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Olfatifar M, Rajabnia M, Sadeghi A, Rabbani A, Shahrokh S, Habibi MA, Pezeshgi Modarres M, Zali MR, Houri H. The epidemiological trends and projected future of primary sclerosing cholangitis by 2040: An updated meta-analysis and modeling study. PLoS One 2025; 20:e0322479. [PMID: 40323942 PMCID: PMC12052114 DOI: 10.1371/journal.pone.0322479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 03/23/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND AND AIMS Primary sclerosing cholangitis (PSC) exhibits varying incidence and prevalence rates across different regions; however, comprehensive global studies examining its geographic distribution and future trends are scarce. This study presents an updated meta-analysis through 2024 and projects the global and regional prevalence of PSC from 2024 to 2040 using an illness-death multi-state model. METHODS We conducted a thorough systematic search across multiple databases to identify all primary studies published until 2024 that reported on the incidence, prevalence, and mortality rates of PSC in various regions. Using the gathered data, we developed an illness-death model to forecast the future prevalence of PSC, covering the years 2024-2040. RESULTS Our meta-analysis revealed that the global pooled incidence and prevalence rates of PSC are 0.65 and 7.52 per 100,000 persons, respectively. Projections indicate that the global prevalence of PSC will rise to 22.98 cases per 100,000 (95% CI: 21.0-24.95), corresponding to an overall increase of 28.3%. Specifically, North America is forecasted to experience a 5.45% increase in PSC cases, reaching 24.76 cases per 100,000 (95% CI: 19.63-29.88), while Western Europe is anticipated to see a more pronounced rise of 28.79%, resulting in a prevalence of 21.48 cases per 100,000 (95% CI: 18.3-24.65) by 2040. CONCLUSIONS Our findings indicate a substantial rise in the number of individuals affected by PSC in recent years and estimate a significant future burden of the disease.
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Affiliation(s)
- Meysam Olfatifar
- Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Mohsen Rajabnia
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirhassan Rabbani
- Department of Transplant & Hepatobiliary Surgery, Shahid Beheshti University of Medical Sciences,Tehran, Iran
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Amin Habibi
- Clinical Research Development Center, Qom University of Medical Sciences, Qom, Iran
| | | | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Houri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Mol B, Werner E, Culver EL, van der Meer AJ, Bogaards JA, Ponsioen CY. Epidemiological and economical burden of cholestatic liver disease. Hepatology 2025:01515467-990000000-01224. [PMID: 40168457 DOI: 10.1097/hep.0000000000001341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 03/24/2025] [Indexed: 04/03/2025]
Abstract
The main cholestatic liver diseases comprise primary sclerosing cholangitis, primary biliary cholangitis, and IgG4-related cholangitis. Despite being classified as rare diseases, these are becoming gradually more important in the field of hepatology since their incidence is slowly rising while the viral hepatitis burden is declining. Cholestatic liver diseases now rank among the 3 most frequent indications for liver transplantation in many Western countries. An accurate understanding of the epidemiology and burden of disease on both the individual and society of cholestatic diseases is of great importance. This review aims to provide a comprehensive overview of the current literature on the epidemiology, health-related quality of life, and economic burden of primary sclerosing cholangitis, primary biliary cholangitis, and IgG4-related cholangitis.
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Affiliation(s)
- Bregje Mol
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, The Netherlands
- Endocrinology and Metabolism, Amsterdam Institute of Gastroenterology, Amsterdam, The Netherlands
| | - Ellen Werner
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Emma L Culver
- Oxford Liver Unit, John Radcliffe Hospital, Oxford, UK
| | - Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Johannes A Bogaards
- Department of Epidemiology and Data Science, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, The Netherlands
- Endocrinology and Metabolism, Amsterdam Institute of Gastroenterology, Amsterdam, The Netherlands
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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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Cooper J, Markovinovic A, Coward S, Herauf M, Shaheen AA, Swain M, Panaccione R, Ma C, Lu C, Novak K, Kroeker KI, Ng SC, Kaplan GG. Incidence and Prevalence of Primary Sclerosing Cholangitis: A Meta-analysis of Population-based Studies. Inflamm Bowel Dis 2024; 30:2019-2026. [PMID: 38052097 PMCID: PMC11532590 DOI: 10.1093/ibd/izad276] [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: 07/04/2023] [Indexed: 12/07/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis is a chronic liver disease associated with significant morbidity, mortality, and healthcare utilization. We conducted a systematic review and meta-analysis of population-based studies of the incidence and prevalence of primary sclerosing cholangitis. METHODS Medline and Embase were systematically searched to identify population-based studies of a defined geographic area and reported the incidence or prevalence of primary sclerosing cholangitis in the general population. Meta-analyses, using random-effects, were performed to calculate overall and country-specific incidence (per 100 000 persons/year) and prevalence rates (per 100 000 persons) with 95% confidence intervals. RESULTS The 14 studies on incidence and the 12 for prevalence originated from North America, Asia, Europe, and Oceania. Incidence and prevalence rates of primary sclerosing cholangitis were 0.87 (95% confidence interval, 0.59-1.29) and 13.53 (95% confidence interval, 10.20-17.94) per 100 000 persons, respectively. CONCLUSIONS Both the prevalence and incidence of primary sclerosing cholangitis is low in the general population. Future studies on the incidence and prevalence of primary sclerosing cholangitis in the general population should be directed at Asia, Africa, and Latin America to allow for a more robust assessment of the global epidemiology of primary sclerosing cholangitis.
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Affiliation(s)
- Jared Cooper
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Ante Markovinovic
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Stephanie Coward
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Michelle Herauf
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Abdel-Aziz Shaheen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Mark Swain
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Remo Panaccione
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Christopher Ma
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Cathy Lu
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Kerri Novak
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Karen I Kroeker
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Siew C Ng
- Department of Medicine and Therapeutics, LKS Institute of Digestive Disease, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Gilaad G Kaplan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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Xu X, Meng T, Shi L, Duan W, Niu J, Ding H, Xie W, Zhou L, Wang B, Li J, Zhang L, Wang Y, Ou X, Zhao X, You H, Jia J, Kong Y. Prevalence and clinical profiles of primary sclerosing cholangitis in China: Data from electronic medical records and systematic literature retrieval. J Autoimmun 2024; 147:103264. [PMID: 38843578 DOI: 10.1016/j.jaut.2024.103264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 04/20/2024] [Accepted: 05/21/2024] [Indexed: 07/16/2024]
Abstract
BACKGROUND & AIMS Epidemiology of primary sclerosing cholangitis (PSC) is lacking in China. We aimed to estimate the period prevalence and depict the clinical features of PSC in China. METHODS We identified and included PSC cases between 2000 and 2023 from two sources: electronic medical records (EMR) and systematical literature retrieval (SLR). The period prevalence of PSC was estimated by the multiplier method. Rate ratios (RRs) for PSC prevalence in relation to macroeconomic indicators were calculated by the negative binomial regression model. RESULTS A total of 1358 PSC cases were retrieved from 299 hospitals (162 from EMR and 1196 from SLR). Males accounted for 55.7 % of the PSC cases and 25.7 % had concomitant inflammatory bowel disease (IBD). The estimated period prevalence of PSC from 2000 to 2023 was 2.36 (95 % CI: 1.82, 3.34) per 100,000. Males had a numerically higher PSC prevalence than females (2.56, 95 % CI: 1.97, 3.63 vs. 2.14, 95 % CI: 1.65, 3.04 per 100,000). The highest prevalence of PSC was in East China at 4.87 (95 % CI: 3.44, 7.18) per 100,000, followed by North China at 2.94 (95 % CI: 2.33, 3.74) per 100,000, and the lowest in South China at 0.92 (95 % CI: 0.66, 1.30) per 100,000. Regional per capita GDP (RR 1.65, 95 % CI: 1.03, 2.65) and healthcare expenditure (RR 1.94, 95 % CI: 1.13, 3.38) were identified to be associated with PSC prevalence. CONCLUSION Our study showed the estimated PSC prevalence varied within China, but was generally lower than that in Western countries.
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Affiliation(s)
- Xiaoqian Xu
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Clinical Epidemiology and EBM Unit, Beijing Clinical Research Institute, Beijing, China
| | - Tongtong Meng
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Lichen Shi
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Clinical Epidemiology and EBM Unit, Beijing Clinical Research Institute, Beijing, China
| | - Weijia Duan
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Junqi Niu
- Hepatology Department, Center of Infectious Diseases and Pathogen Biology, First Hospital of Jilin University, Changchun, China
| | - Huiguo Ding
- Department of Hepatology and Gastroenterology, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Wen Xie
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Lingyi Zhang
- Department of Hepatology, Lanzhou University Second Hospital, Lanzhou, China
| | - Yu Wang
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiaojuan Ou
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xinyan Zhao
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hong You
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
| | - Yuanyuan Kong
- National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Clinical Epidemiology and EBM Unit, Beijing Clinical Research Institute, Beijing, China.
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Kim YS, Hurley EH, Park Y, Ko S. Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD): a condition exemplifying the crosstalk of the gut-liver axis. Exp Mol Med 2023; 55:1380-1387. [PMID: 37464092 PMCID: PMC10394020 DOI: 10.1038/s12276-023-01042-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/17/2023] [Accepted: 04/17/2023] [Indexed: 07/20/2023] Open
Abstract
The close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) provides a good opportunity to comprehend the gut-liver axis. The gut and the liver have reciprocal interactions, including how gut inflammation influences the liver through immune cells and the microbiota and how the microbiota in the gut modifies bile acids, which are produced and secreted from the liver. PSC-IBD shows distinct clinical findings from classical IBD. In addition, a distinct genetic predisposition and unique microbiota composition suggest that PSC-IBD is an independent disease entity. Understanding the pathogenesis of PSC-IBD helps to develop novel and effective therapeutic agents. Given the high risk of malignancies associated with PSC-IBD, it is critical to identify patients at high risk and implement appropriate surveillance and monitoring strategies. In this review, we provide an overview of PSC-IBD, which exemplifies the gut-liver axis.
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Affiliation(s)
- You Sun Kim
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - 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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Jadaun SS, Mehtani R, Hasnain A, Bhatia S, Moond V, Kumar M, Kuhad V, Singh S, Agarwal S, Gupta S, Saigal S. Good outcomes of living donor liver transplant in primary sclerosing cholangitis: an experience from North India. Hepatol Int 2023; 17:499-506. [PMID: 36376772 PMCID: PMC9662766 DOI: 10.1007/s12072-022-10442-4] [Citation(s) in RCA: 2] [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: 07/20/2022] [Accepted: 10/14/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. In the absence of effective medical therapy, liver transplant is the definitive treatment for advanced stage. However, recurrence of PSC after liver transplant is of concern which can lead to graft failure and may require retransplant. There are limited data on outcomes of living donor liver transplant (LDLT) in PSC. Also, in LDLT as donors are genetically related there can be an increased risk of recurrence. We conducted this retrospective study to analyze the outcomes of LDLT in PSC at a tertiary liver transplant center in north India. METHODS We conducted a retrospective analysis of 3213 transplant recipients who underwent LDLT from January 2006 to May 2021. Of these 26 (0.80%) patients had PSC as indication for liver transplantation (PSC = 24, PSC-AIH overlap = 2). Data analysis was done to look for baseline demographics, clinical details, transplant outcomes, PSC recurrence, and survival. RESULTS Mean age of study group was 42 (± 13.8) years and 19 patients (73.1%) were males. All patients had decompensated cirrhosis at the time of transplant. Mean CTP score and MELD score were 9.5 (± 1.8) and 18.9 (± 7.1), respectively. Sixteen patients received modified right lobe graft, seven extended right lobe graft and five patients received left lateral graft. Median graft weight and mean graft to recipient weight ratio (GRWR) were 633.5 (IQR 473.5-633.5) grams and 1.23 (± 0.42), respectively. Most common biliary anastomosis was hepaticojejunostomy, done in 19 (73.1%) while duct to duct anastomosis was performed in 7 (26.9%) patients. Median follow-up was 96 (36-123) months. One patient had ulcerative colitis and none had cholangiocarcinoma. Two (7.7%) patients had bile leak during early post-transplant period. Three (11.1%) patients developed graft rejection and were managed successfully with steroid pulses. Three patients died during early post-transplant period while seven deaths occurred during long-term follow-up including one death due to COVID-19. Five (21.73%) patients had recurrence of PSC of which two patients had graft loss including one after retransplantation. The one year graft and patient survival rate was 88.5%. CONCLUSION LDLT can be performed in PSC with good long-term outcomes with a risk of PSC recurrence in about one-fifth patients.
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Affiliation(s)
- Shekhar Singh Jadaun
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Hepatology and Liver Transplant Medicine Saket, Max Super Speciality Hospital, New Delhi, 110017 India
| | - Rohit Mehtani
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Hepatology and Liver Transplant Medicine Saket, Max Super Speciality Hospital, New Delhi, 110017 India
| | - Ana Hasnain
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Hepatology and Liver Transplant Medicine Saket, Max Super Speciality Hospital, New Delhi, 110017 India
| | - Sushant Bhatia
- Liver Transplant and Gastrointestinal Surgery, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Vikash Moond
- Liver Transplant and Gastrointestinal Surgery, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Mukesh Kumar
- Liver Transplant and Gastrointestinal Surgery, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Vikash Kuhad
- Student’s Scientific Circle of Surgery, Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Ul. Smoluchowskiego 17, 80-214 Gdańsk, Poland
| | - Shweta Singh
- Anesthesia and Critical Care, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Shaleen Agarwal
- Liver Transplant and Gastrointestinal Surgery, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Subhash Gupta
- Liver Transplant and Gastrointestinal Surgery, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Sanjiv Saigal
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Hepatology and Liver Transplant Medicine Saket, Max Super Speciality Hospital, New Delhi, 110017 India
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Longitudinal analysis of transplant candidates with primary sclerosing cholangitis in an Asian liver transplant center. Eur J Gastroenterol Hepatol 2023; 35:480-487. [PMID: 36719819 DOI: 10.1097/meg.0000000000002516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a rare disease in Asia, and few studies have investigated the disease in this ethnicity, particularly in wait-listed patients for liver transplantation (LT). We aimed to investigate the prognostic factors and outcomes of wait-listed patients with PSC in an Asian transplant center. METHODS Survival was retrospectively analyzed. RESULTS Eighteen (10 male and 8 female) wait-listed patients with PSC, with a median age at diagnosis of 44.5 years, were included. Compared with men, women had significantly higher aspartate aminotransferase to platelet ratio index scores (3.28 vs. 1.13; P = 0.012) and bilirubin levels (7.68 vs. 4.03 mg/dl; P = 0.043) and more often presented with decompensating events, including ascites [5 (63%) vs. 1 (10%); P = 0.043] and splenomegaly [8 (100%) vs. 4 (40%); P = 0.013]. Compared with the non-LT group, the LT group exhibited a superior survival rate for women ( P = 0.004) but not for men. In the univariable analysis, significant risk factors associated with overall survival included malignancies with a hazard ratio (95% confidence interval) of 5.53 (1.00-30.51) and esophageal varices (EV) [4.18 (1.05-16.61)], whereas female gender [25.00 (1.49-500.00)], LT [0.09 (0.01-0.80)] and EV [39.03 (2.92-521.96)] were indicated in the multivariable analysis. CONCLUSIONS For Asian wait-listed patients with PSC, EV and female gender were the risk factors related to overall survival, and LT was the protective factor. Our experiences suggested that LT brings more benefits in female patients. Strategies are needed to provide equivalent transplant benefits.
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Taneja S, Mehtani R, De A, Mitra S, Rathi S, Verma N, Premkumar M, Minz R, Duseja A, Das A, Singh V, Dhiman RK, Chawla YK. Spectrum of Autoimmune Liver Disease and Real-World Treatment Experience from a Tertiary Care Hospital. J Clin Exp Hepatol 2023; 13:241-251. [PMID: 36950480 PMCID: PMC10025584 DOI: 10.1016/j.jceh.2022.11.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 11/01/2022] [Indexed: 11/12/2022] Open
Abstract
Background and aims Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. Methods A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC. Results Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P = 0.034), high albumin (OR 1.91 [1.05-3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P = 0.020) predicted complete response. Conclusion AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response.
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Key Words
- ACLF, acute-on-chronic liver failure
- AIH, autoimmune hepatitis
- AILD, Autoimmune liver diseases
- ALF, acute liver failure
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- AMA, anti-mitochondrial antibody
- ASMA, anti-smooth muscle antibody
- AST, aspartate aminotransferase
- ELISA, enzyme-linked immunosorbent assay
- IBD, inflammatory bowel disease
- INR, international normalized ratio
- IgG, immunoglobulin G
- LC-1, liver cytosol 1
- LKM-1, liver kidney microsomal 1
- LSM, liver stiffness measurement
- LT, liver transplant
- MMF, mycophenolate mofetil
- MRCP, magnetic resonance cholangiopancreatography
- PBC, primary biliary cholangitis
- PSC, primary sclerosing cholangitis
- SLA, soluble liver antigen
- UDCA, ursodeoxycholic acid
- ULN, upper limit of normal
- autoimmune hepatitis
- cirrhosis
- overlap syndromes
- primary biliary cholangitis
- primary sclerosing cholangitis
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Affiliation(s)
- Sunil Taneja
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Rohit Mehtani
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Arka De
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Suvradeep Mitra
- Department of Immunopathology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Sahaj Rathi
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Ranjana Minz
- Department of Immunopathology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Ashim Das
- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Radha K. Dhiman
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Yogesh K. Chawla
- Department of Hepatology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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10
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Hov JR, Karlsen TH. The microbiota and the gut-liver axis in primary sclerosing cholangitis. Nat Rev Gastroenterol Hepatol 2023; 20:135-154. [PMID: 36352157 DOI: 10.1038/s41575-022-00690-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/13/2022] [Indexed: 11/11/2022]
Abstract
Primary sclerosing cholangitis (PSC) offers unique opportunities to explore the gut-liver axis owing to the close association between liver disease and colonic inflammation. It is well established that the gut microbiota in people with PSC differs from that of healthy individuals, but details of the microbial factors that demarcate PSC from inflammatory bowel disease (IBD) without PSC are poorly understood. In this Review, we aim to provide an overview of the latest literature on the gut microbiome in PSC and PSC with IBD, critically examining hypotheses on how microorganisms could contribute to the pathogenesis of PSC. A particular emphasis will be put on pathogenic features of the gut microbiota that might explain the occurrence of bile duct inflammation and liver disease in the context of IBD, and we postulate the potential existence of a specific yet unknown factor related to the gut-liver axis as causative in PSC. Available data are scrutinized in the perspective of therapeutic approaches related to the gut-liver axis.
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Affiliation(s)
- Johannes R Hov
- Norwegian PSC Research Center and Section of gastroenterology and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Tom H Karlsen
- Norwegian PSC Research Center and Section of gastroenterology and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway. .,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
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11
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Zhang Y, Gao X, He Z, Jia H, Chen M, Wang X, Hong L, Cui Y, Wan J. Prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis: A systematic review and meta-analysis. Liver Int 2022; 42:1814-1822. [PMID: 35689520 DOI: 10.1111/liv.15339] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 05/05/2022] [Accepted: 06/08/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND AIM Previous studies have established an association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC). The disease burden of IBD in PSC patients was not well estimated. The study aimed to quantify the pooled prevalence of IBD in PSC and to investigate whether subtypes of PSC and sex influence the prevalence of IBD. METHODS PubMed, Embase, and Web of Science were searched through November 2021 for studies reporting data on IBD among PSC patients. The outcomes were the prevalence of IBD in patients with PSC, as well as the association (odds ratio [OR]) of IBD in PSC according to subtype and sex. RESULTS Based on the analysis of 25 studies, the prevalence of IBD in patients with PSC was 71.1% (95% CI 68.2-75.1%), most commonly in UC (55.9%, 95% CI 52.5-59.3%). The pooled prevalence of IBD was 76.9% in Australia (95% CI 71.2-82.6%, 1 study), 75.9% (95% CI 69.5-82.3%, 4 studies) in North America, 70.9% (95% CI 65.8-76.0%, 17 studies) in Europe and 67.0% (95% CI 57.9-76.0%, 2 studies) in Asia. Male PSC patients had a higher prevalence of IBD (OR 1.67, 95% CI 1.52-1.83) and UC (OR 2.02, 95% CI 1.56-2.63) and a lower prevalence of CD (OR 0.77, 95% CI 0.67-0.88) than female patients. Large duct PSC patients had a higher prevalence of IBD (OR 2.57, 95% CI 2.03-3.25) and UC (OR 4.51, 95% CI 1.22-16.71) than small duct PSC patients. CONCLUSIONS The study provided the first pooled estimates of the burden of IBD in patients with PSC and could be used as the basis for risk stratification of PSC patients.
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Affiliation(s)
- Yujie Zhang
- Department of Histology and Embryology, School of Basic Medicine, Xi'an Medical University, Xi'an, China
| | - Xinbao Gao
- Medical affairs, Tigermed Consulting Co., Ltd, Hangzhou, China
| | - Zhiyi He
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research and Department of Prosthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Hui Jia
- Department of gastroenterology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Min Chen
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Xuan Wang
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Liu Hong
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Yuanyuan Cui
- Department of Histology and Embryology, School of Basic Medicine, Xi'an Medical University, Xi'an, China
| | - Jian Wan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
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12
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Trivedi PJ, Bowlus CL, Yimam KK, Razavi H, Estes C. Epidemiology, Natural History, and Outcomes of Primary Sclerosing Cholangitis: A Systematic Review of Population-based Studies. Clin Gastroenterol Hepatol 2022; 20:1687-1700.e4. [PMID: 34474162 DOI: 10.1016/j.cgh.2021.08.039] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/19/2021] [Accepted: 08/23/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The aim of this study was to quantify the global epidemiology of primary sclerosing cholangitis (PSC), alongside the incidence of liver transplantation, cancer, and death, through robust systematic review of population-based data. METHODS We searched MEDLINE and EMBASE up to and including June 30, 2020 to identify population-based studies reporting the incidence and/or prevalence of PSC. Studies that did not report original data, or of exclusively pediatric-onset disease (diagnosis age <16 years) or exclusively PSC-associated with inflammatory bowel disease were excluded. RESULTS Of 4922 published studies, 17 fulfilled inclusion criteria; 16 documenting incidence and 14 prevalence. The highest reported incidence of PSC was reported in Northern Europe (Finland, 1.58 and Norway, 1.3 per-100,000 population, respectively) and North America (Minnesota, 1.47); with the lowest being observed across the Mediterranean Basin (Italy, 0.1). Prevalence ranged from 31.7 in Finland and 23.99 in Minnesota, to 1.33 in Singapore and 0.0 in Alaska. Of studies reporting temporal occurrence, an increase in disease incidence was observed across North America and Northern Europe (4 studies), alongside an increase in prevalence over time (4 studies). The incidence and risks for clinical outcomes were presented by 9 of the included studies. Median transplant-free survival ranged from 9.7 (United States) to 20.6 years (Netherlands), with standardized mortality ratios of 2.5 and 4.2 compared with the control population. The standardized incidence of cholangiocarcinoma ranged from 235 (Finland) to 398 (Netherlands). CONCLUSIONS Estimates of PSC incidence and prevalence vary, with most studies conducted in North America and Western Europe; the latter showing a steady increase in disease occurrence over time. Further research is needed to understand changes in disease epidemiology, including etiological drivers, the implications of rising case burden on health care policy, and better appreciation of PSC in the developing world.
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Affiliation(s)
- Palak J Trivedi
- National Institute for Health Research Birmingham Biomedical Research Centre, Centre for Liver and Gastroenterology Research, University of Birmingham, Birmingham, United Kingdom; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom; Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom; Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, United Kingdom
| | | | - Kidist K Yimam
- Department of Hepatology and Liver Transplantation California Pacific Medical Center, San Francisco, California
| | - Homie Razavi
- Center for Disease Analysis Foundation, Lafayette, Colorado
| | - Chris Estes
- Center for Disease Analysis Foundation, Lafayette, Colorado.
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13
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Da Cunha T, Vaziri H, Wu GY. Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: A Review. J Clin Transl Hepatol 2022; 10:531-542. [PMID: 35836773 PMCID: PMC9240248 DOI: 10.14218/jcth.2021.00344] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 10/12/2021] [Accepted: 11/22/2021] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis is a disease affecting around 0.006-0.016% of the population. Of these, around 75% have concomitant inflammatory bowel disease (IBD) according to the most recent epidemiological studies. Several theories have been proposed regarding the pathogenesis of primary sclerosing cholangitis (PSC). These include changes in the function of cholangiocytes, effects of the gut microbiome, association with specific human leukocyte antigen haplotypes and dysregulation of the immune system. However, these do not explain the observed association with IBD. Moreover, there are considerable differences in the frequency and outcomes between patients with PSC and ulcerative colitis compared with PSC and Crohn's disease. The aim of this review is to appraise the most recent studies that have contributed to the epidemiology, advances in the pathophysiology, and characterization of important clinical aspects of the association of PSC and IBD.
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Affiliation(s)
- Teresa Da Cunha
- Correspondence to: Teresa Da Cunha, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA. ORCID: https://orcid.org/0000-0002-8319-7608. Tel: +1-860-706-2133, Fax: +1-860-679-3159, E-mail:
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14
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Park JK, Kim D, Lee JM, Lee KH, Lee KT, Park JK, Lee JK. Clinical Utility of Personalized Serum IgG Subclass Ratios for the Differentiation of IgG4-Related Sclerosing Cholangitis (IgG4-SC) from Primary Sclerosing Cholangitis (PSC) and Cholangiocarcinoma (CCA). J Pers Med 2022; 12:855. [PMID: 35743640 PMCID: PMC9225113 DOI: 10.3390/jpm12060855] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/10/2022] [Accepted: 05/21/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The differential diagnosis of immunoglobulin G4-sclerosing cholangitis (IgG4-SC) from primary sclerosing cholangitis (PSC) or cholangiocarcinoma (CCA) is important. In this study, we aimed to find the best combinations of serum IgG subclasses and IgG4 levels for differentiating IgG4-SC from PSC or CCA. METHODS In total, 31 patients with IgG4-SC, 27 patients with PSC, and 40 patients with CCA were enrolled from 2003 to 2017 at a single tertiary referral center. We retrospectively assessed the IgG4, IgG4/IgG1, IgG4/(IgG1+IgG3), and (IgG4+IgG2)/(IgG1+IgG3) in each of the patients. ROC curves were established to obtain the optimal cutoff value for each parameter. McNemar's test was used to compare the sensitivities, specificities, and accuracies of diagnostic algorithms. RESULTS In differentiating IgG4-SC from PSC, the accuracies of IgG4/IgG1 ≥ 0.087 and of IgG4/(IgG1+IgG3) ≥ 0.081 were significantly higher than that of IgG4 ≥ 135 mg/dL alone (78% vs. 66%, p = 0.025). Serum IgG4 ≥ 52 mg/dL showed the best accuracy for differentiation of IgG4-SC from CCA, with a sensitivity and specificity of 80% and 82%, respectively, but this was statistically not significant (p = 0.405). CONCLUSIONS The serum IgG4/IgG1 or IgG4/(IgG1+IgG3) level may help to differentiate IgG4-SC from PSC. IgG4 alone is the most accurate serologic marker for the differentiation of IgG4-SC from CCA.
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Affiliation(s)
- Jae Keun Park
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441, Korea;
| | - Dongwuk Kim
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
| | - Jeong Min Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
| | - Kwang Hyuck Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul 16419, Korea
| | - Kyu Taek Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
| | - Joo Kyung Park
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
| | - Jong Kyun Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
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15
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Yano K, Moroi R, Shiga H, Tarasawa K, Shimoyama Y, Kuroha M, Hamada S, Kakuta Y, Fushimi K, Fujimori K, Kinouchi Y, Masamune A. Analysis of the disease activity of ulcerative colitis with and without concomitant primary sclerosing cholangitis: An investigation using a nationwide database in Japan. JGH Open 2022; 6:50-56. [PMID: 35071788 PMCID: PMC8762614 DOI: 10.1002/jgh3.12693] [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: 09/15/2021] [Revised: 11/22/2021] [Accepted: 12/01/2021] [Indexed: 11/07/2022]
Abstract
Aims Primary sclerosing cholangitis (PSC) is a relatively common complication of ulcerative colitis (UC). Only a few studies have investigated the impact of PSC on the clinical course of UC, and their conclusions are contradictory. Therefore, we aimed to compare the disease activity of UC with and without PSC. Methods and Results We collected UC patient data using the Diagnosis Procedure Combination database system in Japan and classified eligible admissions into two groups based on their diagnosis of either UC alone or UC associated with PSC. We then compared therapeutic details (medical treatment and surgery) between the two groups. Multivariable logistic regression analysis and propensity score matching was also performed. The rates of systemic steroid injection and infliximab administration in patients with PSC were lower than those in patients without PSC (21% vs. 28%, P = 0.012, 9.6% vs. 16%, P = 0.01, respectively). The rates of surgery, colorectal cancer, duration of hospital stay, and in-hospital mortality did not differ between the two groups. Multivariable analysis revealed that concomitant PSC was a clinical factor that reduced the odds of systemic steroid injection (odds ratio [OR] = 0.66, 95% confidence interval [CI]: 0.49-0.90, P = 0.008) and infliximab (OR = 0.48, 95% CI: 0.32-0.74, P = 0.0008) administration. Conclusion UC patients with PSC might have less UC disease activity than those with UC alone.
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Affiliation(s)
- Kota Yano
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Rintaro Moroi
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Hisashi Shiga
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Kunio Tarasawa
- Department of Health Administration and Policy Tohoku University Graduate School of Medicine Sendai Japan
| | - Yusuke Shimoyama
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Masatake Kuroha
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Shin Hamada
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Yoichi Kakuta
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics Tokyo Medical and Dental University Graduate School of Medicine Bunkyo Japan
| | - Kenji Fujimori
- Department of Health Administration and Policy Tohoku University Graduate School of Medicine Sendai Japan
| | - Yoshitaka Kinouchi
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
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16
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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: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 07/29/2021] [Indexed: 12/24/2022]
Affiliation(s)
- Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, the Netherlands
| | - David N Assis
- Department of Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
| | - Kirsten M Boberg
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine, and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; ERN RARE Liver, Hamburg, Germany
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, California
| | - Mark Deneau
- University of Utah and Intermountain Primary Children's Hospital, Salt Lake City, Utah
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free Hospital and Institute for Liver and Digestive Health, University College London, London, United Kingdom; ERN RARE Liver, Hamburg, Germany
| | - Lars Aabakken
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine, and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; ERN RARE Liver, Hamburg, Germany
| | - Martti Färkkilä
- Abdominal Center, Helsinki University Hospital, Helsinki, Finland; ERN RARE Liver, Hamburg, Germany
| | - Bret Petersen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Christian Rupp
- Department of Internal Medicine IV, Gastroenterology, and Hepatology, University Hospital Heidelberg, Heidelberg, Germany
| | - Stefan G Hübscher
- Institute of Immunology and Immunotherapy, University of Birmingham and, Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, United Kingdom
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Nardelli MJ, Bittencourt PL, Cançado GGL, Faria LC, Villela-Nogueira CA, Rotman V, Silva de Abreu E, Maria Farage Osório F, Evangelista AS, Sampaio Costa Mendes L, Ferraz de Campos Mazo D, Hyppolito EB, de Souza Martins A, Codes L, Signorelli IV, Perez Medina Gomide G, Agoglia L, Alexandra Pontes Ivantes C, Ferreira de Almeida e Borges V, Coral GP, Eulira Fontes Rezende R, Lucia Gomes Ferraz M, Raquel Benedita Terrabuio D, Luiz Rachid Cançado E, Couto CA. Clinical Features and Outcomes of Primary Sclerosing Cholangitis in the Highly Admixed Brazilian Population. Can J Gastroenterol Hepatol 2021; 2021:7746401. [PMID: 34805028 PMCID: PMC8604588 DOI: 10.1155/2021/7746401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 10/15/2021] [Accepted: 10/19/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is associated with a broad phenotypic spectrum in different populations from diverse ethnic and racial backgrounds. This study aimed to describe the clinical characteristics and outcomes of PSC in a multicenter cohort of patients from Brazil. METHODS Data from the Brazilian Cholestasis Study Group were retrospectively reviewed to assess demographic information and clinical characteristics of PSC, as well as the outcomes, such as transplantation-free survival. RESULTS This cohort included 210 patients. After excluding 33 (15.7%) patients with PSC and overlap syndrome of autoimmune hepatitis, 177 (97 males, median age 33 (21-42) years) with clear-cut PSC were eligible for this study. Most of the patients (n = 139, 78.5%) were symptomatic, and 104 (58.7%) had advanced PSC at the time of diagnosis. Concurrent inflammatory bowel disease was observed in 78 (58.6%) of the investigated patients (n = 133), and most of them had ulcerative colitis (n = 61, 78.2%). The 1- and 5-year survival free of liver transplantation or death were 92.3 ± 2.1% and 66.9 ± 4.2%, respectively, and baseline advanced PSC, pruritus, and elevated bilirubin levels were independent risk factors for the composite adverse outcome. Females were significantly older and had lower bilirubin levels than males at baseline, but survival was not associated with sex. Approximately 12.4% (n = 22) of patients with PSC died, and 32.8% (n = 58) underwent liver transplantation at a median follow-up time of 5.3 and 3.2 years. CONCLUSION Multiethnic Brazilian PSC patients exhibited a less pronounced male predominance and a lower frequency of inflammatory bowel disease than Caucasians. Adverse outcomes were more frequent, probably due to advanced disease at baseline.
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Affiliation(s)
| | - Paulo Lisboa Bittencourt
- Hospital Português, Salvador, Brazil
- Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil
| | - Guilherme Grossi Lopes Cançado
- Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Hospital da Polícia Militar de Minas Gerais, Belo Horizonte, Brazil
| | - Luciana Costa Faria
- Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Cristiane Alves Villela-Nogueira
- Faculdade de Medicina, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Vivian Rotman
- Faculdade de Medicina, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | - Andreia Silva Evangelista
- Faculdade de Medicina, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | | | | | | | | | | | - Luciana Agoglia
- Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, Brazil
| | | | | | | | | | | | | | | | - Claudia Alves Couto
- Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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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: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Introduction: PSC is a rare liver disease that leads frequently to cirrhosis and need for liver transplantation. No medical treatment is of proven value. Liver transplantation is the only curative therapy available. There is a big medical need to find medical therapy that can alter the natural history of the disease.Areas covered: The authors highlight advances in PSC, based on recent literature retrieved from PubMed until September 2020 regarding both medical and endoscopic biliary therapy.Future possibilities for treatment of PSC are discussed.Expert opinion: Biliary endoscopy is the cornerstone in the treatment of dominant strictures. Single-user peroral cholangioscopy is an emerging modality. Balloon dilatation therapy is the treatment of choice of dominant strictures. The most promising medical therapies showing efficacy in phase II trials are nor-Ursodeoxycholic acid, obethicolic acid, the non-steroidal FXR agonist Cilofexor and Aldafermin, a synthetic analogue of FGF-19. Antibiotics, particularly vancomycin have shown potential benefits, particularly in children but phase III studies are lacking. In observational studies of effects of biological therapy in patients with IBD/PSC adalimumab was associated with reduction in ALP. Results of liver transplantation are favorable but recurrence can be of clinical relevance particularly in patients transplanted before the age of 40.
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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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19
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[Surgical treatment of primary sclerosing cholangitis : Experiences from 30 years in a single center cohort with 173 consecutive patients]. Chirurg 2021; 92:148-157. [PMID: 32488382 PMCID: PMC7875955 DOI: 10.1007/s00104-020-01197-5] [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] [Indexed: 10/31/2022]
Abstract
BACKGROUND In recent years substantial progress has been made in the treatment, surveillance and understanding of the pathogenesis of primary sclerosing cholangitis (PSC); however, in most cases liver transplantation (LTX) is still the only curative option for cancer or end-stage liver disease (ELD). In rare cases a partial liver resection is a possible curative treatment of a PSC-associated cholangiocellular carcinoma (CCC). These operations represent a significant additional burden for PSC patients. OBJECTIVE Due to the rarity of PSC detailed studies regarding hepato-pancreato-biliary (HPB) surgery are lacking. The aim of this study was to analyze the surgical indications and prognosis of PSC patients. PATIENTS AND METHODS A single center retrospective cohort study from 1990 to 2020 was carried out. In this study patients with PSC were included and investigated with respect to factors associated with surgery and the prognosis. RESULTS As a consequence of PSC-associated conditions, in 62 patients (36%) a major HPB operation or explorative laparotomy was necessary. The prevalence of chronic inflammatory bowel disease was significantly higher in these patients (P < 0.019). An LTX was carried out in 46 patients (73%) because of ELD. A liver resection (LR) was performed in 8 patients (11%) and 9 patients only underwent an explorative laparotomy. The overall survival in the LTX subgroup was significantly longer than patients who underwent LR and explorative laparotomy (258 months; 95% confidence interval, CI 210-306 months vs. 88 months; 95% CI 16-161 months vs. 13 months; 95% CI 3-23 months; p < 0.05, respectively). CONCLUSION The majority of patients with PSC have to be operated on because of the disease with substantial risks for morbidity and mortality. Curative treatment options are lacking, thus underlining the need for effective early detection and treatment strategies for PSC-CCC.
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Mehta TI, Weissman S, Fung BM, Tabibian JH. Geoepidemiologic variation in outcomes of primary sclerosing cholangitis. World J Hepatol 2020; 12:116-124. [PMID: 32685104 PMCID: PMC7336294 DOI: 10.4254/wjh.v12.i4.116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/15/2020] [Accepted: 03/24/2020] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, progressive, hepatobiliary disease characterized by inflammation and fibrosis of the intra- and extra-hepatic bile ducts. Its natural history is one that generally progresses towards cirrhosis, liver failure, cholangiocarcinoma, and ultimately disease-related death, with a median liver transplantation-free survival time of approximately 15-20 years. However, despite its lethal nature, PSC remains a heterogenous disease with significant variability in outcomes amongst different regions of the world. There are also many regions where the outcomes of PSC have not been studied, limiting the overall understanding of this disease worldwide. In this review, we present the geoepidemiologic variations in outcomes of PSC, with a focus on survival pre- and post-liver transplantation as well as the concurrence of inflammatory bowel disease and hepatobiliary neoplasia.
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Affiliation(s)
- Tej I Mehta
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57108, United States
| | - Simcha Weissman
- Department of Medicine, Hackensack University-Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Brian M Fung
- Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
| | - James H Tabibian
- Department of Medicine, UCLA-Olive View Medical Center, Sylmar, CA 91342, and Health Sciences Clinical Associate Professor, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States.
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21
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Tanaka A. IgG4-Related Sclerosing Cholangitis and Primary Sclerosing Cholangitis. Gut Liver 2020; 13:300-307. [PMID: 30205418 PMCID: PMC6529173 DOI: 10.5009/gnl18085] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 07/02/2018] [Accepted: 07/02/2018] [Indexed: 12/13/2022] Open
Abstract
Sclerosing cholangitis (SC) is defined as a condition with progressive stenosis and destruction of the bile ducts due to diffuse inflammation and fibrosis and currently includes three categories: primary sclerosing cholangitis (PSC), secondary cholangitis, and IgG4-related sclerosing cholangitis (IgG4-SC). SC categories share similar clinical features, such as cholestasis. Patients with SC present with cholestatic symptoms, including jaundice and pruritus, and blood tests reveal elevation of cholestatic enzymes. Cholangiography, endoscopic or magnetic, is inevitably required for making a diagnosis. Although the presentation of IgG4-SC and PSC are similar, the comorbidities, treatment response, and outcomes differ significantly, and therefore, it is strongly advisable to be familiar with these two diseases to make a correct diagnosis. Differentiation of cholangiocarcinoma from IgG4-SC and PSC is also extremely important. In this review, the clinical characteristics, comorbidities, treatment and outcomes of IgG4-SC and PSC will be outlined based on experience mainly from Japan.
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Affiliation(s)
- Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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22
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Barner-Rasmussen N, Pukkala E, Jussila A, Färkkilä M. Epidemiology, risk of malignancy and patient survival in primary sclerosing cholangitis: a population-based study in Finland. Scand J Gastroenterol 2020; 55:74-81. [PMID: 31902255 DOI: 10.1080/00365521.2019.1707277] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Background: There are only a few and mostly small population-based epidemiological studies of primary sclerosing cholangitis (PSC).Objective: We aimed to estimate prevalence and incidence rates of PSC, and survival and malignancy risk for PSC patients in a large population-based study.Methods: We retrieved 632 PSC patients from 1990 to 2015 in the Hospital District of Helsinki and Uusimaa (HUS), comprising 29% of the Finnish population. Mortality information of the PSC patients was obtained from the national Population Registry, malignancy information from the Finnish Cancer Registry and the causes of death from the Statistics Finland. Standardized incidence ratio and standardized mortality ratio (SMR) were calculated for predefined malignancy types.Results: The crude incidence of PSC in the HUS area was 1.58/100,000 person-years, and the point prevalence in 2015 was 31.7/100,000 inhabitants. The mean time from diagnosis to death was 21.9 years. The risk for any malignancy was three-fold and the risk for colorectal carcinoma was five-fold when comparing with the general population. During the first year after diagnosis of PSC, the risk for cholangiocarcinoma is 900-fold compared to the general population and after that 150-fold. SMR for all malignant neoplasms was 5.9 (95% CI 4.2-8.1).Conclusion: We found that the incidence of PSC in the HUS area in Finland is similar or higher than previously reported from other countries. The prevalence is markedly higher than reported elsewhere, probably due to the active search of the disease, suggesting that the disease is underdiagnosed.
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Affiliation(s)
- Nina Barner-Rasmussen
- Department of Gastroenterology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Eero Pukkala
- Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.,Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Airi Jussila
- Faculty of Social Sciences, Tampere University, Tampere, Finland.,Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - Martti Färkkilä
- Department of Gastroenterology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
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23
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Greuter T, Vavricka SR. Extraintestinal manifestations in inflammatory bowel disease - epidemiology, genetics, and pathogenesis. Expert Rev Gastroenterol Hepatol 2019; 13:307-317. [PMID: 30791773 DOI: 10.1080/17474124.2019.1574569] [Citation(s) in RCA: 126] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to the gut. Extraintestinal manifestations (EIMs) are frequently observed and involve the joints, eyes, hepatobiliary tract, and skin. Areas covered: In this review, we discuss classical EIM focusing on epidemiology, genetics, and pathogenesis, highlighting recent advances in the understanding of EIM. We further discuss treatment-induced immunological phenomena, which are increasingly recognized and might challenge IBD-treating physicians in the era of biological treatment. Expert opinion: EIM considerably contributes to morbidity and mortality. Genetic studies have revealed a common genetic background between EIM and IBD and among specific EIM. Identified protein interactions have been shown to cluster in shared biological pathways. However - despite these recent advances - pathogenesis of EIM is at best partially understood. Several pathogenic mechanisms have been proposed such as upregulation of tumor necrosis factor, aberrant lymphocyte homing, and cross-reactive antigen presentation. It still remains unclear whether EIM is a direct result of the inflammatory process in the gut or rather a consequence of a shared genetic background leading to dysfunctional immune responses to environmental stimuli. Exploration and understanding of EIM genetics and pathophysiology will pave the road for better and more efficacious treatment options in the future.
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Affiliation(s)
- Thomas Greuter
- a Department of Gastroenterology and Hepatology , University Hospital Zurich , Zurich , Switzerland
| | - Stephan R Vavricka
- a Department of Gastroenterology and Hepatology , University Hospital Zurich , Zurich , Switzerland.,b Center for Gastroenterology and Hepatology , Zurich , Switzerland
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24
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Mertz A, Nguyen NA, Katsanos KH, Kwok RM. Primary sclerosing cholangitis and inflammatory bowel disease comorbidity: an update of the evidence. Ann Gastroenterol 2019; 32:124-133. [PMID: 30837784 PMCID: PMC6394256 DOI: 10.20524/aog.2019.0344] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Accepted: 11/29/2018] [Indexed: 12/12/2022] Open
Abstract
Comorbid primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) represent a unique disease phenotype with a different risk profile than PSC or IBD alone. While the pathogenetic mechanisms behind both diseases remain unclear, recent studies have targeted several immune-mediated pathways in an attempt to find a potential therapeutic target. Patients with PSC-associated IBD typically exhibit pancolitis with a right-to-left intestinal inflammatory gradient associated with a greater incidence of backwash ileitis and rectal sparing. Although there is an increased incidence of pancolitis in this population, bowel symptoms tend to be less significant than in IBD alone. Likewise, the degree of inflammation and symptoms of PSC-associated IBD are characteristically less clinically significant. Despite the relatively quiescent clinical presentation of PSC-associated IBD, there is an increased risk for colorectal and hepatobiliary malignancy making vigilance for malignancy essential.
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Affiliation(s)
- Andrew Mertz
- Department of Internal Medicine (Andrew Mertz), Walter Reed National Military Medical Center Bethesda, MD, USA
| | - Nhu An Nguyen
- Gastroenterology (Nhu An Nguyen, Ryan M. Kwok), Walter Reed National Military Medical Center Bethesda, MD, USA
| | - Konstantinos H Katsanos
- Gastroenterology, Medical School and University Hospital of Ioannina, Greece (Konstantinos H. Katsanos)
| | - Ryan M Kwok
- Gastroenterology (Nhu An Nguyen, Ryan M. Kwok), Walter Reed National Military Medical Center Bethesda, MD, USA
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25
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Isayama H, Tazuma S, Kokudo N, Tanaka A, Tsuyuguchi T, Nakazawa T, Notohara K, Mizuno S, Akamatsu N, Serikawa M, Naitoh I, Hirooka Y, Wakai T, Itoi T, Ebata T, Okaniwa S, Kamisawa T, Kawashima H, Kanno A, Kubota K, Tabata M, Unno M, Takikawa H. Clinical guidelines for primary sclerosing cholangitis 2017. J Gastroenterol 2018; 53:1006-1034. [PMID: 29951926 PMCID: PMC8930933 DOI: 10.1007/s00535-018-1484-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 06/11/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is relatively rare disease and pathogenesis and methods of treatments were still not established. Then, we had conducted the making clinical guidelines to manage patients with PSC based on the literature review and expert opinions. These clinical guidelines were made for the medical doctors on the management of PSC, except child case of PSC. METHODS We had employed modified Delphi method. The production committee decided guidelines, strength of recommendations and evidence level after reviewed literatures systematically, and The Expert panel evaluated those. The Scientific Committee of the Japan Biliary Association (JBA) evaluated revised guidelines, and the Public comments were collected on web site of JBA. RESULTS We had made 16 guidelines about epidemiology/pathophysiology, diagnostics, therapy and prognosis. Also, we had made both diagnostic and therapeutic flow chart. CONCLUSIONS We hope that these guidelines will contribute to the improvement and development of the medical care of PSC.
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Affiliation(s)
- Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Susumu Tazuma
- Department of General Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Toshio Tsuyuguchi
- Department of Medicine and Gastroenterology, Chiba University, Chiba, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Suguru Mizuno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Yoshiki Hirooka
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinji Okaniwa
- Department of Gastroenterology, Iida Municipal Hospital, Nagano, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Komagome Metropolitan Hospital, Tokyo, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Atsushi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Keiichi Kubota
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Masami Tabata
- Department of Surgery, Matsusaka Central General Hospital, Matsusaka, Mie, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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26
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Tabibian JH, Bowlus CL. WITHDRAWN: Primary sclerosing cholangitis: A review and update. LIVER RESEARCH 2018. [DOI: 10.1016/j.livres.2017.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Tabibian JH, Bowlus CL. Primary sclerosing cholangitis: A review and update. LIVER RESEARCH (BEIJING, CHINA) 2017; 1:221-230. [PMID: 29977644 PMCID: PMC6028044 DOI: 10.1016/j.livres.2017.12.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease of uncertain etiology characterized biochemically by cholestasis and histologically and cholangiographically by fibro-obliterative inflammation of the bile ducts. In a clinically significant proportion of patients, PSC progresses to cirrhosis, end-stage liver disease, and/or hepatobiliary cancer, though the disease course can be highly variable. Despite clinical trials of numerous pharmacotherapies over several decades, safe and effective medical therapy remains to be established. Liver transplantation is an option for select patients with severe complications of PSC, and its outcomes are generally favorable. Periodic surveillance testing for pre- as well as post-transplant patients is a cornerstone of preventive care and health maintenance. Here we provide an overview of PSC including its epidemiology, etiopathogenesis, clinical features, associated disorders, surveillance, and emerging potential therapies.
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Affiliation(s)
- James H. Tabibian
- Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
- Division of Gastroenterology, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Christopher L. Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic disease leading to fibrotic scarring of the intrahepatic and extrahepatic bile ducts, causing considerable morbidity and mortality via the development of cholestatic liver cirrhosis, concurrent IBD and a high risk of bile duct cancer. Expectations have been high that genetic studies would determine key factors in PSC pathogenesis to support the development of effective medical therapies. Through the application of genome-wide association studies, a large number of disease susceptibility genes have been identified. The overall genetic architecture of PSC shares features with both autoimmune diseases and IBD. Strong human leukocyte antigen gene associations, along with several susceptibility genes that are critically involved in T-cell function, support the involvement of adaptive immune responses in disease pathogenesis, and position PSC as an autoimmune disease. In this Review, we survey the developments that have led to these gene discoveries. We also elaborate relevant interpretations of individual gene findings in the context of established disease models in PSC, and propose relevant translational research efforts to pursue novel insights.
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Abstract
PURPOSE OF REVIEW Primary sclerosing cholangitis (PSC) is a rare, idiopathic biliary disease often with an insidious onset, variable disease course, and premature death related to benign and malignant PSC-related sequelae. This review aims to discuss the epidemiology, clinical variants, and natural history of PSC, incorporating data from recent population-based studies. RECENT FINDINGS PSC naturally leads to cirrhosis, cholangiocarcinoma, other hepatobiliary malignancies, dominant strictures, hepatic osteodystrophy, and bacterial cholangitis. The incidence of PSC appears to be increasing, the reasons for which are unclear. The time from diagnosis to liver transplant appears to be longer in more recent studies compared with earlier studies, suggesting a better overall prognosis than previously believed. In addition, with an increasing number of patients undergoing liver transplantation for PSC, the frequency of death because of liver failure has decreased, whereas cancer-related deaths have increased among patients with PSC. SUMMARY PSC is a heterogeneous disease with a variety of clinical outcomes, both fatal and nonfatal. The progression of liver fibrosis in an individual patient is difficult to predict and may vary from a relatively benign, nonprogressive form to a rapidly progressive form with the need for liver transplantation.
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Pan HY, Dai YN, Zheng JN, Shi KQ, Poucke SV, Zou H, Zheng MH. National incidence of autoimmune liver diseases and its relationship with the human development index. Oncotarget 2016; 7:46273-46282. [PMID: 27323833 PMCID: PMC5216797 DOI: 10.18632/oncotarget.10090] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2016] [Accepted: 06/02/2016] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and immunoglobulin G4 related cholangitis represent the major autoimmune liver diseases (AILD). However, the relationship between AILD incidence and socioeconomic development levels is yet to be explored. RESULTS A total of 43 studies were included. There was a positive but not significant correlation between the PBC incidence and HDI on a global level (r=0.348, P=0.082). However, in Europe, a significantly positive correlation existed between the PBC incidence and HDI (r=0.455, P=0.044). No statistical correlation between PSC incidence and HDI was observed (r=0.116, P=0.706). The incidence of AIH revealed a positive correlation with the national HDI both globally (r=0.638, P=0.014) and in Europe (r=0.644, P=0.045). Moreover, the PBC incidence demonstrated a positive correlation with the health index (r=0.422, P=0.036), but a negative correlation with the education index (r= -0.650, P<0.01). Moreover, the income index presented a positive correlation with both the PSC incidence (r=0.599, P=0.031) and the AIH incidence (r=0.649, P=0.012). METHODS PubMed was searched to identify relevant epidemiological studies on AILD. The human development index (HDI) was applied as an indicator for socioeconomic development. HDI data were obtained and calculated based on the 2014 Human Development Report. Pearson coefficient and linear regression analysis were conducted to estimate the correlation between incidence and HDI. CONCLUSIONS There is positive association between the national incidence of AILD and the socioeconomic status, as measured by HDI. In less-developed countries, the incidence of AILD, especially PBC and AIH, might be less common.
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Affiliation(s)
- Hong-Ying Pan
- Department of Infection Diseases, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Yi-Ning Dai
- Department of Infection Diseases, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Ji-Na Zheng
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- School of The First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Ke-Qing Shi
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
| | - Sven Van Poucke
- Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain Therapy, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Hai Zou
- Department of Infection Diseases, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Ming-Hua Zheng
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
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Tanaka A, Mertens JC. Ulcerative Colitis with and without Primary Sclerosing Cholangitis: Two Different Diseases? Inflamm Intest Dis 2016; 1:9-14. [PMID: 29922654 DOI: 10.1159/000445259] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2016] [Accepted: 03/08/2016] [Indexed: 12/20/2022] Open
Abstract
Background Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin and an important hepatobiliary complication of inflammatory bowel diseases (IBD), especially ulcerative colitis (UC). When further differentiated, about 3-8% of UC patients suffer from PSC, whereas among Crohn's disease patients the reported prevalence of PSC is probably between 1 and 3.5%. Although it was reported from Japan that the frequency of PSC in UC was only 34%, the same registry data indicated that the prevalence was up to 57% among young patients with PSC even in Japan, which is comparable to the 60-80% in Europe and the US. Additionally, the clinical features of UC in patients with PSC are different from those in patients without PSC, for instance, rectal sparing and right-sided dominance. Summary The strong link between atypical IBD and PSC suggests that the pathogenesis of PSC involves pathology of the gut, including abnormal gut microbiota and aberrant activation of mucosal lymphocytes. These seem to be different in UC PSC as compared to the pathology of typical UC. Key Messages The key to solving the question 'Is there a difference between East and West?' are genetic studies, genome-wide association studies of PSC in particular, which have already been performed in the West and are strongly warranted in the East.
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Affiliation(s)
- Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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Nakamoto N, Schnabl B. Does the Intestinal Microbiota Explain Differences in the Epidemiology of Liver Disease between East and West? Inflamm Intest Dis 2016; 1:3-8. [PMID: 27243019 DOI: 10.1159/000443196] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Changes in bacterial communities are associated with the pathogenesis of many diseases including inflammatory bowel disease and liver disease. Dysbiosis can induce intestinal inflammation resulting in increased intestinal permeability and bacterial translocation. The majority of chronic liver diseases are associated with bacterial translocation resulting in or enhancing an inflammatory response in the liver. Intestinal inflammation and a dysfunctional intestinal barrier are not sufficient to cause liver disease in the absence of an additional liver insult. In this article, the authors summarize differences in intestinal microbiota composition between Eastern and Western countries. The authors specifically discuss whether differences in microbiota composition could explain the epidemiological differences in liver disease found in Asia and Europe/the USA.
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Affiliation(s)
| | - Bernd Schnabl
- Department of Medicine, University of California, San Diego, La Jolla, Calif., USA; Department of Medicine, VA San Diego Healthcare System, San Diego, Calif., USA
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Seo N, Kim SY, Lee SS, Byun JH, Kim JH, Kim HJ, Lee MG. Sclerosing Cholangitis: Clinicopathologic Features, Imaging Spectrum, and Systemic Approach to Differential Diagnosis. Korean J Radiol 2016; 17:25-38. [PMID: 26798213 PMCID: PMC4720808 DOI: 10.3348/kjr.2016.17.1.25] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 10/23/2015] [Indexed: 12/14/2022] Open
Abstract
Sclerosing cholangitis is a spectrum of chronic progressive cholestatic liver disease characterized by inflammation, fibrosis, and stricture of the bile ducts, which can be classified as primary and secondary sclerosing cholangitis. Primary sclerosing cholangitis is a chronic progressive liver disease of unknown cause. On the other hand, secondary sclerosing cholangitis has identifiable causes that include immunoglobulin G4-related sclerosing disease, recurrent pyogenic cholangitis, ischemic cholangitis, acquired immunodeficiency syndrome-related cholangitis, and eosinophilic cholangitis. In this review, we suggest a systemic approach to the differential diagnosis of sclerosing cholangitis based on the clinical and laboratory findings, as well as the typical imaging features on computed tomography and magnetic resonance (MR) imaging with MR cholangiography. Familiarity with various etiologies of sclerosing cholangitis and awareness of their typical clinical and imaging findings are essential for an accurate diagnosis and appropriate management.
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Affiliation(s)
- Nieun Seo
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
| | - Moon-Gyu Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
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Nakazawa T, Naitoh I, Hayashi K, Sano H, Miyabe K, Shimizu S, Joh T. Inflammatory bowel disease of primary sclerosing cholangitis: A distinct entity? World J Gastroenterol 2014; 20:3245-3254. [PMID: 24696608 PMCID: PMC3964396 DOI: 10.3748/wjg.v20.i12.3245] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 10/04/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
This is a review of the characteristic findings of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) and their usefulness in the diagnosis of sclerosing cholangitis. PSC is a chronic inflammatory disease characterized by idiopathic fibrous obstruction and is frequently associated with IBD. IBD-associated with PSC (PSC-IBD) shows an increased incidence of pancolitis, mild symptoms, and colorectal malignancy. Although an increased incidence of pancolitis is a characteristic finding, some cases are endoscopically diagnosed as right-sided ulcerative colitis. Pathological studies have revealed that inflammation occurs more frequently in the right colon than the left colon. The frequency of rectal sparing and backwash ileitis should be investigated in a future study based on the same definition. The cholangiographic findings of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are similar to those of PSC. The rare association between IBD and IgG4-SC and the unique characteristics of PSC-IBD are useful findings for distinguishing PSC from IgG4-SC.
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Tanaka A, Tazuma S, Okazaki K, Tsubouchi H, Inui K, Takikawa H. Nationwide survey for primary sclerosing cholangitis and IgG4-related sclerosing cholangitis in Japan. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2013; 21:43-50. [PMID: 24353071 DOI: 10.1002/jhbp.50] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND We previously conducted nationwide surveys for primary sclerosing cholangitis (PSC) in Japan, and demonstrated several characteristic features of Japanese PSC patients, yet patients with IgG4-related sclerosing cholangitis (IgG4-SC) might be misdiagnosed as PSC. Since the clinical diagnostic criteria of IgG4-SC were established in 2012, we again conducted a nationwide survey to investigate the characteristics of PSC and IgG4-SC lacking pancreatic involvement. METHODS The design was a questionnaire-based, multi-center retrospective study. The enrolled subjects were patients with PSC and IgG4-SC without pancreatic involvement diagnosed after 2005. RESULTS We enrolled 197 PSC and 43 IgG4-SC patients without pancreatic lesions. The male dominance was significantly evident in IgG4-SC (P = 0.006). In patients with PSC, two peaks in age distribution were clearly observed. IgG4-SC was not detected in any patient younger than 45 years of age. At presentation, serum albumin and IgM were significantly higher in PSC, while serum IgG and IgG4 were significantly elevated in IgG4-SC. Inflammatory bowel disease (IBD) was detected in only 68/197 PSC patients (34%). The prognosis of IgG4-SC was considerably better than that of PSC. CONCLUSION We confirmed several interesting clinical details of PSC in Japanese patients: two peaks in the age distribution and lower prevalence of IBD.
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Affiliation(s)
- Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
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Tanaka A, Takikawa H. Geoepidemiology of primary sclerosing cholangitis: A critical review. J Autoimmun 2013; 46:35-40. [DOI: 10.1016/j.jaut.2013.07.005] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Accepted: 07/11/2013] [Indexed: 12/20/2022]
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Eaton JE, Talwalkar JA, Lazaridis KN, Gores GJ, Lindor KD. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology 2013; 145:521-36. [PMID: 23827861 PMCID: PMC3815445 DOI: 10.1053/j.gastro.2013.06.052] [Citation(s) in RCA: 289] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 05/18/2013] [Accepted: 06/24/2013] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis (PSC), first described in the mid-1850s, is a complex liver disease that is heterogeneous in its presentation. PSC is characterized by chronic cholestasis associated with chronic inflammation of the biliary epithelium, resulting in multifocal bile duct strictures that can affect the entire biliary tree. Chronic inflammation leads to fibrosis involving the hepatic parenchyma and biliary tree, which can lead to cirrhosis and malignancy. The etiology of PSC is not fully understood, which in part explains the lack of effective medical therapy for this condition. However, we have begun to better understand the molecular pathogenesis of PSC. The recognition of specific clinical subtypes and their pattern of progression could improve phenotypic and genotypic classification of the disease. We review our current understanding of this enigmatic disorder and discuss important topics for future studies.
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Affiliation(s)
- John E. Eaton
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN
| | - Jayant A. Talwalkar
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN,Corresponding Author: Jayant A. Talwalkar, M.D., M.P.H., Professor of Medicine, Division of Gastroenterology & Hepatology, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, Secretary: 507-284-4823, Fax: 507-284-0538,
| | | | - Gregory J. Gores
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN
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Prideaux L, Kamm MA, De Cruz PP, Chan FKL, Ng SC. Inflammatory bowel disease in Asia: a systematic review. J Gastroenterol Hepatol 2012; 27:1266-80. [PMID: 22497584 DOI: 10.1111/j.1440-1746.2012.07150.x] [Citation(s) in RCA: 264] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The incidence and prevalence of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are lower in Asia than in the West. However, across Asia the incidence and prevalence of IBD has increased rapidly over the last two to four decades. These changes may relate to increased contact with the West, westernization of diet, increasing antibiotics use, improved hygiene, vaccinations, or changes in the gut microbiota. Genetic factors also differ between Asians and the Caucasians. In Asia, UC is more prevalent than CD, although CD incidence is rapidly increasing in certain areas. There is a male predominance of CD in Asia, but a trend towards equal sex distribution for UC. IBD is diagnosed at a slightly older age than in the West, and there is rarely a second incidence peak as in the West. A positive family history is much less common than in the West, as are extra-intestinal disease manifestations. There are clear ethnic differences in incidence within countries in Asia, and an increased incidence in IBD in migrants from Asia to the West. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.
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Affiliation(s)
- Lani Prideaux
- Department of Gastroenterology St Vincent's Hospital Melbourne and University of Melbourne, Fitzroy, Victoria, Australia
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tract leading to progressive obstruction, fibrosis and eventually liver cirrhosis. In some countries it ranks among the most frequent indications for liver transplantation. PSC is also a carcinogenic condition in which the risk of hepatobiliary carcinoma, especially cholangiocarcinoma, is greatly increased. Patients with associated inflammatory bowel disease involving the colon run an increased risk of colorectal carcinoma. Currently, there is no medical therapy with a proven benefit in halting disease progression.
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Affiliation(s)
- Cyriel Y Ponsioen
- Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
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Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol 2012; 56:1181-1188. [PMID: 22245904 DOI: 10.1016/j.jhep.2011.10.025] [Citation(s) in RCA: 439] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2011] [Revised: 09/29/2011] [Accepted: 10/03/2011] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Studies on the epidemiology of primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) show variable outcome. We aimed at systematically reviewing the incidence and prevalence rates, as well as geographical distribution and temporal trends of PSC and PBC. DATA SOURCES A systematic search of literature was performed in Medline and EMBASE (search last conducted January 10th, 2011). STUDY SELECTION Population-based epidemiological studies reporting incidence and/or prevalence rates for PSC or PBC in a defined geographical area of at least 100,000 adult inhabitants were considered relevant. DATA EXTRACTION Study area, study period, number of patients, number of inhabitants, incidence per 100,000 inhabitants per year, prevalence per 100,000 inhabitants, method of case-finding, method of case-ascertainment, male/female ratio and in case of PSC, occurrence of inflammatory bowel diseases (IBD) were extracted from retrieved articles. RESULTS The literature search yielded 2286 abstracts of which 31 articles fulfilled all inclusion criteria. Studies varied in size from 10 to 770 patients in catchment areas from 100,312 to 19,230,000 inhabitants. The incidence and prevalence rates for PSC range from 0 to 1.3 per 100,000 inhabitants/year and 0-16.2 per 100,000 inhabitants, respectively. PBC incidence rates range from 0.33 to 5.8 per 100,000 inhabitants/year and prevalence rates range from 1.91 to 40.2 per 100,000 inhabitants; prevalence rates are increasing in time. CONCLUSIONS Incidence and prevalence rates of both PSC and PBC vary widely and seem to be increasing. True population-based studies are scarce and therefore large population-based studies combining meticulous case-finding and case-ascertainment strategies are necessary.
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Affiliation(s)
- Kirsten Boonstra
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
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Fosby B, Karlsen TH, Melum E. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis. World J Gastroenterol 2012; 18:1-15. [PMID: 22228965 PMCID: PMC3251800 DOI: 10.3748/wjg.v18.i1.1] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2011] [Revised: 06/15/2011] [Accepted: 06/22/2011] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to fibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can influence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible influence of rejection on the risk of recurrent disease in the allograft.
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Ngu JH, Gearry RB, Wright AJ, Stedman CAM. Inflammatory bowel disease is associated with poor outcomes of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2011; 9:1092-7; quiz e135. [PMID: 21893134 DOI: 10.1016/j.cgh.2011.08.027] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2011] [Revised: 08/19/2011] [Accepted: 08/27/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about the exact etiology of primary sclerosing cholangitis (PSC); epidemiologic data are scarce. We performed a population-based epidemiologic study of PSC in Canterbury, New Zealand. METHODS By using multiple case-finding methods, we searched public and private adult and pediatric outpatient clinics, hospital discharge summaries, and radiology and pathology reports to identify all cases of PSC in the region. Cases were included if PSC was identified by endoscopic retrograde cholangiography, magnetic resonance cholangiography, or liver biopsy analysis (n = 79). RESULTS The incidence of PSC in 2008 was 1.6 per 100,000 persons (95% confidence interval [CI], 0.5-2.7). The point prevalence on December 31, 2008, was 11.7 per 100,000 persons (95% CI, 8.7-14.8). The mean and median ages at diagnosis were 50 years (95% CI, 46-53 years) and 49 years (range, 17-80 years), respectively. Patients who had inflammatory bowel disease (IBD) presented with PSC earlier than those without IBD (P = .003), were more likely to develop serious malignant complications (P = .017), and were more likely to require liver transplantation or die (P = .03). CONCLUSIONS In a population-based epidemiology study of PSC in Canterbury, New Zealand, we observed large differences between PSC patients with or without concurrent IBD in age at diagnosis, development of cancer, mortality, and requirement for liver transplantation. IBD therefore affects outcomes of patients with PSC, an important observation that requires further study.
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Affiliation(s)
- Jing Hieng Ngu
- Department of Gastroenterology, Christchurch Hospital, Christchurch, Canterbury, New Zealand
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic fibroinflammatory syndrome involving the biliary tract, often accompanied by inflammatory bowel disease (IBD). This syndrome is a prototype disease linking chronic inflammation to carcinogenesis. Indeed, PSC is associated with an increased risk of cholangiocarcinoma (CCA), gallbladder cancer, hepatocellular carcinoma (HCC), and colorectal cancer. Herein, we review the risk for these malignancies in PSC and discuss rational cancer surveillance strategies for these patients. Where evidence is limited, we suggest a pragmatic approach. In this regard, we recommend interval screening for CCA with noninvasive imaging modalities and serum carbohydrate antigen 19-9 determinations annually. These imaging studies also serve to screen for gallbladder cancer and HCC. Screening for colorectal cancer is more firmly established in PSC patients with IBD and includes colonoscopy at the time of PSC diagnosis and, thereafter, at 1-2-year intervals. We also highlight areas where more information is required, such as management of biliary tract dysplasia and cancer chemoprevention in PSC.
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Affiliation(s)
- Nataliya Razumilava
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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Toy E, Balasubramanian S, Selmi C, Li CS, Bowlus CL. The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population. BMC Gastroenterol 2011; 11:83. [PMID: 21767410 PMCID: PMC3160402 DOI: 10.1186/1471-230x-11-83] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2011] [Accepted: 07/18/2011] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease often associated with inflammatory bowel diseases (IBD). Current epidemiological data are limited to studies of predominantly Caucasian populations. Our aim was to define the epidemiology of PSC in a large, ethnically diverse US population. METHODS The Northern California Kaiser Permanente (KP) database includes records from over 3 million people and was searched for cases of PSC between January 2000 and October 2006. All identified charts were reviewed for diagnosis confirmation, IBD co-morbidity, and major natural history endpoints. RESULTS We identified 169 (101 males) cases fulfilling PSC diagnostic criteria with a mean age at diagnosis of 44 years (range 11-81). The age-adjusted point prevalence was 4.15 per 100,000 on December 31, 2005. The age-adjusted incidence per 100,000 person-years was not significantly greater in men 0.45 (95% CI 0.33-0.61) than women 0.37 (95% CI 0.26-0.51). IBD was present in 109/169 (64.5%) cases and was significantly more frequent in men than women with PSC (73.3% and 51.5%, respectively, p = 0.005). The cumulative average yearly mortality rate was 1.9%. Age and serum sodium, creatinine and bilirubin at diagnosis and albumin at last entry were identified as significant factors associated with death, liver transplant or cholangiocarcinoma. CONCLUSIONS The incidence and prevalence of PSC observed in a representative Northern California population are lower compared to previous studies in Caucasian populations and this might reflect differences in the incidence of PSC among various ethnic groups.
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Affiliation(s)
- Elaine Toy
- Department of Medicine, University of California Davis Medical Center, Sacramento, CA, USA
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Andraus W, Haddad L, Nacif LS, Silva FD, Blasbalg R, D'Albuquerque LAC. The best approach for diagnosing primary sclerosing cholangitis. Clinics (Sao Paulo) 2011; 66:1987-1989. [PMID: 22086533 PMCID: PMC3203975 DOI: 10.1590/s1807-59322011001100022] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Wellington Andraus
- Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
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Parés A. [Primary sclerosing cholangitis: diagnosis, prognosis and treatment]. GASTROENTEROLOGIA Y HEPATOLOGIA 2011; 34:41-52. [PMID: 20435377 DOI: 10.1016/j.gastrohep.2010.02.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2010] [Accepted: 02/12/2010] [Indexed: 05/29/2023]
Abstract
Primary sclerosing cholangitis is a chronic cholestatic disease characterized by inflammation with fibrosis and obliteration of the intra- and extrahepatic bile ducts. This disease is usually associated with ulcerative colitis. The process of chronic cholestasis eventually leads to biliary cirrhosis. The prevalence of primary sclerosing cholangitis is low in southern Europe but is especially high in Scandinavian countries. The etiopathogenesis is unknown but immune disorders, potential toxic agents or intestinal infections, ischemic injury to the bile ducts, and possibly alterations in hepatobiliary transporters are known to play a role. The disease manifests at the age of approximately 40 years, mainly in men with clinical and laboratory features of cholestasis but may also be asymptomatic. There are specific forms in which the small intrahepatic bile ducts are involved, mainly affecting children, as well as overlap syndromes with autoimmune hepatitis. A form characterized by an increase in IgG4 has been described, which is usually associated with autoimmune pancreatitis. The key diagnostic procedure is endoscopic retrograde cholangiography, although magnetic resonance cholangiography is the first diagnostic procedure that should be used since it is equally informative and non-invasive. Liver biopsy is not essential for diagnosis. Primary sclerosing cholangitis is a progressive disease with a probability of transplant-free survival of 18 years in asymptomatic forms and of 8.5 years in symptomatic forms. Cholangiocarcinoma can result from the disease and confers a poor prognosis. There is no specific treatment although ursodeoxycholic acid improves the biochemical alterations of cholestasis. Liver transplantation is the last therapeutic resort with good results in terms of survival although the disease can recur in the transplanted liver.
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Affiliation(s)
- Albert Parés
- Unidad de Hepatología, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Universidad de Barcelona, Barcelona, Spain.
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Bowlus CL, Li CS, Karlsen TH, Lie BA, Selmi C. Primary sclerosing cholangitis in genetically diverse populations listed for liver transplantation: unique clinical and human leukocyte antigen associations. Liver Transpl 2010; 16:1324-30. [PMID: 21031548 PMCID: PMC2967453 DOI: 10.1002/lt.22161] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Primary sclerosing cholangitis (PSC) is well characterized in European populations. We aimed to characterize clinical characteristics and human leukocyte antigen (HLA) associations in a population of European American, Hispanic, and African American PSC patients listed for liver transplantation (LT). Population-stratified demographic, clinical, and HLA data from 6767 LT registrants of the United Network for Organ Sharing who had a diagnosis of PSC (4.7% of the registrants) were compared to data from registrants with other diagnoses. Compared to European Americans and Hispanics, African Americans were significantly younger (46.6 ± 13.7, 42.3 ± 15.9, and 39.7 ± 13.1 years, respectively; P = 0.002) and were listed with a higher Model for End-Stage Liver Disease score (15.2 ± 7.5, 14.9 ± 7.6, and 18.1 ± 9.3, respectively; P = 0.001); they were also less frequently noted to have inflammatory bowel disease in comparison with European Americans (71.4% versus 60.5%, P < 0.01). In multivariate analysis, African origin was a significant factor associated with listing for LT with PSC (odds ratio with respect to European Americans = 1.325, 95% confidence interval = 1.221-1.438). HLA associations in European Americans, Hispanics, and African Americans with PSC versus alcoholic liver disease were detected for HLA-B8, HLA-DR13, and protective HLA-DR4. However, HLA-DR3, which is in linkage disequilibrium with HLA-B8, showed associations only in European Americans and Hispanics. In conclusion, African Americans with PSC who are listed for LT differ clinically from European Americans and Hispanics. The association with HLA-B8 but not HLA-DR3 in African Americans should make possible the refinement of the HLA associations in PSC.
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Affiliation(s)
| | - Chin-Shang Li
- Department of Public Health Sciences, Division of Biostatistics, University of California Davis
| | - Tom H. Karlsen
- Norwegian PSC research center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Benedicte A. Lie
- Institute of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Carlo Selmi
- Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, IRCCS Istituto Clinico Humanitas, University of Milan, Italy
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Karlsen TH, Schrumpf E, Boberg KM. Primary sclerosing cholangitis. Best Pract Res Clin Gastroenterol 2010; 24:655-66. [PMID: 20955968 DOI: 10.1016/j.bpg.2010.07.005] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2010] [Revised: 07/15/2010] [Accepted: 07/16/2010] [Indexed: 01/31/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic bile duct disease leading to fibrotic biliary strictures and liver cirrhosis. The patient population is heterogeneous with regard to disease progression and the presence of co-morbidities, complicating the practical handling of patients as well as studies of pathogenetic mechanisms. The aetiology of PSC is unknown, but the recent findings of several robust susceptibility genes emphasise the importance of genetic risk factors. There is no effective medical treatment available to delay the disease progression, but endoscopic therapy of biliary stenoses may be indicated. Follow-up of patients includes management of the inflammatory bowel disease that is found in the majority of cases along with investigations aimed at the early detection of cholangiocarcinoma and colorectal cancer, which also occur at increased frequencies. In the present review, we aim to summarise the present knowledge of PSC with a particular emphasis on the possible basis of disease variability.
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Affiliation(s)
- Tom H Karlsen
- Norwegian PSC Research Center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway.
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