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For: Gulamhusein AF, Eaton JE, Tabibian JH, Atkinson EJ, Juran BD, Lazaridis KN. Duration of Inflammatory Bowel Disease Is Associated With Increased Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis and IBD. Am J Gastroenterol 2016;111:705-711. [PMID: 27002801 PMCID: PMC5027894 DOI: 10.1038/ajg.2016.55] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 01/02/2016] [Indexed: 12/11/2022]

For:	Gulamhusein AF, Eaton JE, Tabibian JH, Atkinson EJ, Juran BD, Lazaridis KN. Duration of Inflammatory Bowel Disease Is Associated With Increased Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis and IBD. Am J Gastroenterol 2016;111:705-711. [PMID: 27002801 PMCID: PMC5027894 DOI: 10.1038/ajg.2016.55] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 01/02/2016] [Indexed: 12/11/2022]

Number

Cited by Other Article(s)

Durak MB. Effect of dominant stricture and disease duration on prognosis in primary sclerosing cholangitis. Indian J Gastroenterol 2025;44:263-264. [PMID: 39110400 DOI: 10.1007/s12664-024-01660-9] [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: 03/30/2025]

Vajsova A, Cahova M, Bajer L, Sticova E, Juskova I, Hlavaty M, Fabian O. Unique clinical, morphological, and molecular characteristics of tumors associated with PSC-IBD. Virchows Arch 2025;486:651-661. [PMID: 40102272 PMCID: PMC12018527 DOI: 10.1007/s00428-025-04072-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/27/2025] [Accepted: 03/04/2025] [Indexed: 03/20/2025]

Manns MP, Bergquist A, Karlsen TH, Levy C, Muir AJ, Ponsioen C, Trauner M, Wong G, Younossi ZM. Primary sclerosing cholangitis. Nat Rev Dis Primers 2025;11:17. [PMID: 40082445 DOI: 10.1038/s41572-025-00600-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/07/2025] [Indexed: 03/16/2025]

Abstract

Primary sclerosing cholangitis (PSC) is a chronic biliary inflammation associated with periductular fibrosis of the intrahepatic and extrahepatic bile ducts leading to strictures, bacterial cholangitis, decompensated liver disease and need for liver transplantation. This rare focal liver disease affects all races and ages, with a predominance of young males. There is an up to 88% association with inflammatory bowel disease. Although the aetiology is unknown and the pathophysiology is poorly understood, PSC is regarded as an autoimmune liver disease based on a strong immunogenetic background. Further, the associated risk for various malignancies, particularly cholangiocellular carcinoma, is also poorly understood. No medical therapy has been approved so far nor has been shown to improve transplant-free survival. However, ursodeoxycholic acid is widely used since it improves the biochemical parameters of cholestasis and is safe at low doses. MRI of the biliary tract is the primary imaging technology for diagnosis. Endoscopic interventions of the bile ducts should be limited to clinically relevant strictures for balloon dilatation, biopsy and brush cytology. End-stage liver disease with decompensation is an indication for liver transplantation with recurrent PSC in up to 38% of patients. Several novel therapeutic strategies are in various stages of development, including apical sodium-dependent bile acid transporter and ileal bile acid transporter inhibitors, integrin inhibitors, peroxisome proliferator-activated receptor agonists, CCL24 blockers, recombinant FGF19, CCR2/CCR5 inhibitors, farnesoid X receptor bile acid receptor agonists, and nor-ursodeoxycholic acid. Manipulation of the gut microbiome includes faecal microbiota transplantation. This article summarizes present knowledge and defines unmet medical needs to improve quality of life and survival.

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Leung KK, Li W, Hansen B, Gulamhusein A, Lapointe-Shaw L, Shaheen AA, Ricciuto A, Benchimol EI, Flemming JA, Hirschfield GM. Primary sclerosing cholangitis-inflammatory bowel disease: Epidemiology, mortality, and impact of diagnostic sequence. JHEP Rep 2025;7:101272. [PMID: 40041117 PMCID: PMC11876923 DOI: 10.1016/j.jhepr.2024.101272] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 10/31/2024] [Accepted: 11/05/2024] [Indexed: 03/06/2025] Open

Abstract

Background & Aims

Primary sclerosing cholangitis (PSC) carries significant morbidity and mortality compared with inflammatory bowel disease (IBD). We characterized epidemiology trends and outcomes in those with PSC-IBD and IBD, paying particular attention to the impact of PSC-IBD diagnostic sequence on outcomes.

Methods

Incidence and prevalence of PSC-IBD and IBD (2002-2018) were evaluated using validated health administrative data-derived cohorts from Ontario, Canada (population ∼15 million). Transplant and death outcomes were assessed, with PSC-IBD diagnostic sequence as the exposure of interest.

Results

Incidence of PSC-IBD and IBD was 0.46 and 24.6/100,000 person-years (PYs) respectively, whereas prevalence was 5.53 and 588/100,000 PY respectively. Incidence/prevalence of PSC-IBD increased over time, unlike for IBD. Age at IBD diagnosis was earlier among those with PSC-IBD compared with those with IBD alone. Higher socioeconomic status associated with high PSC-IBD incidence rates and fastest incidence rise. Those diagnosed with IBD before PSC had higher risk of transplant/death compared with PSC before IBD (hazard ratio [HR] 1.34, 95% CI 1.02-1.75), driven by an increased risk of death (HR 2.73, 95% CI 1.68-4.45). PSC-IBD had a 4.5-fold greater risk of transplant/death compared with IBD alone. Liver-related and luminal gastrointestinal disease, particularly hepatopancreatobiliary malignancy, were predominant causes of death among those with PSC-IBD, while cardiovascular and respiratory diseases were predominant among those with IBD.

Conclusions

Population-level data support distinct epidemiological patterns among people living with PSC-IBD compared with IBD, including a higher socioeconomic status and worse outcomes in those found to have IBD before PSC.

Impact and implications

Individuals with primary sclerosing cholangitis (PSC) face increased morbidity and mortality compared with the general population and those with inflammatory bowel disease (IBD); yet, most individuals with PSC are found to have concomitant IBD during their lifetime. This study describes the distinctive epidemiological differences and mortality trends at the population level between PSC-IBD and IBD. While PSC-IBD remains a rare condition, diagnoses are on the rise (particularly among higher socioeconomic status populations), with most patients being diagnosed with IBD before PSC; this group also experienced higher mortality post-PSC diagnosis compared with those diagnosed with PSC first, with a large proportion of deaths caused by liver- and gut-related causes. Practical applications of these findings include further studies to evaluate whether earlier identification of PSC-IBD affects disease outcomes, as well as educating patients, clinicians, and policymakers on the importance of recognizing PSC-IBD as a distinct entity from IBD alone.

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Affiliation(s)

Kristel K. Leung The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada Departments of Medicine & Public Health Sciences, Queen's University, Kingston, ON, Canada
Wenbin Li ICES-Queen's, Kingston, ON, Canada
Bettina Hansen The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada Department of Biostatistics & Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
Aliya Gulamhusein The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
Lauren Lapointe-Shaw Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada ICES, Toronto, ON, Canada Women's College Institute for Health System Solutions and Virtual Care, Women's College Hospital, Division of General Internal Medicine and Geriatrics, University Health Network and Sinai Health System, Toronto, ON, Canada
Abdel Aziz Shaheen Gastroenterology, Department of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada
Amanda Ricciuto SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada Department of Paediatrics, University of Toronto, Toronto, ON, Canada
Eric I. Benchimol Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada ICES, Toronto, ON, Canada SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada Department of Paediatrics, University of Toronto, Toronto, ON, Canada Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, ON, Canada
Jennifer A. Flemming Departments of Medicine & Public Health Sciences, Queen's University, Kingston, ON, Canada ICES-Queen's, Kingston, ON, Canada
Gideon M. Hirschfield The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

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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]

Maier JA, Castiglioni S, Petrelli A, Cannatelli R, Ferretti F, Pellegrino G, Sarzi Puttini P, Fiorina P, Ardizzone S. Immune-Mediated Inflammatory Diseases and Cancer - a dangerous liaison. Front Immunol 2024;15:1436581. [PMID: 39359726 PMCID: PMC11445042 DOI: 10.3389/fimmu.2024.1436581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 08/29/2024] [Indexed: 10/04/2024] Open

Sharma R, Majee C, Mazumder R, Mazumder A, Tyagi PK, Chaitanya MVNL. Insight Into the Role of Alkaloids in the Different Signalling Pathways of Cholangiocarcinoma. JOURNAL OF NATURAL REMEDIES 2024:43-58. [DOI: 10.18311/jnr/2024/34661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 09/19/2023] [Indexed: 01/04/2025]

Mousavere I, Kalampokis G, Fousekis F, Karayiannis P, Baltayiannis G, Christodoulou D. An overview of recent treatment options for primary sclerosing cholangitis. Ann Gastroenterol 2023;36:589-598. [PMID: 38023975 PMCID: PMC10662072 DOI: 10.20524/aog.2023.0834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 09/26/2023] [Indexed: 12/01/2023] Open

Pascale A, Rosmorduc O, Duclos-Vallée JC. New epidemiologic trends in cholangiocarcinoma. Clin Res Hepatol Gastroenterol 2023;47:102223. [PMID: 37797807 DOI: 10.1016/j.clinre.2023.102223] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 09/14/2023] [Accepted: 10/02/2023] [Indexed: 10/07/2023]

Rennebaum F, Demmig C, Schmidt HH, Vollenberg R, Tepasse PR, Trebicka J, Gu W, Ullerich H, Kabar I, Cordes F. Elevated Liver Fibrosis Progression in Isolated PSC Patients and Increased Malignancy Risk in a PSC-IBD Cohort: A Retrospective Study. Int J Mol Sci 2023;24:15431. [PMID: 37895106 PMCID: PMC10607359 DOI: 10.3390/ijms242015431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 10/18/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open

Abstract

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (CU), and rarely with Crohn's disease (CD). Various long-term analyses show different rates of cancer and the need for orthotopic liver transplantation (OLT) in patients with isolated PSC and with concomitant IBD, respectively. However, data on the detailed course of PSC with or without IBD are limited. We aimed to analyze the clinical disease course of PSC patients without IBD compared to PSC patients with UC and CD, respectively. A retrospective data analysis of patients with isolated PSC (n = 41) and of patients with concomitant IBD (n = 115) was performed. In detail, PSC disease characteristics including occurrence of dominant stenoses, liver cirrhosis, OLT and malignancy, as well as the temporal course of PSC activity and disease progression, were analyzed. A multivariable Cox regression model and a Fine-Gray competing risk model were further used for the independent risk factor analysis of cirrhosis development and OLT. Patients with isolated PSC were significantly older at first diagnosis than patients with PSC-IBD (39 vs. 28 years, p = 0.02). A detailed analysis of the course of PSC revealed a faster PSC progression after initial diagnosis in isolated PSC patients compared to PSC-IBD including significantly earlier diagnosis of dominant stenoses (29 vs. 74 months, p = 0.021) and faster progression to liver cirrhosis (38 vs. 103 months, p = 0.027). Patients with isolated PSC have a higher risk of developing cirrhosis than patients with PSC-IBD (Gray's test p = 0.03). OLT was more frequently performed in male patients with isolated PSC compared to males with coincident IBD (48% (n = 13) vs. 33% (n = 25), p = 0.003). Colorectal carcinoma was significantly more often diagnosed in patients with PSC-IBD than in isolated PSC (8.7% vs. 0%, p = 0.042). Patients with isolated PSC seem to have a different clinical course of disease than PSC patients with concomitant IBD characterized by a more pro-fibrotic disease course with earlier onset of liver cirrhosis and dominant stenosis but with less malignancy. These data may be interpreted as either a more progressive disease course of isolated PSC or a later diagnosis of the disease at an advanced disease stage. The different clinical courses of PSC and the underlying mechanisms of the gut-liver axis need further attention.

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Affiliation(s)

Florian Rennebaum Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
Claudia Demmig Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
Hartmut H. Schmidt Department of Hepatology, Gastroenterology and Transplantation Medicine, University Hospital Essen, 45147 Essen, Germany;
Richard Vollenberg Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
Phil-Robin Tepasse Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
Jonel Trebicka Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
Wenyi Gu Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
Hansjoerg Ullerich Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
Iyad Kabar Department of Internal Medicine, University Teaching Hospital Raphaelsklinik Münster, 48143 Münster, Germany;
Friederike Cordes Department of Internal Medicine II Gastroenterology, University Teaching Hospital Euregio-Klinik Nordhorn, 48527 Nordhorn, Germany;

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Catanzaro E, Gringeri E, Burra P, Gambato M. Primary Sclerosing Cholangitis-Associated Cholangiocarcinoma: From Pathogenesis to Diagnostic and Surveillance Strategies. Cancers (Basel) 2023;15:4947. [PMID: 37894314 PMCID: PMC10604939 DOI: 10.3390/cancers15204947] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/09/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open

Kim YS, Hurley EH, Park Y, Ko S. Treatment of primary sclerosing cholangitis combined with inflammatory bowel disease. Intest Res 2023;21:420-432. [PMID: 37519211 PMCID: PMC10626010 DOI: 10.5217/ir.2023.00039] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 04/28/2023] [Accepted: 04/29/2023] [Indexed: 08/01/2023] Open

Wentworth BJ, Khot R, Caldwell SH. The Many Faces of Primary Sclerosing Cholangitis: Controversy Abounds. Dig Dis Sci 2023;68:3514-3526. [PMID: 37358638 DOI: 10.1007/s10620-023-08003-2] [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: 12/04/2022] [Accepted: 03/10/2023] [Indexed: 06/27/2023]

Nanjundappa RH, Christen U, Umeshappa CS. Distinct immune surveillance in primary biliary cholangitis and primary sclerosing cholangitis is linked with discrete cholangiocarcinoma risk. Hepatol Commun 2023;7:e0218. [PMID: 37555943 PMCID: PMC10412426 DOI: 10.1097/hc9.0000000000000218] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 06/10/2023] [Indexed: 08/10/2023] Open

Martinez Lyons A, Boulter L. NOTCH signalling - a core regulator of bile duct disease? Dis Model Mech 2023;16:dmm050231. [PMID: 37605966 PMCID: PMC10461466 DOI: 10.1242/dmm.050231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/23/2023] Open

Yoshida H, Shiokawa M, Kuwada T, Muramoto Y, Ota S, Nishikawa Y, Maeda H, Kakiuchi N, Okamoto K, Yamazaki H, Yokode M, Nakamura T, Matsumoto S, Hirano T, Okada H, Marui S, Sogabe Y, Matsumori T, Mima A, Uza N, Eso Y, Takai A, Takahashi K, Ueda Y, Kodama Y, Chiba T, Seno H. Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis. J Gastroenterol 2023;58:778-789. [PMID: 37310456 PMCID: PMC10366314 DOI: 10.1007/s00535-023-02006-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 05/31/2023] [Indexed: 06/14/2023]

Affiliation(s)

Hiroyuki Yoshida Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Masahiro Shiokawa Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takeshi Kuwada Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Yuya Muramoto Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Sakiko Ota Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Yoshihiro Nishikawa Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Hirona Maeda Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan
Nobuyuki Kakiuchi Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan
Kanako Okamoto Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Hajime Yamazaki Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Masataka Yokode Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Takeharu Nakamura Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Shimpei Matsumoto Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Tomonori Hirano Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Hirokazu Okada Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Saiko Marui Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Yuko Sogabe Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Tomoaki Matsumori Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Atsushi Mima Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Norimitsu Uza Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Yuji Eso Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Atsushi Takai Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Ken Takahashi Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Yoshihide Ueda Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
Yuzo Kodama Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
Tsutomu Chiba Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan Kansai Electric Power Hospital, Osaka, Japan
Hiroshi Seno Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

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Kim YS, Hurley EH, Park Y, Ko S. Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD): a condition exemplifying the crosstalk of the gut-liver axis. Exp Mol Med 2023;55:1380-1387. [PMID: 37464092 PMCID: PMC10394020 DOI: 10.1038/s12276-023-01042-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/17/2023] [Accepted: 04/17/2023] [Indexed: 07/20/2023] Open

Hu C, Iyer RK, Juran BD, McCauley BM, Atkinson EJ, Eaton JE, Ali AH, Lazaridis KN. Predicting cholangiocarcinoma in primary sclerosing cholangitis: using artificial intelligence, clinical and laboratory data. BMC Gastroenterol 2023;23:129. [PMID: 37076803 PMCID: PMC10114387 DOI: 10.1186/s12876-023-02759-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 04/06/2023] [Indexed: 04/21/2023] Open

Eder P, Łodyga M, Gawron-Kiszka M, Dobrowolska A, Gonciarz M, Hartleb M, Kłopocka M, Małecka-Wojciesko E, Radwan P, Reguła J, Zagórowicz E, Banasiewicz T, Durlik M, Rydzewska G. Guidelines for the management of ulcerative colitis. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology. PRZEGLAD GASTROENTEROLOGICZNY 2023;18:1-42. [PMID: 37007752 PMCID: PMC10050986 DOI: 10.5114/pg.2023.125882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 02/24/2023] [Indexed: 03/17/2023]

Affiliation(s)

Piotr Eder Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Poznan University Clinical Hospital, Poznan, Poland
Michał Łodyga Department of Internal Medicine, Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland
Magdalena Gawron-Kiszka Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
Agnieszka Dobrowolska Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Poznan University Clinical Hospital, Poznan, Poland
Maciej Gonciarz Department of Gastroenterology and Internal Medicine, Military Institute of Medicine, Warsaw, Poland
Marek Hartleb Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
Maria Kłopocka Department of Gastroenterology and Nutrition Disorders, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
Ewa Małecka-Wojciesko Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
Piotr Radwan Chair and Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Lublin, Poland
Jarosław Reguła Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
Edyta Zagórowicz Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
Tomasz Banasiewicz Department of General, Endocrinological and Gastroenterological Oncology Surgery, Poznan University of Medical Sciences, Poznan University Clinical Hospital, Poznan, Poland
Marek Durlik Department of Gastroenterological Surgery and Transplantology, National Medical Institute of Ministry of Inferior and Administration, Warsaw, Poland
Grażyna Rydzewska Department of Gastroenterology with the Inflammatory Bowel Disease Subdivision, National Medical Institute of Ministry of Inferior and Administration, Warsaw, Poland Collegium Medicum, Jan Kochanowski University, Kielce, Poland

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Bowlus CL, Arrivé L, Bergquist A, Deneau M, Forman L, Ilyas SI, Lunsford KE, Martinez M, Sapisochin G, Shroff R, Tabibian JH, Assis DN. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023;77:659-702. [PMID: 36083140 DOI: 10.1002/hep.32771] [Citation(s) in RCA: 125] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 01/28/2023]

Neuzillet C, Artru P, Assenat E, Edeline J, Adhoute X, Sabourin JC, Turpin A, Coriat R, Malka D. Optimizing Patient Pathways in Advanced Biliary Tract Cancers: Recent Advances and a French Perspective. Target Oncol 2023;18:51-76. [PMID: 36745342 PMCID: PMC9928940 DOI: 10.1007/s11523-022-00942-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2022] [Indexed: 02/07/2023]

Su N, Dawuti W, Hu Y, Zhao H. Noninvasive cholangitis and cholangiocarcinoma screening based on serum Raman spectroscopy and support vector machine. Photodiagnosis Photodyn Ther 2022;40:103156. [PMID: 36252780 DOI: 10.1016/j.pdpdt.2022.103156] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 09/17/2022] [Accepted: 10/11/2022] [Indexed: 11/06/2022]

Attauabi M, Wewer MD, Bendtsen F, Seidelin JB, Burisch J. Inflammatory Bowel Diseases Affect the Phenotype and Disease Course of Coexisting Immune-Mediated Inflammatory Diseases: A Systematic Review With Meta-Analysis. Inflamm Bowel Dis 2022;28:1756-1765. [PMID: 35134921 DOI: 10.1093/ibd/izac003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Indexed: 02/06/2023]

Abstract

BACKGROUND

It is unclear whether inflammatory bowel diseases (IBDs) affect the phenotype and severity of co-occurring immune-mediated inflammatory diseases (IMIDs). We aimed to investigate the characteristics of IMIDs in relation to co-occurring IBD.

METHODS

We conducted a systematic review of Medline and EMBASE databases from inception to September 2020. We identified studies reporting the phenotype, severity, or disease course of IMIDs among patients with or without co-occurring IBD. A meta-analysis was conducted using random effects models.

RESULTS

The electronic search yielded 13 220 studies that we narrowed down to 73 eligible studies for full-text review, including 42 on primary sclerosing cholangitis, 12 on axial spondyloarthropathies, and 8 studies on psoriasis. In primary sclerosing cholangitis, IBD was associated with less frequent involvement of extrahepatic bile ducts (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.33-0.75), longer liver transplantation-free survival (hazard ratio, 0.70; 95% CI, 0.60-0.82), and no increased risk of cholangiocarcinoma (RR, 0.88; 95% CI, 0.59-1.31). Patients with axial spondyloarthropathies and co-occurring IBD were characterized by an increased risk of dactylitis (RR, 2.06; 95% CI, 1.24-3.42), a lower Bath Ankylosing Spondylitis Radiology Index (mean difference [MD] = -2.28; 95% CI, -3.26 to -1.30), and better Schober's test results (MD = 1.07; 95% CI, 0.64-1.49). Psoriasis and co-occurring IBD was associated with reduced disease severity (RR, 1.41; 95% CI, 1.02-1.96) and less frequent presentation in nails (RR, 0.14; 95% CI, 0.05-0.42), with no apparent impact on psoriatic arthritis (RR, 0.94; 95% CI, 0.27-3.31).

CONCLUSIONS

This systematic review with meta-analysis found IBD is associated with a distinct disease phenotype among the IMIDs investigated. Our findings emphasize the importance of multidisciplinary approaches to patients with co-occurring IMIDs and IBD.

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Bodofsky S, Freeman RH, Hong SS, Chundury A, Hathout L, Deek MP, Jabbour SK. Inflammatory bowel disease-associated malignancies and considerations for radiation impacting bowel: a scoping review. J Gastrointest Oncol 2022;13:2565-2582. [PMID: 36388654 PMCID: PMC9660071 DOI: 10.21037/jgo-22-138] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 08/12/2022] [Indexed: 11/30/2022] Open

Abstract

Background

Inflammatory bowel disease (IBD), subdivided into Crohn's disease (CD) and ulcerative colitis (UC), is an auto-inflammatory gastrointestinal condition with an established increased risk of certain malignancies. Compared to sporadic cancers in the general population, IBD-associated malignancies present unique challenges to providing quality care. Radiation therapy (RT) targeting IBD-associated malignancies may directly impact inflamed bowel, with special considerations for the risk of toxicities. Historically, patients with IBD have been less likely to receive radiotherapy in proximity to bowel due to a poor understanding of the potential for acute and chronic toxicities and unclear treatment outcomes. We present a scoping review, to more fully assess IBD-associated malignancies and their treatment. As opposed to a systematic review, this approach allows us to analyze the broadest range of literature, including experimental and non-experimental research, and reflect on current guidelines and practices.

Methods

Literature search: a systematic, scoping search of published literature was conducted using applicable PRISMA scoping review (ScR) guidelines. The literature search was conducted on PubMed and was searched systematically by screening all publications from January 1990 to June 2021. Citations from the included articles were also manually searched. Relevant National Comprehensive Cancer Network guidelines were reviewed. Final query was December 2021 in editing. Articles were selected for full text reading if the abstract reported on malignancy in IBD or bowel toxicities.

Results

The pelvic malignancies found in the IBD patient population, including colorectal carcinoma, anal carcinoma, lymphoma, small bowel adenocarcinoma (SBA), and prostate cancer (PCa) are outlined in this scoping review. Additional cancers that have a contested relationship with IBD, including cervical, bladder, and upper GI cancers, are also explored. This review provides literature guided recommendations on the eligibility of patients with IBD to receive RT, management of IBD during and after treatment, and counseling for radiation-induced toxicities.

Conclusions

After review of the literature, IBD should not be considered an absolute contraindication to radiation therapy, given the lack of evidence for increased toxicities, and the evolution of RT techniques which limit radiation dose to the bowel.

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Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, Schramm C, Trauner M. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022;77:761-806. [PMID: 35738507 DOI: 10.1016/j.jhep.2022.05.011] [Citation(s) in RCA: 152] [Impact Index Per Article: 50.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/16/2022] [Indexed: 02/07/2023]

Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma. Cancers (Basel) 2022;14:cancers14092120. [PMID: 35565248 PMCID: PMC9104786 DOI: 10.3390/cancers14092120] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 04/15/2022] [Indexed: 11/17/2022] Open

Sadraei N, Jafari H, Sadraee A, Zeinali-Rafsanjani B, Rastgooyan H, Zahergivar A. Assessment of Three-Phasic CT Scan Findings of Cirrhosis Due to Primary Sclerosing Cholangitis Versus Cryptogenic Cirrhosis. Cureus 2022;14:e23956. [PMID: 35547407 PMCID: PMC9085709 DOI: 10.7759/cureus.23956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/30/2022] [Indexed: 11/06/2022] Open

Abstract

BACKGROUND

The CT findings of cirrhosis caused by primary sclerosing cholangitis (PSC) differ from cryptogenic cirrhosis. PSC could become complicated with biliary cirrhosis and cholangiocarcinoma. This study aimed at augmenting the information on the role of the three-phasic-abdominopelvic CT scan in PSC.

MATERIAL AND METHODS

A total of 185 CT scans were retrospectively reviewed, including 100 patients with cryptogenic cirrhosis and 85 patients with PSC-cirrhosis. Different morphologic criteria were compared, including segmental atrophy/hypertrophy, hepatic contour, portal-hypertension, perihilar lymphadenopathy, biliary tree dilatation, gallbladder appearance. Inflammatory-bowel-disease (IBD) and cholangiocarcinoma frequency, presence of perihilar lymph nodes (LNs), and their size during end-stage PSC cirrhosis are investigated.

RESULTS

Six findings occur more frequently with PSC than those diagnosed with cryptogenic cirrhosis. Modified caudate/right lobe (m-CRL) ratio >0.73, moderate and severe lobulated liver contour, lateral left lobe atrophy, over distended gallbladder (GB), biliary tree dilatation and wall thickening, and LN sizes were higher in PSC patients as compared to cryptogenic cirrhosis (P < 0.005). Ascites and portosystemic collateral formations were significant in cryptogenic cirrhosis compared to PSC patients (P < 0.005). Cholangiocarcinoma frequency in PSC patients was 14.7%, and the frequency of inflammatory bowel disease (IBD) was 57.6%. Further, 22.4% of the patients were diagnosed with IBD and PSC simultaneously. The LN number and size in PSC patients were not different between those with or without cholangiocarcinoma.

CONCLUSION

Using three-phasic CT scans and PSC characteristics could be considered as an additional suggestion besides pathology measures. Diagnosis of PSC based on histological findings could be a last resort due to its invasive essence and specific characteristics of PSC in imaging.

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Aghamohammad S, Sepehr A, Miri ST, Najafi S, Rohani M, Pourshafiea MR. The effects of the probiotic cocktail on modulation of the NF-kB and JAK/STAT signaling pathways involved in the inflammatory response in bowel disease model. BMC Immunol 2022;23:8. [PMID: 35240996 PMCID: PMC8896082 DOI: 10.1186/s12865-022-00484-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 02/24/2022] [Indexed: 01/06/2023] Open

Núñez F P, Castro F, Mezzano G, Quera R, Diaz D, Castro L. Hepatobiliary manifestations in inflammatory bowel disease: A practical approach. World J Hepatol 2022;14:319-337. [PMID: 35317174 PMCID: PMC8891676 DOI: 10.4254/wjh.v14.i2.319] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 09/10/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open

Beheshti-Maal A, Tamimi A, Iravani S, Memarnejadian A, Sorouri M, Aghdaei HA, Zali MR, Hossein Khannazer N, Vosough M. PSC associated inflammatory bowel disease: a distinct entity. Expert Rev Gastroenterol Hepatol 2022;16:129-139. [PMID: 35078376 DOI: 10.1080/17474124.2022.2031979] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Lu Y, Han S, Zhang S, Wang K, Lv L, McClements DJ, Xiao H, Berglund B, Yao M, Li L. The role of probiotic exopolysaccharides in adhesion to mucin in different gastrointestinal conditions. Curr Res Food Sci 2022;5:581-589. [PMID: 35340998 PMCID: PMC8943218 DOI: 10.1016/j.crfs.2022.02.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 02/19/2022] [Accepted: 02/28/2022] [Indexed: 12/18/2022] Open

Gaspar R, Branco CC, Macedo G. Liver manifestations and complications in inflammatory bowel disease: A review. World J Hepatol 2021;13:1956-1967. [PMID: 35070000 PMCID: PMC8727205 DOI: 10.4254/wjh.v13.i12.1956] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/27/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open

Mala A, Foteinogiannopoulou K, Koutroubakis IE. Solid extraintestinal malignancies in patients with inflammatory bowel disease. World J Gastrointest Oncol 2021;13:1956-1980. [PMID: 35070035 PMCID: PMC8713323 DOI: 10.4251/wjgo.v13.i12.1956] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 07/06/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open

Abbas N, Quraishi MN, Trivedi P. Emerging drugs for the treatment of primary sclerosing cholangitis. Curr Opin Pharmacol 2021;62:23-35. [PMID: 34894541 DOI: 10.1016/j.coph.2021.11.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 11/02/2021] [Accepted: 11/07/2021] [Indexed: 12/11/2022]

Losurdo G, Brescia IV, Lillo C, Mezzapesa M, Barone M, Principi M, Ierardi E, Di Leo A, Rendina M. Liver involvement in inflammatory bowel disease: What should the clinician know? World J Hepatol 2021;13:1534-1551. [PMID: 34904028 PMCID: PMC8637677 DOI: 10.4254/wjh.v13.i11.1534] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/06/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open

Montano-Loza AJ, Allegretti JR, Cheung A, Ebadi M, Jones D, Kerkar N, Levy C, Rizvi S, Vierling JM, Alvarez F, Bai W, Gilmour S, Gulamhusein A, Guttman O, Hansen BE, MacParland S, Mason A, Onofrio F, Santamaria P, Stueck A, Swain M, Vincent C, Ricciuto A, Hirschfield G. Single Topic Conference on Autoimmune Liver Disease from the Canadian Association for the Study of the Liver. CANADIAN LIVER JOURNAL 2021;4:401-425. [PMID: 35989897 PMCID: PMC9235119 DOI: 10.3138/canlivj-2021-0006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 02/09/2021] [Indexed: 11/20/2022]

Affiliation(s)

Aldo J Montano-Loza Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
Jessica R Allegretti Division of Gastroenterology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Angela Cheung Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
Maryam Ebadi Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
David Jones Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
Nanda Kerkar Division of Gastroenterology, Hepatology and Nutrition, Golisano Children’s Hospital at Strong, University of Rochester Medical Center, New York, USA
Cynthia Levy Schiff Center for Liver Diseases, University of Miami, Miami, Florida, USA
Sumera Rizvi Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
John M Vierling Baylor College of Medicine, Houston, Texas, USA
Fernando Alvarez Department of Pediatrics, Hôpital Sainte-Justine, University of Montreal, Montreal, Quebec, Canada
Wayne Bai Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
Susan Gilmour Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada
Aliya Gulamhusein Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
Orlee Guttman Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
Bettina E Hansen Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
Sonya MacParland Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
Andrew Mason Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
Fernanda Onofrio Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
Pere Santamaria Department of Microbiology, Immunology & Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
Ashley Stueck Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
Mark Swain Calgary Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
Catherine Vincent Department of Medicine, University of Montreal, Montreal, Quebec, Canada
Amanda Ricciuto Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada
Gideon Hirschfield Toronto Centre for Liver Disease, University Health Network & Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada

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Saffioti F, Mavroeidis VK. Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis. World J Gastrointest Oncol 2021;13:1336-1366. [PMID: 34721770 PMCID: PMC8529934 DOI: 10.4251/wjgo.v13.i10.1336] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/05/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open

Abstract

Primary sclerosing cholangitis (PSC) is a premalignant condition and a well-documented risk factor for cholangiocarcinoma (CCA) which is the most common malignancy in this setting and the leading cause of deaths in the recent years, with an increasing incidence. PSC-associated CCA has a geographical distribution that follows the incidence of PSC, with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries. It may arise at any location along the biliary tree but is most common in the perihilar area. Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection, which is otherwise the treatment of choice with curative intent in patients with resectable tumours, providing a radical resection with clear margins can be achieved. This largely relates to the commonly advanced stage of liver disease at presentation, which allows consideration for liver resection only for a very limited number of suitable patients with PSC. On the other hand, remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) for the treatment of perihilar CCA, within specific criteria. Excellent results have been achieved particularly for PSC patients with this cancer, who seem to benefit the most from this treatment, having converted this into an accepted indication for transplantation and the standard of care in several experienced centres. Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results. However, as recent studies have shown favourable outcomes in early intrahepatic CCA, it may be that under defined criteria, OLT may play a more prominent role in the future. Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent, when feasible. This review provides insight about particular features of CCA in the setting of PSC, with a main focus on its incidence, considerations relating to its anatomical location and implications to treatment and outcomes, through the viewpoint of historical evolution of management, and future perspectives.

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Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA. Can J Gastroenterol Hepatol 2021;2021:9936932. [PMID: 34545326 PMCID: PMC8449715 DOI: 10.1155/2021/9936932] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 08/24/2021] [Indexed: 01/06/2023] Open

Abstract

BACKGROUND

Patients diagnosed with ulcerative colitis (UC) associated with primary sclerosis cholangitis (PSC) and sessile serrated adenoma (SSA) are rare. The present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA.

METHODS

DNA was extracted from the blood sample and tissue sample of SSA, followed by the whole exome sequencing (WES) analysis. Bioinformatics analysis was utilized to predict the deleteriousness of the identified variants. Multiple sequence alignment and conserved protein domain analyses were performed using online software. Sanger sequencing was used to validate the identified variants. Expression and diagnostic analysis of identified mutated genes was performed in the GSE119600 dataset (peripheral blood samples of PSC and UC) and GSE43841 dataset (tumor samples of SSA).

RESULTS

In the present study, a total of 842 single nucleotide variants (SNVs) in 728 genes were identified in the blood sample. Two variants, integrin beta 4 (ITGB4) (c.C2503G; p.P835A) and a mucin 3A (MUC3A) (c.C1019T; p.P340L), were further analyzed. MUC3A was associated with inflammatory bowel disease. Sanger sequence in blood revealed that the ITGB4 mutation was fully cosegregated with the result of WES in the patient. Additionally, a variant, tumor protein p53 gene (TP53) (c.86delA; p.N29Tfs ^∗ 15) was identified in the tissue sample of SSA. Compared to that in normal controls, ITGB4 was upregulated in both UC and PSC, MUC3A was, respectively, upregulated and downregulated in PSC and UC, and TP53 was downregulated in SSA. ITGB4 and TP53 had a potential diagnostic value for UC, PSC and SSA.

CONCLUSIONS

The present study demonstrated that the ITGB4 (c.C2503G; p.P835A) and MUC3A (c.C1019T; p.P340L) mutations may be the potential causative variants in a patient with UC associated with PSC and SSA. TP53 (c.86delA; p.N29Tfs ^∗ 15) mutation may be associated with SSA in this patient.

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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]

Mawardi M, Alalwan A, Fallatah H, Abaalkhail F, Hasosah M, Shagrani M, Alghamdi MY, Alghamdi AS. Cholestatic liver disease: Practice guidelines from the Saudi Association for the Study of Liver diseases and Transplantation. Saudi J Gastroenterol 2021;27:S1-S26. [PMCID: PMC8411950 DOI: 10.4103/sjg.sjg_112_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/26/2021] [Accepted: 05/16/2021] [Indexed: 11/04/2022] Open

Fung BM, Tabibian JH. Primary sclerosing cholangitis-associated cholangiocarcinoma: special considerations and best practices. Expert Rev Gastroenterol Hepatol 2021;15:487-496. [PMID: 33682586 DOI: 10.1080/17474124.2021.1900732] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 03/05/2021] [Indexed: 10/22/2022]

Rigopoulou EI, Dalekos GN. Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases. Cancers (Basel) 2021;13:1023. [PMID: 33804480 PMCID: PMC7957658 DOI: 10.3390/cancers13051023] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/17/2021] [Accepted: 02/24/2021] [Indexed: 12/24/2022] Open

Erichsen R, Olén O, Sachs MC, Pedersen L, Halfvarson J, Askling J, Ekbom A, Ludvigsson JF, Sørensen HT. Hepatobiliary Cancer Risk in Patients with Inflammatory Bowel Disease: A Scandinavian Population-Based Cohort Study. Cancer Epidemiol Biomarkers Prev 2021;30:886-894. [PMID: 33627380 DOI: 10.1158/1055-9965.epi-20-1241] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 01/02/2021] [Accepted: 02/19/2021] [Indexed: 11/16/2022] Open

Abstract

BACKGROUND

Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among patients with IBD.

METHODS

This Swedish/Danish population-based cohort study (1969-2017) followed patients with IBD and 1:10 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up.

RESULTS

Among the 97,496 patients with ulcerative colitis/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths, and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall hazard ratios (HR) were 1.83 [95% confidence interval (CI), 1.41-2.38] for HCC-, 7.33 (95% CI, 5.81-9.25) for ICC-, and 4.46 (95% CI, 3.49-5.70) for ECC-deaths. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among patients with ulcerative colitis with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 patients with Crohn's disease (median follow-up 11 years), 10-year-mortality from HCC (n = 28), ICC (n = 28), and ECC (n = 24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95% CI, 1.31-2.93), 3.33 (95% CI, 2.19-5.09), and 3.10 (95% CI, 1.97-4.87). One of 28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC.

CONCLUSIONS

Risk of HCC-, ICC-, and ECC-deaths was low in patients with IBD and decreased over time. However, a large proportion of deaths occurred after PSC.

IMPACT

Guidelines on specific surveillance strategies for patients with IBD with PSC, but not those without PSC, are needed.

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Chahal D, Shamatutu C, Salh B, Davies J. The impact of primary sclerosing cholangitis or inflammatory bowel disease on cholangiocarcinoma phenotype, therapy, and survival. JGH Open 2020;4:1128-1134. [PMID: 33319047 PMCID: PMC7731823 DOI: 10.1002/jgh3.12405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 07/20/2020] [Accepted: 07/23/2020] [Indexed: 12/12/2022]

Abstract

Background and Aim

Primary sclerosing cholangitis (PSC), with or without inflammatory bowel disease (IBD), confers the risk of cholangiocarcinoma. Isolated IBD may be an independent risk factor for cholangiocarcinoma. We sought to compare cholangiocarcinoma phenotype and outcomes between patients with PSC, IBD, and neither.

Methods

Patients with malignancy were separated into cohorts by the presence of PSC and IBD. Data regarding demographics, clinical presentation, therapeutic regimens, and survival were collected. Statistical analysis was carried out using GraphPad and R‐Studio.

Results

Of 946 patients, 22 had PSC, and 18 had isolated IBD. PSC and IBD patients were younger than controls (P < 0.001, P = 0.01). Cholangiocarcinoma prevalence was estimated at 0.01% for IBD patients, 0.6% for PSC patients, and 0.002% for all other patients. All cohorts most often presented at stage 4. PSC patients presented more often at stage 3 (P = 0.04) and with perihilar disease (P = 0.001). Patients with PSC or IBD received less chemotherapy (P = 0.004, 0.01). Median overall survivals were 15 months (PSC), 11 months (IBD), and 10 months (controls) (P = 0.79). Patients with intrahepatic tumors had longer survival (P < 0.001). Curative intent resection improved survival in all cohorts (P < 0.001). Multivariate regression identified resection as a predictor of improved survival. Extrahepatic, perihilar, gallbladder, and unspecified biliary tumors were predictors of death.

Conclusions

Cholangiocarcinoma presents at a late stage and portends dismal survival regardless of PSC or IBD status. Survival was dependent on tumor location and surgical resection. These data suggest that efforts should focus on developing protocols that are able to detect and treat cholangiocarcinoma in high‐risk populations (PSC) at an early stage.

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Lavu S, Therneau TM, Harmsen WS, Mara KC, Wongjarupong N, Hassan M, Ali HA, Antwi S, Giama NH, Miyabe K, Roberts LR. Effect of Statins on the Risk of Extrahepatic Cholangiocarcinoma. Hepatology 2020;72:1298-1309. [PMID: 32119126 PMCID: PMC8155698 DOI: 10.1002/hep.31146] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 12/23/2019] [Indexed: 12/28/2022]

Abstract

BACKGROUND AND AIMS

Statins have been proven to be cytotoxic to human cholangiocarcinoma cells by inhibiting cell division and inducing apoptosis. We aimed to determine the effect of statin use on the risk of cancer development and survival in patients with extrahepatic cholangiocarcinoma (ECC), including perihilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA).

APPROACH AND RESULTS

A total of 394 patients with ECC and hyperlipidemia who received care at Mayo Clinic Rochester between 2005 and 2015 were matched by age, sex, race, ethnicity, and residency to 788 controls with hyperlipidemia. Clinical and outcome data were abstracted. The odds ratios (ORs) for risk and hazard ratios for outcomes were calculated. The mean age and standard deviation (SD) for cases and controls was 65.6 years (13.8). The number of statin users in cases and controls was 73 (19%) and 403 (51%), respectively. Hepatitis C virus infection (OR, 15.84; 95% confidence interval [CI], 4.06-61.87; P < 0.001) was the most significant risk factor for pCCA followed by inflammatory bowel disease and cirrhosis, whereas other liver disease, including biliary stone disease (OR, 4.06; CI, 2.24-7.36; P < 0.001), was the only significant risk factor for dCCA. Statin use was associated with significantly reduced risk for all ECC (OR, 0.22; CI, 0.16-0.29) as well as for the subtypes pCCA (OR, 0.3; CI, 0.21-0.41) and dCCA (OR, 0.06; CI, 0.03-0.14), all P < 0.0001. Moderate-intensity dosage was found to decrease the risk of ECC (OR, 0.48; CI, 0.34-0.67; P < 0.001). Comparing statin ever users to nonusers, patients with dCCA who used statins had significantly overall better survival (hazard ratio = 0.53; CI, 0.29-0.97; P = 0.04).

CONCLUSIONS

This case-control study suggests that statins decrease the risk of ECC and may improve survival in patients with dCCA. Additional validation studies are warranted.

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Song J, Li Y, Bowlus CL, Yang G, Leung PSC, Gershwin ME. Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis (PSC): a Comprehensive Review. Clin Rev Allergy Immunol 2020;58:134-149. [PMID: 31463807 DOI: 10.1007/s12016-019-08764-7] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Abstract

Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC) and carries a high rate of mortality. Although the pathogenesis of CCA in PSC is largely unknown, inflammation-driven carcinogenesis concomitant with various genetic and epigenetic abnormalities are underlying factors. The majority of CCA cases develop from a dominant stricture (DS), which is defined as a stricture with a diameter < 1.5 mm in the common bile duct or < 1.0 mm in the hepatic duct. In PSC patients presenting with an abrupt aggravation of jaundice, pain, fatigue, pruritus, weight loss, or worsening liver biochemistries, CCA should be suspected and evaluated utilizing a variety of diagnostic modalities. However, early recognition of CCA in PSC remains a major challenge. Importantly, 30-50% of CCA in PSC patients are observed within the first year following the diagnosis of PSC followed by an annual incidence ranging from 0.5 to 1.5 per 100 persons, which is nearly 10 to 1000 times higher than that in the general population. Cumulative 5-year, 10-year, and lifetime incidences are 7%, 8-11%, and 9-20%, respectively. When PSC-associated CCA is diagnosed, most tumors are unresectable, and no effective medications are available. Given the poor therapeutic outcome, the surveillance and management of PSC patients who are at an increased risk of developing CCA are of importance. Such patients include older males with large-duct PSC and possibly concurrent ulcerative colitis. Thus, more attention should be paid to patients with these clinical features, in particular within the first year after PSC diagnosis. In contrast, CCA is less frequently observed in pediatric or female PSC patients or in those with small-duct PSC or concurrent Crohn's disease. Recently, new biomarkers such as antibodies to glycoprotein 2 have been found to be associated with an increased risk of developing CCA in PSC. Herein, we review the literature on the pathogenesis, incidence, clinical features, and risk factors, with a focus on various diagnostic modalities of PSC-associated CCA.

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Buckholz AP, Brown RS. Cholangiocarcinoma: Diagnosis and Management. Clin Liver Dis 2020;24:421-436. [PMID: 32620281 DOI: 10.1016/j.cld.2020.04.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

Jakubczyk D, Leszczyńska K, Górska S. The Effectiveness of Probiotics in the Treatment of Inflammatory Bowel Disease (IBD)-A Critical Review. Nutrients 2020;12:nu12071973. [PMID: 32630805 PMCID: PMC7400428 DOI: 10.3390/nu12071973] [Citation(s) in RCA: 184] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/19/2020] [Accepted: 06/30/2020] [Indexed: 12/17/2022] Open

Mehta TI, Weissman S, Fung BM, Tabibian JH. Geoepidemiologic variation in outcomes of primary sclerosing cholangitis. World J Hepatol 2020;12:116-124. [PMID: 32685104 PMCID: PMC7336294 DOI: 10.4254/wjh.v12.i4.116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/15/2020] [Accepted: 03/24/2020] [Indexed: 02/06/2023] Open

Sato K, Glaser S, Alvaro D, Meng F, Francis H, Alpini G. Cholangiocarcinoma: novel therapeutic targets. Expert Opin Ther Targets 2020;24:345-357. [PMID: 32077341 PMCID: PMC7129482 DOI: 10.1080/14728222.2020.1733528] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 02/19/2020] [Indexed: 02/06/2023]