HospitalWoodvilleSouth AustraliaAustralia
- Faculty of Health SciencesSchool of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
| | - Kate D. Lynch
- Faculty of Health SciencesSchool of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
- IBD ServiceDepartment of Gastroenterology and HepatologyRoyal Adelaide HospitalAdelaideSouth AustraliaAustralia
| | - Samuel P. Costello
- Department of GastroenterologyThe Queen Elizabeth HospitalWoodvilleSouth AustraliaAustralia
- Faculty of Health SciencesSchool of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
| |
Collapse
|
|
22
|
Zhang CC, Rupp C, Exarchos X, Mehrabi A, Koschny R, Schaible A, Sauer P. Scheduled endoscopic treatment of biliary anastomotic and nonanastomotic strictures after orthotopic liver transplantation. Gastrointest Endosc 2023; 97:42-49. [PMID: 36041507 DOI: 10.1016/j.gie.2022.08.034] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/13/2022] [Accepted: 08/20/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Biliary strictures after liver transplantation are associated with significant morbidity and mortality. Although various endoscopic treatment strategies are available, consensus on a particular strategy is lacking. Moreover, the influence of endoscopic therapy on overall survival has not been studied. This retrospective study aimed to evaluate the impact of scheduled endoscopic dilatation of biliary strictures after orthotopic liver transplantation on therapeutic success, adverse events, and survival. METHODS Between 2000 and 2016, patients with post-transplant anastomotic and nonanastomotic strictures were treated with balloon dilatation at defined intervals until morphologic resolution and clinical improvement. The primary clinical endpoint was overall survival, whereas secondary outcomes were technical and sustained clinical success, adverse events, treatment failure, and recurrence. RESULTS Overall, 165 patients with a mean follow-up of 8 years were included; anastomotic and nonanastomotic strictures were diagnosed in 110 and 55 patients, respectively. Overall survival was significantly higher in patients with anastomotic strictures than in those with nonanastomotic strictures (median, 17.6 vs 13.9 years; log-rank: P < .05). Sustained clinical success could be achieved significantly more frequently in patients with anastomotic strictures (79.1% vs 54.5%, P < .001), and such patients showed significantly superior overall survival (19.7 vs 7.7 years; log-rank: P < .001). Sustained clinical success and the presence of nonanastomotic strictures were independently associated with better and worse outcomes (P < .05), respectively. CONCLUSIONS Scheduled endoscopic treatment of biliary anastomotic and nonanastomotic strictures after liver transplantation is effective and safe, with high success rates. The implementation of this strategy controls symptoms and significantly improves survival.
Collapse
Affiliation(s)
| | - Christian Rupp
- Interdisciplinary Center of Endoscopy, University Hospital Heidelberg, Heidelberg, Germany
| | - Xenophon Exarchos
- Interdisciplinary Center of Endoscopy, University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ronald Koschny
- Interdisciplinary Center of Endoscopy, University Hospital Heidelberg, Heidelberg, Germany
| | - Anja Schaible
- Interdisciplinary Center of Endoscopy, University Hospital Heidelberg, Heidelberg, Germany
| | - Peter Sauer
- Interdisciplinary Center of Endoscopy, University Hospital Heidelberg, Heidelberg, Germany
| |
Collapse
|
|
23
|
Han S, Shah RJ. Benefit of endoscopic stenting for dominant strictures in patients with primary sclerosing cholangitis. Endosc Int Open 2022; 10:E1163-E1168. [PMID: 36118630 PMCID: PMC9473835 DOI: 10.1055/a-1873-0961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 06/09/2022] [Indexed: 11/23/2022] Open
Abstract
Background and study aims Dominant strictures (DS) occur in up to 60 % of patients with primary sclerosing cholangitis (PSC). Data regarding the long-term effects of stenting vs. dilation remain limited. The aim of this study was to compare the two treatment modalities in terms of transplantation-free survival. Patients and methods This single-center, retrospective study examined patients with PSC and DS treated endoscopically with a minimum of 1 year follow-up. Patients were divided into two cohorts: 1) those who received dilation alone; and 2) those who received both dilation and stenting. The primary outcome was transplantation-free survival, defined as time after index ERCP to liver transplantation. Results In all, 169 patients (54 in dilation cohort, 115 in stenting cohort) were included. The stenting cohort had a significantly higher Mayo PSC Risk Score (1.8 ± 1.1 vs. 0.9 ± 1.2) and presented with cholangitis more frequently (22.6 % vs. 1.9 %). During a follow-up period of 1198 person-years, 69 (40.8 %) patients received transplantation at a mean of 3.4 (± 2.9) years. There was no difference in transplantation rate in the stenting cohort [68 (95 % CI 5.2-8.8) per 100 person-years] compared to the dilation cohort [3.7 (95 % CI 2.1-6.0) per 100 person-years] and no difference in risk for transplantation (dilation cohort adjusted hazards ratio 0.67, 95 % CI 0.33-1.32). Conclusions Despite a higher Mayo Risk Score in the stenting group, there was no difference in transplantation-free survival between patients managed with stenting vs. dilation alone. Stenting, therefore, may offer benefit in patients with advanced PSC and DS.
Collapse
Affiliation(s)
- Samuel Han
- Division of Gastroenterology, Hepatology, and Nutrition. The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
| | - Raj J. Shah
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| |
Collapse
|
|
24
|
Shin IS, Moon JH. Endoscopic stenting of dominant strictures in patients with primary sclerosing cholangitis: When, how, and for how long? Endosc Int Open 2022; 10:E1169-E1171. [PMID: 36118640 PMCID: PMC9473820 DOI: 10.1055/a-1916-8992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Affiliation(s)
- Il Sang Shin
- Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Jong Ho Moon
- Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
| |
Collapse
|
|
25
|
Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, Schramm C, Trauner M. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761-806. [PMID: 35738507 DOI: 10.1016/j.jhep.2022.05.011] [Citation(s) in RCA: 162] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/16/2022] [Indexed: 02/07/2023]
Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
Collapse
|
|
26
|
Natt N, Michael F, Michael H, Dubois S, Al Mazrou'i A. ERCP-Related Adverse Events in Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis. Can J Gastroenterol Hepatol 2022; 2022:2372257. [PMID: 35910039 PMCID: PMC9334029 DOI: 10.1155/2022/2372257] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 06/23/2022] [Indexed: 11/18/2022] Open
Abstract
Background and Aims While endoscopic retrograde cholangiopancreatography (ERCP) is a valuable diagnostic and therapeutic tool in primary sclerosing cholangitis (PSC), there is conflicting data on associated adverse events. The aims of this systematic review and meta-analysis are to (1) compare ERCP-related adverse events in patients with and without PSC and (2) determine risk factors for ERCP-related adverse events in PSC. Methods Embase, PubMed, and CENTRAL were searched between January 1, 2000, and May 12, 2021. Eligible studies included adults with PSC undergoing ERCP and reported at least one ERCP-related adverse event (cholangitis, pancreatitis, bleeding, and perforation) or an associated risk factor. The risk of bias was assessed with the Newcastle-Ottawa scale and Cochrane Risk of Bias 2. Raw event rates were used to calculate odds ratios (ORs) and then pooled using random-effects models. Results Twenty studies met eligibility criteria, of which four were included in a meta-analysis comparing post-ERCP adverse events in patients with PSC (n = 715) to those without PSC (n = 9979). We found a significant threefold increase in the 30-day odds of cholangitis in PSC compared to those without (OR 3.263, 95% CI 1.076-9.896; p=0.037). However, there were no significant differences in post-ERCP pancreatitis (PEP), bleeding, or perforation. Due to limitations in primary data, only risk factors contributing to PEP could be analyzed. Accidental passage of the guidewire into the pancreatic duct (OR 7.444, 95% CI 3.328-16.651; p < 0.001; I 2 = 65.0%) and biliary sphincterotomy (OR 4.802, 95% CI 1.916-12.033; p=0.001; I 2 = 73.1%) were associated with higher odds of PEP in a second meta-analysis including five studies. Conclusions In the context of limited comparative data and heterogeneity, PSC patients undergoing ERCP have higher odds of cholangitis despite the majority receiving antibiotics. Additionally, accidental wire passage and biliary sphincterotomy increased the odds of PEP. Future studies on ERCP-related risks and preventive strategies are needed.
Collapse
Affiliation(s)
- Navneet Natt
- Northern Ontario School of Medicine University, Sudbury and Thunder Bay, Ontario, Canada
| | - Faith Michael
- Northern Ontario School of Medicine University, Sudbury and Thunder Bay, Ontario, Canada
| | | | - Sacha Dubois
- Northern Ontario School of Medicine University, Sudbury and Thunder Bay, Ontario, Canada
- Centre for Applied Health Research, St. Joseph's Care Group, Thunder Bay, Ontario, Canada
- School of Nursing, Faculty of Health and Behavioural Sciences, Lakehead University, Thunder Bay, Ontario, Canada
| | - Ahmed Al Mazrou'i
- Northern Ontario School of Medicine University, Sudbury and Thunder Bay, Ontario, Canada
- Department of Gastroenterology, Health Sciences North, Sudbury, Ontario, Canada
| |
Collapse
|
|
27
|
Klein F, Wellhöner F, Plumeier I, Kahl S, Chhatwal P, Vital M, Voigtländer T, Pieper DH, Manns MP, Lenzen H, Solbach P, Heidrich B. The biliary microbiome in ischaemic-type biliary lesions can be shaped by stenting but is resilient to antibiotic treatment. Liver Int 2022; 42:1070-1083. [PMID: 35152539 DOI: 10.1111/liv.15194] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 02/02/2022] [Accepted: 02/07/2022] [Indexed: 02/13/2023]
Abstract
This study aims to characterize the biliary microbiome as neglected factor in patients with ischaemic-type biliary lesions (ITBL) after liver transplantation. Therefore, the V1-V2 region of the 16S rRNA gene was sequenced in 175 bile samples. Samples from patients with anastomotic strictures (AS) served as controls. Multivariate analysis and in silico metagenomics were applied cross-sectionally and longitudinally. The microbial community differed significantly between ITBL and AS in terms of alpha and beta diversity. Both, antibiotic treatment and stenting were associated independently with differences in the microbial community structure. In contrast to AS, in ITBL stenting was associated with pronounced differences in the biliary microbiome, whereas no differences associated with antibiotic treatment could be observed in ITBL contrasting the pronounced differences found in AS. Bacterial pathways involved in the production of antibacterial metabolites were increased in ITBL with antibiotic treatment. After liver transplantation, the biliary tract harbours a complex microbial community with significant differences between ITBL and AS. Fundamental changes in the microbial community in ITBL can be achieved with biliary stenting. However, the effect of antibiotic treatment in ITBL was minimal. Therefore, antibiotics should be administered wisely in order to reduce emerging resistance of the biliary microbiome towards external antibiotics.
Collapse
Affiliation(s)
- Friederike Klein
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Hannover/Braunschweig, Germany.,Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Freya Wellhöner
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Iris Plumeier
- Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Silke Kahl
- Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Patrick Chhatwal
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
| | - Marius Vital
- Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Torsten Voigtländer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Dietmar H Pieper
- Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Henrike Lenzen
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hanover, Germany
| | - Philipp Solbach
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Hannover/Braunschweig, Germany.,Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hanover, Germany
| | - Benjamin Heidrich
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Hannover/Braunschweig, Germany.,Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| |
Collapse
|
|
28
|
Sbeit W, Khoury T, Goldin E, Mahamid M. Three-months duration of fully-covered metal stent for refractory dominant extra-hepatic biliary stricture among primary sclerosing cholangitis patients: efficacy and safety. Surg Endosc 2022; 36:2412-2417. [PMID: 33977375 DOI: 10.1007/s00464-021-08522-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 04/30/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Dominant stricture (DS) is a main cause of complication among patients with Primary Sclerosing Cholangitis (PSC). Endoscopic treatment options include dilation and plastic stenting, each with its own benefits and drawbacks. AIMS The aim of the current study is to assess the safety and efficacy of fully-covered metal stent (FCMS) in these patients. METHODS A retrospective study of PSC patients with refractory DS, defined as strictures resistance to conventional therapy (balloon dilatation, plastic biliary stent insertion or both) and who underwent FCMS insertion for 3 months were included. The primary outcome was defined as clinical and laboratory improvement, while secondary outcomes were DS resolution upon stent removal and cholangiographic DS recurrence at 12-months after FCMS extraction. RESULTS Twenty patients were enrolled from January 2016 through January 2020. Improvement in weakness and pruritus were seen in 80% and 35%, 75% and 65%, 75% and 35% of patients at 1-3 and 6 months following FCMS removal, respectively. Similarly, consistent improvement in all liver enzymes and total bilirubin were seen in up to 6 month following stent removal. Only one patient (5%) needed premature FCMS removal due to cholangitis 1 week after stent placement and 2 cases (10%) of stent related pancreatitis were encountered. At 3-months all remaining stents were softly removed. Cholangiographic DS resolution was demonstrated in 13 patients (65%) after stent removal at 3-months, and DS recurred in 4 patients (4/13 = 30.7%) at 12-months following stent removal. Notably, only proximal biliary DS location showed a trend for DS recurrence (OR 28.6, P = 0.06). CONCLUSION Temporary 3 months duration FCMS was feasible, safe and effective treatment option among patients with PSC related refractory DS.
Collapse
Affiliation(s)
- Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
| | - Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel.
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel.
| | - Eran Goldin
- Department of Gastroenterology and Liver Diseases, Faculty of Medicine, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Mahmud Mahamid
- Department of Gastroenterology and Liver Diseases, Faculty of Medicine, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel
| |
Collapse
|
|
29
|
Keihanian T, Barakat MT, Tejaswi S, Mishra R, Carlson CJ, Brandabur JJ, Girotra M. Role of Endoscopic Retrograde Cholangiopancreatography in the Diagnosis and Management of Cholestatic Liver Diseases. Clin Liver Dis 2022; 26:51-67. [PMID: 34802663 DOI: 10.1016/j.cld.2021.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Cholestatic liver diseases (CLDs) occur as a result of bile duct injury, emanating into duct obstruction and bile stasis. Advances in radiological imaging in the last decade has replaced endoscopic retrograde cholangiopancreatography (ERCP) as the first diagnostic tool, except in certain groups of patients, such as those with ischemic cholangiopathy (IsC) or early stages of primary sclerosing cholangitis (PSC). ERCP provides an opportunity for targeted tissue acquisition for histopathological evaluation and carries a diverse therapeutic profile to restore bile flow. The aim of this review article is to appraise the diagnostic and therapeutic roles of ERCP in CLDs.
Collapse
Affiliation(s)
- Tara Keihanian
- Division of Gastroenterology, Baylor College of Medicine, 7200 Cambridge Street, Suite A8, Houston, TX 77030, USA
| | - Monique T Barakat
- Division of Gastroenterology, Stanford University School of Medicine, 300 Pasteur Drive # 5244, Stanford, CA 94304, USA
| | - Sooraj Tejaswi
- Division of Gastroenterology, Sutter Medical Group, 2068 John Jones Road, Davis, CA 95161, USA
| | - Rajnish Mishra
- Digestive Health Institute, Swedish Medical Center, 1221 Madison Street, Arnold Pavilion, Suite 1220, Seattle, WA 98104, USA
| | - Christopher J Carlson
- Digestive Health Institute, Swedish Medical Center, 1221 Madison Street, Arnold Pavilion, Suite 1220, Seattle, WA 98104, USA
| | - John J Brandabur
- Digestive Health Institute, Swedish Medical Center, 1221 Madison Street, Arnold Pavilion, Suite 1220, Seattle, WA 98104, USA
| | - Mohit Girotra
- Digestive Health Institute, Swedish Medical Center, 1221 Madison Street, Arnold Pavilion, Suite 1220, Seattle, WA 98104, USA.
| |
Collapse
|
|
30
|
Acher AW, Rahnemai-Azar AA, Weber SM, Pawlik TM. Surgical Approach to Pancreas, Liver, Biliary Physiologic Impairment. THE IASGO TEXTBOOK OF MULTI-DISCIPLINARY MANAGEMENT OF HEPATO-PANCREATO-BILIARY DISEASES 2022:31-49. [DOI: 10.1007/978-981-19-0063-1_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
31
|
Ponsioen CY, Assis DN, Boberg KM, Bowlus CL, Deneau M, Thorburn D, Aabakken L, Färkkilä M, Petersen B, Rupp C, Hübscher SG. Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process. Gastroenterology 2021; 161:1764-1775.e5. [PMID: 34384749 DOI: 10.1053/j.gastro.2021.07.046] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 07/29/2021] [Indexed: 12/24/2022]
Affiliation(s)
- Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, the Netherlands
| | - David N Assis
- Department of Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
| | - Kirsten M Boberg
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine, and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; ERN RARE Liver, Hamburg, Germany
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, California
| | - Mark Deneau
- University of Utah and Intermountain Primary Children's Hospital, Salt Lake City, Utah
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free Hospital and Institute for Liver and Digestive Health, University College London, London, United Kingdom; ERN RARE Liver, Hamburg, Germany
| | - Lars Aabakken
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine, and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; ERN RARE Liver, Hamburg, Germany
| | - Martti Färkkilä
- Abdominal Center, Helsinki University Hospital, Helsinki, Finland; ERN RARE Liver, Hamburg, Germany
| | - Bret Petersen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Christian Rupp
- Department of Internal Medicine IV, Gastroenterology, and Hepatology, University Hospital Heidelberg, Heidelberg, Germany
| | - Stefan G Hübscher
- Institute of Immunology and Immunotherapy, University of Birmingham and, Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | | |
Collapse
|
|
32
|
Ferreira MTGB, Ribeiro IB, de Moura DTH, McCarty TR, da Ponte Neto AM, Farias GFA, de Miranda Neto AA, de Oliveira PVAG, Bernardo WM, de Moura EGH. Stent versus Balloon Dilation for the Treatment of Dominant Strictures in Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis. Clin Endosc 2021; 54:833-842. [PMID: 34192839 PMCID: PMC8652153 DOI: 10.5946/ce.2021.052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 01/30/2021] [Accepted: 02/02/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND/AIMS The endoscopic management of primary sclerosing cholangitis (PSC)-associated dominant strictures remains challenging. This systematic review and meta-analysis aimed to compare balloon dilation and stent placement in the treatment of dominant strictures among PSC patients. METHODS Literature searches on MEDLINE, EMBASE, Cochrane CENTRAL and Lilacs/Bireme were performed for studies published until December 2020. Measured outcomes included clinical efficacy, stricture recurrence, cumulative recurrencefree rate, transplant rate, 5-year survival rate, and adverse events (i.e., pancreatitis, cholangitis, bleeding, perforation and death). RESULTS A total of 5 studies (n=467) were included. Based on pooled analyses, there were no differences in clinical efficacy (risk difference [RD], -0.13; 95% confidence interval [CI], -0.58 to 0.33; I2=93%) or transplant rates (RD, -0.09; 95% CI, -0.19 to 0.01; I2=0%); however, the risk of occurrence of adverse events was lower with balloon dilatation than with stent placement (RD,-0.34; 95% CI, -0.45 to -0.23; I2=61%). Among the types of adverse events reported, only the rates of cholangitis/bacteremia were significantly lower in balloon dilation patients (RD, -0.19; 95% CI, -0.25 to -0.13; I2=51%). CONCLUSION Compared to balloon dilation, stent placement for dominant strictures in PSC appeared to have higher complication rates without significant differences in efficacy.
Collapse
Affiliation(s)
| | - Igor Braga Ribeiro
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – HC/FMUSP, São Paulo, SP, Brazil
| | - Diogo Turiani Hourneaux de Moura
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – HC/FMUSP, São Paulo, SP, Brazil
| | - Thomas R. McCarty
- Division of Gasteoenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Alberto Machado da Ponte Neto
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – HC/FMUSP, São Paulo, SP, Brazil
| | - Galileu Ferreira Ayala Farias
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – HC/FMUSP, São Paulo, SP, Brazil
| | - Antônio Afonso de Miranda Neto
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – HC/FMUSP, São Paulo, SP, Brazil
| | - Pedro Victor Aniz Gomes de Oliveira
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – HC/FMUSP, São Paulo, SP, Brazil
| | - Wanderley Marques Bernardo
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – HC/FMUSP, São Paulo, SP, Brazil
| | | |
Collapse
|
|
33
|
Eaton JE, Haseeb A, Rupp C, Eusebi LH, van Munster K, Voitl R, Thorburn D, Ponsioen CY, Enders FT, Petersen BT, Abu Dayyeh BK, Baron TH, Chandrasekhara V, Gostout CJ, Levy MJ, Martin J, Storm AC, Dierkhising R, Kamath PS, Gores GJ, Topazian M. Predictors of Jaundice Resolution and Survival After Endoscopic Treatment of Primary Sclerosing Cholangitis. Hepatol Commun 2021; 6:809-820. [PMID: 34558848 PMCID: PMC8948596 DOI: 10.1002/hep4.1813] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 06/28/2021] [Accepted: 07/12/2021] [Indexed: 12/15/2022] Open
Abstract
The benefit of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of primary sclerosing cholangitis (PSC) remains controversial. To identify predictors of jaundice resolution after ERCP and whether resolution is associated with improved patient outcomes, we conducted a retrospective cohort study of 124 patients with jaundice and PSC. These patients underwent endoscopic biliary balloon dilation and/or stent placement at an American tertiary center, with validation in a separate cohort of 102 patients from European centers. Jaundice resolved after ERCP in 52% of patients. Median follow‐up was 4.8 years. Independent predictors of jaundice resolution included older age (P = 0.048; odds ratio [OR], 1.03 for every 1‐year increase), shorter duration of jaundice (P = 0.059; OR, 0.59 for every 1‐year increase), lower Mayo Risk Score (MRS) (P = 0.025; OR, 0.58 for every 1‐point increase), and extrahepatic location of the most advanced biliary stricture (P = 0.011; OR, 3.13). A logistic regression model predicted jaundice resolution with area under the receiver operator characteristic curve of 0.67 (95% confidence interval, 0.5‐0.79) in the validation set. Independent predictors of death or transplant during follow‐up included higher MRS at the time of ERCP (P < 0.0001; hazard ratio [HR], 2.33 for every 1‐point increase), lower total serum bilirubin before ERCP (P = 0.031; HR, 0.91 for every 1 mg/dL increase), and persistence of jaundice after endoscopic therapy (P = 0.003; HR, 2.30). Conclusion: Resolution of jaundice after endoscopic treatment of biliary strictures is associated with longer transplant‐free survival of patients with PSC. The likelihood of resolution is affected by demographic, hepatic, and biliary variables and can be predicted using noninvasive data. These findings may refine the use of ERCP in patients with jaundice with PSC.
Collapse
Affiliation(s)
- John E. Eaton
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Abdul Haseeb
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Christian Rupp
- Department of Internal Medicine IVUniversity Hospital of HeidelbergHeidelbergGermany
| | - Leonardo H. Eusebi
- Sheila Sherlock Liver CentreRoyal Free Hospital and the University College London Institute of Liver and Digestive HealthLondonUnited Kingdom
| | - Kim van Munster
- Amsterdam Universitair Medische CentraAmsterdamthe Netherlands
| | - Robert Voitl
- Department of Internal Medicine IVUniversity Hospital of HeidelbergHeidelbergGermany
| | - Douglas Thorburn
- Sheila Sherlock Liver CentreRoyal Free Hospital and the University College London Institute of Liver and Digestive HealthLondonUnited Kingdom
| | | | - Felicity T. Enders
- Division of Biomedical Statistics and InformaticsMayo ClinicRochesterMNUSA
| | - Bret T. Petersen
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | | | - Todd H. Baron
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | | | | | - Michael J. Levy
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - John Martin
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Andrew C. Storm
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Ross Dierkhising
- Division of Biomedical Statistics and InformaticsMayo ClinicRochesterMNUSA
| | - Patrick S. Kamath
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Gregory J. Gores
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Mark Topazian
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| |
Collapse
|
|
34
|
Waldthaler A, Schramm C, Bergquist A. Present and future role of endoscopic retrograde cholangiography in primary sclerosing cholangitis. Eur J Med Genet 2021; 64:104231. [PMID: 33905896 DOI: 10.1016/j.ejmg.2021.104231] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 04/20/2021] [Accepted: 04/21/2021] [Indexed: 12/12/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a rare, inflammatory cholestatic liver disease that causes biliary strictures which can lead to secondary complications. About 30-50% of PSC patients develop dominant strictures (DS) in the biliary tree, which are both the cause of jaundice and bacterial cholangitis as well as predilection spots for development of neoplastic development. Cancer is the most common cause of death in PSC. A central concern is to distinguish malignant from benign strictures, which eventually is done by invasive methods to obtain a brush cytology or biopsy sample, in most cases via endoscopic retrograde cholangiography-pancreatography (ERCP). Since medical therapies, like ursodesoxycholic acid or immunosuppressive drugs have no proven effect, therapeutic ERCP has become the primary management strategy to improve symptoms and in some patients may slow down disease progression. This article aims at outlining the current and emerging methods in ERCP in PSC patients.
Collapse
Affiliation(s)
- A Waldthaler
- Department of Medicine Huddinge, Functional Unit Endoscopy, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; European Reference Network for Hepatological Diseases (ENR RARE-LIVER), Sweden.
| | - C Schramm
- Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; European Reference Network for Hepatological Diseases (ENR RARE-LIVER), Sweden
| | - A Bergquist
- Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; European Reference Network for Hepatological Diseases (ENR RARE-LIVER), Sweden
| |
Collapse
|
|
35
|
Rabiee A, Silveira MG. Primary sclerosing cholangitis. Transl Gastroenterol Hepatol 2021; 6:29. [PMID: 33824933 DOI: 10.21037/tgh-20-266] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/19/2020] [Indexed: 12/15/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.
Collapse
Affiliation(s)
- Anahita Rabiee
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Marina G Silveira
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| |
Collapse
|
|
36
|
Björnsson ES, Kalaitzakis E. Recent advances in the treatment of primary sclerosing cholangitis. Expert Rev Gastroenterol Hepatol 2021; 15:413-425. [PMID: 33283566 DOI: 10.1080/17474124.2021.1860751] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Introduction: PSC is a rare liver disease that leads frequently to cirrhosis and need for liver transplantation. No medical treatment is of proven value. Liver transplantation is the only curative therapy available. There is a big medical need to find medical therapy that can alter the natural history of the disease.Areas covered: The authors highlight advances in PSC, based on recent literature retrieved from PubMed until September 2020 regarding both medical and endoscopic biliary therapy.Future possibilities for treatment of PSC are discussed.Expert opinion: Biliary endoscopy is the cornerstone in the treatment of dominant strictures. Single-user peroral cholangioscopy is an emerging modality. Balloon dilatation therapy is the treatment of choice of dominant strictures. The most promising medical therapies showing efficacy in phase II trials are nor-Ursodeoxycholic acid, obethicolic acid, the non-steroidal FXR agonist Cilofexor and Aldafermin, a synthetic analogue of FGF-19. Antibiotics, particularly vancomycin have shown potential benefits, particularly in children but phase III studies are lacking. In observational studies of effects of biological therapy in patients with IBD/PSC adalimumab was associated with reduction in ALP. Results of liver transplantation are favorable but recurrence can be of clinical relevance particularly in patients transplanted before the age of 40.
Collapse
Affiliation(s)
- Einar S Björnsson
- Department of Internal Medicine, Faculty of Medicine, University of Iceland, Division of Gastroenterology and Hepatology, Landspitali University Hospital of Iceland
| | - Evangelos Kalaitzakis
- Department of Internal Medicine, University Hospital Heraklion, Faculty of Medicine, University of Crete, Rethymno, Greece
| |
Collapse
|
|
37
|
Marcus E, Stone P, Krooupa AM, Thorburn D, Vivat B. Quality of life in primary sclerosing cholangitis: a systematic review. Health Qual Life Outcomes 2021; 19:100. [PMID: 33743710 PMCID: PMC7981996 DOI: 10.1186/s12955-021-01739-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 03/09/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a rare bile duct and liver disease which can considerably impact quality of life (QoL). As part of a project developing a measure of QoL for people with PSC, we conducted a systematic review with four review questions. The first of these questions overlaps with a recently published systematic review, so this paper reports on the last three of our initial four questions: (A) How does QoL in PSC compare with other groups?, (B) Which attributes/factors are associated with impaired QoL in PSC?, (C) Which interventions are effective in improving QoL in people with PSC?. METHODS We systematically searched five databases from inception to 1 November 2020 and assessed the methodological quality of included studies using standard checklists. RESULTS We identified 28 studies: 17 for (A), ten for (B), and nine for (C). Limited evidence was found for all review questions, with few studies included in each comparison, and small sample sizes. The limited evidence available indicated poorer QoL for people with PSC compared with healthy controls, but findings were mixed for comparisons with the general population. QoL outcomes in PSC were comparable to other chronic conditions. Itch, pain, jaundice, severity of inflammatory bowel disease, liver cirrhosis, and large-duct PSC were all associated with impaired QoL. No associations were found between QoL and PSC severity measured with surrogate markers of disease progression or one of three prognostic scoring systems. No interventions were found to improve QoL outcomes. CONCLUSION The limited findings from included studies suggest that markers of disease progression used in clinical trials may not reflect the experiences of people with PSC. This highlights the importance for clinical research studies to assess QoL alongside clinical and laboratory-based outcomes. A valid and responsive PSC-specific measure of QoL, to adequately capture all issues of importance to people with PSC, would therefore be helpful for clinical research studies.
Collapse
Affiliation(s)
- Elena Marcus
- Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London, 6th Floor, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK.
- University College London Institute of Liver and Digestive Health, UCL Royal Free Campus, Royal Free Hospital, London, UK.
| | - Paddy Stone
- Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London, 6th Floor, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK
| | - Anna-Maria Krooupa
- Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London, 6th Floor, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK
| | - Douglas Thorburn
- University College London Institute of Liver and Digestive Health, UCL Royal Free Campus, Royal Free Hospital, London, UK
- Sheila Sherlock Liver Unit, Royal Free Hospital, London, UK
| | - Bella Vivat
- Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London, 6th Floor, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK
| |
Collapse
|
|
38
|
Prokopič M, Beuers U. Management of primary sclerosing cholangitis and its complications: an algorithmic approach. Hepatol Int 2020; 15:6-20. [PMID: 33377990 PMCID: PMC7886831 DOI: 10.1007/s12072-020-10118-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 11/25/2020] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease, characterized by multiple strictures and dilatations of the intra- and extrahepatic bile ducts, leading to progressive liver fibrosis, in 10–15% cholangiocarcinoma, and ultimately end-stage liver disease. The pathogenesis is poorly understood, but (epi-)genetic factors, mechanisms of innate and adaptive immunity, toxic effects of hydrophobic bile acids, and possibly intestinal dysbiosis appear to be involved. The strong link with inflammatory bowel disease (IBD) is associated with a markedly enhanced risk of colorectal cancer which next to cholangiocarcinoma represents the most serious diagnostic challenge in long-term PSC management. Despite extensive research, no medical treatment has been proven so far to prolong the time to liver transplantation (LTx), which remains the effective treatment in late-stage disease. Recurrence of PSC after LTx is observed in up to 20% of patients. Here, we briefly summarize actual views on PSC pathogenesis and provide an algorithmic approach to diagnostic procedures and recommendations for the management of PSC and its complications. We describe promising treatment options subject to current clinical trials.
Collapse
Affiliation(s)
- Michal Prokopič
- Department of Gastroenterology and Hepatology and Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location AMC, AGEM, C2-327, Meibergdreef 9, 1100 DE, Amsterdam, The Netherlands.,Department of Gastroenterology, Comenius University Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology and Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location AMC, AGEM, C2-327, Meibergdreef 9, 1100 DE, Amsterdam, The Netherlands.
| |
Collapse
|
|
39
|
van Munster KN, Dijkgraaf MGW, van Gennep S, Beuers U, Ponsioen CY. The Simple Cholestatic Complaints Score is a valid and quick patient-reported outcome measure in primary sclerosing cholangitis. Liver Int 2020; 40:2758-2766. [PMID: 32841496 PMCID: PMC7702029 DOI: 10.1111/liv.14644] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 08/13/2020] [Accepted: 08/14/2020] [Indexed: 01/29/2023]
Abstract
BACKGROUND Measuring symptoms and disease burden in patients with primary sclerosing cholangitis (PSC) is increasingly important for daily practice and clinical trials. The Simple Cholestatic Complaints Score (SCCS) is a four-item questionnaire, that measures cholestatic symptoms (pruritus, fatigue, RUQ abdominal pain and fever) in PSC patients. The aim of this study was to evaluate reliability and validity of SCCS in a Dutch population. METHODS The study population consisted of 212 patients from the Dutch prospective PSC registry. Data were collected via digital surveys. Reliability was evaluated by internal consistency and reproducibility. Construct-, criterion- and discriminant validity were determined. The ability to detect clinical change with SCCS was evaluated in patients who underwent endoscopic intervention. Simple Cholestatic Complaints Score collected by email and by a mobile application were compared. RESULTS A total of 153 patients completed the questionnaire. Internal consistency was moderate and increased to 0.71 after removal of the fever item. Test-re-test reproducibility was high (intraclass correlation coefficient = 0.96). Criterion validity was good (all > 0.82). Construct validity was in line with a priori hypothesized correlations in 80%. SCCS was able to differentiate between clinically different groups. There was no difference between inflammatory bowel disease (IBD) and non-IBD patients. Simple Cholestatic Complaints Score was responsive to change after endoscopic intervention in successfully treated patients. Simple Cholestatic Complaints Score measurement by digital questionnaire and a mobile application was comparable. CONCLUSION The SCCS is a valid instrument to measure cholestatic symptoms in PSC patients. Because of its quick and easy to use properties it is suitable for frequent monitoring of symptoms in clinical trials and daily practice.
Collapse
Affiliation(s)
- Kim N. van Munster
- Department of Gastroenterology and HepatologyAmsterdam University Medical Centerslocation AMCAmsterdam Gastroenterology & MetabolismAmsterdamThe Netherlands
| | - Marcel G. W. Dijkgraaf
- Department of Epidemiology and Data ScienceAmsterdam University Medical CentersUniversity of AmsterdamAmsterdamThe Netherlands
| | - Sara van Gennep
- Department of Gastroenterology and HepatologyAmsterdam University Medical Centerslocation AMCAmsterdam Gastroenterology & MetabolismAmsterdamThe Netherlands
| | - Ulrich Beuers
- Department of Gastroenterology and HepatologyAmsterdam University Medical Centerslocation AMCAmsterdam Gastroenterology & MetabolismAmsterdamThe Netherlands
| | - Cyriel Y. Ponsioen
- Department of Gastroenterology and HepatologyAmsterdam University Medical Centerslocation AMCAmsterdam Gastroenterology & MetabolismAmsterdamThe Netherlands
| |
Collapse
|
|
40
|
Abstract
The evolution of advanced pancreaticobiliary endoscopy in the past 50 years is remarkable. Endoscopic retrograde cholangiopancreatography (ERCP) has progressed from a diagnostic test to an almost entirely therapeutic procedure. The endoscopist must have a clear understanding of the indications for ERCP to avoid unnecessary complications, including post-ERCP pancreatitis. Endoscopic ultrasound initially was used as a diagnostic tool but now is equipped with accessary channels allowing endoscopic ultrasound-guided interventions in various pancreaticobiliary conditions. This review discusses the endoscopic management of common pancreatic and biliary diseases along with the techniques, indications, outcomes, and complications of pancreaticobiliary endoscopy.
Collapse
Affiliation(s)
- Catherine F Vozzo
- Department of Gastroenterology, Cleveland Clinic, 9500 Euclid Avenue / A30, Cleveland, OH 44195, USA
| | - Madhusudhan R Sanaka
- Department of Gastroenterology, Cleveland Clinic, 9500 Euclid Avenue / Q30, Cleveland, OH 44195, USA.
| |
Collapse
|
|
41
|
Ip S, Bhanji RA, Ebadi M, Mason AL, Montano-Loza AJ. De novo and recurrent liver disease. Best Pract Res Clin Gastroenterol 2020; 46-47:101688. [PMID: 33158472 DOI: 10.1016/j.bpg.2020.101688] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/03/2020] [Accepted: 09/18/2020] [Indexed: 01/31/2023]
Abstract
Decompensated cirrhosis due to nonalcoholic steatohepatitis (NASH), and autoimmune liver diseases (AILD) are the most common indications for liver transplantation (LT). AILD include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). NASH and AILD share some peculiarities as they can recur in the new graft, compromising the quality of life, and graft and patient survival. De novo NASH or AIH connotes the development of these liver diseases in patients transplanted for other indications. The diagnosis of recurrent or de novo liver disease usually requires a liver biopsy aside from recurrent PSC, which can be diagnosed with compatible imaging studies and exclusion of other causes of biliary strictures. The treatment of recurrent NASH is lifestyle modifications aiming for weight loss. Recurrent and de novo AIH is usually treated with corticosteroids with or without azathioprine. Recurrent PBC should be treated with ursodeoxycholic acid. There are no proven treatment options for recurrent PSC. Patients with graft failure should be considered for repeat LT. Future investigations should use standardized diagnostic criteria for each disease, seek diagnostic biomarkers, and evaluate treatments that improve outcomes.
Collapse
Affiliation(s)
- Stephen Ip
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Rahima A Bhanji
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Maryam Ebadi
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Andrew L Mason
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| | - Aldo J Montano-Loza
- From the Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
| |
Collapse
|
|
42
|
Bhat P, Aabakken L. Role of Endoscopy in Primary Sclerosing Cholangitis. Clin Endosc 2020; 54:193-201. [PMID: 32380796 PMCID: PMC8039754 DOI: 10.5946/ce.2020.019-iden] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 03/23/2020] [Indexed: 11/24/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a progressive disease of the bile ducts that usually results in chronic liver disease often requiring liver transplantation. Endoscopy remains crucial to the care of these patients, although magnetic resonance cholangiopancreatography has replaced endoscopic retrograde cholangiopancreatography (ERCP) as the primary imaging modality for diagnosis. For detection of dysplasia or cholangiocarcinoma, ERCP with intraductal sampling remains compulsory. Moreover, dominant strictures play an important part in the disease development, and management by balloon dilatation or stenting could contribute to long-term prognosis. In addition, endoscopy offers management for adverse events such as bile leaks and anastomotic strictures after liver transplantation. Finally, the special phenotype of inflammatory bowel disease associated with PSC as well as the frequent occurrence of portal hypertension mandates close follow-up with colonoscopy and upper endoscopy. With the emergence of novel techniques, the endoscopist remains a key member of the multidisciplinary team caring for PSC patients.
Collapse
Affiliation(s)
- Purnima Bhat
- Gastroenterology and Hepatology Unit, Canberra Hospital, Canberra, Australia.,College of Health and Medicine, Australian National University, Canberra, Australia
| | - Lars Aabakken
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
| |
Collapse
|
|
43
|
Role of Peroral Cholangioscopy in the Diagnosis of Primary Sclerosing Cholangitis. Diagnostics (Basel) 2020; 10:diagnostics10050268. [PMID: 32365686 PMCID: PMC7277921 DOI: 10.3390/diagnostics10050268] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 04/23/2020] [Accepted: 04/27/2020] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is characterized by idiopathic biliary stricture followed by progressive cholestasis and fibrosis. When diagnosing PSC, its differentiation from other types of sclerosing cholangitis and cholangiocarcinoma is necessary. The cholangioscopic findings of PSC have not been investigated sufficiently. PSC and IgG4-related sclerosing cholangitis are difficult to distinguish by peroral cholangioscopy (POCS), but POCS is useful for excluding cholangiocarcinoma. POCS findings vary according to the condition and stage of disease. In the active phase, findings such as mucosal erythema, ulceration, fibrinous white exudate, and an irregular surface are observed and may reflect strong inflammation in the biliary epithelium. On the other hand, findings such as scarring, pseudodiverticula, and bile duct stenosis appear in the chronic phase and may reflect fibrosis and stenosis resulting from repeated inflammation. Observation of inside the bile duct by POCS might confirm the current PSC activity. Because POCS offers not only information regarding the diagnosis of PSC and PSC-associated cholangiocarcinoma but also the current statuses of biliary inflammation and stenosis, POCS could significantly contribute to the diagnosis and treatment of PSC once the characteristic findings of PSC are confirmed by future studies.
Collapse
|
|
44
|
Wong MY, Saxena P, Kaffes AJ. Benign Biliary Strictures: A Systematic Review on Endoscopic Treatment Options. Diagnostics (Basel) 2020; 10:diagnostics10040221. [PMID: 32326542 PMCID: PMC7235774 DOI: 10.3390/diagnostics10040221] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 04/02/2020] [Accepted: 04/14/2020] [Indexed: 01/18/2023] Open
Abstract
Benign biliary strictures can be difficult to manage. Untreated biliary strictures can lead to complications, such as chronic cholestasis, jaundice, recurrent sepsis, and secondary biliary cirrhosis, which can have severe ramifications. The management landscape is constantly evolving, with the development of modifiable self-expandable metal stents and biodegradable stents. This review critically appraises current endoscopic treatment strategies, in particular focusing on the shortfalls, such as stent migration and stricture recurrence. It also proposes a treatment algorithm based on aetiologias and the location of the strictures.
Collapse
Affiliation(s)
- May Y.W. Wong
- Interventional Endoscopy, Chris O Brien Lifehouse, Missenden Road, Camperdown 2050, Australia; (M.Y.W.W.); (P.S.)
| | - Payal Saxena
- Interventional Endoscopy, Chris O Brien Lifehouse, Missenden Road, Camperdown 2050, Australia; (M.Y.W.W.); (P.S.)
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Missenden Road, Camperdown 2050, Australia
- Department of Medicine, University of Sydney, Camperdown 2050, Australia
| | - Arthur J. Kaffes
- Interventional Endoscopy, Chris O Brien Lifehouse, Missenden Road, Camperdown 2050, Australia; (M.Y.W.W.); (P.S.)
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Missenden Road, Camperdown 2050, Australia
- Department of Medicine, University of Sydney, Camperdown 2050, Australia
- Correspondence:
| |
Collapse
|
|
45
|
Koskensalo V, Tenca A, Udd M, Lindström O, Rainio M, Jokelainen K, Kylänpää L, Färkkilä M. Diclofenac does not reduce the risk of acute pancreatitis in patients with primary sclerosing cholangitis after endoscopic retrograde cholangiography. United European Gastroenterol J 2020; 8:462-471. [PMID: 32213036 DOI: 10.1177/2050640620912608] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The European Society of Gastrointestinal Endoscopy recommends rectal indomethacin or diclofenac before endoscopic retrograde cholangiopancreatography (ERCP) to prevent post-ERCP pancreatitis. However, data on the prophylactic effect in patients with primary sclerosing cholangitis (PSC) are lacking. METHODS This was a retrospective case-control study. In 2009-2018, a total of 2000 ERCPs were performed in 931 patients with PSC. Case procedures (N = 1000 after November 2013) were performed after administration of rectal diclofenac. Control procedures (N = 1000 before November 2013) were performed with the same indication but without diclofenac. Acute post-ERCP pancreatitis and other ERCP-related adverse events (AEs) were evaluated. RESULTS Post-ERCP pancreatitis developed in 49 (4.9%) procedures in the diclofenac group and 62 (6.2%) procedures in the control group (p = 0.241). No difference existed between the groups in terms of the severity of pancreatitis or any other acute AEs. The risk of pancreatitis was elevated in patients with native papilla: 11.4% in the diclofenac group and 8.7% in the control group (p = 0.294). In adjusted logistic regression, diclofenac did not reduce the risk of pancreatitis (odds ratio (OR) = 1.074, 95% confidence interval 0.708-1.629, p = 0.737). However, in generalised estimation equations with the advanced model, diclofenac seemed to diminish the risk of pancreatitis (OR = 0.503) but not significantly (p = 0.110). CONCLUSION In this large patient cohort in a low-risk unit, diclofenac does not seem to reduce the risk of post-ERCP pancreatitis in patients with PSC. The trend in the pancreatitis rate after ERCP is decreasing. The evaluation of the benefits of diclofenac among PSC patients warrants a randomised controlled study targeted to high-risk patients and procedures.
Collapse
Affiliation(s)
- Vilja Koskensalo
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Andrea Tenca
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| | - Marianne Udd
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Outi Lindström
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Mia Rainio
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Kalle Jokelainen
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| | - Leena Kylänpää
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Martti Färkkilä
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Abdominal Centre, Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| |
Collapse
|
|
46
|
Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities. J Gastroenterol 2020; 55:588-614. [PMID: 32222826 PMCID: PMC7242240 DOI: 10.1007/s00535-020-01681-z] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 03/05/2020] [Indexed: 02/04/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a progressive liver disease, histologically characterized by inflammation and fibrosis of the bile ducts, and clinically leading to multi-focal biliary strictures and with time cirrhosis and liver failure. Patients bear a significant risk of cholangiocarcinoma and colorectal cancer, and frequently have concomitant inflammatory bowel disease and autoimmune disease manifestations. To date, no medical therapy has proven significant impact on clinical outcomes and most patients ultimately need liver transplantation. Several treatment strategies have failed in the past and whilst prescription of ursodeoxycholic acid (UDCA) prevails, controversy regarding benefits remains. Lack of statistical power, slow and variable disease progression, lack of surrogate biomarkers for disease severity and other challenges in trial design serve as critical obstacles in the development of effective therapy. Advances in our understanding of PSC pathogenesis and biliary physiology over recent years has however led to a surge of clinical trials targeting various mechanistic compartments and currently raising hopes for imminent changes in patient management. Here, in light of pathophysiology, we outline and critically evaluate emerging treatment strategies in PSC, as tested in recent or ongoing phase II and III trials, stratified per a triad of targets of nuclear and membrane receptors regulating bile acid metabolism, immune modulators, and effects on the gut microbiome. Furthermore, we revisit the UDCA trials of the past and critically discuss relevant aspects of clinical trial design, including how the choice of endpoints, alkaline phosphatase in particular, may affect the future path to novel, effective PSC therapeutics.
Collapse
|
|
47
|
Rupp C, Hippchen T, Bruckner T, Klöters-Plachky P, Schaible A, Koschny R, Stiehl A, Gotthardt DN, Sauer P. Effect of scheduled endoscopic dilatation of dominant strictures on outcome in patients with primary sclerosing cholangitis. Gut 2019; 68:2170-2178. [PMID: 30910856 PMCID: PMC6872453 DOI: 10.1136/gutjnl-2018-316801] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 02/16/2019] [Accepted: 03/08/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Scheduled endoscopic dilatation of dominant strictures (DS) in primary sclerosing cholangitis (PSC) might improve outcome relative to endoscopic treatment on demand, but evidence is limited. Since randomisation is difficult in clinical practice, we present a large retrospective study comparing scheduled versus on-demand endoscopic retrograde cholangiopancreatography (ERCP) based on patient preferences. DESIGN Between 1987 and 2017, all new patients with PSC had been offered scheduled ERCP with dilatation of a DS if diagnosed; the latter was repeated at defined intervals until morphological resolution, independent of clinical symptoms (treatment group). Patients who refused participation were clinically evaluated annually and received endoscopic treatment only on demand (control group). The primary clinical endpoint was transplantation-free survival. Secondary outcomes were overall survival, bacterial cholangitis episodes, hepatic decompensation of liver cirrhosis and endoscopy-related adverse events. RESULTS The final study included 286 patients, 133 (46.5%) receiving scheduled ERCP and 153 (53.5%) receiving on-demand ERCP. After a mean follow-up of 9.9 years, the rate of transplantation-free survival was higher in patients receiving scheduled ERCP (51% vs 29.3%; p<0.001), as was transplantation-free survival time (median: 17.9 vs 15.2 years; log-rank: p=0.008). However, the benefit of scheduled ERCP was significant only in patients with the initial (17.1%) or later (45.5%) diagnosis of a DS (17.8 vs 11.1 years; log-rank: p<0.001). IBD (p=0.03), DS (p=0.006), higher Mayo Risk Score (p=0.02) and non-adherence to scheduled endoscopy (p=0.005) were independently associated with transplantation-free survival. CONCLUSION In our large retrospective study, regular ERCP with endoscopic balloon dilatation significantly benefits patients with PSC with DS, diagnosed both at initial presentation and during surveillance, even if asymptomatic. Further studies have to find out how to best identify stricture patients non-invasively.
Collapse
Affiliation(s)
- Christian Rupp
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany,Department of Internal Medicine IV, Interdisciplinary Endoscopy Center, University Hospital Heidelberg, Heidelberg, Germany
| | - Theresa Hippchen
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany
| | - Thomas Bruckner
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Petra Klöters-Plachky
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany
| | - Anja Schaible
- Department of General, Visceral and Transplantation Surgery, Interdisciplinary Endoscopy Center, University Hospital of Heidelberg, Heidelberg, Germany
| | - Ronald Koschny
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany,Department of Internal Medicine IV, Interdisciplinary Endoscopy Center, University Hospital Heidelberg, Heidelberg, Germany
| | - Adolf Stiehl
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany
| | - Daniel Nils Gotthardt
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany
| | - Peter Sauer
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany,Department of Internal Medicine IV, Interdisciplinary Endoscopy Center, University Hospital Heidelberg, Heidelberg, Germany
| |
Collapse
|
|
48
|
Cazzagon N, Chazouillères O, Corpechot C, El Mouhadi S, Chambenois E, Desaint B, Chaput U, Lemoinne S, Arrivé L. Predictive criteria of response to endoscopic treatment for severe strictures in primary sclerosing cholangitis. Clin Res Hepatol Gastroenterol 2019; 43:387-394. [PMID: 30772328 DOI: 10.1016/j.clinre.2019.01.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 12/17/2018] [Accepted: 01/10/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of this study was to identify predictive criteria of improvement after endoscopic treatment (ET) for severe strictures of extrahepatic bile ducts in patients with primary sclerosing cholangitis (PSC). METHODS PSC patients who had at least one ET for severe stricture were included. Features of magnetic resonance cholangiography (MRC), performed before ET, were evaluated according to a standard model of interpretation, and a radiologic qualitative score of probability of improvement after ET was built. Score 3 (likely) was given in case of severe common bile duct (CBD) stricture with marked dilatation without severe strictures of upstream ducts, Score 1 (unlikely) was given in case of severe multiple strictures of secondary ducts without biliary dilatation and Score 2 (undeterminate) was given to an intermediate pattern. The response to ET was assessed at 2 months (T2-response) from the last ET and at 12 months (T12-response) from inclusion. RESULTS Thirty-one patients were included. All had severe stricture (reduction ≥ 75% of the diameter) of CBD and 50% had severe stricture of right and/or left hepatic duct (LHD) at MRC before ET. According to the qualitative score, 16 patients had Score 3, 7 had Score 1 and 9 had Score 2. T12-response was obtained in 50% of patients. In univariate analysis, short LHD strictures, bilirubin, transaminases, pruritus and Score 3 were associated with T12-response. Increased bilirubin and transaminases were independent predictive factors of T12-response (HR 24, 95% CI: 3.4-170.4, P = 0.001 and 23.8, 95% CI: 3.4-169.4, P = 0.002, respectively). CONCLUSION MRC, together with biochemical features, may contribute to identify the PSC patients who are likely to be improved after ET for severe strictures of extrahepatic bile ducts.
Collapse
Affiliation(s)
- Nora Cazzagon
- Reference center for inflammatory biliary disease and autoimmune hepatitis (MIVB), Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, 75012 Paris, France; Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy
| | - Olivier Chazouillères
- Reference center for inflammatory biliary disease and autoimmune hepatitis (MIVB), Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, 75012 Paris, France
| | - Christophe Corpechot
- Reference center for inflammatory biliary disease and autoimmune hepatitis (MIVB), Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, 75012 Paris, France
| | - Sanaâ El Mouhadi
- Department of Radiology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris AP-HP, Sorbonne university, 75012 Paris, France
| | - Edouard Chambenois
- Department of Radiology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris AP-HP, Sorbonne university, 75012 Paris, France
| | - Benoit Desaint
- Reference center for inflammatory biliary disease and autoimmune hepatitis (MIVB), Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, 75012 Paris, France; Endoscopic department, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Paris, France
| | - Ulriikka Chaput
- Reference center for inflammatory biliary disease and autoimmune hepatitis (MIVB), Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, 75012 Paris, France; Endoscopic department, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Paris, France
| | - Sara Lemoinne
- Reference center for inflammatory biliary disease and autoimmune hepatitis (MIVB), Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, 75012 Paris, France
| | - Lionel Arrivé
- Department of Radiology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris AP-HP, Sorbonne university, 75012 Paris, France.
| |
Collapse
|
|
49
|
Chapman MH, Thorburn D, Hirschfield GM, Webster GGJ, Rushbrook SM, Alexander G, Collier J, Dyson JK, Jones DE, Patanwala I, Thain C, Walmsley M, Pereira SP. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut 2019; 68:1356-1378. [PMID: 31154395 PMCID: PMC6691863 DOI: 10.1136/gutjnl-2018-317993] [Citation(s) in RCA: 178] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 02/21/2019] [Accepted: 03/24/2019] [Indexed: 12/11/2022]
Abstract
These guidelines on the management of primary sclerosing cholangitis (PSC) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included medical representatives from hepatology and gastroenterology groups as well as patient representatives from PSC Support. The guidelines aim to support general physicians, gastroenterologists and surgeons in managing adults with PSC or those presenting with similar cholangiopathies which may mimic PSC, such as IgG4 sclerosing cholangitis. It also acts as a reference for patients with PSC to help them understand their own management. Quality of evidence is presented using the AGREE II format. Guidance is meant to be used as a reference rather than for rigid protocol-based care as we understand that management of patients often requires individual patient-centred considerations.
Collapse
Affiliation(s)
- Michael Huw Chapman
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Liver Unit, Royal Free London NHS Foundation Trust, London, UK
| | | | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, University Health Network and University of Toronto, Toronto, Canada
| | | | - Simon M Rushbrook
- Department of Hepatology, Norfolk and Norwich University Hospitals NHS Trust, Norwich, UK
| | | | | | - Jessica K Dyson
- Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - David Ej Jones
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - Imran Patanwala
- Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
- University of Liverpool, Liverpool, UK
| | | | | | - Stephen P Pereira
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Institute for Liver & Digestive Health, University College London, London, UK
| |
Collapse
|
|
50
|
Menon S, Holt A. Large-duct cholangiopathies: aetiology, diagnosis and treatment. Frontline Gastroenterol 2019; 10:284-291. [PMID: 31288256 PMCID: PMC6583582 DOI: 10.1136/flgastro-2018-101098] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 12/06/2018] [Accepted: 12/09/2018] [Indexed: 02/04/2023] Open
Abstract
Cholangiopathies describe a group of conditions affecting the intrahepatic and extrahepatic biliary tree. Impairment to bile flow and chronic cholestasis cause biliary inflammation, which leads to more permanent damage such as destruction of the small bile ducts (ductopaenia) and biliary cirrhosis. Most cholangiopathies are progressive and cause end-stage liver disease unless the physical obstruction to biliary flow can be reversed. This review considers large-duct cholangiopathies, such as primary sclerosing cholangitis, ischaemic cholangiopathy, portal biliopathy, recurrent pyogenic cholangitis and Caroli disease.
Collapse
Affiliation(s)
- Shyam Menon
- Department of Hepatology and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK,Department of Gastroenterology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | - Andrew Holt
- Department of Hepatology and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| |
Collapse
|