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McNally BB, Carey EJ. Cholestatic liver diseases: modern therapeutics. Expert Rev Gastroenterol Hepatol 2025; 19:365-370. [PMID: 40011221 DOI: 10.1080/17474124.2025.2473490] [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: 11/08/2024] [Revised: 02/03/2025] [Accepted: 02/25/2025] [Indexed: 02/28/2025]
Abstract
INTRODUCTION Cholestatic liver disease encompasses a broad group of disorders related to impaired normal bile formation, secretion, or excretion. These diseases present with symptoms of fatigue, jaundice, pruritus, and biochemical changes. AREAS COVERED We focus on updates in the management of autoimmune cholestatic liver disease. The mainstay therapy in PBC is UDCA (ursodeoxycholic acid), but OCA (obeticholic acid) can be considered if suboptimal response or intolerance. Fibrates have shown some promising effects in PBC patients who have not responded to or are intolerant of UDCA and/or OCA; however, they are not FDA approved. Peroxisome Proliferator-Activated Receptor Agonists (PPARs) have emerged as a promising new class of oral agents in PBC. Also, Ileal Bile Acid Transporter (IBAT) inhibitors are being investigated for the treatment of pruritus related to PBC. There are no available treatments for PSC; however, there have been previous investigations into many agents. There are ongoing clinical trials investigating the role of various antibiotics, PPARs, and immunomodulators for the treatment of PSC. EXPERT OPINION Ongoing investigations into the treatment of both PBC and PSC are essential. We anticipate that alternative management strategies for PBC and PSC will continue to arise in the next 5-10 years.
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Affiliation(s)
- Bridgette B McNally
- Mayo Clinic Arizona, Department of Gastroenterology & Hepatology, Division of Hepatology, Phoenix, Arizona, USA
| | - Elizabeth J Carey
- Mayo Clinic Arizona, Department of Gastroenterology & Hepatology, Division of Hepatology, Phoenix, Arizona, USA
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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.
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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
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Barner-Rasmussen N, Molinaro A, Mol B, Ponsioen C, Bergquist A, Kautiainen H, Färkkilä MA. Surveillance of primary sclerosing cholangitis - a comparison of scheduled or on-demand ERCP with annual MRI surveillance: a multicenter study. Endoscopy 2025. [PMID: 39875118 DOI: 10.1055/a-2511-3422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Primary sclerosing cholangitis (PSC) is associated with a high risk of hepatobiliary malignancy, especially cholangiocarcinoma (CCA). There are no good tumor markers to screen for CCA, and current recommendations for PSC monitoring are mainly based on expert opinions. The optimal strategy to assess disease progression and screen for CCA - the main cause of death of PSC patients - remains unclear. We aimed to compare three different surveillance strategies and their effect on patient outcomes.Data from three distinct PSC cohorts with different surveillance strategies - scheduled endoscopic retrograde cholangiopancreatography (ERCP), annual magnetic resonance imaging/cholangiopancreatography (MRI/MRCP) surveillance, and on-demand ERCP according to ESGE/EASL guidelines - was collected. Patients with PSC diagnosed in 1990 or later were included and the last day of follow-up was 31 December 2023. The composite end point consisted of hepatobiliary malignancy, liver transplantation, or liver-related death.1629 PSC patients were included, with a median follow-up of 8-11 years. The cumulative incidence of the composite end point was lowest in the group undergoing scheduled ERCP (14.1%, 95%CI 12.0%-16.4%) and highest in the on-demand ERCP cohort (35.0%, 95%CI 28.4%-42.0%). Although the cumulative incidence of CCA was lower in the scheduled ERCP group than in the other groups, it did not differ statistically significantly from the MRI/MRCP surveillance group. No differences were seen in liver-related deaths between the surveillance strategies.In this study comparing scheduled ERCP, annual MRI/MRCP surveillance, and on-demand ERCP, the strategy based on scheduled ERCP using individual risk stratification is associated with better overall prognosis and outcome.
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Affiliation(s)
- Nina Barner-Rasmussen
- Department of Gastroenterology, HUS Abdominal Center, Helsinki University Central Hospital, Helsinki, Finland
| | - Antonio Molinaro
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden
| | - Bregje Mol
- Department of Gastroenterology and Hepatology, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands
| | - Cyriel Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands
| | - Annika Bergquist
- Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden
| | - Hannu Kautiainen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
- Primary Health Care, Folkhalsan Research Centre, Helsinki, Finland
| | - Martti A Färkkilä
- Department of Gastroenterology, HUS Abdominal Center, Helsinki University Central Hospital, Helsinki, Finland
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Färkkilä M, Åberg F, Alfthan H, Jokelainen K, Puustinen L, Kautiainen H, Tenca A. Surrogate markers of bile duct disease progression in primary sclerosing cholangitis - A prospective study with repeated ERCP examinations. JHEP Rep 2024; 6:101161. [PMID: 39290402 PMCID: PMC11405802 DOI: 10.1016/j.jhepr.2024.101161] [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: 03/01/2024] [Revised: 06/14/2024] [Accepted: 06/25/2024] [Indexed: 09/19/2024] Open
Abstract
Background & Aims Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis (PSC) are lacking. We evaluated the predictive value of serum and biliary biochemistry for the progression of bile duct disease in PSC using repeated endoscopic retrograde cholangiopancreatography (ERCP) examinations to identify surrogate markers for more personalized surveillance. Methods We conducted a prospective analysis including patients with PSC who underwent ERCP for confirmation of diagnosis, monitoring of disease progression, or dysplasia surveillance. ERCP findings were scored, and dilatation was performed if a dominant stricture was diagnosed or if a cytology brush could not be passed. Bile samples were aspirated for biliary IL8 and calprotectin. We analysed optimal cut-off values and AUCs for 20 laboratory markers and evaluated their association with the time to an ERCP score increase of ≥2 points or first dilatation, whichever came first. Of the 1,002 patients, 653 had ≥2 ERCP examinations and ≥3 years of follow-up. After excluding patients with PSC-overlap syndrome or initial dilatation, 398 patients were included. Results Of the patients included, 62% had mild or moderate and 38% had advanced bile duct disease. During follow-up, 41% of patients demonstrated progression of disease. Biliary calprotectin (AUC 0.76; 95% CI 0.69 to 0.82) and IL8 (AUC 0.76; 95% CI 0.69 to 0.84) were the only variables that demonstrated predictive value for disease progression and/or need for dilatation. Conclusions Biliary calprotectin and IL8 are promising surrogate markers for identifying patients with PSC at risk of progression and determining the timing for subsequent imaging. Conventional liver function tests may not be sensitive or specific enough to monitor PSC progression, particularly in the short term. Impact and implications Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis are lacking. In this prospective study, based on sequential endoscopic retrograde cholangiopancreatography examinations, biliary calprotectin and IL8 levels turned out to be more sensitive for predicting bile duct progression than traditional liver function tests, such as alkaline phosphatase, in the short term. These findings could lead to more personalized patient surveillance and improve clinical practice by providing a more accurate method for monitoring disease progression and treatment responses. Additionally, these markers have potential as surrogate endpoints in clinical drug trials. The limitation is that measurement of biliary IL8 and calprotectin requires endoscopic retrograde cholangiopancreatography with bile sampling.
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Affiliation(s)
- Martti Färkkilä
- Helsinki University, Finland
- Department of Gastroenterology, Helsinki University Hospital, Abdominal Center, Helsinki, Finland
| | - Fredrik Åberg
- Transplantation and Liver Surgery, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Henrik Alfthan
- Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Kalle Jokelainen
- Department of Gastroenterology, Helsinki University Hospital, Abdominal Center, Helsinki, Finland
| | - Lauri Puustinen
- Department of Gastroenterology, Helsinki University Hospital, Abdominal Center, Helsinki, Finland
| | - Hannu Kautiainen
- Folkhälsan Research Center, Helsinki, Finland and Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Andrea Tenca
- Department of Gastroenterology, Helsinki University Hospital, Abdominal Center, Helsinki, Finland
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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.
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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
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Morelli MC, Gambato M, Martini S, Carrai P, Toniutto P, Giannelli V, Donato F, Lenci I, Pasulo L, Mazzarelli C, Ferrarese A, Rendina M, Grieco A, Lanza AG, Baroni GS, De Maria N, Marenco S, Mameli L, Ponziani FR, Vitale G, Burra P. Trends in liver transplantation for primary sclerosing cholangitis. Dig Liver Dis 2024; 56:1343-1349. [PMID: 38233315 DOI: 10.1016/j.dld.2024.01.175] [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: 09/18/2023] [Revised: 01/04/2024] [Accepted: 01/08/2024] [Indexed: 01/19/2024]
Abstract
BACKGROUND Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated. AIM We performed a national survey to investigate the listing criteria, comorbidities, and outcomes. METHODS In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years. RESULTS From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence). CONCLUSIONS Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death.
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Affiliation(s)
- Maria Cristina Morelli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Internal Medicine Unit for the treatment of Severe Organ Failure, Bologna, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Padua University Hospital, Padova, Italy
| | - Silvia Martini
- Gastrohepatology Unit, AOU Città della Salute e della Scienza di Torino, Torino, Italy
| | - Paola Carrai
- Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School and Hospital, Pisa, Italy
| | - Pierluigi Toniutto
- Hepatology and Liver Transplant Unit, Department of Medical Area, Udine University Hospital, Udine, Italy
| | - Valerio Giannelli
- San Camillo Hospital, Department of Transplantation and General Surgery, Rome, Italy
| | - Francesca Donato
- Gastroenterology and Hepatology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Ilaria Lenci
- Hepatology and Transplant Unit, Fondazione Policlinico Tor Vergata, Roma, Italy
| | - Luisa Pasulo
- Gastroenterology and Transplant Hepatology Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Chiara Mazzarelli
- Gastroenterology and Hepatology Department, Liver Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Alberto Ferrarese
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, Verona, Italy
| | - Maria Rendina
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Italy
| | - Antonio Grieco
- Liver Transplant Medicine Unit, Gastroenterological Area, Department of Gastroenterological, Endocrine and Metabolic Sciences, Fondazione Policlinico Universitario Gemelli, Catholic University of the Sacred Heart, Rome, Italy
| | | | | | - Nicola De Maria
- Gastroenterology Unit, Department of Medical Specialties, University of Modena and Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Simona Marenco
- Department of Internal Medicine, Gastroenterology Unit, Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genova 16132, Italy
| | - Laura Mameli
- Liver and Pancreas Transplant Center, Azienda Ospedaliera Brotzu Cagliari, Italy
| | - Francesca Romana Ponziani
- Hepatology Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Giovanni Vitale
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Internal Medicine Unit for the treatment of Severe Organ Failure, Bologna, Italy.
| | - Patrizia Burra
- Multivisceral Transplant Unit, Padua University Hospital, Padova, Italy
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Husnain A, Aadam A, Borhani A, Riaz A. Atlas for Cholangioscopy and Cholecystoscopy: A Primer for Diagnostic and Therapeutic Endoscopy in the Biliary Tree and Gallbladder. Semin Intervent Radiol 2024; 41:278-292. [PMID: 39165656 PMCID: PMC11333118 DOI: 10.1055/s-0044-1788340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2024]
Abstract
Percutaneous endoscopy of the biliary system (cholangioscopy) and gallbladder (cholecystoscopy) has significantly impacted diagnostic and therapeutic approaches to many diseases in interventional radiology, overcoming previous challenges related to scope size and rigidity. The current endoscopes offer enhanced maneuverability within narrow tubular structures such as bile ducts. Before endoscopy, reliance on 2D imaging modalities limited real-time visualization during percutaneous procedures. Percutaneous endoscopy provides 3D perspectives, enabling a better appreciation of normal structures, targeted biopsy of lesions, and accurate deployment of therapeutic interventions. This review aims to explore percutaneous endoscopic findings across various biliary and gallbladder pathologies.
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Affiliation(s)
- Ali Husnain
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Aziz Aadam
- Department of Medicine, Section of Gastroenterology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Amir Borhani
- Department of Radiology, Section of Abdominal Imaging, Northwestern Memorial Hospital, Chicago, Illinois
| | - Ahsun Riaz
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, Illinois
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Tan N, Ngu N, Worland T, Lee T, Abrahams T, Freeman E, Hannah N, Gazelakis K, Madden RG, Lynch KD, Valaydon Z, Sood S, Dev A, Bell S, Thompson AJ, Ding JN, Nicoll AJ, Liu K, Pandya K, Gow P, Lubel J, Kemp W, Roberts SK, Majeed A. Surveillance MRI is associated with improved survival in patients with primary sclerosing cholangitis. Hepatol Commun 2024; 8:e0442. [PMID: 38696372 PMCID: PMC11068143 DOI: 10.1097/hc9.0000000000000442] [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] [Received: 10/29/2023] [Accepted: 01/16/2024] [Indexed: 05/04/2024] Open
Abstract
BACKGROUND The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable. METHODS The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates. RESULTS A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172). CONCLUSIONS In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC.
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Affiliation(s)
- Natassia Tan
- Department of Gastroenterology and Hepatology, The Alfred, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| | - Natalie Ngu
- Central Clinical School, Monash University, Melbourne, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Australia
| | - Thomas Worland
- Department of Gastroenterology and Hepatology, Austin Health, Melbourne, Australia
| | - Tanya Lee
- Department of Gastroenterology and Hepatology, St Vincent’s Health, Melbourne, Australia
| | - Tobie Abrahams
- Department of Gastroenterology and Hepatology, St Vincent’s Health, Melbourne, Australia
| | - Elliot Freeman
- Department of Gastroenterology and Hepatology, The Alfred, Melbourne, Australia
| | - Nicholas Hannah
- Department of Gastroenterology and Hepatology, Melbourne Health, Melbourne, Australia
- University of Melbourne, Melbourne, Australia
| | - Kathryn Gazelakis
- Department of Gastroenterology and Hepatology, Western Health, Melbourne, Australia
| | - Richie G Madden
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - Kate D Lynch
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - Zina Valaydon
- Department of Gastroenterology and Hepatology, Western Health, Melbourne, Australia
| | - Siddharth Sood
- Department of Gastroenterology and Hepatology, Melbourne Health, Melbourne, Australia
- University of Melbourne, Melbourne, Australia
| | - Anouk Dev
- Central Clinical School, Monash University, Melbourne, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Australia
| | - Sally Bell
- Central Clinical School, Monash University, Melbourne, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Australia
| | - Alexander J Thompson
- Department of Gastroenterology and Hepatology, St Vincent’s Health, Melbourne, Australia
- University of Melbourne, Melbourne, Australia
| | - John Nik Ding
- Department of Gastroenterology and Hepatology, St Vincent’s Health, Melbourne, Australia
- University of Melbourne, Melbourne, Australia
| | - Amanda J Nicoll
- Central Clinical School, Monash University, Melbourne, Australia
- Department of Gastroenterology and Hepatology, Eastern Health, Melbourne, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia
| | - Keval Pandya
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia
| | - Paul Gow
- Department of Gastroenterology and Hepatology, Austin Health, Melbourne, Australia
- University of Melbourne, Melbourne, Australia
| | - John Lubel
- Department of Gastroenterology and Hepatology, The Alfred, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| | - William Kemp
- Department of Gastroenterology and Hepatology, The Alfred, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| | - Stuart K Roberts
- Department of Gastroenterology and Hepatology, The Alfred, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| | - Ammar Majeed
- Department of Gastroenterology and Hepatology, The Alfred, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
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Are VS, Gromski MA, Akisik F, Vilar-Gomez E, Lammert C, Ghabril M, Vuppalanchi R, Chalasani N. Primary Sclerosing Cholangitis Limited to Intrahepatic Bile Ducts Has Distinctly Better Prognosis. Dig Dis Sci 2024; 69:1421-1429. [PMID: 38347369 DOI: 10.1007/s10620-023-08260-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 07/25/2023] [Indexed: 04/19/2024]
Abstract
BACKGROUND There are two sub-phenotypes of large-duct primary sclerosing cholangitis (PSC): isolated intrahepatic PSC (IIPSC) and extrahepatic disease with or without intrahepatic (extra/intrahepatic). AIMS This study examined the differences in outcomes in patients with IIPSC compared to extra/intrahepatic and small-duct PSC. METHODS Patients with PSC treated at our institution from 1998 to 2019 were investigated. Biochemistries, clinical events, and survival were assessed by chart review and National Death Index. Cox-proportional hazards were used to determine the risk of clinical outcomes based on biliary tract involvement. RESULTS Our cohort comprised 442 patients with large-duct PSC (57 had IIPSC, 385 had extra/intrahepatic PSC) and 23 with small-duct PSC. Median follow-up in the IIPSC group was not significantly different from the extra/intrahepatic group [7 vs. 6 years, P = 0.06]. Except for lower age (mean 37.9 vs. 43.0 years, P = 0.045), the IIPSC group was not different from the extra/intrahepatic. The IIPSC group had longer transplant-free survival (log-rank P = 0.001) with a significantly lower risk for liver transplantation (12% vs. 34%, P < 0.001). The IIPSC group had a lower risk of death or transplantation than the extra/intrahepatic PSC group [HR: 0.34, 95% CI: 0.17-0.67, P < 0.001]. No bile duct or gallbladder cancers developed in patients with IIPSC, compared to 24 in the extra/intrahepatic group. The clinical characteristics and outcomes of IIPSC were similar to 23 individuals with small-duct PSC. CONCLUSIONS Patients with IIPSC have a favorable prognosis similar to small-duct PSC. These data are important for counseling patients and designing therapeutic trials for PSC.
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Affiliation(s)
- Vijay S Are
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Mark A Gromski
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Fatih Akisik
- Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Craig Lammert
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
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10
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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
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11
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Vanhanen E, Ovissi A, Kolho KL, Tenca A. Magnetic resonance cholangiography in the diagnosis of dominant strictures in pediatric-onset primary sclerosing cholangitis. Dig Liver Dis 2023; 55:1496-1501. [PMID: 37286450 DOI: 10.1016/j.dld.2023.05.024] [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: 02/13/2023] [Revised: 04/25/2023] [Accepted: 05/20/2023] [Indexed: 06/09/2023]
Abstract
BACKGROUND Magnetic resonance cholangiopancreaticography (MRCP) has become the primary imaging modality in primary sclerosing cholangitis (PSC). Endoscopic retrograde cholangiopancreaticography (ERCP) is recommended when a dominant stricture (DS) of bile ducts is suspected in MRCP. However, MRCP criteria for DS are lacking. AIMS To evaluate the diagnostic accuracy of MRCP in the diagnosis of DS in patients with pediatric-onset PSC. METHODS ERCP and MRCP images of patients with pediatric-onset PSC (n=36) were evaluated for the presence of DS applying the diameter-based ERCP criteria. The diagnostic accuracy of MRCP in detecting DS was calculated using ERCP as the gold standard. RESULTS The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and accuracy of MRCP for detecting DS were 62%, 89%, 5.6, 0.43, and 81%. Most common reasons for incongruent ERCP/MRCP assessment were (1) MRCP stenosis not fulfilling the diameter criteria of ERCP, resulting in false negative MRCP evaluation, and (2) lack of filling pressure in MRCP, resulting in false positive MRCP evaluation. CONCLUSION The high positive likelihood ratio of MRCP in detecting DS suggests that MRCP is a useful tool in the follow-up of PSC. However, diameter limits of DS should probably be less strict in MRCP than in ERCP.
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Affiliation(s)
- Enni Vanhanen
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Ali Ovissi
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Kaija-Leena Kolho
- Department of Paediatric Gastroenterology, Children's Hospital, University of Helsinki and University Hospital, Helsinki, Finland
| | - Andrea Tenca
- Abdominal Center, Endoscopy Unit, University of Helsinki and Helsinki University Hospital, POB 340, 00029 HUS, Helsinki, Finland.
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12
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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.
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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
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13
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Kim YS, Hurley EH, Park Y, Ko S. Treatment of primary sclerosing cholangitis combined with inflammatory bowel disease. Intest Res 2023; 21:420-432. [PMID: 37519211 PMCID: PMC10626010 DOI: 10.5217/ir.2023.00039] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 04/28/2023] [Accepted: 04/29/2023] [Indexed: 08/01/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a progressive cholestatic, inflammatory, and fibrotic disease that is strongly associated with inflammatory bowel disease (IBD). PSC-IBD represents a unique disease entity and patients with this disease have an increased risk of malignancy development, such as colorectal cancer and cholangiocarcinoma. The pathogenesis of PSC-IBD involves genetic and environmental factors such as gut dysbiosis and bile acids alteration. However, despite the advancement of disease characteristics, no effective medical therapy has proven to have a significant impact on the prognosis of PSC. The treatment options for patients with PSC-IBD do not differ from those for patients with PSC alone. Potential candidate drugs have been developed based on the pathogenesis of PSC-IBD, such as those that target modulation of bile acids, inflammation, fibrosis, and gut dysbiosis. In this review, we summarize the current medical treatments for PSC-IBD and the status of new emerging therapeutic agents.
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Affiliation(s)
- You Sun Kim
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Edward H. Hurley
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Yoojeong Park
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Sungjin Ko
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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14
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Shah YR, Nombera-Aznaran N, Guevara-Lazo D, Calderon-Martinez E, Tiwari A, Kanumilli S, Shah P, Pinnam BSM, Ali H, Dahiya DS. Liver transplant in primary sclerosing cholangitis: Current trends and future directions. World J Hepatol 2023; 15:939-953. [PMID: 37701917 PMCID: PMC10494561 DOI: 10.4254/wjh.v15.i8.939] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/23/2023] [Accepted: 08/11/2023] [Indexed: 08/22/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic and progressive immune-mediated cholangiopathy causing biliary tree inflammation and scarring, leading to liver cirrhosis and end-stage liver disease. Diagnosis of PSC is challenging due to its nonspecific symptoms and overlap with other liver diseases. Despite the rising incidence of PSC, there is no proven medical therapy that can alter the natural history of the disease. While liver transplantation (LT) is the most effective approach for managing advanced liver disease caused by PSC, post-transplantation recurrence of PSC remains a challenge. Therefore, ongoing research aims to develop better therapies for PSC, and continued efforts are necessary to improve outcomes for patients with PSC. This article provides an overview of PSC's pathogenesis, clinical presentation, and management options, including LT trends and future aspects. It also highlights the need for improved therapeutic options and ethical considerations in providing equitable access to LT for patients with PSC. Additionally, the impact of liver transplant on the quality of life and psychological outcomes of patients with PSC is discussed. Ongoing research into PSC's pathogenesis and post-transplant recurrence is crucial for improved understanding of the disease and more effective treatment options.
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Affiliation(s)
- Yash R Shah
- Department of Internal Medicine, Trinity Health Oakland, Pontiac, MI 48341, United States
| | | | - David Guevara-Lazo
- Faculty of Medicine, Universidad Peruana Cayetano Heredia, Lima 15102, Peru
| | - Ernesto Calderon-Martinez
- Department of Internal Medicine, Universidad Nacional Autonoma de Mexico, Ciudad De Mexico 04510, Mexico
| | - Angad Tiwari
- Department of Internal Medicine, Maharani Laxmi Bai Medical College, Jhansi 284001, India
| | | | - Purva Shah
- Department of Postgraduate Education, Harvard Medical School, Boston, MA 02115, United States
| | - Bhanu Siva Mohan Pinnam
- Department of Internal Medicine, John H. Stroger Hospital of Cook County, Chicago, IL 60612, United States
| | - Hassam Ali
- Department of Internal Medicine, East Carolina University/Brody School of Medicine, Greenville, NC 27858, United States
| | - Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology and Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, United States.
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15
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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: 125] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [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
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16
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Morgan MA, Khot R, Sundaram KM, Ludwig DR, Nair RT, Mittal PK, Ganeshan DM, Venkatesh SK. Primary sclerosing cholangitis: review for radiologists. Abdom Radiol (NY) 2023; 48:136-150. [PMID: 36063181 PMCID: PMC9852001 DOI: 10.1007/s00261-022-03655-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/13/2022] [Accepted: 08/15/2022] [Indexed: 01/22/2023]
Abstract
Primary sclerosing cholangitis is a rare chronic inflammatory disease affecting the bile ducts, which can eventually result in bile duct strictures, cholestasis and cirrhosis. Patients are often asymptomatic but may present with clinical features of cholestasis. Imaging plays an important role in the diagnosis and management. This review covers the pathophysiology, clinical features, imaging findings as well as methods of surveillance and post-transplant appearance.
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Affiliation(s)
- Matthew A. Morgan
- Department of Radiology, University of Pennsylvania Health System, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA, USA
| | - Rachita Khot
- Radiology and Medical Imaging, University of Virginia Health, 1215 Lee Street, Charlottesville, VA, USA
| | - Karthik M. Sundaram
- Department of Radiology, University of Pennsylvania Health System, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA, USA
| | - Daniel R. Ludwig
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, Saint Louis, MO, USA
| | - Rashmi T. Nair
- Department of Radiology, University of Kentucky, 800 Rose Street, Room HX 313B, Lexington, KY 40536-0293, USA
| | - Pardeep K. Mittal
- Medical College of Georgia at Augusta University, 1120 15th street BA −1411, Augusta, GA 30912, USA
| | - Dhakshina M. Ganeshan
- The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Unit 1473, Houston, TX 77030, USA
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17
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Park JW, Kim JH, Kim SE, Jung JH, Jang MK, Park SH, Lee MS, Kim HS, Suk KT, Kim DJ. Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: Current Knowledge of Pathogenesis and Therapeutics. Biomedicines 2022; 10:biomedicines10061288. [PMID: 35740310 PMCID: PMC9220082 DOI: 10.3390/biomedicines10061288] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/24/2022] [Accepted: 05/28/2022] [Indexed: 02/07/2023] Open
Abstract
Cholangiopathies encompass various biliary diseases affecting the biliary epithelium, resulting in cholestasis, inflammation, fibrosis, and ultimately liver cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the most important progressive cholangiopathies in adults. Much research has broadened the scope of disease biology to genetic risk, epigenetic changes, dysregulated mucosal immunity, altered biliary epithelial cell function, and dysbiosis, all of which interact and arise in the context of ill-defined environmental triggers. An in-depth understanding of the molecular pathogenesis of these cholestatic diseases will help clinicians better prevent and treat diseases. In this review, we focus on the main underlying mechanisms of disease initiation and progression, and novel targeted therapeutics beyond currently approved treatments.
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Affiliation(s)
- Ji-Won Park
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 200-010, Korea
| | - Jung-Hee Kim
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 200-010, Korea
| | - Sung-Eun Kim
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 200-010, Korea
| | - Jang Han Jung
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 200-010, Korea
| | - Myoung-Kuk Jang
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 200-010, Korea
| | - Sang-Hoon Park
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
| | - Myung-Seok Lee
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
| | - Hyoung-Su Kim
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 200-010, Korea
| | - Ki Tae Suk
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 200-010, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon-si 24252, Korea; (J.-W.P.); (J.-H.K.); (S.-E.K.); (J.H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (H.-S.K.); (K.T.S.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 200-010, Korea
- Correspondence: ; Tel.: +82-33-240-5646
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18
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Özdirik B, Maibier M, Scherf M, Nicklaus JM, Frohme J, Puengel T, Meyer zum Büschenfelde D, Tacke F, Mueller T, Sigal M. Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated with Severity of Fibrosis in Patients with Primary Sclerosing Cholangitis. J Clin Med 2022; 11:jcm11092479. [PMID: 35566603 PMCID: PMC9105770 DOI: 10.3390/jcm11092479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 04/23/2022] [Accepted: 04/26/2022] [Indexed: 12/07/2022] Open
Abstract
The soluble urokinase-type plasminogen activator receptor (suPAR) has evolved as a useful biomarker for different entities of chronic liver disease. However, its role in patients with primary sclerosing cholangitis (PSC) is obscure. We analyzed plasma levels of suPAR in 84 patients with PSC and compared them to 68 patients with inflammatory bowel disease (IBD) without PSC and to 40 healthy controls. Results are correlated with clinical records. suPAR concentrations were elevated in patients with PSC compared to patients with IBD only and to healthy controls (p < 0.001). Elevated suPAR levels were associated with the presence of liver cirrhosis (p < 0.001) and signs of portal hypertension (p < 0.001). suPAR revealed a high accuracy for the discrimination of the presence of liver cirrhosis comparable to previously validated noninvasive fibrosis markers (area under the curve (AUC) 0.802 (95%CI: 0.702−0.902)). Further, we demonstrated that suPAR levels may indicate the presence of acute cholangitis episodes (p < 0.001). Finally, despite the high proportion of PSC patients with IBD, presence of IBD and its disease activity did not influence circulating suPAR levels. suPAR represents a previously unrecognized biomarker for diagnosis and liver cirrhosis detection in patients with PSC. However, it does not appear to be confounded by intestinal inflammation in the context of IBD.
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Affiliation(s)
- Burcin Özdirik
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.M.); (M.S.); (J.M.N.); (J.F.); (T.P.); (F.T.); (T.M.); (M.S.)
- Berlin Institute of Health, 10178 Berlin, Germany
- Correspondence: ; Tel.: +49-30-450-656-004; Fax: +49-30-450-553-902
| | - Martin Maibier
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.M.); (M.S.); (J.M.N.); (J.F.); (T.P.); (F.T.); (T.M.); (M.S.)
| | - Maria Scherf
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.M.); (M.S.); (J.M.N.); (J.F.); (T.P.); (F.T.); (T.M.); (M.S.)
| | - Jule Marie Nicklaus
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.M.); (M.S.); (J.M.N.); (J.F.); (T.P.); (F.T.); (T.M.); (M.S.)
| | - Josephine Frohme
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.M.); (M.S.); (J.M.N.); (J.F.); (T.P.); (F.T.); (T.M.); (M.S.)
| | - Tobias Puengel
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.M.); (M.S.); (J.M.N.); (J.F.); (T.P.); (F.T.); (T.M.); (M.S.)
- Berlin Institute of Health, 10178 Berlin, Germany
| | - Dirk Meyer zum Büschenfelde
- Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, 13353 Berlin, Germany;
- Labor Berlin—Charité Vivantes GmbH, 13353 Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.M.); (M.S.); (J.M.N.); (J.F.); (T.P.); (F.T.); (T.M.); (M.S.)
| | - Tobias Mueller
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.M.); (M.S.); (J.M.N.); (J.F.); (T.P.); (F.T.); (T.M.); (M.S.)
| | - Michael Sigal
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.M.); (M.S.); (J.M.N.); (J.F.); (T.P.); (F.T.); (T.M.); (M.S.)
- Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, 10115 Berlin, Germany
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19
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Subhash A, Buxbaum JL, Tabibian JH. Peroral cholangioscopy: Update on the state-of-the-art. World J Gastrointest Endosc 2022; 14:63-76. [PMID: 35316979 PMCID: PMC8908329 DOI: 10.4253/wjge.v14.i2.63] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/25/2021] [Accepted: 01/17/2022] [Indexed: 02/06/2023] Open
Abstract
Peroral cholangioscopy (POC) is an endoscopic procedure that allows direct intraductal visualization of the biliary tract. POC has emerged as a vital tool for indeterminate biliary stricture evaluation and treatment of difficult biliary stones. Over several generations of devices, POC has fulfilled additional clinical needs where other diagnostic or therapeutic modalities have been inadequate. With adverse event rates comparable to standard endoscopic retrograde cholangioscopy and unique technical attributes, the role of POC is likely to continue expand. In this frontiers article, we highlight the existing and growing clinical applications of POC as well as areas of ongoing research.
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Affiliation(s)
- Amith Subhash
- Department of Gastroenterology, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV 89102, United States
| | - James L Buxbaum
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, NV 90033, United States
| | - James H Tabibian
- David Geffen School of Medicine at UCLA, Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, NV 90095, United States
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20
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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] [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.
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21
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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: 34] [Impact Index Per Article: 8.5] [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
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22
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Are VS, Vilar-Gomez E, Gromski MA, Akisik F, Lammert C, Ghabril M, Chalasani N, Vuppalanchi R, Nephew LD. Racial differences in primary sclerosing cholangitis mortality is associated with community socioeconomic status. Liver Int 2021; 41:2703-2711. [PMID: 34240538 DOI: 10.1111/liv.15008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 06/17/2021] [Accepted: 07/05/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Natural history and outcomes data in PSC are mostly derived from cohorts where Blacks have been underrepresented. It is unknown if there are differences in mortality between Blacks and Whites with PSC. METHODS PSC patients seen at our institution from June 1988 to Jan 2019 were identified by merging prospective ERCP hepatology-clinic databases and liver-transplant registry. Data on race, clinical events, and death was obtained through chart review. Data on community health were collected using indices from county health rankings. Cumulative incidence of death was calculated using liver transplant (LT) as a competing risk. RESULTS Of 449 patients, 404 were White and 45 were Black. The median-duration of follow-up was 7 years (IQR:3, 13). Black patients were younger at presentation than White patients (36.3 vs 42.5 years., P = .013). Disease severity as indicated by Mayo Risk Score categories (low 27% vs 31%, intermediate 54% vs 49% and high 19% vs 19%, P = .690), comorbidity burden and frequency of cirrhosis (42% vs 35%, P = .411) were similar between Blacks and Whites. Cumulative incidence of liver-related death, with LT as a competing risk was significantly higher in Blacks compared to Whites (sHR 1.80, 95%CI 1.25, 2.61, P = .002). There was a significant interaction between race and community socioeconomic factors that attenuated the racial difference in mortality (sHR 1.01, 95%CI 0.99, 1.04, P = .345). CONCLUSIONS Blacks with PSC present at a younger age with a similar disease severity as Whites but have higher liver related mortality that is mediated in part through community health.
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Affiliation(s)
- Vijay S Are
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mark A Gromski
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Fatih Akisik
- Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Craig Lammert
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Lauren D Nephew
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
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23
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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.
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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
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24
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Reporting standards for primary sclerosing cholangitis using MRI and MR cholangiopancreatography: guidelines from MR Working Group of the International Primary Sclerosing Cholangitis Study Group. Eur Radiol 2021; 32:923-937. [PMID: 34363134 DOI: 10.1007/s00330-021-08147-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 05/30/2021] [Accepted: 06/06/2021] [Indexed: 12/12/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic inflammatory disorder affecting the bile ducts and is characterized by biliary strictures, progressive liver parenchymal fibrosis, and an increased risk of hepatobiliary malignancies primarily cholangiocarcinoma (CCA). PSC may lead to portal hypertension, liver decompensation, and liver failure with the need for liver transplantation. Magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) are considered the imaging standard for diagnosis and follow-up in patients with PSC. Currently, there are no universally accepted reporting standards and definitions for MRI/MRCP features. Controversies exist about the definition of a high-grade stricture and there is no widely agreed approach to their management. The members of the MRI working group of the International Primary Sclerosing Cholangitis Study Group (IPSCSG) sought to define terminologies and reporting standards for describing MRI/MRCP features that would be applied to diagnosis and surveillance of disease progression, and potentially for evaluating treatment response in clinical trials. In this extensive review, the technique of MRI/MRCP and assessment of image quality for the evaluation of PSC is briefly described. The definitions and terminologies for severity and length of strictures, duct wall thickening and hyperenhancement, and liver parenchyma signal intensity changes are outlined. As CCA is an important complication of PSC, standardized reporting criteria for CCA developing in PSC are summarized. Finally, the guidelines for reporting important changes in follow-up MRI/MRCP studies are provided. KEY POINTS: • Primary sclerosing cholangitis is a chronic inflammatory disorder affecting the bile ducts, causing biliary strictures and liver fibrosis and an increased risk of cholangiocarcinoma. • This consensus document provides definitions and suggested reporting standards for MRI and MRCP features of primary sclerosing cholangitis, which will allow for a standardized approach to diagnosis, assessment of disease severity, follow-up, and detection of complications. • Standardized definitions and reporting of MRI/MRCP features of PSC will facilitate comparison between studies, promote longitudinal assessment during management, reduce inter-reader variability, and enhance the quality of care and communication between health care providers.
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25
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Wiecek S, Wojtyniak A, Pindur B, Machnikowska-Sokołowska M, Gruszczyńska K, Grzybowska-Chlebowczyk U. Analysis of the Clinical Course of Primary Sclerosing Cholangitis in Paediatric Population-Single Center Study. ACTA ACUST UNITED AC 2021; 57:medicina57070663. [PMID: 34199130 PMCID: PMC8304821 DOI: 10.3390/medicina57070663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 06/15/2021] [Accepted: 06/24/2021] [Indexed: 11/25/2022]
Abstract
Background and Objectives: Primary sclerosing cholangitis (PSC) is a rare cholestatic disease of the liver of unknown etiology, severe course and poor prognosis. PSC most often co-occurs with inflammatory bowel diseases (IBD), especially with ulcerative colitis (UC). The aim of the study was the analysis of the clinical course of primary sclerosing cholangitis in children, hospitalized in the Gastroenterology Unit in Katowice. Materials and Methods: The analysis included 30 patients, aged from 7 to 18 years, 21/30 boys (70%) and 9/30 girls (30%), diagnosed with PSC in the years 2009–2019. The analysis included the age at diagnosis, clinical symptoms, course of the disease, coexisting diseases, laboratory and imaging results, and complications. Results: The average age at diagnosis was 13 years. 22/30 (73.3%) patients suffered from UC, 4/30 (13.3%) were diagnosed with Crohn’s disease (CD), 2/30 (6.66%) with Eosinophilic Colitis (EC). 2/30 patients (6.66%) had no clinical evidence of coexistent IBD to date. In addition, 7/30 (23.3%) had an overlap syndrome of primary sclerosing cholangitis/autoimmune hepatitis. When PSC was detected before IBD (6/30–20%), patients had complications more often compared to those diagnosed with IBD first or PSC and IBD at the same time. At the moment of diagnosis 6/30 (20%) patients presented with abdominal pain, which was the most common symptom, 3/30 (10%) jaundice, while 17/30 (56.6%) were asymptomatic but had abnormal results of the laboratory tests. Conclusions: Monitoring liver markers in IBD patients is important since most PSC cases are asymptomatic and their elevation might be the first sign of the disease. Patients diagnosed with PSC before IBD diagnosis are more likely to have a more aggressive course of the disease.
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Affiliation(s)
- Sabina Wiecek
- Department of Paediatrics, Faculty of Medical Sciences, Medical University of Silesia, 16 Medykow Street, 40-752 Katowice, Poland
| | - Alicja Wojtyniak
- Student Scientific Club, Department of Paediatrics, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland
| | - Barbara Pindur
- Student Scientific Club, Department of Paediatrics, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland
| | | | - Katarzyna Gruszczyńska
- Department of Radiology and Nuclear Medicine, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland
| | - Urszula Grzybowska-Chlebowczyk
- Department of Paediatrics, Faculty of Medical Sciences, Medical University of Silesia, 16 Medykow Street, 40-752 Katowice, Poland
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26
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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.
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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
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27
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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: 25] [Impact Index Per Article: 6.3] [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.
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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
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28
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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: 8] [Impact Index Per Article: 2.0] [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.
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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
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29
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McCain JD, Chascsa DM, Lindor KD. Assessing and managing symptom burden and quality of life in primary sclerosing cholangitis patients. Expert Opin Orphan Drugs 2021. [DOI: 10.1080/21678707.2021.1898370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Josiah D. McCain
- Department of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA
| | - David M. Chascsa
- Department of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA
- Department of Transplant Center, Mayo Clinic, Phoenix, Arizona, USA
| | - Keith D. Lindor
- Office of University Provost, Arizona State University, Arizona, USA
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30
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Dumonceau JM, Delhaye M, Charette N, Farina A. Challenging biliary strictures: pathophysiological features, differential diagnosis, diagnostic algorithms, and new clinically relevant biomarkers - part 1. Therap Adv Gastroenterol 2020; 13:1756284820927292. [PMID: 32595761 PMCID: PMC7298429 DOI: 10.1177/1756284820927292] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 04/16/2020] [Indexed: 02/04/2023] Open
Abstract
It is frequently challenging to make the correct diagnosis in patients with biliary strictures. This is particularly important as errors may have disastrous consequences. Benign-appearing strictures treated with stents may later be revealed to be malignant and unnecessary surgery for benign strictures carries a high morbidity rate. In the first part of the review, the essential information that clinicians need to know about diseases responsible for biliary strictures is presented, with a focus on the most recent data. Then, the characteristics and pitfalls of the methods used to make the diagnosis are summarized. These include serum biomarkers, imaging studies, and endoscopic modalities. As tissue diagnosis is the only 100% specific tool, it is described in detail, including techniques for tissue acquisition and their yields, how to prepare samples, and what to expect from the pathologist. Tricks to increase diagnostic yields are described. Clues are then presented for the differential diagnosis between primary and secondary sclerosing cholangitis, IgG4-related sclerosing cholangitis, cholangiocarcinoma, pancreatic cancer, autoimmune pancreatitis, and less frequent diseases. Finally, algorithms that will help to achieve the correct diagnosis are proposed.
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Affiliation(s)
- Jean-Marc Dumonceau
- Department of Gastroenterology, Charleroi
University Hospitals, Chaussée de Bruxelles 140, Charleroi, 6042,
Belgium
| | - Myriam Delhaye
- Department of Gastroenterology,
Hepatopancreatology and GI Oncology, Erasme University Hospital, Brussels,
Belgium
| | - Nicolas Charette
- Department of Gastroenterology, Charleroi
University Hospitals, Charleroi, Belgium
| | - Annarita Farina
- Department of Medicine, Geneva University,
Geneva, Switzerland
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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.
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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
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Zhang CC, Voitl R, Hippchen T, Weiss KH, Sauer P, Rupp C. Evaluation of two functional CD24 polymorphisms in primary sclerosing cholangitis. Scand J Gastroenterol 2020; 55:581-587. [PMID: 32329406 DOI: 10.1080/00365521.2020.1755357] [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] [Indexed: 02/04/2023]
Abstract
Background: Primary sclerosing cholangitis (PSC) is a progressive liver disease and characterized by chronic inflammation, sclerosis and strictures of bile ducts. Several genetic risk factors might contribute to pathogenesis. Functional single nucleotide polymorphisms (SNPs) in the CD24 gene have been associated with the development of autoimmune and autoinflammatory diseases and might contribute to the susceptibility for inflammatory bowel disease (IBD).Aim: This retrospective study aimed to evaluate the impact of two functional CD24 SNPs on clinical features and disease progression in patients with PSC.Methods: A C to T coding polymorphism (rs8734) and a TG deletion in the 3´- untranslated region (rs3838646) were genotyped. The study cohort comprises of 359 PSC patients for rs3838646 genotype and 335 PSC patients for rs8734 genotype. Clinical and laboratory parameters were collected by chart review.Results: For the rs8734 genotype, 175 patients (52.2%) were found to be homozygous wildtype ('Ala/Ala'), 127 (37.9%) patients were heterozygous ('Ala/Val') and 33 patients (9.9%) were homozygous mutant ('Val/Val'). The rs8734genotype was associated with a decreased risk for dominant strictures at first diagnosis of PSC (p = .04). For the rs3838646 genotype, 322 patients (89.7%) were found to be homozygous wildtype ('TG/TG'); 37 showed the 'TG/del' genotype (10.3%). The 'TG/del'genotype was associated with alower risk of IBD (p = .01).There was no influence of both CD24 SNPs with clinical end points or transplantation-free survival in our PSC cohort.Conclusion: Our results suggest a mild association of the rs8734 CD24 genotype with dominant strictures at first diagnosis of PSC. The rs3838646 CD24 genotype is associated with a lower rate of IBD. Both SNPs seem to modulate the clinical phenotype without major pathogenetic importance for disease progression in PSC.
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Affiliation(s)
| | - Robert Voitl
- Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany
| | - Theresa Hippchen
- Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany
| | - Karl-Heinz Weiss
- Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany
| | - Peter Sauer
- Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christian Rupp
- Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany
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Grigoriadis A, Morsbach F, Voulgarakis N, Said K, Bergquist A, Kartalis N. Inter-reader agreement of interpretation of radiological course of bile duct changes between serial follow-up magnetic resonance imaging/3D magnetic resonance cholangiopancreatography of patients with primary sclerosing cholangitis. Scand J Gastroenterol 2020; 55:228-235. [PMID: 32024405 DOI: 10.1080/00365521.2020.1720281] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objectives: Interpretation of MRI/MRCP in primary sclerosing cholangitis (PSC) at a single time point has low inter-reader agreement. Agreement of interpretation of the dynamic course of duct changes in follow-up MRI/MRCP is of clinical importance but remains unknown. Our aims are therefore to assess the inter-reader agreement of interpretation of the course of duct changes in PSC and investigate if elimination of 3 D MRCP affects inter-reader agreement.Materials and Methods: We studied 40 consecutive PSC-patients who underwent two liver MRI/MRCPs at two time points. Two readers independently evaluated the course of duct changes between the two time points in two imaging sets, one with and one without 3 D MRCP. The intraclass correlation coefficient (ICC) was calculated for evaluation of inter-reader and intra-reader agreement between the two time points and two imaging sets accordingly.Results: Inter-reader agreement of the interpretation of the course of duct changes between the two time points was poor (ICC up to 0.224). Elimination of 3 D MRCP neither improved inter-reader agreement which was again poor (ICC up to 0.26) nor did it change considerably the way readers interpret the course of ducts changes (ICC for intra-reader agreement between 0.809 and 0.978).Conclusions: Inter-reader agreement of the interpretation of radiological course of duct changes is poor in serial follow-up MRI/MRCP of PSC-patients. Elimination of 3 D MRCP does not increase inter-reader agreement but maintains an excellent intra-reader agreement for the interpretation of the dynamic course of bile duct changes.Key pointsInter-reader agreement of interpretation of radiological course of bile duct changes between serial follow-up MRI/MRCP examinations of patients with PSC is poor.Absence of 3D MRCP does not affect considerably the way readers interpret the radiological course of bile ducts changes.When MRCP is absent or of low quality, utilization of other sequences seems to be helpful as an alternative for bile duct evaluation.
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Affiliation(s)
- Aristeidis Grigoriadis
- Division of Radiology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm, Sweden.,Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden
| | - Fabian Morsbach
- Division of Radiology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm, Sweden.,Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
| | - Nikolaos Voulgarakis
- Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden
| | - Karouk Said
- Division of Hepatology, Department of Upper GI Disease, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Stockholm, Sweden
| | - Annika Bergquist
- Division of Hepatology, Department of Upper GI Disease, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Stockholm, Sweden
| | - Nikolaos Kartalis
- Division of Radiology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm, Sweden.,Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden
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Song C, Lewis S, Kamath A, Hectors S, Putra J, Kihira S, Bane O, Ahmad J, Babb J, Thung S, Taouli B. Primary sclerosing cholangitis: diagnostic performance of MRI compared to blood tests and clinical scoring systems for the evaluation of histopathological severity of disease. Abdom Radiol (NY) 2020; 45:354-364. [PMID: 31844914 DOI: 10.1007/s00261-019-02366-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE To assess the diagnostic performance of magnetic resonance imaging (MRI) compared to blood tests and clinical scoring systems for the evaluation of histopathologic severity in patients with primary sclerosing cholangitis (PSC). MATERIALS Fifty-one patients (M/F 37/14, mean age 41 years) with PSC who underwent MRI and liver histopathology were included in this IRB-approved retrospective study. Two radiologists independently graded the severity of biliary abnormalities on magnetic resonance cholangiopancreatography (MRCP) using a standardized scoring system, parenchymal enhancement, and diffusion-weighted imaging (DWI) signal. Liver function tests, Mayo Risk score, APRI, FIB-4 Index, MELD, and Child-Pugh scores were recorded. Histopathology was assessed using a modified Nakanuma's scoring system. Correlation and diagnostic performance of MRI scores and blood tests for assessment of PSC histopathologic disease severity were evaluated. RESULTS Findings of cirrhosis and portal hypertension were the only imaging features diagnostic of advanced PSC (stages 3 and 4) with AUC up to 0.90 (p < 0.001) for both observers. Parenchymal enhancement and overall qualitative biliary ductal abnormality identified advanced PSC stage with AUC up to 0.767 (p = 0.002) only for one observer. There was weak correlation between the overall qualitative biliary ductal abnormality on MRCP and histopathologic stage (r = 0.36, p = 0.01) for one observer. FIB-4 index, Child-Pugh, MELD, Mayo Risk, APRI, and alkaline phosphatase demonstrated good to excellent performance for advanced PSC stage (AUCs 0.672-0.915, p < 0.045). CONCLUSIONS MRI findings of cirrhosis/portal hypertension, blood tests, and clinical scoring systems had high performance for advanced histopathologic PSC stage diagnosis, while the severity of biliary abnormalities on MRI did not.
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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: 35] [Impact Index Per Article: 5.8] [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.
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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
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AGA Clinical Practice Update on Surveillance for Hepatobiliary Cancers in Patients With Primary Sclerosing Cholangitis: Expert Review. Clin Gastroenterol Hepatol 2019; 17:2416-2422. [PMID: 31306801 DOI: 10.1016/j.cgh.2019.07.011] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 06/19/2019] [Accepted: 07/08/2019] [Indexed: 02/07/2023]
Abstract
DESCRIPTION The purpose of this clinical practice update is to define key principles in the surveillance of hepatobiliary cancers including cholangiocarcinoma, gallbladder adenocarcinoma, and hepatocellular carcinoma in patients with primary sclerosing cholangitis (PSC). METHODS The recommendations outlined in this expert review are based on available published evidence including observational studies and systematic reviews, and incorporates expert opinion where applicable. BEST PRACTICE ADVICE 1: Surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with PSC regardless of disease stage, especially in the first year after diagnosis and in patients with ulcerative colitis and those diagnosed at an older age. BEST PRACTICE ADVICE 2: Surveillance for cholangiocarcinoma and gallbladder cancer should include imaging by ultrasound, computed tomography, or magnetic resonance imaging, with or without serum carbohydrate antigen 19-9, every 6 to 12 months BEST PRACTICE ADVICE 3: Endoscopic retrograde cholangiopancreatography with brush cytology should not be used routinely for surveillance of cholangiocarcinomas in PSC. BEST PRACTICE ADVICE 4: Cholangiocarcinomas should be investigated by endoscopic retrograde cholangiopancreatography with brush cytology with or without fluorescence in situ hybridization analysis and/or cholangioscopy in PSC patients with worsening clinical symptoms, worsening cholestasis, or a dominant stricture. BEST PRACTICE ADVICE 5: Fine-needle aspiration of perihilar biliary strictures should be used with caution in PSC patients considered to be liver transplant candidates because of concerns for tumor seeding if the lesion is a cholangiocarcinoma. BEST PRACTICE ADVICE 6: Surveillance for cholangiocarcinoma should not be performed in PSC patients with small-duct PSCs or those younger than age 20. BEST PRACTICE ADVICE 7: The decision to perform a cholecystectomy in PSC patients with a gallbladder polyp should be based on the size and growth of the polyp, as well as the clinical status of the patient, with the knowledge of the increased risk of gallbladder cancer in polyps greater than 8 mm. BEST PRACTICE ADVICE 8: Surveillance for hepatocellular carcinoma in PSC patients with cirrhosis should include ultrasound, computed tomography, or magnetic resonance imaging, with or without α-fetoprotein every 6 months.
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Schiavon LDL, Ejima FH, Menezes MRD, Bittencourt PL, Moreira AM, Farias AQ, Chagas AL, Assis AMD, Mattos ÂZD, Salomão BC, Terra C, Martins FPB, Carnevale FC, Rezende GFDM, Paulo GAD, Pereira GHS, Leal Filho JMDM, Meneses JD, Costa LSND, Carneiro MDV, Álvares-DA-Silva MR, Soares MVA, Pereira OI, Ximenes RO, Durante RFS, Ferreira VA, Lima VMD. RECOMMENDATIONS FOR INVASIVE PROCEDURES IN PATIENTS WITH DISEASES OF THE LIVER AND BILIARY TRACT: REPORT OF A JOINT MEETING OF THE BRAZILIAN SOCIETY OF HEPATOLOGY (SBH), BRAZILIAN SOCIETY OF DIGESTIVE ENDOSCOPY (SOBED) AND BRAZILIAN SOCIETY OF INTERVENTIONAL RADIOLOGY AND ENDOVASCULAR SURGERY (SOBRICE). ARQUIVOS DE GASTROENTEROLOGIA 2019; 56:213-231. [PMID: 31460590 DOI: 10.1590/s0004-2803.201900000-42] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 04/12/2019] [Indexed: 12/12/2022]
Abstract
Liver and biliary tract diseases are common causes of morbidity and mortality worldwide. Invasive procedures are usually performed in those patients with hepatobiliary diseases for both diagnostic and therapeutic purposes. Defining proper indications and restraints of commonly used techniques is crucial for proper patient selection, maximizing positive results and limiting complications. In 2018, the Brazilian Society of Hepato-logy (SBH) in cooperation with the Brazilian Society of Interventional Radiology and Endovascular surgery (SOBRICE) and the Brazilian Society of Digestive Endoscopy (SOBED) sponsored a joint single-topic meeting on invasive procedures in patients with hepatobiliary diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to guide clinicians, gastroenterologists, hepatologists, radiologists, and endoscopists for the proper use of invasive procedures for management of patients with hepatobiliary diseases.
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Affiliation(s)
- Leonardo de Lucca Schiavon
- Universidade Federal de Santa Catarina, Faculdade de Medicina, Departamento de Clínica Médica, Florianópolis, SC, Brasil
| | | | - Marcos Roberto de Menezes
- Instituto do Câncer do Estado de São Paulo, Setor de Diagnóstico por Imagem, São Paulo, SP, Brasil.,Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | | | | | - Aírton Mota Moreira
- Universidade de São Paulo, Faculdade de Medicina, Serviço de Radiologia Intervencionista do Instituto de Radiologia, São Paulo, SP, Brasil
| | - Alberto Queiroz Farias
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | - Aline Lopes Chagas
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | - André Moreira de Assis
- Universidade de São Paulo, Faculdade de Medicina, Serviço de Radiologia Intervencionista do Instituto de Radiologia, São Paulo, SP, Brasil.,Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Ângelo Zambam de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, RS, Brasil
| | | | - Carlos Terra
- Universidade do Estado do Rio de Janeiro, Faculdade de Medicina, Departamento de Gastroenterologia, RJ, Brasil.,Hospital Federal de Lagoa, Departamento de Gastroenterologia, Rio de Janeiro, RJ, Brasil
| | | | - Francisco Cesar Carnevale
- Instituto de Radiologia da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | | | | | | | - Joaquim Maurício da Motta Leal Filho
- Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | - Juliana de Meneses
- Instituto Hospital de Base do Distrito Federal, Brasília, DF, Brasil.,Instituto Nacional do Câncer, Brasília, DF, Brasil
| | - Lucas Santana Nova da Costa
- Instituto Hospital de Base do Distrito Federal, Brasília, DF, Brasil.,Hospital Sírio-Libanês Unidade Brasília, Brasília, DF, Brasil
| | - Marcos de Vasconcelos Carneiro
- Hospital das Forças Armadas, Brasília, DF, Brasil.,Universidade Católica de Brasília, Curso de Medicina, Brasília, DF, Brasil
| | - Mário Reis Álvares-DA-Silva
- Universidade Federal do Rio Grande do Sul, Faculdade de Medicina, Departamento de Medicina Interna, Rio Grande do Sul, RS, Brasil
| | - Mayra Veloso Ayrimoraes Soares
- Hospital Sírio-Libanês Unidade Brasília, Brasília, DF, Brasil.,Universidade de Brasília, Serviço de Radiologia, Brasília, DF, Brasil
| | - Osvaldo Ignácio Pereira
- Instituto de Radiologia da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | - Rafael Oliveira Ximenes
- Hospital das Clínicas da Universidade Federal de Goiás, Serviço de Gastroenterologia e Hepatologia, Goiás, GO, Brasil
| | | | - Valério Alves Ferreira
- Instituto Hospital de Base do Distrito Federal, Brasília, DF, Brasil.,Hospital Santa Marta, Brasília, DF, Brasil
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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.
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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.
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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: 172] [Impact Index Per Article: 28.7] [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.
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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
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40
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Fung BM, Tabibian JH. Biliary endoscopy in the management of primary sclerosing cholangitis and its complications. LIVER RESEARCH 2019; 3:106-117. [PMID: 31341699 PMCID: PMC6656407 DOI: 10.1016/j.livres.2019.03.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, idiopathic, cholestatic liver disease characterized by inflammation and fibrosis of the intrahepatic and/or extrahepatic bile ducts. It can affect individuals of all age groups and gender, has no established pharmacotherapy, and is associated with a variety of neoplastic (e.g. cholangiocarcinoma) and non-neoplastic (e.g. dominant strictures) hepatobiliary complications. Given these considerations, endoscopy plays a major role in the care of patients with PSC. In this review, we discuss and provide updates regarding endoscopic considerations in the management of hepatobiliary manifestations and complications of PSC. Where evidence is limited, we suggest pragmatic approaches based on currently available data and expert opinion.
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Affiliation(s)
- Brian M. Fung
- University of California Los Angeles-Olive View Internal Medicine Residency Program, Sylmar, CA, USA
| | - James H. Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-University of California Los Angeles Medical Center, Sylmar, CA, USA
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41
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Malik A, Kardashian AA, Zakharia K, Bowlus CL, Tabibian JH. Preventative care in cholestatic liver disease: Pearls for the specialist and subspecialist. LIVER RESEARCH 2019; 3:118-127. [PMID: 32042471 PMCID: PMC7008979 DOI: 10.1016/j.livres.2019.04.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cholestatic liver diseases (CLDs) encompass a variety of disorders of abnormal bile formation and/or flow. CLDs often lead to progressive hepatic insult and injury and following the development of cirrhosis and associated complications. Many such complications are clinically silent until they manifest with severe sequelae, including but not limited to life-altering symptoms, metabolic disturbances, cirrhosis, and hepatobiliary diseases as well as other malignancies. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common CLDs, and both relate to mutual as well as unique complications. This review provides an overview of PSC and PBC, with a focus on preventive measures aimed to reduce the incidence and severity of disease-related complications.
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Affiliation(s)
- Adnan Malik
- Department of Public Health and Business Administration, The University of Alabama at Birmingham, Birmingham, AL, USA
- Department of Internal Medicine, Beaumont Hospital, Dearborn, MI, USA
| | - Ani A. Kardashian
- University of California Los Angeles Gastroenterology Fellowship Training Program, Vatche and Tamar Manoukian Division of Digestive Diseases, Los Angeles, CA, USA
| | - Kais Zakharia
- Division of Gastroenterology and Hepatology, University of Iowa, Iowa, IA, USA
| | - Christopher L. Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
| | - James H. Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-University of California Los Angeles Medical Center, Sylmar, CA, USA
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42
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Primary Sclerosing Cholangitis: A Concise Review of Diagnosis and Management. Dig Dis Sci 2019; 64:632-642. [PMID: 30725292 DOI: 10.1007/s10620-019-05484-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/19/2019] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterized by progressive idiopathic stricturing of the biliary system, typically leading to cirrhosis, end-stage liver disease, and colonic or hepatobiliary malignancy. Its presentation is often that of asymptomatic alkaline phosphatase elevation. When symptoms are present, they typically include fatigue, pruritus, or jaundice. The diagnosis can be confirmed via cholangiography, either magnetic resonance cholangiography (MRCP) or endoscopic retrograde cholangiography if the former is inconclusive. The clinical course is marked by progressive liver disease leading to cirrhosis with its attendant complications of portal hypertension, often including recurrent episodes of cholangitis. Greater elevation in alkaline phosphatase or liver stiffness is associated with worse clinical outcomes. Management includes endoscopic treatment of symptomatic biliary strictures and evaluation of dominant strictures as no adequate medical treatment is available. Multiple medical therapies are under evaluation. Ultimately, liver transplantation may be necessary for management of decompensated cirrhosis or disabling symptoms. There is also a markedly increased risk of cancer, notably including cholangiocarcinoma and gallbladder and colorectal cancers (particularly in patients with colitis). Cancer screening can be done with semi-annual liver imaging (MRCP or ultrasound) and colonoscopy every 1-2 years in those with colitis.
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43
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Marya NB, Tabibian JH. Role of endoscopy in the management of primary sclerosing cholangitis. World J Gastrointest Endosc 2019; 11:84-94. [PMID: 30788027 PMCID: PMC6379747 DOI: 10.4253/wjge.v11.i2.84] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/29/2019] [Accepted: 01/30/2019] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare but prominent fibroinflammatory cholangiopathy which can affect individuals of essentially any age. It carries a median survival of 15-20 years, regardless of age at diagnosis, and is a foremost risk factor for cholangiocarcinoma. Given the chronic and progressive nature of PSC, its inherent risk for biliary tract and other complications, and the paucity of effective pharmacotherapies, endoscopy plays a major role in the care of many patients with this disorder. In this review, we discuss the endoscopic management of PSC, including established and evolving approaches to the diagnosis and treatment of its benign as well as malignant sequelae. Owing to the rarity of PSC and dearth of high-quality evidence, we propose pragmatic approaches based on both currently available data and expert opinion.
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Affiliation(s)
- Neil Bharat Marya
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Gastroenterology Fellowship Training Program, Los Angeles, CA 90095, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
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Ponsioen CY, Lindor KD, Mehta R, Dimick-Santos L. Design and Endpoints for Clinical Trials in Primary Sclerosing Cholangitis. Hepatology 2018; 68:1174-1188. [PMID: 29574971 DOI: 10.1002/hep.29882] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 02/11/2018] [Accepted: 03/13/2018] [Indexed: 12/15/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a rare and chronic liver disease for which there is no effective therapy. Interest has grown in developing treatments for this condition, with several agents proposed as potential therapies. However, there is a lack of clarity about how to measure clinical benefit in trials involving patients with this complex and rare disease. This article reviews regulatory information, the available literature on natural history, as well as potential candidate clinical and surrogate endpoints for PSC. (Hepatology 2018; 00:000-000).
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Affiliation(s)
- Cyriel Y Ponsioen
- Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Keith D Lindor
- College of Health Solutions, Arizona State University, Phoenix, AZ
| | - Ruby Mehta
- Division of Gastroenterology and Inborn Errors Products, United States Food and Drug Administration, Silver Spring, MD
| | - Lara Dimick-Santos
- Division of Gastroenterology and Inborn Errors Products, United States Food and Drug Administration, Silver Spring, MD
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45
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Peiseler M, Reiners D, Pinnschmidt HO, Sebode M, Jung F, Hartl J, Zenouzi R, Ehlken H, Groth S, Schachschal G, Rösch T, Weiler-Normann C, Lohse AW, Schramm C. Risk of endoscopic biliary interventions in primary sclerosing cholangitis is similar between patients with and without cirrhosis. PLoS One 2018; 13:e0202686. [PMID: 30125307 PMCID: PMC6101401 DOI: 10.1371/journal.pone.0202686] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 08/06/2018] [Indexed: 12/12/2022] Open
Abstract
Background Endoscopic retrograde cholangiography (ERC) is a mainstay of therapy in patients with primary sclerosing cholangitis (PSC) and obstructive cholestasis. Patients with liver cirrhosis have an increased risk of surgical complications and are more susceptible to infections. Since PSC often progresses to cirrhosis, we aimed to assess whether ERC is associated with increased risk of complications in patients with PSC and cirrhosis. Methods Out of 383 patients with PSC, 208 patients received endoscopic treatment between 2009–2017. Seventy patients had cirrhosis when ERC was performed and 138 patients had no signs of cirrhosis. Overall, 663 ERC procedures were analysed, with 250 ERC in patients with cirrhosis and 413 ERC in patients without cirrhosis. Data were analysed retrospectively from a prospectively acquired database using repeated measures logistic regression. Results Overall, 40 procedure-related complications were documented in 663 ERC interventions (6%). The rate of complications was similar between patients with and without cirrhosis (4.4% vs. 7.0%). First-time ERC was associated with a higher risk of complications (17.5% vs. 4.9%). Biliary sphincterotomy, stent placement and female sex, but not presence of liver cirrhosis, were identified as risk factors for overall complications in multivariate analysis. Patients without cirrhosis showed a significant decline of ALP and bilirubin levels after the first two interventions. In contrast, in patients with cirrhosis, ALP and bilirubin levels did not significantly decline after ERC. Conclusions In patients with PSC, cirrhosis was not a risk factor for post-ERC complications. Therefore, cirrhosis should not preclude endoscopic intervention in patients with clear clinical indication.
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Affiliation(s)
- Moritz Peiseler
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
- * E-mail: (MP); (CS)
| | - David Reiners
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Hans O. Pinnschmidt
- Department of Medical Biometry and Epidemiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Marcial Sebode
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Franziska Jung
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Johannes Hartl
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Roman Zenouzi
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Hanno Ehlken
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
- Department of Interdisciplinary Endoscopy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Groth
- Department of Interdisciplinary Endoscopy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Schachschal
- Department of Interdisciplinary Endoscopy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Thomas Rösch
- Department of Interdisciplinary Endoscopy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Christina Weiler-Normann
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
- Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Ansgar W. Lohse
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Schramm
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
- Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
- * E-mail: (MP); (CS)
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Abstract
Primary sclerosing cholangitis (PSC) is a rare but clinically important cholestatic liver disease. Histopathologically and cholangiographically, PSC is characterized by intra- and/or extra-hepatic bile duct inflammation and fibro-obliteration, which ultimately leads to biliary cirrhosis and related sequelae, including development of hepatobiliary and colorectal carcinomata. PSC can be diagnosed at essentially any age and carries a median survival of 15-20 years, regardless of age at diagnosis, and is a foremost risk factor for cholangiocarcinoma. Given the chronic and progressive nature of PSC, its inherent association with both neoplastic and non-neoplastic biliary tract complications, and the lack of effective pharmacotherapies, alimentary and biliary tract endoscopy plays a major role in the care of patients with PSC. Areas covered: Here, we provide a narrative review on endoscopic management of PSC, including established and evolving applications to the diagnosis and treatment of both its benign and malignant complications. Expert commentary: Due to the rarity of PSC and the considerable patient-years required to rigorously study major endpoints, there remains a paucity of high-quality evidence regarding its management. As the advanced endoscopic repertoire expands, so has the interest in developing best practices in PSC, which we discuss herein.
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Affiliation(s)
- James H Tabibian
- a Division of Gastroenterology, Department of Medicine , Olive View-UCLA Medical Center , Sylmar , CA , USA
| | - Todd H Baron
- b Division of Gastroenterology and Hepatology , University of North Carolina at Chapel Hill , Chapel Hill , NC , USA
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47
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Zenouzi R, Liwinski T, Yamamura J, Weiler-Normann C, Sebode M, Keller S, Lohse AW, Schramm C. Follow-up magnetic resonance imaging/3D-magnetic resonance cholangiopancreatography in patients with primary sclerosing cholangitis: challenging for experts to interpret. Aliment Pharmacol Ther 2018; 48:169-178. [PMID: 29741240 DOI: 10.1111/apt.14797] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 02/19/2018] [Accepted: 04/18/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND In patients with primary sclerosing cholangitis follow-up magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is performed by many centres, particularly for the early detection of biliary malignancies and strictures. Clinically meaningful MRI-based definitions of primary sclerosing cholangitis related complications are, however, lacking. AIM To investigate how primary sclerosing cholangitis experts interpret follow-up MRI/MRCP with a focus on conclusions that may impact clinical decision-making in primary sclerosing cholangitis. METHODS Within the International Primary Sclerosing Cholangitis Study Group, an online survey on 16 real-life primary sclerosing cholangitis cases including clinical and biochemical information as well as a T2-weighted liver MRI/3D-MRCP was conducted. The interpretation of images and subsequent recommendations were assessed using a multiple-choice questionnaire. An inter-rater reliability calculation (Fleiss' kappa) was performed and factors potentially affecting the interpretation of magnetic resonance images were analysed using generalised linear mixed-effect models. RESULTS Forty-four members/associates of the International Primary Sclerosing Cholangitis Study Group (median experience in the care of primary sclerosing cholangitis patients: 14 years) completed the survey. The MRI interpretation significantly varied among the participants. The lowest agreement was found with respect to the indication to perform subsequent endoscopic retrograde cholangiopancreatography (ERCP; Κ = 0.12, 95%CI 0.11-0.14). Elevated total bilirubin was the variable with the strongest effect on the rate of suspected dominant strictures, cholangiocarcinoma or ERCP recommendations. Liver cirrhosis did not prevent participants from recommending ERCP. Overall, the survey participants' recommendations contrasted the real-life management and outcome. CONCLUSIONS In primary sclerosing cholangitis, the interpretation of follow-up MRI/3D-MRCP significantly varies even among experts and seems to be primarily affected by bilirubin levels. Generally accepted MRI-based definitions of primary sclerosing cholangitis-related complications are urgently needed.
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Affiliation(s)
- R Zenouzi
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - T Liwinski
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - J Yamamura
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - C Weiler-Normann
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - M Sebode
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - S Keller
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - A W Lohse
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - C Schramm
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
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48
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Kalani A, Tabibian JH, Lindor KD. Emerging therapeutic targets for primary sclerosing cholangitis. Expert Opin Orphan Drugs 2018. [DOI: 10.1080/21678707.2018.1490643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Amir Kalani
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Gastroenterology Fellowship Training Program, Los Angeles, CA, USA
| | - James H. Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Keith D. Lindor
- Professor of Medicine and Senior Advisor to the Provost, College of Health Solutions, Arizona State University, USA
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49
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Dyson JK, Beuers U, Jones DEJ, Lohse AW, Hudson M. Primary sclerosing cholangitis. Lancet 2018; 391:2547-2559. [PMID: 29452711 DOI: 10.1016/s0140-6736(18)30300-3] [Citation(s) in RCA: 268] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Revised: 11/24/2017] [Accepted: 01/03/2018] [Indexed: 12/13/2022]
Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterised by intrahepatic or extrahepatic stricturing, or both, with bile duct fibrosis. Inflammation and fibrosis of bile ducts and the liver are followed by impaired bile formation or flow and progressive liver dysfunction. Patients might be asymptomatic at presentation or might have pruritus, fatigue, right upper quadrant pain, recurrent cholangitis, or sequelae of portal hypertension. The key diagnostic elements are cholestatic liver biochemistry and bile duct stricturing on cholangiography. Genetic and environmental factors are important in the cause of the disease, with the intestinal microbiome increasingly thought to play a pathogenetic role. Approximately 70% of patients have concurrent inflammatory bowel disease and patients require colonoscopic screening and surveillance. Primary sclerosing cholangitis is associated with increased malignancy risk and surveillance strategies for early cholangiocarcinoma detection are limited. No single drug has been proven to improve transplant-free survival. Liver transplantation is effective for advanced disease but at least 25% of patients develop recurrent disease in the graft.
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Affiliation(s)
- Jessica K Dyson
- Department of Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - David E J Jones
- Department of Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - Ansgar W Lohse
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Mark Hudson
- Department of Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle, UK
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50
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Sedki M, Levy C. Update in the Care and Management of Patients with Primary Sclerosing Cholangitis. Curr Gastroenterol Rep 2018; 20:29. [PMID: 29886518 DOI: 10.1007/s11894-018-0635-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
PURPOSE OF REVIEW Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease for which specific medical therapy is not available. The goals of treatment are primarily early detection and management of complications. In this review, we discuss novel therapies under evaluation and provide the foundation for surveillance strategies. RECENT FINDINGS Drugs under investigation include norursodeoxycholic acid, nuclear receptor agonists, anti-fibrotics, antibiotics, and anti-inflammatory drugs. Endoscopic therapy is indicated for symptomatic dominant strictures and in the work-up of malignancies. Recently, the use of stents was associated with an increased rate of complications compared to balloon dilatation; and long-term stenting should be avoided. Malignancies currently account for most of the PSC-related mortality. Many drugs are emerging for the treatment of PSC but liver transplantation is the only treatment modality shown to prolong survival. PSC recurrence occurs in up to 35% of transplanted allografts within a median of 5 years. Surveillance for hepatobiliary and colorectal malignancies is indicated.
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Affiliation(s)
- Mai Sedki
- Department of Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, FL, USA
| | - Cynthia Levy
- Division of Hepatology, University of Miami Miller School of Medicine, 1500 NW 12th Avenue, Suite 1101, Miami, FL, USA.
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