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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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2
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Kellermayer R, Carbone M, Horvath TD, Szigeti RG, Buness C, Hirschfield GM, Lewindon PJ. Identifying a therapeutic window of opportunity for people living with primary sclerosing cholangitis: Embryology and the overlap of inflammatory bowel disease with immune-mediated liver injury. Hepatology 2024:01515467-990000000-00881. [PMID: 38743006 DOI: 10.1097/hep.0000000000000926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 04/25/2024] [Indexed: 05/16/2024]
Abstract
Primary sclerosing cholangitis (PSC) is a variably progressive, fibrosis-causing autoimmune disorder of the intrahepatic and extrahepatic bile ducts of unclear etiology. PSC is commonly (in 60%-90% of cases) associated with an inflammatory bowel disease (IBD) like PSC-IBD and less commonly with an autoimmune hepatitis (AIH) like PSC-AIH or AIH-overlap disorder. Hepatologists and Gastroenterologists often consider these combined conditions as distinctly different from the classical forms in isolation. Here, we review recent epidemiologic observations and highlight that PSC-IBD and PSC-AIH overlap appear to represent aspects of a common PSC clinico-pathological pathway and manifest in an age-of-presentation-dependent manner. Particularly from the pediatric experience, we hypothesize that all cases of PSC likely originate from a complex "Early PSC"-"IBD"-"AIH" overlap in which PSC defines the uniquely and variably associated "AIH" and "IBD" components along an individualized lifetime continuum. We speculate that a distinctly unique, "diverticular autoimmunity" against the embryonic cecal- and hepatic diverticulum-derived tissues may be the origin of this combined syndrome, where "AIH" and "IBD" variably commence then variably fade while PSC progresses with age. Our hypothesis provides an explanation for the age-dependent variation in the presentation and progression of PSC. This is critical for the optimal targeting of studies into PSC etiopathogenesis and emphasizes the concept of a "developmental window of opportunity for therapeutic mitigation" in what is currently recognized as an irreversible disease process. The discovery of such a window would be critically important for the targeting of interventions, both the administration of current therapies and therapeutic trial planning.
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Affiliation(s)
- Richard Kellermayer
- Division of Pediatric Gastroenterology, Department of Pediatrics, Texas Children's Hospital; Baylor College of Medicine, Houston, Texas, USA
- USDA/ARS Children's Nutrition Research Center (CNRC), Houston, Texas, USA
| | - Marco Carbone
- Centre for Autoimmune Liver Diseases, School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
- Liver Unit, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Thomas D Horvath
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Reka G Szigeti
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA
| | - Cynthia Buness
- Global Liver Institute Pediatric and Rare Liver Diseases Research Council, Washington DC, USA
- Autoimmune Liver Disease Network for Kids (A-LiNK), Stanford University, Stanford, CA, USA
- National Patient Advocate Foundation, Washington DC, USA
| | - Gideon M Hirschfield
- Department of Medicine, Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada
| | - Peter J Lewindon
- Queensland Children's Hospital, Brisbane, QLD, Australia University of Queensland, Brisbane, QLD, Australia
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3
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Are VS, Gromski MA, Akisik F, Vilar-Gomez E, Lammert C, Ghabril M, Vuppalanchi R, Chalasani N. Primary Sclerosing Cholangitis Limited to Intrahepatic Bile Ducts Has Distinctly Better Prognosis. Dig Dis Sci 2024; 69:1421-1429. [PMID: 38347369 DOI: 10.1007/s10620-023-08260-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 07/25/2023] [Indexed: 04/19/2024]
Abstract
BACKGROUND There are two sub-phenotypes of large-duct primary sclerosing cholangitis (PSC): isolated intrahepatic PSC (IIPSC) and extrahepatic disease with or without intrahepatic (extra/intrahepatic). AIMS This study examined the differences in outcomes in patients with IIPSC compared to extra/intrahepatic and small-duct PSC. METHODS Patients with PSC treated at our institution from 1998 to 2019 were investigated. Biochemistries, clinical events, and survival were assessed by chart review and National Death Index. Cox-proportional hazards were used to determine the risk of clinical outcomes based on biliary tract involvement. RESULTS Our cohort comprised 442 patients with large-duct PSC (57 had IIPSC, 385 had extra/intrahepatic PSC) and 23 with small-duct PSC. Median follow-up in the IIPSC group was not significantly different from the extra/intrahepatic group [7 vs. 6 years, P = 0.06]. Except for lower age (mean 37.9 vs. 43.0 years, P = 0.045), the IIPSC group was not different from the extra/intrahepatic. The IIPSC group had longer transplant-free survival (log-rank P = 0.001) with a significantly lower risk for liver transplantation (12% vs. 34%, P < 0.001). The IIPSC group had a lower risk of death or transplantation than the extra/intrahepatic PSC group [HR: 0.34, 95% CI: 0.17-0.67, P < 0.001]. No bile duct or gallbladder cancers developed in patients with IIPSC, compared to 24 in the extra/intrahepatic group. The clinical characteristics and outcomes of IIPSC were similar to 23 individuals with small-duct PSC. CONCLUSIONS Patients with IIPSC have a favorable prognosis similar to small-duct PSC. These data are important for counseling patients and designing therapeutic trials for PSC.
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Affiliation(s)
- Vijay S Are
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Mark A Gromski
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Fatih Akisik
- Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Craig Lammert
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
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4
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Yu S, Vidal B, Peric M, Rosenbaum MW, Cates JMM, Gonzalez RS. Comparative histologic features among liver biopsies with biliary-pattern injury and confirmed clinical diagnoses. Hum Pathol 2024; 146:8-14. [PMID: 38479481 DOI: 10.1016/j.humpath.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 03/05/2024] [Accepted: 03/08/2024] [Indexed: 03/22/2024]
Abstract
Biliary-pattern injury in the liver (eg, duct injury, ductular reaction, cholestasis) can occur in several conditions, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), large duct obstruction (LDO), and drug-induced liver injury (DILI). While the histologic changes in these conditions have been individually well described, distinguishing among them remains often challenging, particularly when biopsy samples are limited in size, robust clinical information is unavailable, and/or the pathologist does not feel confident in evaluating liver disease. This study evaluated histologic features that could aid the diagnosis of biliary-pattern injury on biopsy. We reviewed 121 liver biopsies from clinically confirmed cases of PBC, PSC, chronic LDO, or DILI for multiple clinical and histologic parameters. The rates of these histologic findings were then compared among different entities. Onion-skin fibrosis was seen in 14% of PSC in comparison to 0%, 5%, and 0% of PBC, DILI, and chronic LDO (P = 0.031). Florid duct lesions were identified in 21% of PBC compared to 2% of PSC and 0% of DILI and LDO (P = 0.0065). Similarly, 42% of PBC showed lobular granulomas, compared to 7% of PSC, 11% of DILI, and 33% of chronic LDO (P = 0.0001). Cholestasis was more commonly seen in DILI (42%) and chronic LDO (83%) than in PBC (4%) and PSC (16%) (P < 0.0001). Lobular chronic inflammation was found in a significantly higher percentage of PBC and LDO than of PSC and DILI (P = 0.0009). There were significantly fewer cases of PBC showing neutrophils in ductular reaction than PSC, DILI, and LDO (P = 0.0063). Histologic findings that can help suggest a diagnosis in liver biopsies with biliary-pattern injury include florid duct lesions, lobular granulomas, lack of neutrophils in ductular reaction, and lobular chronic inflammation in PBC; onion-skin fibrosis in PSC; cholestasis and feathery degeneration in DILI; and lobular granulomas, lobular chronic inflammation, cholestasis, and feathery degeneration in chronic LDO. These findings are likely most helpful when complicating factors interfere with biopsy interpretation.
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Affiliation(s)
- Sanhong Yu
- Department of Pathology, Yale School of Medicine, New Heaven, CT, USA
| | - Barbara Vidal
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Masa Peric
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Matthew W Rosenbaum
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | | | - Raul S Gonzalez
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA, USA.
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5
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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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Lawson KL, Wang HL. Primary Sclerosing Cholangitis, Small Duct Primary Sclerosing Cholangitis, IgG4-Related Sclerosing Cholangitis, and Ischemic Cholangiopathy: Diagnostic Challenges on Biopsy. Surg Pathol Clin 2023; 16:533-548. [PMID: 37536887 DOI: 10.1016/j.path.2023.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
Pathologists face many challenges when diagnosing sclerosing biliary lesions on liver biopsy. First, histologic findings tend to be nonspecific with similar to identical features seen in numerous conditions, from benign to outright malignant. In addition, the patchy nature of many of these entities amplifies the inherent limitations of biopsy sampling. The end result often forces pathologists to issue descriptive sign outs that require careful clinical correlation; however, certain clinical, radiologic, and histologic features may be of diagnostic assistance. In this article, we review key elements of four sclerosing biliary processes whose proper identification has significant prognostic and therapeutic implications.
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Affiliation(s)
- Katy L Lawson
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Ronald Reagan UCLA Medical Center, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
| | - Hanlin L Wang
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Ronald Reagan UCLA Medical Center, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
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7
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Sticova E, Fabian O. Morphological aspects of small-duct cholangiopathies: A minireview. World J Hepatol 2023; 15:538-553. [PMID: 37206655 PMCID: PMC10190694 DOI: 10.4254/wjh.v15.i4.538] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/03/2023] [Accepted: 03/22/2023] [Indexed: 04/20/2023] Open
Abstract
The biliary system consists of intrahepatic and extrahepatic bile ducts lined by biliary epithelial cells (cholangiocytes). Bile ducts and cholangiocytes are affected by a variety of disorders called cholangiopathies, which differ in aetiology, pathogenesis, and morphology. Classification of cholangiopathies is complex and reflects pathogenic mechanisms (immune-mediated, genetic, drug- and toxin-induced, ischaemic, infectious, neoplastic), predominant morphological patterns of biliary injury (suppurative and non-suppurative cholangitis, cholangiopathy), and specific segments of the biliary tree affected by the disease process. While the involvement of large extrahepatic and intrahepatic bile ducts is typically visualised using radiology imaging, histopathological examination of liver tissue obtained by percutaneous liver biopsy still plays an important role in the diagnosis of cholangiopathies affecting the small intrahepatic bile ducts. To increase the diagnostic yield of a liver biopsy and determine the optimal therapeutic approach, the referring clinician is tasked with interpreting the results of histopathological examination. This requires knowledge and understanding of basic morphological patterns of hepatobiliary injury and an ability to correlate microscopic findings with results obtained by imaging and laboratory methods. This minireview describes the morphological aspects of small-duct cholangiopathies pertaining to the diagnostic process.
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Affiliation(s)
- Eva Sticova
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
- Department of Pathology, The Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague 10000, 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, The Third faculty of Medicine, Charles University and Thomayer University Hospital, Prague 14059, Czech Republic
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8
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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: 146] [Impact Index Per Article: 48.7] [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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9
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Da Cunha T, Vaziri H, Wu GY. Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: A Review. J Clin Transl Hepatol 2022; 10:531-542. [PMID: 35836773 PMCID: PMC9240248 DOI: 10.14218/jcth.2021.00344] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 10/12/2021] [Accepted: 11/22/2021] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis is a disease affecting around 0.006-0.016% of the population. Of these, around 75% have concomitant inflammatory bowel disease (IBD) according to the most recent epidemiological studies. Several theories have been proposed regarding the pathogenesis of primary sclerosing cholangitis (PSC). These include changes in the function of cholangiocytes, effects of the gut microbiome, association with specific human leukocyte antigen haplotypes and dysregulation of the immune system. However, these do not explain the observed association with IBD. Moreover, there are considerable differences in the frequency and outcomes between patients with PSC and ulcerative colitis compared with PSC and Crohn's disease. The aim of this review is to appraise the most recent studies that have contributed to the epidemiology, advances in the pathophysiology, and characterization of important clinical aspects of the association of PSC and IBD.
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Affiliation(s)
- Teresa Da Cunha
- Correspondence to: Teresa Da Cunha, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA. ORCID: https://orcid.org/0000-0002-8319-7608. Tel: +1-860-706-2133, Fax: +1-860-679-3159, E-mail:
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10
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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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11
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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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12
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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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13
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Rabiee A, Silveira MG. Primary sclerosing cholangitis. Transl Gastroenterol Hepatol 2021; 6:29. [PMID: 33824933 DOI: 10.21037/tgh-20-266] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/19/2020] [Indexed: 12/15/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.
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Affiliation(s)
- Anahita Rabiee
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Marina G Silveira
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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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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15
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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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16
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Ali AH, Damman J, Shah SB, Davies Y, Hurwitz M, Stephen M, Lemos LM, Carey EJ, Lindor KD, Buness CW, Alrabadi L, Berquist WE, Cox KL. Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. Scand J Gastroenterol 2020; 55:941-950. [PMID: 32633158 DOI: 10.1080/00365521.2020.1787501] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Oral vancomycin (OV) in primary sclerosing cholangitis (PSC) has been evaluated as a potential therapeutic agent. We report the long-term biochemical course and outcomes of patients with PSC treated with OV. METHODS Patients were enrolled in 2 open-label clinical trials (ClinicalTrials.gov Identifier: NCT01802073 and NCT01322386) and offered OV at 50 mg/kg/day in 3 divided doses if weight <30kg, and 500 mg 3 times/day if weight ≥30kg. Patients with biliary strictures requiring stenting or awaiting liver transplant were excluded. Liver biochemistry, MRCP and histology were documented at baseline and while on OV. The primary outcome was a decrease in elevated gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and/or alanine aminotransferase (ALT) from baseline. RESULTS 30 subjects were enrolled, and 29 additional subjects who learned of the clinical trial requested OV (total n = 59; median age was 13.5 years [range, 1.5-44 years]; 64.4% were male; and 94.9% had inflammatory bowel disease [IBD]). The median treatment duration was 2.7 years (range, 0.2-14 years). Ninety-six percent (57/59), 81.3% (48/59), and 94.9% (56/59) experienced reduction of GGT, ALP, and ALT, respectively. Furthermore, 39% (23/59), 22% (13/59), and 55.9% (33/59) experienced normalization of GGT, ALP, and ALT, respectively, within the first 6 months of OV treatment. One patient underwent liver transplantation 8 years after beginning OV treatment, and one developed biliary strictures requiring endoscopic intervention. OV was well-tolerated by patients, and no patient developed treatment-related adverse events. CONCLUSION In PSC, OV was well-tolerated and was associated with improvement in liver chemistry. A randomized placebo-controlled clinical trial is warranted.
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Affiliation(s)
- Ahmad Hassan Ali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA.,Division of Hepatology, University of Missouri-Columbia, Columbia, MO, USA.,Texas Tech University Health Sciences Center, Amarillo, TX, USA
| | - Jennifer Damman
- Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA, USA
| | - Shamita B Shah
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA.,Division of Gastroenterology, Ochsner Clinic Foundation, New Orleans, LA, USA
| | - Yinka Davies
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA
| | - Melissa Hurwitz
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, Palo Alto, CA, USA
| | - Mariam Stephen
- Lucile Packard Children's Hospital, Stanford University, Stanford, CA, USA
| | - Leta M Lemos
- Sacramento Pediatric Gastroenterology, Sacramento, CA, USA
| | - Elizabeth J Carey
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA
| | - Keith D Lindor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA.,College of Health Solutions, Arizona State University, Phoenix, AZ, USA
| | - Cynthia W Buness
- National Patient Advocate Foundation, Arizona State University, Phoenix, AZ, USA
| | - Leina Alrabadi
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA
| | - William E Berquist
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, Palo Alto, CA, USA
| | - Kenneth L Cox
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, Palo Alto, CA, USA
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17
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Dumonceau JM, Delhaye M, Charette N, Farina A. Challenging biliary strictures: pathophysiological features, differential diagnosis, diagnostic algorithms, and new clinically relevant biomarkers - part 1. Therap Adv Gastroenterol 2020; 13:1756284820927292. [PMID: 32595761 PMCID: PMC7298429 DOI: 10.1177/1756284820927292] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 04/16/2020] [Indexed: 02/04/2023] Open
Abstract
It is frequently challenging to make the correct diagnosis in patients with biliary strictures. This is particularly important as errors may have disastrous consequences. Benign-appearing strictures treated with stents may later be revealed to be malignant and unnecessary surgery for benign strictures carries a high morbidity rate. In the first part of the review, the essential information that clinicians need to know about diseases responsible for biliary strictures is presented, with a focus on the most recent data. Then, the characteristics and pitfalls of the methods used to make the diagnosis are summarized. These include serum biomarkers, imaging studies, and endoscopic modalities. As tissue diagnosis is the only 100% specific tool, it is described in detail, including techniques for tissue acquisition and their yields, how to prepare samples, and what to expect from the pathologist. Tricks to increase diagnostic yields are described. Clues are then presented for the differential diagnosis between primary and secondary sclerosing cholangitis, IgG4-related sclerosing cholangitis, cholangiocarcinoma, pancreatic cancer, autoimmune pancreatitis, and less frequent diseases. Finally, algorithms that will help to achieve the correct diagnosis are proposed.
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Affiliation(s)
- Jean-Marc Dumonceau
- Department of Gastroenterology, Charleroi
University Hospitals, Chaussée de Bruxelles 140, Charleroi, 6042,
Belgium
| | - Myriam Delhaye
- Department of Gastroenterology,
Hepatopancreatology and GI Oncology, Erasme University Hospital, Brussels,
Belgium
| | - Nicolas Charette
- Department of Gastroenterology, Charleroi
University Hospitals, Charleroi, Belgium
| | - Annarita Farina
- Department of Medicine, Geneva University,
Geneva, Switzerland
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18
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Ringe KI, Bergquist A, Lenzen H, Kartalis N, Manns MP, Wacker F, Grigoriadis A. Clinical features and MRI progression of small duct primary sclerosing cholangitis (PSC). Eur J Radiol 2020; 129:109101. [PMID: 32505896 DOI: 10.1016/j.ejrad.2020.109101] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 05/25/2020] [Accepted: 05/26/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE First, to evaluate and describe the clinical and MRI progression of patients with small duct primary sclerosing cholangitis (sdPSC), and second, to look for MRI features associated with disease progression to large duct PSC. METHOD 16 patients (7 female, 9 male; median age 27 years) with diagnosis of sdPSC and available MR imaging were included in this retrospective dual-center study. Liver function tests (LFTs) and imaging was reviewed in consensus by two radiologists at baseline and follow-up, and compared by means of non-parametric tests, with p < 0.05 deemed significant. RESULTS At baseline and follow-up patients had a cholestatic liver profile with elevated LFTs. Progressive liver deformity, heterogeneous enhancement and hilar lymphadenopathy were common findings. In 9 patients follow-up MRI was available with a mean interval between imaging of 10.6 years (range 3.6-15.3 years). 5 patients (55.5 %) developed cholangiographic changes diagnostic of large duct PSC. No correlation was observed between MRI findings or LFTs at baseline and the endpoint of developing PSC typical cholangiographic changes at follow-up imaging (p > 0.05). CONCLUSIONS More than half of sdPSC patients developed cholangiographic changes, supporting that sdPSC may be an early stage of large duct PSC rather than an entity of its own. Larger studies are needed to address the value of MRI for prediction of sdPSC disease progression.
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Affiliation(s)
- Kristina I Ringe
- Hannover Medical School, Department of Diagnostic and Interventional Radiology, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
| | - Annika Bergquist
- Karolinska University Hospital, Division of Upper GI Diseases, Unit of Liver Disease, Karolinska Institutet, Stockholm, Sweden
| | - Henrike Lenzen
- University Hospital Essen, Department of Gastroenterology and Hepatology, University of Duisburg Essen, Hufelandstrasse 55, 45147 Essen, Germany; Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Str. 1, 30625 Hannover, Germany
| | - Nikolaos Kartalis
- Karolinska University Hospital, Division of Radiology, Karolinska Institutet, Stockholm, Sweden
| | - Michael P Manns
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Str. 1, 30625 Hannover, Germany
| | - Frank Wacker
- Hannover Medical School, Department of Diagnostic and Interventional Radiology, Carl-Neuberg Str. 1, 30625 Hannover, Germany
| | - Aristeidis Grigoriadis
- Karolinska University Hospital, Division of Radiology, Karolinska Institutet, Stockholm, Sweden
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19
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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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20
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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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21
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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] [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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22
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AGA Clinical Practice Update on Surveillance for Hepatobiliary Cancers in Patients With Primary Sclerosing Cholangitis: Expert Review. Clin Gastroenterol Hepatol 2019; 17:2416-2422. [PMID: 31306801 DOI: 10.1016/j.cgh.2019.07.011] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 06/19/2019] [Accepted: 07/08/2019] [Indexed: 02/07/2023]
Abstract
DESCRIPTION The purpose of this clinical practice update is to define key principles in the surveillance of hepatobiliary cancers including cholangiocarcinoma, gallbladder adenocarcinoma, and hepatocellular carcinoma in patients with primary sclerosing cholangitis (PSC). METHODS The recommendations outlined in this expert review are based on available published evidence including observational studies and systematic reviews, and incorporates expert opinion where applicable. BEST PRACTICE ADVICE 1: Surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with PSC regardless of disease stage, especially in the first year after diagnosis and in patients with ulcerative colitis and those diagnosed at an older age. BEST PRACTICE ADVICE 2: Surveillance for cholangiocarcinoma and gallbladder cancer should include imaging by ultrasound, computed tomography, or magnetic resonance imaging, with or without serum carbohydrate antigen 19-9, every 6 to 12 months BEST PRACTICE ADVICE 3: Endoscopic retrograde cholangiopancreatography with brush cytology should not be used routinely for surveillance of cholangiocarcinomas in PSC. BEST PRACTICE ADVICE 4: Cholangiocarcinomas should be investigated by endoscopic retrograde cholangiopancreatography with brush cytology with or without fluorescence in situ hybridization analysis and/or cholangioscopy in PSC patients with worsening clinical symptoms, worsening cholestasis, or a dominant stricture. BEST PRACTICE ADVICE 5: Fine-needle aspiration of perihilar biliary strictures should be used with caution in PSC patients considered to be liver transplant candidates because of concerns for tumor seeding if the lesion is a cholangiocarcinoma. BEST PRACTICE ADVICE 6: Surveillance for cholangiocarcinoma should not be performed in PSC patients with small-duct PSCs or those younger than age 20. BEST PRACTICE ADVICE 7: The decision to perform a cholecystectomy in PSC patients with a gallbladder polyp should be based on the size and growth of the polyp, as well as the clinical status of the patient, with the knowledge of the increased risk of gallbladder cancer in polyps greater than 8 mm. BEST PRACTICE ADVICE 8: Surveillance for hepatocellular carcinoma in PSC patients with cirrhosis should include ultrasound, computed tomography, or magnetic resonance imaging, with or without α-fetoprotein every 6 months.
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23
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Chascsa DM, Lindor KD. Cancer risk, screening and surveillance in primary sclerosing cholangitis. MINERVA GASTROENTERO 2019; 65:214-228. [PMID: 31220911 DOI: 10.23736/s1121-421x.19.02586-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory condition mainly of the large bile ducts, affecting predominantly young men, and is associated with the presence of inflammatory bowel disease. There is no known cure for PSC, which progresses to cirrhosis or death over 10-20 years. Hepatobiliary malignancy, especially cholangiocarcinoma, is a feared complication associated with poor overall survival. Screening and surveillance appear to improve overall outcomes. To capture as many relevant studies, broad search criteria were employed within the PubMed database. Given the high prevalence of IBD and its own associations with the development of malignancy two separate search strategies were employed. Results were filtered by English language. The first search identified the risks, epidemiological factors and surveillance strategies for patients with PSC at risk for developing malignancy. MeSH terms included: cholangitis, sclerosing, digestive system neoplasms, liver neoplasms, biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms, colonic neoplasms, rectal neoplasms, or pancreatic neoplasms, risk factors, risk, surveillance, epidemiology and screen. The second included inflammatory bowel diseases, Crohn's, or colitis, and assessed for additional malignancies such as lymphoma and skin neoplasms. A total of 288 results returned with 21 duplicates; 267 remaining abstracts were assessed for relevance for inclusion by the authors. Patients with PSC show significantly higher than average risk for the development of hepatobiliary and colonic malignancies including cholangiocarcinoma, gallbladder carcinoma and colorectal carcinoma. Yearly ultrasound surveillance followed with more definitive cross-sectional imaging is prudent to arrive in a timely diagnosis of carcinoma, reducing morbidity and mortality.
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Affiliation(s)
- David M Chascsa
- Departments of Gastroenterology and Hepatology and Transplant Center, Mayo Clinic, Phoenix, AZ, USA -
| | - Keith D Lindor
- Office of University Provost, Arizona State University, Phoenix, AZ, USA
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Joosse ME, Haisma SM, Sterk MFM, van Munster KN, Ponsioen CIJ, Houwen RHJ, Koot BGP, de Meij T, van Rheenen PF, de Koning BAE. Disease progression in paediatric- and adult-onset sclerosing cholangitis: Results from two independent Dutch registries. Liver Int 2019; 39:1768-1775. [PMID: 31152478 DOI: 10.1111/liv.14159] [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: 01/15/2019] [Revised: 05/15/2019] [Accepted: 05/20/2019] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Sclerosing cholangitis (SC) is a severe liver disease leading to destruction of bile ducts. It is believed to run a milder course in children than in adults. To test this assumption, we evaluated time-to-complication curves in two independent paediatric-onset cohorts from the same geographical area. METHODS Short-term disease outcomes were evaluated with an online clinical registry that was filled with data on children with SC diagnosed between 2000 and 2017 and who were followed bi-annually thereafter. Long-term disease outcomes were evaluated in a paediatric-onset subcohort derived from a previously published population-based study from the Netherlands. Time-to-complication in the first cohort was defined as the time from diagnosis until portal hypertension, biliary obstructions and infections, development of malignancy, or liver transplantation, whichever came first. In the second cohort time-to-complication was defined as the time until liver transplantation or PSC-related death. RESULTS Median age at diagnosis in the first cohort (n = 86) was 12.3 years. In the first 5 years post-diagnosis 23% of patients developed complications. The patients in the population-based study (n = 683) were stratified into those diagnosed before the age of 18 years ('paediatric-onset' subcohort, n = 43) and those diagnosed after the age of 18 years ('adult-onset' subcohort, n = 640). Median age at diagnosis was 14.6 and 40.2 years, respectively. Median time-to-complication in the paediatric-onset and adult-onset subcohorts was not statistically different. CONCLUSION Paediatric and adult-onset SC run a similar long-term disease course. Paediatricians who treat children with SC should monitor them closely to recognize early complications and control long-term sequelae.
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Affiliation(s)
- Maria E Joosse
- Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Sjoukje M Haisma
- University of Groningen, University Medical Center Groningen, Pediatric Gastroenterology Hepatology and Nutrition, Groningen, the Netherlands
| | - Marlou F M Sterk
- Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Kim N van Munster
- Department of Gastroenterology & Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Cyriel I J Ponsioen
- Department of Gastroenterology & Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Roderick H J Houwen
- Department of Pediatric Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Bart G P Koot
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Tim de Meij
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Department of Pediatric Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
| | - Patrick F van Rheenen
- University of Groningen, University Medical Center Groningen, Pediatric Gastroenterology Hepatology and Nutrition, Groningen, the Netherlands
| | - Barbara A E de Koning
- Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands
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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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26
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Fung BM, Tabibian JH. Biliary endoscopy in the management of primary sclerosing cholangitis and its complications. LIVER RESEARCH 2019; 3:106-117. [PMID: 31341699 PMCID: PMC6656407 DOI: 10.1016/j.livres.2019.03.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, idiopathic, cholestatic liver disease characterized by inflammation and fibrosis of the intrahepatic and/or extrahepatic bile ducts. It can affect individuals of all age groups and gender, has no established pharmacotherapy, and is associated with a variety of neoplastic (e.g. cholangiocarcinoma) and non-neoplastic (e.g. dominant strictures) hepatobiliary complications. Given these considerations, endoscopy plays a major role in the care of patients with PSC. In this review, we discuss and provide updates regarding endoscopic considerations in the management of hepatobiliary manifestations and complications of PSC. Where evidence is limited, we suggest pragmatic approaches based on currently available data and expert opinion.
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Affiliation(s)
- Brian M. Fung
- University of California Los Angeles-Olive View Internal Medicine Residency Program, Sylmar, CA, USA
| | - James H. Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-University of California Los Angeles Medical Center, Sylmar, CA, USA
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27
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Primary Sclerosing Cholangitis: A Concise Review of Diagnosis and Management. Dig Dis Sci 2019; 64:632-642. [PMID: 30725292 DOI: 10.1007/s10620-019-05484-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/19/2019] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterized by progressive idiopathic stricturing of the biliary system, typically leading to cirrhosis, end-stage liver disease, and colonic or hepatobiliary malignancy. Its presentation is often that of asymptomatic alkaline phosphatase elevation. When symptoms are present, they typically include fatigue, pruritus, or jaundice. The diagnosis can be confirmed via cholangiography, either magnetic resonance cholangiography (MRCP) or endoscopic retrograde cholangiography if the former is inconclusive. The clinical course is marked by progressive liver disease leading to cirrhosis with its attendant complications of portal hypertension, often including recurrent episodes of cholangitis. Greater elevation in alkaline phosphatase or liver stiffness is associated with worse clinical outcomes. Management includes endoscopic treatment of symptomatic biliary strictures and evaluation of dominant strictures as no adequate medical treatment is available. Multiple medical therapies are under evaluation. Ultimately, liver transplantation may be necessary for management of decompensated cirrhosis or disabling symptoms. There is also a markedly increased risk of cancer, notably including cholangiocarcinoma and gallbladder and colorectal cancers (particularly in patients with colitis). Cancer screening can be done with semi-annual liver imaging (MRCP or ultrasound) and colonoscopy every 1-2 years in those with colitis.
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28
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Selvaraj EA, Culver EL, Bungay H, Bailey A, Chapman RW, Pavlides M. Evolving role of magnetic resonance techniques in primary sclerosing cholangitis. World J Gastroenterol 2019; 25:644-658. [PMID: 30783369 PMCID: PMC6378540 DOI: 10.3748/wjg.v25.i6.644] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/25/2019] [Accepted: 01/28/2019] [Indexed: 02/06/2023] Open
Abstract
Development of non-invasive methods to risk-stratify patients and predict clinical endpoints have been identified as one of the key research priorities in primary sclerosing cholangitis (PSC). In addition to serum and histological biomarkers, there has been much recent interest in developing imaging biomarkers that can predict disease course and clinical outcomes in PSC. Magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) continue to play a central role in the diagnosis and follow-up of PSC patients. Magnetic resonance (MR) techniques have undergone significant advancement over the last three decades both in MR data acquisition and interpretation. The progression from a qualitative to quantitative approach in MR acquisition techniques and data interpretation, offers the opportunity for the development of objective and reproducible imaging biomarkers that can potentially be incorporated as an additional endpoint in clinical trials. This review article will discuss how the role of MR techniques have evolved over the last three decades from emerging as an alternative diagnostic tool to endoscopic retrograde cholangiopancreatography, to being instrumental in the ongoing search for imaging biomarker of disease stage, progression and prognosis in PSC.
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Affiliation(s)
- Emmanuel A Selvaraj
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
- Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
- Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford OX3 9DU, United Kingdom
| | - Emma L Culver
- Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
- Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford OX3 9DU, United Kingdom
| | - Helen Bungay
- Department of Radiology, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
| | - Adam Bailey
- Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
- Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford OX3 9DU, United Kingdom
| | - Roger W Chapman
- Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
| | - Michael Pavlides
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
- Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
- Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford OX3 9DU, United Kingdom
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Adike A, Carey EJ, Lindor KD. Primary sclerosing cholangitis in children versus adults: lessons for the clinic. Expert Rev Gastroenterol Hepatol 2018; 12:1025-1032. [PMID: 30199272 DOI: 10.1080/17474124.2018.1521719] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a rare cholestatic disorder that presents with multifocal biliary strictures. PSC has a variable course but often leads to progressive liver disease, and most patients will eventually require liver transplantation. PSC has a strong association with inflammatory bowel disease and autoimmune liver disease. Areas covered: The objective of this article is to compare and contrast the clinical features and natural history of PSC in children to adults. We performed a PubMed search of the English literature using keywords 'primary sclerosing cholangitis', 'PSC', 'children', and 'pediatric.' Expert commentary: While certain features of PSC are similar in the pediatric and adult population, there are unique features of pediatric PSC. More longitudinal studies are needed to better understand the natural history of pediatric PSC. It is conceivable that treatment for PSC that will alter the course of disease may become available in the future.
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Affiliation(s)
- Abimbola Adike
- 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
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30
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Tabibian JH, Bowlus CL. WITHDRAWN: Primary sclerosing cholangitis: A review and update. LIVER RESEARCH 2018. [DOI: 10.1016/j.livres.2017.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Abstract
Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease of uncertain etiology characterized biochemically by cholestasis and histologically and cholangiographically by fibro-obliterative inflammation of the bile ducts. In a clinically significant proportion of patients, PSC progresses to cirrhosis, end-stage liver disease, and/or hepatobiliary cancer, though the disease course can be highly variable. Despite clinical trials of numerous pharmacotherapies over several decades, safe and effective medical therapy remains to be established. Liver transplantation is an option for select patients with severe complications of PSC, and its outcomes are generally favorable. Periodic surveillance testing for pre- as well as post-transplant patients is a cornerstone of preventive care and health maintenance. Here we provide an overview of PSC including its epidemiology, etiopathogenesis, clinical features, associated disorders, surveillance, and emerging potential therapies.
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Affiliation(s)
- James H. Tabibian
- Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
- Division of Gastroenterology, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Christopher L. Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
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32
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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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33
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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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34
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Marco TM, Hiram VV, Lenin PR. Primary Sclerosing Cholangitis in an Elderly Patient: A Diagnostic Challenge. Ann Geriatr Med Res 2017. [DOI: 10.4235/agmr.2017.21.3.138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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35
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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] [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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36
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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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Czaja AJ, Carpenter HA. Autoimmune Hepatitis Overlap Syndromes and Liver Pathology. Gastroenterol Clin North Am 2017; 46:345-364. [PMID: 28506369 DOI: 10.1016/j.gtc.2017.01.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
Autoimmune hepatitis (AIH) may have an atypical serum alkaline phosphatase elevation, antimitochondrial antibodies, histologic features of bile duct injury/loss, or cholangiographic findings of focal biliary strictures and dilations. These manifestations characterize the overlap syndromes. Patients can be classified as having AIH with features of primary biliary cholangitis, primary sclerosing cholangitis, or a cholestatic syndrome. The gold standard of diagnosis is clinical judgment. Histologic evaluation is a major diagnostic component. Treatment is based on algorithms; outcomes vary depending on the predominant disease component. Combination therapy has been the principal recommendation.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA.
| | - Herschel A Carpenter
- Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA
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Filipec Kanizaj T, Mijic M. Inflammatory bowel disease in liver transplanted patients. World J Gastroenterol 2017; 23:3214-3227. [PMID: 28566881 PMCID: PMC5434427 DOI: 10.3748/wjg.v23.i18.3214] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 04/13/2017] [Accepted: 04/21/2017] [Indexed: 02/06/2023] Open
Abstract
Most common hepatobiliary manifestation of inflammatory bowel disease (IBD) are primary sclerosing cholangitis (PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation (LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Anti-tumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic disease leading to fibrotic scarring of the intrahepatic and extrahepatic bile ducts, causing considerable morbidity and mortality via the development of cholestatic liver cirrhosis, concurrent IBD and a high risk of bile duct cancer. Expectations have been high that genetic studies would determine key factors in PSC pathogenesis to support the development of effective medical therapies. Through the application of genome-wide association studies, a large number of disease susceptibility genes have been identified. The overall genetic architecture of PSC shares features with both autoimmune diseases and IBD. Strong human leukocyte antigen gene associations, along with several susceptibility genes that are critically involved in T-cell function, support the involvement of adaptive immune responses in disease pathogenesis, and position PSC as an autoimmune disease. In this Review, we survey the developments that have led to these gene discoveries. We also elaborate relevant interpretations of individual gene findings in the context of established disease models in PSC, and propose relevant translational research efforts to pursue novel insights.
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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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Abstract
PURPOSE OF REVIEW Primary sclerosing cholangitis (PSC) is a rare, idiopathic biliary disease often with an insidious onset, variable disease course, and premature death related to benign and malignant PSC-related sequelae. This review aims to discuss the epidemiology, clinical variants, and natural history of PSC, incorporating data from recent population-based studies. RECENT FINDINGS PSC naturally leads to cirrhosis, cholangiocarcinoma, other hepatobiliary malignancies, dominant strictures, hepatic osteodystrophy, and bacterial cholangitis. The incidence of PSC appears to be increasing, the reasons for which are unclear. The time from diagnosis to liver transplant appears to be longer in more recent studies compared with earlier studies, suggesting a better overall prognosis than previously believed. In addition, with an increasing number of patients undergoing liver transplantation for PSC, the frequency of death because of liver failure has decreased, whereas cancer-related deaths have increased among patients with PSC. SUMMARY PSC is a heterogeneous disease with a variety of clinical outcomes, both fatal and nonfatal. The progression of liver fibrosis in an individual patient is difficult to predict and may vary from a relatively benign, nonprogressive form to a rapidly progressive form with the need for liver transplantation.
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Affiliation(s)
- Konstantinos N Lazaridis
- From the Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
| | - Nicholas F LaRusso
- From the Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
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Diagnosis and endoscopic management of primary sclerosing cholangitis. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2016. [DOI: 10.1016/j.tgie.2016.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Adult bile duct strictures: differentiating benign biliary stenosis from cholangiocarcinoma. Med Mol Morphol 2016; 49:189-202. [PMID: 27350291 DOI: 10.1007/s00795-016-0143-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 06/04/2016] [Indexed: 12/17/2022]
Abstract
Biliary epithelial cells preferentially respond to various insults under chronic pathological conditions leading to reactively atypical changes, hyperplasia, or the development of biliary neoplasms (such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and cholangiocarcinoma). Moreover, benign biliary strictures can be caused by a variety of disorders (such as IgG4-related sclerosing cholangitis, eosinophilic cholangitis, and follicular cholangitis) and often mimic malignancies, despite their benign nature. In addition, primary sclerosing cholangitis is a well-characterized precursor lesion of cholangiocarcinoma and many other chronic inflammatory disorders increase the risk of malignancies. Because of these factors and the changes in biliary epithelial cells, biliary strictures frequently pose a diagnostic challenge. Although the ability to differentiate neoplastic from non-neoplastic biliary strictures has markedly progressed with the advance in radiological modalities, brush cytology and bile duct biopsy examination remains effective. However, no single modality is adequate to diagnose benign biliary strictures because of the low sensitivity. Therefore, understanding the underlying causes by compiling the entire clinical, laboratory, and imaging data; considering the under-recognized causes; and collaborating between experts in various fields including cytopathologists with multiple approaches is necessary to achieve an accurate diagnosis.
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Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions. Gut Liver 2016; 10:177-203. [PMID: 26934884 PMCID: PMC4780448 DOI: 10.5009/gnl15352] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms.
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Affiliation(s)
- Albert J. Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN,
USA
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Trivedi PJ, Corpechot C, Pares A, Hirschfield GM. Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists. Hepatology 2016; 63:644-59. [PMID: 26290473 PMCID: PMC4864755 DOI: 10.1002/hep.28128] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Accepted: 08/14/2015] [Indexed: 12/11/2022]
Abstract
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644-659).
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Affiliation(s)
- Palak J. Trivedi
- National Institute for Health Research (NIHR), Birmingham Liver Biomedical Research Unit (BRU), and Center for Liver ResearchUniversity of BirminghamBirminghamUnited Kingdom
| | - Christophe Corpechot
- National Reference Center for Inflammatory Diseases of the Biliary Tract (MIVB), Rare Liver Diseases Health Network (FILFOIE), Saint‐Antoine HospitalAssistance Publique‐Hôpitaux de Paris (APHP)ParisFrance
| | - Albert Pares
- Liver Unit, Hospital Clínic, CIBERehd, IDIBAPSUniversity of BarcelonaBarcelonaSpain
| | - Gideon M. Hirschfield
- National Institute for Health Research (NIHR), Birmingham Liver Biomedical Research Unit (BRU), and Center for Liver ResearchUniversity of BirminghamBirminghamUnited Kingdom
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Zampetti A, Rinninella E, Manna R, Franceschi F. Scleroderma and liver disease: a case of an association with primary sclerosing cholangitis. Scand J Rheumatol 2015; 45:334-5. [PMID: 26690847 DOI: 10.3109/03009742.2015.1114667] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Affiliation(s)
- A Zampetti
- a Department of Dermatology , Saint Mary's and Hammersmith Hospitals, Imperial College Healthcare, NHS Trust , London , UK.,b Department of Internal Medicine , Agostino Gemelli Hospital, Catholic University of the Sacred Heart , Rome , Italy
| | - E Rinninella
- b Department of Internal Medicine , Agostino Gemelli Hospital, Catholic University of the Sacred Heart , Rome , Italy
| | - R Manna
- b Department of Internal Medicine , Agostino Gemelli Hospital, Catholic University of the Sacred Heart , Rome , Italy
| | - F Franceschi
- b Department of Internal Medicine , Agostino Gemelli Hospital, Catholic University of the Sacred Heart , Rome , Italy
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Bittencourt PL, Cançado ELR, Couto CA, Levy C, Porta G, Silva AEB, Terrabuio DRB, Carvalho Filho RJD, Chaves DM, Miura IK, Codes L, Faria LC, Evangelista AS, Farias AQ, Gonçalves LL, Harriz M, Lopes Neto EPA, Luz GO, Oliveira P, Oliveira EMGD, Schiavon JLN, Seva-Pereira T, Parise ER, Parise ER. Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver. ARQUIVOS DE GASTROENTEROLOGIA 2015; 52 Suppl 1:15-46. [DOI: 10.1590/s0004-28032015000500002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
ABSTRACT In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.
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Sclair SN, Little E, Levy C. Current Concepts in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis. Clin Transl Gastroenterol 2015; 6:e109. [PMID: 26312413 PMCID: PMC4816277 DOI: 10.1038/ctg.2015.33] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 07/23/2015] [Indexed: 12/15/2022] Open
Abstract
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic, cholestatic diseases of the liver with common clinical manifestations. Early diagnosis and treatment of PBC slows progression and decreases the need for transplant. However, one-third of patients will progress regardless of treatment. Bilirubin <1.0 and alkaline phosphatase <2.0 x the upper limit of normal at 1 year after treatment appear to predict 10-year survival. Ursodeoxycholic acid (UDCA) is the recommended treatment for PBC, and recent studies with obeticholic acid showed promising results for UDCA non-responders. Unlike PBC, no therapy has been shown to alter the natural history of PSC. The recommended initial diagnostic test for PSC is magnetic resonance cholangiopancreatography, typically showing bile duct wall thickening, focal bile duct dilatation, and saccular dilatation of the intra- and/or extrahepatic bile ducts. Immunoglobulin 4-associated cholangitis must be excluded when considering the diagnosis of PSC, to allow for proper treatment, and monitoring of disease progression. In addition to the lack of therapy, PSC is a pre-malignant condition and close surveillance is indicated.
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Affiliation(s)
- Seth N Sclair
- Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Ester Little
- Banner University Medical Center, Phoenix, Arizona, USA
| | - Cynthia Levy
- Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
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