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Vajsova A, Cahova M, Bajer L, Sticova E, Juskova I, Hlavaty M, Fabian O. Unique clinical, morphological, and molecular characteristics of tumors associated with PSC-IBD. Virchows Arch 2025; 486:651-661. [PMID: 40102272 PMCID: PMC12018527 DOI: 10.1007/s00428-025-04072-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/27/2025] [Accepted: 03/04/2025] [Indexed: 03/20/2025]
Abstract
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree, leading to significant liver function impairment over time. There is a strong association with inflammatory bowel diseases (IBD), together representing a distinct and complex medical condition. Patients with PSC-IBD face a heightened risk of various cancers, particularly colorectal carcinoma (CRC) and cholangiocarcinoma (CCA) as the most common types. In this review, we aim to characterize the distinctive features of PSC-IBD-associated carcinomas. Cancer pathogenesis in PSC-IBD is shaped by various factors including dysregulated bile acid metabolism, gut dysbiosis, and unique immune responses. PSC-IBD-associated CRC is often right-sided and warrants vigilant monitoring due to its higher incidence and unique morphological features compared to CRC arising in the terrain of IBD alone. CCA shares substantial genetic similarities with extrahepatic CCA and poses diagnostic challenges since it is frequently detected at advanced stages due to symptom overlap with PSC. Besides, reliable predictive biomarkers for targeted therapy remain largely unexplored. The distinct molecular, genetic, and histopathological profiles of CRC and CCA in PSC-IBD underscore the complexity of these malignancies and highlight the need for continued research to develop precise therapeutic strategies.
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Affiliation(s)
- Andrea Vajsova
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, 14021, Czech Republic.
- Institute of Pathology of the First Faculty of Medicine and General Teaching Hospital, Prague, 12800, Czech Republic.
| | - Monika Cahova
- Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, Prague, 14021, Czech Republic
| | - Lukas Bajer
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, 14021 , Czech Republic
- Department of Internal Medicine, Second Faculty of Medicine, Charles University, Prague, 15000, Czech Republic
| | - Eva Sticova
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, 14021, Czech Republic
- Department of Pathology, Royal Vinohrady Teaching Hospital, Srobarova 1150/50, Prague, 10000, Czech Republic
| | - Ivana Juskova
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, 14021, Czech Republic
| | - Mojmir Hlavaty
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, 14021 , Czech Republic
| | - Ondrej Fabian
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, 14021, Czech Republic
- Department of Pathology and Molecular Medicine, 3rd Faculty of Medicine, Charles University and Thomayer Hospital, Prague, 14059, Czech Republic
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Souza M, Lima LCV, Al-Sharif L, Huang DQ. Incidence of Hepatobiliary Malignancies in Primary Sclerosing Cholangitis: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2024:S1542-3565(24)01043-7. [PMID: 39709139 DOI: 10.1016/j.cgh.2024.09.037] [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: 03/01/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND & AIMS Primary sclerosing cholangitis (PSC) is a known risk factor for hepatobiliary malignancies. We conducted a systematic review and meta-analysis of published studies to determine the incidence and risk factors for hepatobiliary malignancies in people with PSC. METHODS Pubmed and Embase databases were searched from inception to April 10, 2024, for cohort studies reporting data on the incidence of cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), or gallbladder cancer (GBC) in PSC. Pooled incidence rates with 95% confidence intervals (CIs) were estimated using a random effects model. RESULTS We identified 51 eligible studies involving 26,482 patients. The total follow-up was 221,258.1 person-years (PYs). The pooled incidence rates for overall PSC were 9.31 (95% CI, 6.84-12.67; I2 = 74%), 1.73 (95% CI, 1.20-2.51; I2 = 55%), and 1.06 (95% CI, 0.85-1.31; I2 = 0%) per 1000 PYs for CCA, HCC, and GBC, respectively. In patients with PSC with inflammatory bowel disease (IBD), rates were 7.16 (95% CI, 4.48-11.44; I2 = 96%), 2.19 (95% CI, 1.48-3.25; I2 = 58%), and 1.52 (95% CI, 1.21-1.90; I2 = 0%) per 1000 PYs, respectively. Subgroup analysis showed that the incidence of CCA was higher in smaller studies (<200 patients), and the incidence of HCC varied significantly by region (P = .03), with Oceania having the highest incidence and Europe having the lowest. Meta-regression determined that PSC-IBD was associated with HCC incidence. CONCLUSION The incidence of CCA in PSC is substantial, whereas HCC and GBC are rare. Patients with PSC-IBD may be at higher risk for HCC. These data should be validated in large, prospective studies, and may guide the development of evidence-based surveillance strategies for hepatobiliary malignancies in PSC.
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Affiliation(s)
- Matheus Souza
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Luan C V Lima
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Lubna Al-Sharif
- Department of Biomedical Sciences and Basic Clinical Skills, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
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Cançado GGL, Hirschfield GM. Management of primary sclerosing cholangitis: Current state-of-the-art. Hepatol Commun 2024; 8:e0590. [PMID: 39774274 PMCID: PMC11567710 DOI: 10.1097/hc9.0000000000000590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 10/08/2024] [Indexed: 01/11/2025] Open
Abstract
Primary sclerosing cholangitis is a chronic liver disease characterized by progressive inflammation and fibrosis of medium-large bile ducts, most commonly in association with inflammatory bowel disease. Most patients have a progressive disease course, alongside a heightened risk of hepatobiliary and colorectal cancer. Medical therapies are lacking, and this, in part, reflects a poor grasp of disease biology. As a result, current management is largely supportive, with liver transplantation an effective life-prolonging intervention when needed, but not one that cures disease. Emerging therapies targeting disease progression, as well as symptoms such as pruritus, continue to be explored. The trial design is increasingly cognizant of the application of thoughtful inclusion criteria, as well as better endpoints aimed at using surrogates of disease that can identify treatment benefits early. This is hoped to facilitate much-needed advances toward developing safe and effective interventions for patients.
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Hussain N, Trivedi PJ. Risk Stratification in Primary Sclerosing Cholangitis: Does Size Matter? Dig Dis Sci 2024; 69:1083-1087. [PMID: 38347370 DOI: 10.1007/s10620-023-08262-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 12/19/2023] [Indexed: 04/19/2024]
Affiliation(s)
- Nasir Hussain
- National Institute of Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), University of Birmingham, Birmingham, UK
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, UK
| | - Palak J Trivedi
- National Institute of Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), University of Birmingham, Birmingham, UK.
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
- Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, UK.
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Are VS, Gromski MA, Akisik F, Vilar-Gomez E, Lammert C, Ghabril M, Vuppalanchi R, Chalasani N. Primary Sclerosing Cholangitis Limited to Intrahepatic Bile Ducts Has Distinctly Better Prognosis. Dig Dis Sci 2024; 69:1421-1429. [PMID: 38347369 DOI: 10.1007/s10620-023-08260-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 07/25/2023] [Indexed: 04/19/2024]
Abstract
BACKGROUND There are two sub-phenotypes of large-duct primary sclerosing cholangitis (PSC): isolated intrahepatic PSC (IIPSC) and extrahepatic disease with or without intrahepatic (extra/intrahepatic). AIMS This study examined the differences in outcomes in patients with IIPSC compared to extra/intrahepatic and small-duct PSC. METHODS Patients with PSC treated at our institution from 1998 to 2019 were investigated. Biochemistries, clinical events, and survival were assessed by chart review and National Death Index. Cox-proportional hazards were used to determine the risk of clinical outcomes based on biliary tract involvement. RESULTS Our cohort comprised 442 patients with large-duct PSC (57 had IIPSC, 385 had extra/intrahepatic PSC) and 23 with small-duct PSC. Median follow-up in the IIPSC group was not significantly different from the extra/intrahepatic group [7 vs. 6 years, P = 0.06]. Except for lower age (mean 37.9 vs. 43.0 years, P = 0.045), the IIPSC group was not different from the extra/intrahepatic. The IIPSC group had longer transplant-free survival (log-rank P = 0.001) with a significantly lower risk for liver transplantation (12% vs. 34%, P < 0.001). The IIPSC group had a lower risk of death or transplantation than the extra/intrahepatic PSC group [HR: 0.34, 95% CI: 0.17-0.67, P < 0.001]. No bile duct or gallbladder cancers developed in patients with IIPSC, compared to 24 in the extra/intrahepatic group. The clinical characteristics and outcomes of IIPSC were similar to 23 individuals with small-duct PSC. CONCLUSIONS Patients with IIPSC have a favorable prognosis similar to small-duct PSC. These data are important for counseling patients and designing therapeutic trials for PSC.
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Affiliation(s)
- Vijay S Are
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Mark A Gromski
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Fatih Akisik
- Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Craig Lammert
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
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Sohal A, Kowdley KV. Novel preclinical developments of the primary sclerosing cholangitis treatment landscape. Expert Opin Investig Drugs 2024; 33:335-345. [PMID: 38480008 DOI: 10.1080/13543784.2024.2330738] [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: 07/10/2023] [Accepted: 03/11/2024] [Indexed: 03/19/2024]
Abstract
INTRODUCTION Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease associated with inflammation, fibrosis, and destruction of intra- and extrahepatic bile ducts. Despite substantial recent advances in our understanding of PSC, the only proven treatment of PSC is liver transplantation. There is an urgent unmet need to find medical therapies for this disorder. AREAS COVERED Multiple drugs are currently under evaluation as therapeutic options for this disease. This article summarizes the literature on the various novel therapeutic options that have been investigated and are currently under development for the treatment of PSC. EXPERT OPINION In the next decade, more than one drug will likely be approved for the treatment of the disease, and we will be looking at combination therapies for the optimal management of the disease.
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Affiliation(s)
- Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, USA
| | - Kris V Kowdley
- Department of Hepatology, Liver Institute Northwest, Seattle, USA
- Elson S. Floyd College of Medicine, Washington State University, Spokane, USA
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Ahmed W, Joshi D, Huggett MT, Everett SM, James M, Menon S, Oppong KW, On W, Paranandi B, Trivedi P, Webster G, Hegade VS. Update on the optimisation of endoscopic retrograde cholangiography (ERC) in patients with primary sclerosing cholangitis. Frontline Gastroenterol 2024; 15:74-83. [PMID: 38487565 PMCID: PMC10935540 DOI: 10.1136/flgastro-2023-102491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 08/28/2023] [Indexed: 03/17/2024] Open
Affiliation(s)
- Wafaa Ahmed
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Deepak Joshi
- Gastroenterology, King's College Hospital Liver Unit, London, UK
| | - Matthew T Huggett
- Gastroenterology, St James's University Hospital, The Leeds Teaching Hospitals NHS Foundation Trust, Leeds, UK
| | - Simon M Everett
- Gastroenterology, St James's University Hospital NHS Trust, Leeds, UK
| | - Martin James
- Gastroenterology, Nottingham University, Nottingham, UK
| | - Shyam Menon
- Department of Hepatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - Wei On
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Bharat Paranandi
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Palak Trivedi
- National Institute for Health Research, Centre for Liver Research, University Hospitals Birmingham, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - George Webster
- Department of Gastroenterology, University College London Hospital NHS Foundation Trust, London, UK
| | - Vinod S Hegade
- Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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8
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Catanzaro E, Gringeri E, Burra P, Gambato M. Primary Sclerosing Cholangitis-Associated Cholangiocarcinoma: From Pathogenesis to Diagnostic and Surveillance Strategies. Cancers (Basel) 2023; 15:4947. [PMID: 37894314 PMCID: PMC10604939 DOI: 10.3390/cancers15204947] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/09/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC), accounting for 2-8% of cases and being the leading cause of death in these patients. The majority of PSC-associated CCAs (PSC-CCA) develop within the first few years after PSC diagnosis. Older age and male sex, as well as concomitant inflammatory bowel disease (IBD) or high-grade biliary stenosis, are some of the most relevant risk factors. A complex combination of molecular mechanisms involving inflammatory pathways, direct cytopathic damage, and epigenetic and genetic alterations are involved in cholangiocytes carcinogenesis. The insidious clinical presentation makes early detection difficult, and the integration of biochemical, radiological, and histological features does not always lead to a definitive diagnosis of PSC-CCA. Surveillance is mandatory, but current guideline strategies failed to improve early detection and consequently a higher patient survival rate. MicroRNAs (miRNAs), gene methylation, proteomic and metabolomic profile, and extracellular vesicle components are some of the novel biomarkers recently applied in PSC-CCA detection with promising results. The integration of these new molecular approaches in PSC diagnosis and monitoring could contribute to new diagnostic and surveillance strategies.
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Affiliation(s)
- Elisa Catanzaro
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Center, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Patrizia Burra
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Martina Gambato
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
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9
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Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, Schramm C, Trauner M. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761-806. [PMID: 35738507 DOI: 10.1016/j.jhep.2022.05.011] [Citation(s) in RCA: 152] [Impact Index Per Article: 50.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/16/2022] [Indexed: 02/07/2023]
Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
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10
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Hrncir HR, Gracz AD. Cellular and transcriptional heterogeneity in the intrahepatic biliary epithelium. GASTRO HEP ADVANCES 2022; 2:108-120. [PMID: 36593993 PMCID: PMC9802653 DOI: 10.1016/j.gastha.2022.07.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 07/19/2022] [Indexed: 01/05/2023]
Abstract
Epithelial tissues comprise heterogeneous cellular subpopulations, which often compartmentalize specialized functions like absorption and secretion to distinct cell types. In the liver, hepatocytes and biliary epithelial cells (BECs; also called cholangiocytes) are the two major epithelial lineages and play distinct roles in (1) metabolism, protein synthesis, detoxification, and (2) bile transport and modification, respectively. Recent technological advances, including single cell transcriptomic assays, have shed new light on well-established heterogeneity among hepatocytes, endothelial cells, and immune cells in the liver. However, a "ground truth" understanding of molecular heterogeneity in BECs has remained elusive, and the field currently lacks a set of consensus biomarkers for identifying BEC subpopulations. Here, we review long-standing definitions of BEC heterogeneity as well as emerging studies that aim to characterize BEC subpopulations using next generation single cell assays. Understanding cellular heterogeneity in the intrahepatic bile ducts holds promise for expanding our foundational mechanistic knowledge of BECs during homeostasis and disease.
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Affiliation(s)
- Hannah R. Hrncir
- Division of Digestive Diseases, Department of Medicine, Emory University, Atlanta, Georgia
- Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, Georgia
| | - Adam D. Gracz
- Division of Digestive Diseases, Department of Medicine, Emory University, Atlanta, Georgia
- Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, Georgia
- Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, Georgia
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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: 5] [Impact Index Per Article: 1.7] [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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Sathiaseelan M, Bolia R, Barallon R, Alex G, Hardikar W, Rajanayagam J. Impact of ulcerative colitis on liver-related outcomes of children with primary sclerosing cholangitis. J Paediatr Child Health 2022; 58:1221-1227. [PMID: 35373867 DOI: 10.1111/jpc.15954] [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: 11/06/2021] [Revised: 03/02/2022] [Accepted: 03/06/2022] [Indexed: 11/26/2022]
Abstract
AIM Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disorder associated with ulcerative colitis (UC). Although the inflammatory bowel disease phenotype has been characterised in patients with PSC, the impact of UC on the course and progression of PSC-UC is less clear. We aimed to evaluate the effects of UC on liver-related outcomes in children with PSC. METHODS Retrospective analysis of children aged ≤18 years diagnosed with PSC with/without UC at a single tertiary paediatric liver unit between January 1998 and May 2016. Patients were followed up until transition to an adult service. Outcomes studied included biliary complications, clinically significant portal hypertension, need for liver transplantation and post-transplantation recurrence. RESULTS Fifty-one children (31 female) were diagnosed with PSC (median age - 11.3 years (interquartile range 7)), follow-up median duration 54 months (interquartile range 56). Thirty-seven (73%) patients had concurrent UC, of which 26 had their diagnosis confirmed prior to or within 6 months of PSC diagnosis (early-onset). PSC complications were more common in children with PSC-UC compared with PSC alone (24/37 (65%) vs. 2/14 (14%); P = 0.001). Furthermore, children with endoscopically mild or moderate UC at diagnosis showed a greater propensity for liver-related complications compared with children with severe UC (24/32 vs. 0/5; P = 0.003). Children with late-onset UC had higher rates of clinically significant portal hypertension (5/11 (45%) vs. 3/26 (12%); P = 0.007) and liver transplantation (5/11(45%) vs. 2/26 (8%); P = 0.02). Children with PSC-UC had significantly higher rates of pancolitis, rectal sparing and milder colitis than those with UC alone. CONCLUSION The presence and a later-onset of UC are associated with more significant progression to end-stage liver disease. There is an inverse trend between UC severity and PSC severity in children with concurrent PSC-UC.
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Affiliation(s)
- Mohana Sathiaseelan
- Department of Gastroenterology, Hepatology and Clinical Nutrition, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Rishi Bolia
- Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, India
| | - Raychel Barallon
- Monash Health, Monash Medical Centre, Victoria, Australia and The University of Melbourne, Department of Medicine, Melbourne, Victoria, Australia
| | - George Alex
- Department of Gastroenterology, Hepatology and Clinical Nutrition, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Winita Hardikar
- Department of Gastroenterology, Hepatology and Clinical Nutrition, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.,Department of Pediatrics, University of Melbourne, Melbourne, Victoria, Australia.,Murdoch Children's Research Institute, Melbourne, Victoria, Australia
| | - Jeremy Rajanayagam
- Department of Gastroenterology, Hepatology and Clinical Nutrition, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.,Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia.,The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
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Hepatic manifestations of systemic disease: an imaging-based review. Pediatr Radiol 2022; 52:852-864. [PMID: 34797394 DOI: 10.1007/s00247-021-05222-5] [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: 06/20/2021] [Revised: 08/28/2021] [Accepted: 10/05/2021] [Indexed: 10/19/2022]
Abstract
The liver is responsible for many processes that maintain human metabolic homeostasis and can be affected by several pediatric systemic diseases. In this manuscript, we explore key pathological findings and imaging features across multiple modalities of a spectrum of congenital, metabolic and autoimmune disorders. Strengthening the radiologists' knowledge regarding potential hepatic manifestations of these systemic diseases will ultimately lead to improved care for pediatric patients.
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14
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Nguyen CM, Kline KT, Stevenson HL, Khan K, Parupudi S. Small duct primary sclerosing cholangitis: A discrete variant or a bridge to large duct disease, a practical review. World J Hepatol 2022; 14:495-503. [PMID: 35582290 PMCID: PMC9055190 DOI: 10.4254/wjh.v14.i3.495] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/12/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
The natural history, associations with inflammatory bowel disease (IBD), and long-term outcomes of large duct primary sclerosing cholangitis (ldPSC) have been well documented. Small duct primary sclerosing cholangitis (sdPSC) is a much less common and relatively more benign variant. The natural history of sdPSC has been difficult to characterize given the limited number of studies in the literature especially with regards to the subset of patients who progress to large duct involvement. It has been unclear whether sdPSC represented a subset of ldPSC, an earlier staging of ldPSC, or a completely separate and distinct entity of its own. Strong associations between sdPSC and IBD have been established with suspicion that concurrent sdPSC-IBD may be a key prognostic factor in determining which patients are at risk of progression to ldPSC. Little is known regarding the discrete circumstances that predisposes some patients with sdPSC to progress to ldPSC. It has been suspected that progression to large biliary duct involvement subjects this subset of patients to potentially developing life-threatening complications. Here the authors conducted a thorough review of the published sdPSC literature using Pubmed searches and cross-referencing to compile all accessible studies regarding cohorts of sdPSC patients in order better characterize the subset of sdPSC patients who progress to ldPSC and the associated outcomes.
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Affiliation(s)
- Christopher M Nguyen
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, United States
| | - Kevin T Kline
- Department of Gastroenterology and Hepatology, The University of Texas Medical Branch, Galveston, TX 77555, United States
| | - Heather L Stevenson
- Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, United States
| | - Kashif Khan
- Department of Gastroenterology and Hepatology, The University of Texas Medical Branch, Galveston, TX 77555, United States
| | - Sreeram Parupudi
- Department of Gastroenterology and Hepatology, The University of Texas Medical Branch, Galveston, TX 77555, United States
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15
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Núñez F P, Castro F, Mezzano G, Quera R, Diaz D, Castro L. Hepatobiliary manifestations in inflammatory bowel disease: A practical approach. World J Hepatol 2022; 14:319-337. [PMID: 35317174 PMCID: PMC8891676 DOI: 10.4254/wjh.v14.i2.319] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 09/10/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are associated with various hepatobiliary disorders. They can occur at any moment in the course of the disease or associated with the treatment. The prevalence of liver dysfunction can reach up to 50% in different studies. Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD, while primary sclerosing cholangitis is the most specific. Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists. The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD, associated diseases or to the therapies used.
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Affiliation(s)
- Paulina Núñez F
- Universidad de los Andes,Inflammatory Bowel Disease Program, Digestive Disease Center, Santiago 7600976, RM, Chile
- Inflammatory Bowel Disease Program, Hospital San Juan de Dios, Universidad de Chile, Santiago 7701230, RM, Chile
| | - Fabiola Castro
- Universidad de los Andes,Hepatology Program, Digestive Disease Center, Santiago 7600976, RM, Chile
| | - Gabriel Mezzano
- Universidad de los Andes,Hepatology Program, Digestive Disease Center, Santiago 7600976, RM, Chile
- Department of Gastroenterology, Hospital del Salvador/Universidad de Chile, Santiago 7600976, RM, Chile
| | - Rodrigo Quera
- Universidad de los Andes,Inflammatory Bowel Disease Program, Digestive Disease Center, Santiago 7600976, RM, Chile
| | - Diego Diaz
- Medicine, Universidad de los Andes, Santiago 770976, RM, Chile
| | - Lorena Castro
- Universidad de los Andes,Hepatology Program, Digestive Disease Center, Santiago 7600976, RM, Chile
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16
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Hensel KO, Kyrana E, Hadzic N, Mann J, Mieli-Vergani G, Gasparetto M, Heuschkel R, Noble-Jamieson G, Samyn M. Sclerosing Cholangitis in Pediatric Inflammatory Bowel Disease: Early Diagnosis and Management Affect Clinical Outcome. J Pediatr 2021; 238:50-56.e3. [PMID: 34303727 DOI: 10.1016/j.jpeds.2021.07.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 07/14/2021] [Accepted: 07/16/2021] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To describe the characteristics and clinical course of children and young persons with inflammatory bowel disease (IBD) and sclerosing cholangitis (SC). STUDY DESIGN Retrospective analysis of clinical characteristics, management, and outcome of two separate cohorts of children and young persons with IBD-SC managed in a tertiary pediatric gastroenterology center and in a tertiary pediatric hepatology center in the UK. RESULTS Eighty-two pediatric patients (31% female) with IBD-SC and a mean age at diagnosis of 11.9 ± 2.8 years were followed up for a mean of 6.8 ± 3.3 years. The most common type of IBD was ulcerative colitis (55%), followed by unclassified IBD (30%) and Crohn's disease (15%). Autoimmune SC (ASC) was diagnosed in 72%, and small duct SC was diagnosed in 28%. Complication-free and native liver survival were 96% and 100%, respectively, at 5 years after diagnosis and 75% and 88%, respectively, at 10 years after diagnosis. Patients in the gastroenterology center, who were diagnosed with liver disease sooner after diagnosis of IBD compared with the hepatology center cohort (mean, 2.7 ± 6.1 months vs 9.3 ± 19.4 months; P = .03), did not develop liver-related complications during follow-up. CONCLUSIONS Our data suggest that children with IBD-SC have better clinical outcomes than have been reported previously, particularly if diagnosed early. We recommend prompt assessment for SC, including liver biopsy and biliary imaging, when liver function abnormalities are detected in a children diagnosed with IBD.
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Affiliation(s)
- Kai O Hensel
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Pediatrics, University of Cambridge, Cambridge, United Kingdom
| | - Eirini Kyrana
- Children's Liver Unit, Leeds General Infirmary, Leeds, United Kingdom
| | - Nedim Hadzic
- Pediatric Liver, GI, and Nutrition Center, King's College Hospital, London, United Kingdom
| | - Jake Mann
- Department of Pediatrics, University of Cambridge, Cambridge, United Kingdom
| | - Giorgina Mieli-Vergani
- Pediatric Liver, GI, and Nutrition Center, King's College Hospital, London, United Kingdom
| | - Marco Gasparetto
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Robert Heuschkel
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Gabriele Noble-Jamieson
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Marianne Samyn
- Pediatric Liver, GI, and Nutrition Center, King's College Hospital, London, United Kingdom.
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17
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Saffioti F, Mavroeidis VK. Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis. World J Gastrointest Oncol 2021; 13:1336-1366. [PMID: 34721770 PMCID: PMC8529934 DOI: 10.4251/wjgo.v13.i10.1336] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/05/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a premalignant condition and a well-documented risk factor for cholangiocarcinoma (CCA) which is the most common malignancy in this setting and the leading cause of deaths in the recent years, with an increasing incidence. PSC-associated CCA has a geographical distribution that follows the incidence of PSC, with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries. It may arise at any location along the biliary tree but is most common in the perihilar area. Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection, which is otherwise the treatment of choice with curative intent in patients with resectable tumours, providing a radical resection with clear margins can be achieved. This largely relates to the commonly advanced stage of liver disease at presentation, which allows consideration for liver resection only for a very limited number of suitable patients with PSC. On the other hand, remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) for the treatment of perihilar CCA, within specific criteria. Excellent results have been achieved particularly for PSC patients with this cancer, who seem to benefit the most from this treatment, having converted this into an accepted indication for transplantation and the standard of care in several experienced centres. Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results. However, as recent studies have shown favourable outcomes in early intrahepatic CCA, it may be that under defined criteria, OLT may play a more prominent role in the future. Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent, when feasible. This review provides insight about particular features of CCA in the setting of PSC, with a main focus on its incidence, considerations relating to its anatomical location and implications to treatment and outcomes, through the viewpoint of historical evolution of management, and future perspectives.
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Affiliation(s)
- Francesca Saffioti
- Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, Oxfordshire, United Kingdom
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital, University College London, London NW3 2QG, United Kingdom
| | - Vasileios K Mavroeidis
- Department of Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, United Kingdom
- Department of Transplant Surgery, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, United Kingdom
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18
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Rogler G, Singh A, Kavanaugh A, Rubin DT. Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management. Gastroenterology 2021; 161:1118-1132. [PMID: 34358489 PMCID: PMC8564770 DOI: 10.1053/j.gastro.2021.07.042] [Citation(s) in RCA: 420] [Impact Index Per Article: 105.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 07/28/2021] [Accepted: 07/28/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel diseases (IBDs) are systemic diseases that manifest not only in the gut and gastrointestinal tract, but also in the extraintestinal organs in many patients. The quality of life for patients with IBD can be substantially affected by these extraintestinal manifestations (EIMs). It is important to have knowledge of the prevalence, pathophysiology, and clinical presentation of EIMs in order to adapt therapeutic options to cover all aspects of IBD. EIMs can occur in up to 24% of patients with IBD before the onset of intestinal symptoms, and need to be recognized to initiate appropriate diagnostic procedures. EIMs most frequently affect joints, skin, or eyes, but can also affect other organs, such as the liver, lung, and pancreas. It is a frequent misconception that a successful therapy of the intestinal inflammation will be sufficient to treat EIMs satisfactorily in most patients with IBD. In general, peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum can be associated with active intestinal inflammation and can improve on standard treatment of the intestinal inflammation. However, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis usually occur independent of disease flares. This review provides a comprehensive overview of epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in IBD.
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Affiliation(s)
- Gerhard Rogler
- Department of Gastroenterology & Hepatology, Department of Medicine, Zurich University Hospital, Zurich, Switzerland
| | - Abha Singh
- University of California, San Diego, La Jolla, CA, USA
| | | | - David T. Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
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19
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Mehta TI, Weissman S, Fung BM, Sotiriadis J, Lindor KD, Tabibian JH. Global incidence, prevalence and features of primary sclerosing cholangitis: A systematic review and meta-analysis. Liver Int 2021; 41:2418-2426. [PMID: 34224208 DOI: 10.1111/liv.15007] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 06/03/2021] [Accepted: 06/08/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Primary sclerosing cholangitis (PSC) is an idiopathic, cholestatic liver disease with a diverse range of clinical manifestations. Inter-regional data on PSC are variable, but its global geoepidemiology has not been well-studied. We aimed to examine the worldwide incidence, prevalence and features of PSC and PSC-inflammatory bowel disease (PSC-IBD). METHODS A systematic search of multiple databases was conducted to identify all original, full-text studies until December 2020 with data regarding the incidence rate (IR) and/or prevalence of PSC. Outcomes were PSC IR, prevalence, features and IBD concurrence. Additionally, a meta-analysis of PSC IR was performed. The study was registered in PROSPERO (CRD42021224550). RESULTS Of the 1003 studies identified, 17 studies spanning three continents were included. PSC IR was 0.60 per 100 000 person-years (PY) (95% confidence interval: 0.37-0.88 per 100 000 PY). In pooled subgroup analysis for studies conducted in Europe and North America, PSC IR was 0.62 and 0.53 per 100 000 PY, respectively. PSC prevalence ranged 0-31.7 per 100 000 persons, with notable inter-regional differences. Mean age at PSC diagnosis was bimodally distributed, with relative peaks at 15 and 35 years. Mean concurrence of IBD with PSC was 50%, with 76% having ulcerative colitis, 17% Crohn's disease and 8% indeterminate/unspecified IBD. CONCLUSION While considerable heterogeneity exists in the geoepidemiology of PSC, overall, the classical dogmata of male predilection, bimodal distribution of mean age and high PSC-IBD concurrence appear to hold true. Despite a seemingly stable IR over time, further studies are needed to better understand the geoepidemiology of PSC.
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Affiliation(s)
- Tej I Mehta
- Department of Radiology, Johns Hopkins University Hospital, Baltimore, MD, USA
| | - Simcha Weissman
- Department of Medicine, Hackensack University-Palisades Medical Center, North Bergen, NJ, USA
| | - Brian M Fung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA
| | - John Sotiriadis
- Division of Gastroenterology and Hepatology, Hackensack University-Palisades Medical Center, North Bergen, NJ, USA
| | - Keith D Lindor
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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20
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Leung KK, Deeb M, Fischer SE, Gulamhusein A. Recurrent Primary Sclerosing Cholangitis: Current Understanding, Management, and Future Directions. Semin Liver Dis 2021; 41:409-420. [PMID: 34182588 DOI: 10.1055/s-0041-1730950] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Patients with primary sclerosing cholangitis (PSC) constitute 5 to 15% of patients listed for liver transplantation worldwide. Although post-transplant outcomes are favorable, recurrent PSC (rPSC) occurs in an important subset of patients, with higher prevalence rates reported with increasing time from transplant. Given its association with poor graft outcomes and risk of retransplant, effort has been made to understand rPSC, its pathophysiology, and risk factors. This review covers these facets of rPSC and focuses on implicated risk factors including pretransplant recipient characteristics, inflammatory bowel-disease-related factors, and donor-specific and transplant-specific factors. Confirming a diagnosis of rPSC requires thoughtful consideration of alternative etiologies so as to ensure confidence in diagnosis, management, subsequent risk assessment, and counseling for patients. Unfortunately, no cure exists for rPSC; however, future large-scale efforts are underway to better characterize the natural history of rPSC and its associated risk factors with hopes of identifying potential key targets for novel therapies.
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Affiliation(s)
- Kristel K Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Maya Deeb
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sandra E Fischer
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
| | - Aliya Gulamhusein
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
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21
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Patel P, Dalal S. Hepatic Manifestations of Inflammatory Bowel Disease. Clin Liver Dis (Hoboken) 2021; 17:292-296. [PMID: 33968391 PMCID: PMC8087932 DOI: 10.1002/cld.1046] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 08/09/2020] [Accepted: 09/25/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Parita Patel
- Section of Gastroenterology, Hepatology, and NutritionUniversity of Chicago Medical CenterChicagoIL
| | - Sushila Dalal
- Section of Gastroenterology, Hepatology, and NutritionUniversity of Chicago Medical CenterChicagoIL
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22
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Rabiee A, Silveira MG. Primary sclerosing cholangitis. Transl Gastroenterol Hepatol 2021; 6:29. [PMID: 33824933 DOI: 10.21037/tgh-20-266] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/19/2020] [Indexed: 12/15/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.
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Affiliation(s)
- Anahita Rabiee
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Marina G Silveira
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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23
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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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24
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Deneau MR, Mack C, Perito ER, Ricciuto A, Valentino PL, Amin M, Amir AZ, Aumar M, Auth M, Broderick A, DiGuglielmo M, Draijer LG, Tavares Fagundes ED, El-Matary W, Ferrari F, Furuya KN, Gupta N, Hochberg JT, Homan M, Horslen S, Iorio R, Jensen MK, Jonas MM, Kamath BM, Kerkar N, Kim KM, Kolho KL, Koot BG, Laborda TJ, Lee CK, Loomes KM, Martinez M, Miethke A, Miloh T, Mogul D, Mohammad S, Mohan P, Moroz S, Ovchinsky N, Palle S, Papadopoulou A, Rao G, Ferreira AR, Sathya P, Schwarz KB, Shah U, Shteyer E, Singh R, Smolka V, Soufi N, Tanaka A, Varier R, Vitola B, Woynarowski M, Zerofsky M, Zizzo A, Guthery SL. The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children. Hepatology 2021; 73:1074-1087. [PMID: 32464706 PMCID: PMC8557635 DOI: 10.1002/hep.31393] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/21/2020] [Accepted: 05/03/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.
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Affiliation(s)
- Mark R. Deneau
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Cara Mack
- University of Colorado School of Medicine, Aurora, CO
| | | | | | | | - Mansi Amin
- Phoenix Children’s Hospital, Phoenix, AZ
| | - Achiya Z. Amir
- The Dana-Dwek Children’s Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | | | - Marcus Auth
- Alder Hey Children’s Hospital, Liverpool, United Kingdom
| | - Annemarie Broderick
- Children’s Health Ireland at Crumlin & University College Dublin, Dublin, Ireland
| | | | | | | | | | | | - Katryn N. Furuya
- University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI
| | - Nitika Gupta
- Emory University School of Medicine, Atlanta, GA
| | | | | | | | | | - M. Kyle Jensen
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Maureen M. Jonas
- Boston Children’s Hospital and Harvard Medical School, Boston, MA
| | | | - Nanda Kerkar
- University of Rochester Medical Center, Rochester, NY
| | | | - Kaija-Leena Kolho
- University of Helsinki Hospital and Tampere University, Helsinki, Finland
| | - Bart G.P. Koot
- Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Trevor J. Laborda
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Christine K. Lee
- Boston Children’s Hospital and Harvard Medical School, Boston, MA
| | | | | | | | | | | | | | | | - Stacy Moroz
- University of Southern California, Los Angeles, CA
| | - Nadia Ovchinsky
- Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | | | - Alexandra Papadopoulou
- First Department of Pediatrics, University of Athens, Children’s Hospital Agia Sofia, Athens, Greece
| | | | | | - Pushpa Sathya
- Memorial University, St. John’s, Newfoundland, Canada
| | - Kathleen B. Schwarz
- Johns Hopkins University, Baltimore, MD
- University of California San Diego, San Diego, CA
| | - Uzma Shah
- Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - Ruchi Singh
- Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | | | | | | | - Raghu Varier
- Northwest Pediatric Gastroenterology LLC, Portland, OR
| | | | | | | | - Andréanne Zizzo
- London Health Sciences Center, Western University, London, Ontario, Canada
| | - Stephen L. Guthery
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
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Song J, Li Y, Bowlus CL, Yang G, Leung PSC, Gershwin ME. Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis (PSC): a Comprehensive Review. Clin Rev Allergy Immunol 2020; 58:134-149. [PMID: 31463807 DOI: 10.1007/s12016-019-08764-7] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC) and carries a high rate of mortality. Although the pathogenesis of CCA in PSC is largely unknown, inflammation-driven carcinogenesis concomitant with various genetic and epigenetic abnormalities are underlying factors. The majority of CCA cases develop from a dominant stricture (DS), which is defined as a stricture with a diameter < 1.5 mm in the common bile duct or < 1.0 mm in the hepatic duct. In PSC patients presenting with an abrupt aggravation of jaundice, pain, fatigue, pruritus, weight loss, or worsening liver biochemistries, CCA should be suspected and evaluated utilizing a variety of diagnostic modalities. However, early recognition of CCA in PSC remains a major challenge. Importantly, 30-50% of CCA in PSC patients are observed within the first year following the diagnosis of PSC followed by an annual incidence ranging from 0.5 to 1.5 per 100 persons, which is nearly 10 to 1000 times higher than that in the general population. Cumulative 5-year, 10-year, and lifetime incidences are 7%, 8-11%, and 9-20%, respectively. When PSC-associated CCA is diagnosed, most tumors are unresectable, and no effective medications are available. Given the poor therapeutic outcome, the surveillance and management of PSC patients who are at an increased risk of developing CCA are of importance. Such patients include older males with large-duct PSC and possibly concurrent ulcerative colitis. Thus, more attention should be paid to patients with these clinical features, in particular within the first year after PSC diagnosis. In contrast, CCA is less frequently observed in pediatric or female PSC patients or in those with small-duct PSC or concurrent Crohn's disease. Recently, new biomarkers such as antibodies to glycoprotein 2 have been found to be associated with an increased risk of developing CCA in PSC. Herein, we review the literature on the pathogenesis, incidence, clinical features, and risk factors, with a focus on various diagnostic modalities of PSC-associated CCA.
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Affiliation(s)
- Junmin Song
- Department of Gastroenterology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People's Republic of China.,Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA
| | - Yang Li
- Department of Intensive Care Unit (ICU), Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, People's Republic of China
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA
| | - GuoXiang Yang
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA
| | - Patrick S C Leung
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA.
| | - M Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA.
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26
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Kozaka K, Sheedy SP, Eaton JE, Venkatesh SK, Heiken JP. Magnetic resonance imaging features of small-duct primary sclerosing cholangitis. Abdom Radiol (NY) 2020; 45:2388-2399. [PMID: 32417935 DOI: 10.1007/s00261-020-02572-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE To evaluate the biliary tree and hepatic parenchymal findings on magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) in small-duct primary sclerosing cholangitis (SD-PSC). METHODS Thirty-nine patients with biopsy-proven primary sclerosing cholangitis (PSC) without any bile duct abnormality on MRCP (n = 15) or ERCP (n = 24) at the time of diagnosis were identified. Follow-up MRCP was available in 36/39 patients (12/15 Baseline MRCP group and 24 Baseline ERCP group). Two radiologists in consensus assessed the MRI/MRCP findings. The baseline MRI/MRCP of 15 SD-PSC patients was compared with MRI/MRCP of 15 normal healthy potential liver donors (Control group). Comparisons were made between SD-PSC patients and the Control group, and between baseline and follow-up MRI/MRCP findings in the SD-PSC patients. RESULTS In the 15 Baseline MRCP SD-PSC subjects, the biliary tree was normal with a trend of larger bile ducts compared to the Control group. Periductal enhancement (arterial phase: 70%, 7/10; delayed phase: 90%, 9/10), heterogeneous parenchymal signal on T2-weighted (53%, 8/15) and post contrast-enhanced images (70%, 7/10), and enlarged periportal lymph nodes (73%, 11/15) were frequently present in patients with SD-PSC. Eight (33%) of 24 SD-PSC patients who had normal MRCP at baseline MRCP or initial follow-up MRCP after normal baseline ERCP showed large-duct PSC (LD-PSC) features on follow-up and the 10-year cumulative incidence for progression to LD-PSC rate was 8.5%. CONCLUSION SD-PSC patients have a normal biliary tree but frequently have peribiliary enhancement, abnormal parenchymal signal intensity, and periportal lymphadenopathy. One-third shows progression to LD-PSC on follow-up.
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Affiliation(s)
- Kazuto Kozaka
- Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200, First Street SW, Rochester, MN, 55905, USA
- Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Shannon P Sheedy
- Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200, First Street SW, Rochester, MN, 55905, USA
| | - John E Eaton
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, 200, First Street SW, Rochester, MN, 55905, USA
| | - Sudhakar K Venkatesh
- Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200, First Street SW, Rochester, MN, 55905, USA
| | - Jay P Heiken
- Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200, First Street SW, Rochester, MN, 55905, USA.
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27
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Deliwala S, Sundus S, Haykal T, Elbedawi MM, Bachuwa G. Small Duct Primary Sclerosing Cholangitis: An Underdiagnosed Cause of Chronic Liver Disease and Cirrhosis. Cureus 2020; 12:e7298. [PMID: 32313739 PMCID: PMC7163339 DOI: 10.7759/cureus.7298] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Classic or large duct primary sclerosing cholangitis (PSC) is part of the PSC spectrum. It is diagnosed on clinical and biochemical findings of cholestasis supported by biliary tree changes on cholangiography, forgoing the need for an invasive liver biopsy. The spectrum contains various PSC variants with distinct clinical courses and outcomes. We present a case of small duct PSC, a rare variant that manifested insidiously with clinical and objective cholestasis but appeared negative on diagnostic cholangiography. Eventually, a liver biopsy was obtained that revealed chronic bilious disease of the small and microscopic ducts with simultaneous changes consistent with liver cirrhosis. Despite presenting like its classical counterpart, small duct PSC can remain undetectable on cholangiography due to the diminutive size of the bile ducts requiring histological confirmation. In contrast to classic PSC, small duct PSC portends a much better prognosis. However, it eventually progresses to the classic form or end-stage liver disease, requiring patients to receive timely surveillance and transplantation referrals. Due to the limited understanding of this disease process, patients with similar presentations often pose a diagnostic dilemma due to the clinical and cholangiographic mismatch. This case aims to reaffirm that a negative cholangiography does not rule out the PSC spectrum and that small duct disease is a rare but growing entity. The paucity in cases emphasizes the importance of isolated reports in guiding workup and management, especially since surveillance schedules and transplantation guidelines have not been formally established.
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Affiliation(s)
- Smit Deliwala
- Internal Medicine, Hurley Medical Center, Michigan State University College of Human Medicine, Flint, USA
| | - Saira Sundus
- Internal Medicine, Hurley Medical Center, Michigan State University, Flint, USA
| | - Tarek Haykal
- Internal Medicine, Hurley Medical Center, Michigan State University, Flint, USA
| | - Mamoon M Elbedawi
- Gastroenterology, Hurley Medical Center, Michigan State University, Flint, USA
| | - Ghassan Bachuwa
- Internal Medicine, Hurley Medical Center, Michigan State University, Flint, USA
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28
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Chang C, Tanaka A, Bowlus C, Gershwin ME. The use of biologics in the treatment of autoimmune liver disease. Expert Opin Investig Drugs 2020; 29:385-398. [PMID: 32102572 DOI: 10.1080/13543784.2020.1733527] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Autoimmune liver diseases include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and juvenile autoimmune hepatitis (JAIH). The pathophysiologic features of each disease vary, but generally include presence of autoantibodies, cytokine abnormalities, and/or T and B cell autoreactivity.Areas covered: This article compares conventional therapy with newer biologics available for treatment of autoimmune liver diseases. Conventional therapy involves the use of immunosuppressive agents, or other treatment modalities for specific autoimmune liver diseases such as ursodeoxycholic acid and fibrates for PBC. Biologics were developed to target the production of autoantibodies by B cells, the presence of proinflammatory cytokines, adhesion molecules or T and B cell activation.Expert opinion: Despite the promise of biologics being able to target specific cellular and humoral pathways, results have been generally poor, and safety has not been as expected. Cases of autoimmune hepatitis have also developed with the use of these biologicals. Reasons for the lack of success of biologics in treating autoimmune liver disease has led to a reevaluation of our understanding of underlying pathogenesis, demonstrating that while our knowledge of the immunity has improved over the past two decades, it is far from complete.
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Affiliation(s)
- Christopher Chang
- Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.,Division of Pediatric Immunology and Allergy, Joe DiMaggio Children's Hospital, Hollywood, FL, USA
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Christopher Bowlus
- Division of Gastroenterology, University of California at Davis, Davis, CA, USA
| | - M Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA
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29
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Adult onset of genetic disorders in bile acid transport in the liver. Hum Pathol 2020; 96:2-7. [DOI: 10.1016/j.humpath.2019.10.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 10/09/2019] [Indexed: 12/27/2022]
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30
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Deneau MR, Valentino PL, Mack C, Alqoaer K, Amin M, Amir AZ, Aumar M, Auth M, Broderick A, DiGuglielmo M, Draijer LG, El-Matary W, Ferrari F, Furuya KN, Gottrand F, Gupta N, Homan M, Jensen MK, Kamath BM, Kim KM, Kolho KL, Koot B, Iorio R, Martinez M, Miloh T, Mohan P, Palle S, Papadopoulou A, Ricciuto A, Saubermann L, Sathya P, Shteyer E, Smolka V, Tanaka A, Varier R, Venkat V, Vitola B, Woynarowski M, Guthery S. Assessing the Validity of Adult-derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children. J Pediatr Gastroenterol Nutr 2020; 70:e12-e17. [PMID: 31651664 DOI: 10.1097/mpg.0000000000002522] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. METHODS We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. RESULTS Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. CONCLUSIONS All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
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Affiliation(s)
| | | | - Cara Mack
- University of Colorado School of Medicine, Aurora, CO
| | | | - Mansi Amin
- Phoenix Children's Hospital, Phoenix, AZ
| | - Achiya Z Amir
- The Dana-Dwek Children's Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | | | - Marcus Auth
- Alder Hey Children's Hospital, Liverpool, United Kingdom
| | | | | | | | | | | | | | | | - Nitika Gupta
- Emory University School of Medicine, Atlanta, GA
| | | | | | | | | | | | - Bart Koot
- Academic Medical Centre, Amsterdam, The Netherlands
| | | | - Mercedes Martinez
- Columbia University College of Physicians and Surgeons, New York, NY
| | | | | | - Sirish Palle
- Emory University School of Medicine, Atlanta, GA
| | | | | | | | - Pushpa Sathya
- Memorial University, St. John's, Newfoundland and Labrador, Canada
| | | | | | | | - Raghu Varier
- Northwest Pediatric Gastroenterology LLC, Portland, OR
| | - Veena Venkat
- University of Pittsburgh Medical Center, Pittsburgh, PA
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31
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Tibdewal P, Bhatt P, Jain A, Gupta D, Bhatia S, Shukla A. Clinical profile and outcome of primary sclerosing cholangitis: A single-centre experience from western India. Indian J Gastroenterol 2019; 38:295-302. [PMID: 31515764 DOI: 10.1007/s12664-019-00968-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 06/03/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Primary sclerosing cholangitis (PSC), a chronic progressive cholestatic liver disease of unknown cause, is uncommon in India. The aim of this study was to define the profile and outcomes of patients with PSC in a tertiary centre from western India. METHODS A retrospective study of the prospectively maintained liver clinic database was searched for cases of PSC between January 2008 and December 2017 with minimum 6 months follow up. All cases were reviewed for clinical profile, inflammatory bowel disease (IBD) co-morbidity and major endpoints like death, cholangiocarcinoma and liver transplantation (LT). RESULTS We identified 28 (18 men) patients with PSC (19, 67% large-duct and 9, 33% small-duct) with a median age of 31.5 years (range 7-63 years) with median duration of follow up of 24 months (6-125 months). Six (21.4%) had autoimmune hepatitis (AIH-PSC) overlap. Inflammatory bowel disease was seen in 12 (43%) cases, all were ulcerative colitis (UC). During follow up, seven patients (25%) developed dominant stricture or recurrent cholangitis, 11 (39%) had portal hypertension, 2 (7%) developed cholangiocarcinoma and 5 (17.8%) progressed to hepatic decompensation on follow up. Ten (35%) patients died, 5 from liver-related complications, 2 from cholangiocarcinoma, 1 each from brain hemorrhage and systemic sepsis and 1 due to unknown cause; 3 underwent liver transplantation. Revised Mayo score of patients who survived was lower than those who died (1.03 vs. 1.86, p value 0.03). CONCLUSION PSC commonly presents in young age and rapidly progresses to decompensation. Prevalence of IBD in PSC is lower and the proportion of small-duct PSC is higher than that observed in western populations.
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Affiliation(s)
- Pratik Tibdewal
- Department of Gastroenterology, Seth GS Medical College, and KEM Hospital, Mumbai 400 012, India
| | - Pratin Bhatt
- Department of Gastroenterology, Seth GS Medical College, and KEM Hospital, Mumbai 400 012, India
| | - Abhinav Jain
- Department of Gastroenterology, Seth GS Medical College, and KEM Hospital, Mumbai 400 012, India
| | - Deepak Gupta
- Department of Gastroenterology, Seth GS Medical College, and KEM Hospital, Mumbai 400 012, India
| | - Shobna Bhatia
- Department of Gastroenterology, Seth GS Medical College, and KEM Hospital, Mumbai 400 012, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GS Medical College, and KEM Hospital, Mumbai 400 012, India.
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32
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Chapman MH, Thorburn D, Hirschfield GM, Webster GGJ, Rushbrook SM, Alexander G, Collier J, Dyson JK, Jones DE, Patanwala I, Thain C, Walmsley M, Pereira SP. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut 2019; 68:1356-1378. [PMID: 31154395 PMCID: PMC6691863 DOI: 10.1136/gutjnl-2018-317993] [Citation(s) in RCA: 178] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 02/21/2019] [Accepted: 03/24/2019] [Indexed: 12/11/2022]
Abstract
These guidelines on the management of primary sclerosing cholangitis (PSC) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included medical representatives from hepatology and gastroenterology groups as well as patient representatives from PSC Support. The guidelines aim to support general physicians, gastroenterologists and surgeons in managing adults with PSC or those presenting with similar cholangiopathies which may mimic PSC, such as IgG4 sclerosing cholangitis. It also acts as a reference for patients with PSC to help them understand their own management. Quality of evidence is presented using the AGREE II format. Guidance is meant to be used as a reference rather than for rigid protocol-based care as we understand that management of patients often requires individual patient-centred considerations.
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Affiliation(s)
- Michael Huw Chapman
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Liver Unit, Royal Free London NHS Foundation Trust, London, UK
| | | | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, University Health Network and University of Toronto, Toronto, Canada
| | | | - Simon M Rushbrook
- Department of Hepatology, Norfolk and Norwich University Hospitals NHS Trust, Norwich, UK
| | | | | | - Jessica K Dyson
- Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - David Ej Jones
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - Imran Patanwala
- Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
- University of Liverpool, Liverpool, UK
| | | | | | - Stephen P Pereira
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Institute for Liver & Digestive Health, University College London, London, UK
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33
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Maurice JB, Thorburn D. Precision medicine in primary sclerosing cholangitis. J Dig Dis 2019; 20:346-356. [PMID: 31099965 DOI: 10.1111/1751-2980.12788] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 05/07/2019] [Indexed: 12/11/2022]
Abstract
Primary sclerosing cholangitis is a rare, complex autoimmune disease in relatively young patients. There is currently no treatment for the disease, resulting in high rates of advanced liver disease leading to death or liver transplantation. However, advances have been made in our understanding of the pathophysiological mechanisms of the disease, particularly from breakthroughs in the underlying genetics. Moreover, large international collaborations have generated important clinical data that have given greater detail on the different disease phenotypes and natural history, generating new risk prediction models. As a result, drug development may be designed to target specific disease mechanisms at known points of the disease natural history. Therefore, more drugs are entering phase II and III development, giving hope that soon patient-specific treatments may be available to treat this difficult disease.
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Affiliation(s)
- James B Maurice
- Department of Hepatology and Liver Transplantation, Royal Free Hospital NHS Foundation Trust, London, UK
| | - Douglas Thorburn
- Department of Hepatology and Liver Transplantation, Royal Free Hospital NHS Foundation Trust, London, UK
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34
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Dalekos GN, Gatselis NK. Variant and Specific Forms of Autoimmune Cholestatic Liver Diseases. Arch Immunol Ther Exp (Warsz) 2019; 67:197-211. [PMID: 31165900 DOI: 10.1007/s00005-019-00550-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver diseases. IgG4-associated sclerosing cholangitis is another distinct immune-mediated cholestatic disorder of unknown aetiology that is frequently associated with autoimmune pancreatitis or other IgG4-related diseases. Although the majority of PBC and PSC patients have a typical presentation, there are common and uncommon important variants or specific subgroups that observed in everyday routine clinical practice. In this updated review, we summarize the published data giving also our own experience on the variants and specific groups of autoimmune cholestatic liver diseases. Actually, we give in detail the underlining difficulties and the rising dilemmas concerning the diagnosis and management of these special conditions in the clinical spectrum of autoimmune cholestatic liver diseases including the IgG4-associated sclerosing cholangitis highlighting also the uncertainties and the potential new eras of the research agenda.
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Affiliation(s)
- George N Dalekos
- Institute of Internal Medicine and Hepatology, Larissa, Greece.
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece.
| | - Nikolaos K Gatselis
- Institute of Internal Medicine and Hepatology, Larissa, Greece
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece
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35
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Goode EC, Clark AB, Mells GF, Srivastava B, Spiess K, Gelson WT, Trivedi PJ, Lynch KD, Castren E, Vesterhus MN, Karlsen TH, Ji S, Anderson CA, Thorburn D, Hudson M, Heneghan MA, Aldersley MA, Bathgate A, Sandford RN, Alexander GJ, Chapman RW, Walmsley M, Hirschfield GM, Rushbrook SM. Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System. Hepatology 2019; 69:2120-2135. [PMID: 30566748 PMCID: PMC6519245 DOI: 10.1002/hep.30479] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Accepted: 12/02/2018] [Indexed: 12/15/2022]
Abstract
We sought to identify factors that are predictive of liver transplantation or death in patients with primary sclerosing cholangitis (PSC), and to develop and validate a contemporaneous risk score for use in a real-world clinical setting. Analyzing data from 1,001 patients recruited to the UK-PSC research cohort, we evaluated clinical variables for their association with 2-year and 10-year outcome through Cox-proportional hazards and C-statistic analyses. We generated risk scores for short-term and long-term outcome prediction, validating their use in two independent cohorts totaling 451 patients. Thirty-six percent of the derivation cohort were transplanted or died over a cumulative follow-up of 7,904 years. Serum alkaline phosphatase of at least 2.4 × upper limit of normal at 1 year after diagnosis was predictive of 10-year outcome (hazard ratio [HR] = 3.05; C = 0.63; median transplant-free survival 63 versus 108 months; P < 0.0001), as was the presence of extrahepatic biliary disease (HR = 1.45; P = 0.01). We developed two risk scoring systems based on age, values of bilirubin, alkaline phosphatase, albumin, platelets, presence of extrahepatic biliary disease, and variceal hemorrhage, which predicted 2-year and 10-year outcomes with good discrimination (C statistic = 0.81 and 0.80, respectively). Both UK-PSC risk scores were well-validated in our external cohort and outperformed the Mayo Clinic and aspartate aminotransferase-to-platelet ratio index (APRI) scores (C statistic = 0.75 and 0.63, respectively). Although heterozygosity for the previously validated human leukocyte antigen (HLA)-DR*03:01 risk allele predicted increased risk of adverse outcome (HR = 1.33; P = 0.001), its addition did not improve the predictive accuracy of the UK-PSC risk scores. Conclusion: Our analyses, based on a detailed clinical evaluation of a large representative cohort of participants with PSC, furthers our understanding of clinical risk markers and reports the development and validation of a real-world scoring system to identify those patients most likely to die or require liver transplantation.
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Affiliation(s)
- Elizabeth C. Goode
- Norfolk and Norwich University HospitalNorwichUnited Kingdom,Academic Department of Medical GeneticsAddenbrooke's Hospital, University of CambridgeCambridgeUnited Kingdom,Wellcome Trust Sanger InstituteHinxton, CambridgeUnited Kingdom,Norwich Medical SchoolUniversity of East AngliaNorwichUnited Kingdom,Cambridge Transplant CentreAddenbrooke's HospitalCambridgeUnited Kingdom
| | - Allan B. Clark
- Norwich Medical SchoolUniversity of East AngliaNorwichUnited Kingdom
| | - George F. Mells
- Academic Department of Medical GeneticsAddenbrooke's Hospital, University of CambridgeCambridgeUnited Kingdom
| | - Brijesh Srivastava
- Academic Department of Medical GeneticsAddenbrooke's Hospital, University of CambridgeCambridgeUnited Kingdom
| | - Kelly Spiess
- Academic Department of Medical GeneticsAddenbrooke's Hospital, University of CambridgeCambridgeUnited Kingdom
| | | | - Palak J. Trivedi
- National Institute for Health Research (NIHR) Birmingham Biomedical Research CentreBirminghamUnited Kingdom,Institute of Immunology & ImmunotherapyUniversity of BirminghamBirminghamUnited Kingdom,Centre for Rare Diseases, Institute of Translational MedicineUniversity Hospitals BirminghamBirminghamUnited Kingdom
| | - Kate D. Lynch
- Translational Gastroenterology UnitJohn Radcliffe Hospital, and Nuffield Department of Medicine, University of OxfordOxfordUnited Kingdom
| | - Edit Castren
- Norfolk and Norwich University HospitalNorwichUnited Kingdom
| | - Mette N. Vesterhus
- Norwegian PSC Research Center, Department of Transplantation MedicineOslo University Hospital RikshospitaletOsloNorway,Institute of Clinical Medicine, Faculty of MedicineUniversity of OsloOsloNorway
| | - Tom H. Karlsen
- Norwegian PSC Research Center, Department of Transplantation MedicineOslo University Hospital RikshospitaletOsloNorway,Institute of Clinical Medicine, Faculty of MedicineUniversity of OsloOsloNorway
| | - Sun‐Gou Ji
- Wellcome Trust Sanger InstituteHinxton, CambridgeUnited Kingdom
| | | | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free HospitalLondonUnited Kingdom
| | - Mark Hudson
- Liver Medicine and Transplantation ServiceFreeman HospitalNewcastleUnited Kingdom
| | | | | | - Andrew Bathgate
- Scottish Liver Transplant UnitRoyal Infirmary of EdinburghEdinburghUnited Kingdom
| | - Richard N. Sandford
- Academic Department of Medical GeneticsAddenbrooke's Hospital, University of CambridgeCambridgeUnited Kingdom
| | - Graeme J. Alexander
- Cambridge Transplant CentreAddenbrooke's HospitalCambridgeUnited Kingdom,Sheila Sherlock Liver Centre, Royal Free HospitalLondonUnited Kingdom
| | - Roger W. Chapman
- Translational Gastroenterology UnitJohn Radcliffe Hospital, and Nuffield Department of Medicine, University of OxfordOxfordUnited Kingdom
| | | | | | - Gideon M. Hirschfield
- National Institute for Health Research (NIHR) Birmingham Biomedical Research CentreBirminghamUnited Kingdom,Institute of Immunology & ImmunotherapyUniversity of BirminghamBirminghamUnited Kingdom,Centre for Rare Diseases, Institute of Translational MedicineUniversity Hospitals BirminghamBirminghamUnited Kingdom,Toronto Centre for Liver DiseaseUniversity Health Network and University of TorontoTorontoCanada
| | - Simon M. Rushbrook
- Norfolk and Norwich University HospitalNorwichUnited Kingdom,Norwich Medical SchoolUniversity of East AngliaNorwichUnited Kingdom
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Vinnitskaya EV, Abdulkhakov SR, Abdurakhmanov DT, Alikhanov RB, Bakulin IG, Belousova EA, Bueverov AO, Burnevitch EZ, Efanov MG, Eremina EY, Ignatova ТМ, Ilchenko LY, Karmazanovsky GG, Knyazev OV, Kulezneva YV, Lopatkina TN, Nekrasova TP, Nikitin IG, Pavlenko VV, Parfenov AI, Podymova SD, Raichelson KL, Reisis AR, Sayfutdinov RG, Skazyvaeva EV, Syutkin VE, Khomeriki SG, Haimenova TY, Sandler YG. Important problems in the diagnosis and treatment of primary sclerosing cholangitis (based on the Russian consensus on diagnosis and treatment autoimmune hepatitis. Moscow, 2018). TERAPEVT ARKH 2019; 91:9-15. [PMID: 31094167 DOI: 10.26442/00403660.2019.02.000075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The article is published based on the results of the Russian Consensus on the diagnosis and treatment of primary sclerosing cholangitis (PSC), discussed at the 44th annual Scientific Session of the CNIIG "Personalized Medicine in the Era of Standards" (March 1, 2018). The aim of the review is to highlight the current issues of classification of diagnosis and treatment of patients with PSC, which causes the greatest interest of specialists. The urgency of the problem is determined by the multivariate nature of the clinical manifestations, by often asymptomatic flow, severe prognosis, complexity of diagnosis and insufficient study of PSC, the natural course of which in some cases can be considered as a function with many variables in terms of the nature and speed of progression with numerous possible clinical outcomes. In addition to progression to portal hypertension, cirrhosis and its complications, PSC can be accompanied by clinical manifestations of obstructive jaundice, bacterial cholangitis, cholangiocarcinoma and colorectal cancer. Magnetic resonance cholangiography is the main method of radial diagnostics of PSC, which allows to obtain an image of bile ducts in an un-invasive way. The use of liver biopsy is best justified when there is a suspicion of small-diameter PSC, autoimmune cross-syndrome PSC-AIG, IgG4-sclerosing cholangitis. Currently, a drug registered to treat primary sclerosing cholangitis which can significantly change the course and prognosis of the disease does not exist. There is no unified view on the effectiveness and usefulness of ursodeoxycholic acid and its dosage in PSC. Early diagnosis and determination of the phenotype of PSC is of clinical importance. It allows to determine the tactics of treatment, detection and prevention of complications.
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Affiliation(s)
- E V Vinnitskaya
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | | | - D T Abdurakhmanov
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - R B Alikhanov
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - I G Bakulin
- I.I. Mechnikov North-Western State Medical University of the Ministry of Health of the Russian Federation, Saint Petersburg, Russia
| | - E A Belousova
- M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia
| | - A O Bueverov
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - E Z Burnevitch
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - M G Efanov
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - E Yu Eremina
- Medical Institut of the N.P. Ogarev Mordovia State University, Saransk, Russia
| | - Т М Ignatova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - L Yu Ilchenko
- N.I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - G G Karmazanovsky
- A.V. Vishnevsky Institute of Surgery of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - O V Knyazev
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - Yu V Kulezneva
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - T N Lopatkina
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - T P Nekrasova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - I G Nikitin
- N.I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - V V Pavlenko
- Stavropol State Medical University of the Ministry of Health of the Russian Federation, Stavropol, Russia
| | - A I Parfenov
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - S D Podymova
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - K L Raichelson
- St Petersburg State University, Saint Petersburg, Russia
| | - A R Reisis
- Central Research Institute of Epidemiology of the Federal Service on Customers, Moscow, Russia
| | - R G Sayfutdinov
- Kazan State Medical Academy - the Branch of Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - E V Skazyvaeva
- I.I. Mechnikov North-Western State Medical University of the Ministry of Health of the Russian Federation, Saint Petersburg, Russia
| | - V E Syutkin
- N.V. Sklifosovsky Research Institute of Emergency Medical Care of the Department of Health of Moscow, Moscow, Russia
| | - S G Khomeriki
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - T Yu Haimenova
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - Yu G Sandler
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
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Primary Sclerosing Cholangitis: A Concise Review of Diagnosis and Management. Dig Dis Sci 2019; 64:632-642. [PMID: 30725292 DOI: 10.1007/s10620-019-05484-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/19/2019] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterized by progressive idiopathic stricturing of the biliary system, typically leading to cirrhosis, end-stage liver disease, and colonic or hepatobiliary malignancy. Its presentation is often that of asymptomatic alkaline phosphatase elevation. When symptoms are present, they typically include fatigue, pruritus, or jaundice. The diagnosis can be confirmed via cholangiography, either magnetic resonance cholangiography (MRCP) or endoscopic retrograde cholangiography if the former is inconclusive. The clinical course is marked by progressive liver disease leading to cirrhosis with its attendant complications of portal hypertension, often including recurrent episodes of cholangitis. Greater elevation in alkaline phosphatase or liver stiffness is associated with worse clinical outcomes. Management includes endoscopic treatment of symptomatic biliary strictures and evaluation of dominant strictures as no adequate medical treatment is available. Multiple medical therapies are under evaluation. Ultimately, liver transplantation may be necessary for management of decompensated cirrhosis or disabling symptoms. There is also a markedly increased risk of cancer, notably including cholangiocarcinoma and gallbladder and colorectal cancers (particularly in patients with colitis). Cancer screening can be done with semi-annual liver imaging (MRCP or ultrasound) and colonoscopy every 1-2 years in those with colitis.
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Inflammatory Hepatobiliary Diseases. Clin Immunol 2019. [DOI: 10.1016/b978-0-7020-6896-6.00076-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Kumagai J, Taida T, Ogasawara S, Nakagawa T, Iino Y, Shingyoji A, Ishikawa K, Akizue N, Yamato M, Takahashi K, Ohta Y, Hamanaka S, Okimoto K, Nakamura M, Ohyama H, Saito K, Kusakabe Y, Maruoka D, Yasui S, Matsumura T, Sugiyama H, Sakai Y, Mikata R, Arai M, Katsuno T, Tsuyuguchi T, Kato N. Clinical characteristics and outcomes of primary sclerosing cholangitis and ulcerative colitis in Japanese patients. PLoS One 2018; 13:e0209352. [PMID: 30571774 PMCID: PMC6301618 DOI: 10.1371/journal.pone.0209352] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Accepted: 12/04/2018] [Indexed: 12/12/2022] Open
Abstract
Background In Western countries, most patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). The number of patients with UC in East Asia has increased markedly over the past two decades. However, current clinical features of PSC and of PSC associated with UC (PSC-UC) have not yet been clarified in East Asia, particularly in Japan. We aimed to reveal the clinical courses and associations with UC in Japanese patients with PSC from the mutual viewpoint of PSC and UC. Methods We retrospectively retrieved medical records of patients with PSC (69) and UC (1242) who were diagnosed at Chiba University Hospital between June 1991 and August 2017. Results In the present cohort, 37 patients had PSC-UC; the cumulative risks of PSC in patients with UC and of UC in patients with PSC were 3.0% and 53.6%, respectively. We confirmed similar distinctive results by a Japanese nationwide survey, noting that younger patients with PSC had a notably high possibility of association with UC. From the viewpoint of the UC cohort, the occurrence of right-sided disease was significantly higher in patients with PSC-UC than in those with UC (16.2% vs. 4.2%, P = 0.003). Pancolitis was more commonly observed in PSC-UC, and proctits/left-sided colitis was less commonly found in patients with UC. The number of patients with young-onset PSC-UC may be increasing similar to an increase in patients with UC in Japan. Conclusions In our cohort, the comorbidity rate of PSC-UC was higher than that obtained in previous reports. The incidence of PSC-UC and UC may increase in the future in East Asia, particularly in Japan.
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Affiliation(s)
- Junichiro Kumagai
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Takashi Taida
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tomoo Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yotaro Iino
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Ayako Shingyoji
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kentaro Ishikawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoki Akizue
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Mutsumi Yamato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Koji Takahashi
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yuki Ohta
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shinsaku Hamanaka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kenichiro Okimoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Masato Nakamura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroshi Ohyama
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Keiko Saito
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yuko Kusakabe
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Daisuke Maruoka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shin Yasui
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tomoaki Matsumura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Harutoshi Sugiyama
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yuji Sakai
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Rintaro Mikata
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Makoto Arai
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tatsuro Katsuno
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Toshio Tsuyuguchi
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
- * E-mail:
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Kerkar N, Chan A. Autoimmune Hepatitis, Sclerosing Cholangitis, and Autoimmune Sclerosing Cholangitis or Overlap Syndrome. Clin Liver Dis 2018; 22:689-702. [PMID: 30266157 DOI: 10.1016/j.cld.2018.06.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Autoimmune hepatitis (AIH) is characterized by elevated serum aminotransferases, immunoglobulin G, autoantibodies, and interface hepatitis, in the absence of a known diagnosis. Presentation is varied. Therapy is with immunosuppression. There is inflammation of the intrahepatic and/or extrahepatic bile ducts in Sclerosing cholangitis (SC) and when associated with inflammatory bowel disease, it is known as primary SC, with Ursodeoxycholic acid used for therapy. The overlap of clinical, biochemical and histological features of AIH and PSC is known as autoimmune sclerosing cholangitis (ASC) or overlap syndrome. Liver transplantation is performed when medical treatment fails and both AIH and PSC may recur post-transplantation.
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Affiliation(s)
- Nanda Kerkar
- Division of Gastroenterology, Hepatology and Nutrition, Golisano Children's Hospital, University of Rochester Medical Center, 601 Elmwood Avenue, Box 667, Rochester, NY 14642, USA.
| | - Albert Chan
- Division of Gastroenterology, Hepatology and Nutrition, Golisano Children's Hospital, University of Rochester Medical Center, 601 Elmwood Avenue, Box 667, Rochester, NY 14642, USA; Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Florida, PO Box 100296, Gainesville, FL 32610, USA
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41
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Dyson JK, Beuers U, Jones DEJ, Lohse AW, Hudson M. Primary sclerosing cholangitis. Lancet 2018; 391:2547-2559. [PMID: 29452711 DOI: 10.1016/s0140-6736(18)30300-3] [Citation(s) in RCA: 273] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Revised: 11/24/2017] [Accepted: 01/03/2018] [Indexed: 12/13/2022]
Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterised by intrahepatic or extrahepatic stricturing, or both, with bile duct fibrosis. Inflammation and fibrosis of bile ducts and the liver are followed by impaired bile formation or flow and progressive liver dysfunction. Patients might be asymptomatic at presentation or might have pruritus, fatigue, right upper quadrant pain, recurrent cholangitis, or sequelae of portal hypertension. The key diagnostic elements are cholestatic liver biochemistry and bile duct stricturing on cholangiography. Genetic and environmental factors are important in the cause of the disease, with the intestinal microbiome increasingly thought to play a pathogenetic role. Approximately 70% of patients have concurrent inflammatory bowel disease and patients require colonoscopic screening and surveillance. Primary sclerosing cholangitis is associated with increased malignancy risk and surveillance strategies for early cholangiocarcinoma detection are limited. No single drug has been proven to improve transplant-free survival. Liver transplantation is effective for advanced disease but at least 25% of patients develop recurrent disease in the graft.
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Affiliation(s)
- Jessica K Dyson
- Department of Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - David E J Jones
- Department of Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - Ansgar W Lohse
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Mark Hudson
- Department of Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle, UK
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Fousekis FS, Theopistos VI, Katsanos KH, Tsianos EV, Christodoulou DK. Hepatobiliary Manifestations and Complications in Inflammatory Bowel Disease: A Review. Gastroenterology Res 2018; 11:83-94. [PMID: 29707074 PMCID: PMC5916631 DOI: 10.14740/gr990w] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Accepted: 03/12/2018] [Indexed: 12/12/2022] Open
Abstract
Liver and biliary track diseases are common extraintestinal manifestations of inflammatory bowel disease (IBD), reported both in Crohn’s disease and ulcerative colitis, and may occur at any time during the natural course of the disease. Their etiology is mainly related to pathophysiological changes induced by IBD, and secondary, due to drugs used in IBD. Fatty liver is considered as the most frequent hepatobiliary manifestation in IBD, while primary sclerosing cholangitis (PSC) is the most correlated hepatobiliary disorder and is more prevalent in patients with ulcerative colitis. PSC can cause serious complications from the liver, biliary tree, and gallbladder and can lead to liver failure. Less frequently, IBD-associated hepatobiliary manifestations include cholelithiasis, granulomatous hepatitis, portal vein thrombosis, IgG4-related cholangiopathy, pyogenic liver abscess, hepatic amyloidosis and primary biliary cirrhosis. Most of the drugs used for IBD treatment may cause liver toxicity. Methotrexate and thiopurines carry the higher risk for hepatotoxicity, and in many cases, dose adjustment may normalize the liver biochemical tests. Reactivation of hepatitis B and C virus during immunosuppressive use, especially during use of biological agents, is a major concern, and adequate screening, vaccination and prophylactic treatment is warranted.
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Affiliation(s)
- Fotios S Fousekis
- Department of Gastroenterology and Hepatology, Medical School of Ioannina, Greece
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Abstract
PURPOSE OF REVIEW To review the characteristics of IBD and PSC that occur in association, as well as their reciprocal influences on disease evolution, in adult and pediatric populations. RECENT FINDINGS IBD co-existing with PSC is genetically and clinically distinct from IBD alone. It is frequently characterized by pancolitis, rectal sparing, and possibly backwash ileitis, as well as a threefold increased risk of colorectal dysplasia. Adults and children with colitis and PSC appear to be at increased risk of active endoscopic and histologic disease in the absence of symptoms compared to individuals without PSC. PSC occurring with Crohn's disease has been observed to be less severe than PSC co-existing with ulcerative colitis, independent of its association with small duct disease. Recent studies suggest that colectomy is associated with a decreased risk of recurrent PSC after liver transplantation, challenging the traditional teaching that PSC and IBD evolve independently. While much about the gut-liver axis in PSC-IBD remains poorly understood, the IBD associated with PSC has a unique phenotype, of which subclinical inflammation is an important component. Additional research is needed to characterize further the potentially protective role of colectomy against recurrent PSC post-liver transplantation and to investigate the influence of IBD control and/or colectomy on PSC progression.
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Affiliation(s)
- Amanda Ricciuto
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G1X8, Canada.
| | - Binita M Kamath
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G1X8, Canada
| | - Anne M Griffiths
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G1X8, Canada
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic immune-mediated disease affecting intra- and extrahepatic bile ducts, primarily the large biliary ducts. Clinical manifestations are broad, and the spectrum encompasses asymptomatic cholestasis, icteric cholangitis with pruritis, cirrhosis, and cholangiocarcinoma. Though rare, PSC has a propensity to affect young to middle-aged males and is strongly associated with inflammatory bowel disease. There is an unmet need for effective medical treatments for PSC, and to date, the only curative therapy is liver transplantation reserved for those with end-stage liver disease. This article addresses the diagnostic and management challenges of PSC, with a succinct analysis of existing therapies, their limitations, and a glimpse into the future of the management of this multifaceted pathologic entity.
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Affiliation(s)
- Sanjeev Sirpal
- Department of Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), University of Montreal, Montreal, QC
| | - Natasha Chandok
- Department of Medicine, University of Western Ontario, London, ON, Canada
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Gossard AA, Gores GJ. Primary Sclerosing Cholangitis: What the Gastroenterologist and Hepatologist Needs to Know. Clin Liver Dis 2017; 21:725-737. [PMID: 28987259 DOI: 10.1016/j.cld.2017.06.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, idiopathic biliary tract disease characterized by segmental strictures. The disease is progressive with no proven treatments and may eventually lead to cirrhosis and end-stage liver disease. Abrupt changes in liver biochemistries, pain, and/or cholangitis may suggest a dominant stricture amenable to endoscopic therapy or the development of cholangiocarcinoma. Patients with PSC are at increased risk of cholangiocarcinoma. There is a strong association with inflammatory bowel disease, and an associated increased risk of colorectal cancer. Colonoscopy every 1 to 2 years is appropriate.
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Affiliation(s)
- Andrea A Gossard
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55901, USA.
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55901, USA
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Deneau MR, El-Matary W, Valentino PL, Abdou R, Alqoaer K, Amin M, Amir AZ, Auth M, Bazerbachi F, Broderick A, Chan A, Cotter J, Doan S, El-Youssef M, Ferrari F, Furuya KN, Gottrand M, Gottrand F, Gupta N, Homan M, Kamath BM, Kim KM, Kolho KL, Konidari A, Koot B, Iorio R, Ledder O, Mack C, Martinez M, Miloh T, Mohan P, O'Cathain N, Papadopoulou A, Ricciuto A, Saubermann L, Sathya P, Shteyer E, Smolka V, Tanaka A, Varier R, Venkat V, Vitola B, Vos MB, Woynarowski M, Yap J, Jensen MK. The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration. Hepatology 2017; 66:518-527. [PMID: 28390159 DOI: 10.1002/hep.29204] [Citation(s) in RCA: 139] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 02/07/2017] [Accepted: 04/04/2017] [Indexed: 12/14/2022]
Abstract
UNLABELLED There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518-527).
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Affiliation(s)
| | | | | | - Reham Abdou
- State University of New York Buffalo, Buffalo, NY
| | - Khaled Alqoaer
- Prince Salman North West Armed Forces Hospital, Tabuk, Saudi Arabia
| | - Mansi Amin
- University of California San Francisco, San Francisco, CA, and Texas Children's Hospital, Houston, TX
| | - Achiya Z Amir
- The Dana-Dwek Children's Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | - Marcus Auth
- Alder Hey Children's Hospital, Liverpool, UK
| | | | | | - Albert Chan
- University of Rochester Medical Center, Rochester, NY
| | | | | | | | | | - Katryn N Furuya
- Mayo Clinic, Rochester, MN
- Nemours Alfred I duPont Hospital For Children, Wilmington, DE
| | | | | | - Nitika Gupta
- Emory University School of Medicine, Atlanta, GA
| | | | | | | | | | - Anastasia Konidari
- University of Liverpool, Liverpool, and University of Manchester, Manchester, UK
| | - Bart Koot
- Academic Medical Centre, Amsterdam, The Netherlands
| | | | - Oren Ledder
- Shaare Zedek Medical Center, Jerusalem, Israel
| | - Cara Mack
- University of Colorado School of Medicine, Aurora, CO
| | - Mercedes Martinez
- Columbia University College of Physicians and Surgeons, New York, NY
| | - Tamir Miloh
- Texas Children's Hospital, Houston, TX, and Phoenix Children's Hospital, Phoenix, AZ
| | | | | | | | | | | | - Pushpa Sathya
- Memorial University, St. John's, Newfoundland and Labrador, Canada
| | | | | | | | - Raghu Varier
- Northwest Pediatric Gastroenterology LLC, Portland, OR
| | - Veena Venkat
- University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Miriam B Vos
- Emory University School of Medicine, Atlanta, GA
| | | | - Jason Yap
- University of Alberta, Edmonton, Alberta, Canada
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Björnsson ES. Primary sclerosing cholangitis: best practices for diagnosis. Expert Opin Orphan Drugs 2017. [DOI: 10.1080/21678707.2017.1358163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Einar S. Björnsson
- Department of Internal Medicine, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Division of Gastroenterology and Hepatology, The National University Hospital of Iceland
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Kalaitzakis E, Björnsson ES. Predictors of the Clinical Course of Primary Sclerosing Cholangitis. Gastroenterology 2017; 152:1829-1830. [PMID: 28461191 DOI: 10.1053/j.gastro.2017.04.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Affiliation(s)
- Evangelos Kalaitzakis
- Digestive Disease Center, Copenhagen University Hospital/Herlev, University of Copenhagen, Copenhagen, Denmark
| | - Einar S Björnsson
- Department of Gastroenterology, Landspitali University Hospital and Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic, cholestatic, idiopathic liver disease that can progress to end-stage liver disease, cirrhosis and cholangiocarcinoma. PSC is an uncommon and highly heterogeneous disease, associated with inflammatory bowel disease and a complex pathophysiology. To date, no medical therapies have proved effective. The only available treatment for end-stage PSC is liver transplant, but recurrence is a significant complication. Areas covered: This review will explore previously tested treatments, discuss current treatment strategies and present viewpoints about future emerging therapies in PSC. We searched PubMed using the noted keywords. We included data from full-text articles published in English. Further relevant articles were identified from the reference lists of review articles. Expert commentary: The development of new therapies in PSC has been challenging. However, with greater awareness of the disease nowadays, new insights into the disease may help in the design of future therapeutic agents in PSC and ultimately in effective therapies.
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Affiliation(s)
- Eduardo A Rodriguez
- a Division of Gastroenterology and Hepatology , Mayo Clinic , Phoenix , AZ , USA
| | - Elizabeth J Carey
- a Division of Gastroenterology and Hepatology , Mayo Clinic , Phoenix , AZ , USA
| | - Keith D Lindor
- a Division of Gastroenterology and Hepatology , Mayo Clinic , Phoenix , AZ , USA.,b College of Health Solutions , Arizona State University , Phoenix , AZ , USA
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Gidwaney NG, Pawa S, Das KM. Pathogenesis and clinical spectrum of primary sclerosing cholangitis. World J Gastroenterol 2017; 23:2459-2469. [PMID: 28465630 PMCID: PMC5394509 DOI: 10.3748/wjg.v23.i14.2459] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 01/21/2017] [Accepted: 03/20/2017] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a disease of the biliary tract, which has been documented in the literature since 1867. This disease has a strong predilection for affecting men and can be seen in individuals as young as 2 years of age. PSC has a strong associated with inflammatory bowel disease, more commonly with ulcerative colitis, and is also part of the clinical spectrum of IgG4-related diseases. Small-duct PSC, a variant of PSC, also has an association with inflammatory bowel disease. The exact pathogenesis of PSC is not well understood at present, however, is likely a combination of a genetic predisposition with alteration of the molecular structure of the gut. Abnormal serum liver chemistry and presence of certain autoimmune markers are usually the first indicators leading to a diagnosis of PCS, however, these may often be normal in early stages of this disease. The diagnosis is made by cholangiography, which is now considered the gold standard. PSC is a known pre-malignant condition. Such patients have an increased risk of developing cholangiocarcinoma, gallbladder neoplasia, and colon cancer. Many new treatment modalities have emerged in the recent past, including anti-tumor necrosis factor- α and anti-integrins; however, liver transplantation is the only known cure for PSC. Despite past and present research, PSC remains an enigmatic biliary disease with few viable treatment options.
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