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Alsakarneh S, Ahmed M, Jaber F, Zulqarnain M, Karagozian R, Francis F, Farraye FA, Hashash JG. Does Timing of Ileal Pouch-Anal Anastomosis Matter in Patients With Primary Sclerosing Cholangitis and Orthotopic Liver Transplantation? A Systematic Review and Meta-analysis. CROHN'S & COLITIS 360 2024; 6:otae036. [PMID: 38974606 PMCID: PMC11224914 DOI: 10.1093/crocol/otae036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Indexed: 07/09/2024] Open
Abstract
Introduction Pouchitis is the most common complication in patients with ileal pouch-anal anastomosis (IPAA), which can develop in up to 66% of patients. There is limited data on the effect of orthoptic liver transplantation (OLT) on the risk of developing pouchitis. We aimed to objectively assess whether OLT itself significantly modifies the risk of developing pouchitis in patients with overlap PSC and inflammatory bowel disease (IBD). Method We searched Medline, Scopus, and Embase databases from inception through September 2023 for studies that describe the outcomes of IPAA in patients with PSC and IBD who also have a history of OLT. Pooled proportions, Odds Ratio (OR), and 95% confidence intervals (CI) for data were calculated utilizing a random effects model. Using the Freeman-Turkey double arcsine transformation (FTT) method, the pooled weight-adjusted estimate of event rates for clinical outcomes in each group was also calculated. Heterogeneity between studies was assessed using the Cochrane Q statistic (I2). Results Seven studies with a total of 291 patients with a history of PSC, IBD, and OLT were identified. The pooled overall risk of pouchitis in PSC/IBD patients with a history of OLT was 65% (95% CI: 0.57-0.72), with no heterogeneity observed in the analysis (I2 = 0%). In a subgroup analysis of patients who had IPAA followed by OLT, 3 studies with 28 patients were included; the pooled risk of pouchitis after IPAA and OLT was 83% (95% CI: 0.71-0.94; I2 = 0%), which was significantly higher (P < .001) than the OLT followed by IPAA group (59%; 95 CI: 0.48-0.71; I2 = 0%). There was no difference in the risk of pouchitis between OLT and non-OLT groups (OR = 1.36; 95% CI: 0.37-5.0). Conclusions Our meta-analysis revelaed that pouchitis is common in patients who underwent OLT for PSC, especially in those who had IPAA before the OLT. OLT before IPAA may reduce the risk of pouchitis. Further larger studies are warranted to reproduce this and investigate the reason behind this difference.
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Affiliation(s)
- Saqr Alsakarneh
- Department of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Mohamed Ahmed
- Department of Gastroenterology and Hepatology, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Fouad Jaber
- Department of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Mir Zulqarnain
- Department of Gastroenterology and Hepatology, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Raffi Karagozian
- Department of Transplant Hepatology, Tufts University, Medford, MA, USA
| | - Fadi Francis
- Department of Transplant Hepatology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Francis A Farraye
- Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Jana G Hashash
- Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
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Abstract
Pouchitis is an acute or chronic inflammatory disease of the ileal reservoir. It is common after restorative proctocolectomy with ileal pouch-anal anastomosis, and treatment of chronic antibiotic-refractory pouchitis has proven challenging. Most cases of acute pouchitis evolve into chronic pouchitis. The aetiology of acute pouchitis is likely to be partly related to the gut microbiota, whereas the pathophysiology of chronic pouchitis involves abnormal interactions between genetic disposition, faecal stasis, the gut microbiota, dysregulated host immunity, surgical techniques, ischaemia and mesentery-related factors. Pouchoscopy with biopsy is the most valuable modality for diagnosis, disease monitoring, assessment of treatment response, dysplasia surveillance and delivery of endoscopic therapy. Triggering or risk factors, such as Clostridioides difficile infection and use of non-steroidal anti-inflammatory drugs, should be modified or eradicated. In terms of treatment, acute pouchitis usually responds to oral antibiotics, whereas chronic antibiotic-refractory pouchitis often requires induction and maintenance therapy with integrin, interleukin or tumour necrosis factor inhibitors. Chronic pouchitis with ischaemic features, fistulae or abscesses can be treated with hyperbaric oxygen therapy.
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Affiliation(s)
- Bo Shen
- Center for Inflammatory Bowel Diseases and the Global Center for Integrated Colorectal Surgery and IBD Interventional Endoscopy, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY, USA.
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Shen B, Yao Q, Scherl EJ. Management of Primary Sclerosing Cholangitis and Extraintestinal Disorders in Patients With Ileal Pouches: A Systematic Review. Dis Colon Rectum 2024; 67:S106-S114. [PMID: 38411984 DOI: 10.1097/dcr.0000000000003231] [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] [Indexed: 02/28/2024]
Abstract
BACKGROUND Restorative proctocolectomy with IPAA improves the quality of life in patients with ulcerative colitis by the removal of diseased large bowel and preservation of the natural route of defecation. Although the surgery may improve preexisting extraintestinal manifestations in the joints, skin, and eyes, extraintestinal manifestations, particularly primary sclerosing cholangitis, can persist after colectomy. OBJECTIVES A systematic review of diagnosis and treatment of liver, joint, skin, and eye manifestations in patients with restorative proctocolectomy and IPAA for ulcerative colitis. DATA SOURCES PubMed, Google Scholar, and Cochrane database. STUDY SELECTION Relevant articles on primary sclerosing cholangitis and extraintestinal manifestations in ileal pouches published between January 2001 and July 2023 in English were included on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. INTERVENTION Diagnosis and treatment of primary sclerosing cholangitis and extraintestinal manifestations in patients with restorative proctocolectomy and IPAA were included. MAIN OUTCOME MEASURES Association between primary sclerosing cholangitis, extraintestinal manifestations, and inflammatory disorders of the pouch and their management. RESULTS Primary sclerosing cholangitis and extraintestinal manifestations are associated with pouchitis, particularly chronic pouchitis. Primary sclerosing cholangitis is associated with chronic pouchitis, enteritis, and possible pouch neoplasia. However, the disease severity and course of primary sclerosing cholangitis and pouchitis do not appear to be parallel. Despite the fact that oral vancomycin or budesonide have been used to treat primary sclerosing cholangitis-associated pouchitis, their impact on the disease course of primary sclerosing cholangitis is not known. Biological therapy for chronic inflammatory disorders of the pouch may also be beneficial for the concurrent extraintestinal manifestations of the joints, skin, and eyes. However, studies on the correlation between the severity of inflammatory pouch disorders and the severity of joint, skin, and eye diseases are lacking. LIMITATIONS This is a qualitative, not quantitative, review of case series and case reports. CONCLUSIONS Primary sclerosing cholangitis and extraintestinal manifestations of the joints, skin, and eyes appear to be associated with inflammatory disorders of the ileal pouch. Although the treatment of pouchitis does not seem to affect the disease course of primary sclerosing cholangitis, effective therapy of inflammatory pouch disorders, particularly with biologics, likely benefits concurrent disorders of the joints, skin, and eyes. See video from the symposium .
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Affiliation(s)
- Bo Shen
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center/NewYork Presbyterian Hospital, New York, New York
| | - QingPing Yao
- Division of Rheumatology, Allergy and Immunology, Stony Brook University Renaissance School of Medicine, New York
| | - Ellen J Scherl
- Division of Gastroenterology and Hepatology, Department of Medicine, New York-Presbyterian/Weill Cornell Medical Center, New York, New York
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Maspero M, Holubar SD, Raj R, Yilmaz S, Prien C, Lavryk O, Pita A, Hashimoto K, Steele SR, Hull TL. Ileal Pouch-anal Anastomosis in Primary Sclerosing Cholangitis-inflammatory Bowel Disease (PSC-IBD): Long-term Pouch and Liver Transplant Outcomes. Ann Surg 2023; 278:961-968. [PMID: 37477000 DOI: 10.1097/sla.0000000000006041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/22/2023]
Abstract
OBJECTIVE To compare the effect of liver transplantation (LT) on ileal pouch-anal anastomosis (IPAA) outcomes in patients with primary sclerosing cholangitis and inflammatory bowel disease (PSC-IBD). BACKGROUND Patients with PSC-IBD may require both IPAA for colitis and LT for PSC. METHODS Patients with PSC-IBD from out institutional pouch registry (1985-2022) were divided according to LT status and timing of LT (before and after IPAA) and their outcomes analyzed. RESULTS A total of 160 patients were included: 112 (70%) nontransplanted at last follow-up; 48 (30%) transplanted, of which 23 (14%) before IPAA and 25 (16%) after. Nontransplanted patients at IPAA had more laparoscopic procedures [37 (46%) vs 8 (18%), P =0.002] and less blood loss (median 250 vs 400 mL, P =0.006). Morbidity and mortality at 90 days were similar. Chronic pouchitis was higher in transplanted compared with nontransplanted patients [32 (67%) vs 51 (45.5%), P =0.03], but nontransplanted patients had a higher rate of chronic antibiotic refractory pouchitis. Overall survival was similar, but nontransplanted patients had more PSC-related deaths (12.5% vs 2%, P =0.002). Pouch survival at 10 years was 90% for nontransplanted patients and 100% for transplanted patients (log-rank P =0.052). Timing of LT had no impact on chronic pouchitis, pouch failure, or overall survival. PSC recurrence was 6% at 10 years. For transplanted patients, graft survival was similar regardless of IPAA timing. CONCLUSIONS In patients with PSC-IBD and IPAA, LT is linked to an increased pouchitis rate but does not affect overall and pouch survival. Timing of LT does not influence short-term and long-term pouch outcomes.
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Affiliation(s)
- Marianna Maspero
- Department of Colon & Rectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Stefan D Holubar
- Department of Colon & Rectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Roma Raj
- Department of HPB Surgery and Liver Transplantation, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Sumeyye Yilmaz
- Department of Colon & Rectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Christopher Prien
- Department of Colon & Rectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Olga Lavryk
- Department of Colon & Rectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Alejandro Pita
- Department of HPB Surgery and Liver Transplantation, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Koji Hashimoto
- Department of HPB Surgery and Liver Transplantation, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Scott R Steele
- Department of Colon & Rectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
| | - Tracy L Hull
- Department of Colon & Rectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH
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Shen B, Kochhar GS, Kariv R, Liu X, Navaneethan U, Rubin DT, Cross RK, Sugita A, D'Hoore A, Schairer J, Farraye FA, Kiran RP, Fleshner P, Rosh J, Shah SA, Chang S, Scherl E, Pardi DS, Schwartz DA, Kotze PG, Bruining DH, Kane SV, Philpott J, Abraham B, Segal J, Sedano R, Kayal M, Bentley-Hibbert S, Tarabar D, El-Hachem S, Sehgal P, McCormick JT, Picoraro JA, Silverberg MS, Bernstein CN, Sandborn WJ, Vermeire S. Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium. Lancet Gastroenterol Hepatol 2021; 6:826-849. [PMID: 34416186 DOI: 10.1016/s2468-1253(21)00101-1] [Citation(s) in RCA: 103] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/12/2021] [Accepted: 03/15/2021] [Indexed: 12/12/2022]
Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.
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Affiliation(s)
- Bo Shen
- Center for Interventional Inflammatory Bowel Disease, Columbia University Irving Medical Center-New-York Presbyterian Hospital, NY, USA.
| | - Gursimran S Kochhar
- Division of Gastroenterology, Hepatology, and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - Revital Kariv
- Department of Gastroenterology, Tel Aviv Sourasky Medical Center and Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Xiuli Liu
- Department of Pathology and Immunology, Washington University, MO, USA
| | - Udayakumar Navaneethan
- IBD Center and IBD Interventional Unit, Center for Interventional Endoscopy, Orlando Health, Orlando, FL, USA
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Raymond K Cross
- Inflammatory Bowel Disease Program, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Akira Sugita
- Department of Clinical Research and Department of Inflammatory Bowel Disease, Yokohama Municipal Citizens Hospital Yokohama, Japan
| | - André D'Hoore
- Department of Abdominal Surgery, University Hospital Leuven, Belgium
| | - Jason Schairer
- Department of Gastroenterology, Henry Ford Health System, Detroit, MI, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Ravi P Kiran
- Division of Colorectal Surgery, Columbia University Irving Medical Center-New-York Presbyterian Hospital, NY, USA
| | - Philip Fleshner
- Division of Colorectal Surgery, University of California-Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Joel Rosh
- Department of Pediatric Gastroenterology, Goryeb Children's Hospital-Atlantic Health, Morristown, NJ, USA
| | - Samir A Shah
- Alpert Medical School of Brown University and Miriam Hospital, Gastroenterology Associates, Providence, RI, USA
| | - Shannon Chang
- Division of Gastroenterology, New York University Langone Health, New York, NY, USA
| | - Ellen Scherl
- New York Presbyterian Hospital, Jill Roberts Center for IBD, Weill Cornell Medicine, Gastroenterology and Hepatology, New York, NY, USA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - David A Schwartz
- Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Paulo G Kotze
- IBD Outpatients Clinic, Catholic University of Paraná, Curitiba, Brazil
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Sunanda V Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jessica Philpott
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH, USA
| | - Bincy Abraham
- Houston Methodist and Weill Cornell Medical College, Houston, TX, USA
| | - Jonathan Segal
- Department of Gastroenterology and Hepatology, Hillingdon Hospital, Uxbridge, UK
| | - Rocio Sedano
- Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada
| | - Maia Kayal
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA
| | - Stuart Bentley-Hibbert
- Department of Radiology, Columbia University Irving Medical Center-New-York Presbyterian Hospital, NY, USA
| | - Dino Tarabar
- IBD Clinical Center, University Hospital Center Dr Dragiša Mišović, Belgrade, Serbia
| | - Sandra El-Hachem
- Division of Gastroenterology, Hepatology, and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - Priya Sehgal
- Division of Digestive and Liver Diseases, Columbia University Irving Medical Center-New-York Presbyterian Hospital, NY, USA
| | - James T McCormick
- Division of Colon and Rectal Surgery, Allegheny Health Network, Pittsburgh, PA, USA
| | - Joseph A Picoraro
- Department of Pediatrics, Columbia University Irving Medical Center-Morgan Stanley Children's Hospital, New York, NY, USA
| | - Mark S Silverberg
- Mount Sinai Hospital Inflammatory Bowel Disease Centre, Toronto, ON, Canada
| | - Charles N Bernstein
- Inflammatory Bowel Disease Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
| | - William J Sandborn
- Department of Gastroenterology, University of California San Diego, San Diego, CA, USA
| | - Séverine Vermeire
- Department of Gastroenterology, University hospitals Leuven, Leuven, Belgium
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Fousekis FS, Theopistos VI, Mitselos IV, Skamnelos A, Kavvadias A, Katsanos KH, Christodoulou DK. Specific Features of Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis. J Clin Med Res 2019; 11:81-88. [PMID: 30700999 PMCID: PMC6340671 DOI: 10.14740/jocmr3680] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 11/20/2018] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic and progressive disease of the biliary tract. PSC is strongly associated with inflammatory bowel disease (IBD), mainly with ulcerative colitis, and most PSC patients have underlying IBD. The pathophysiological interactions between IBD and PSC are unclear, although it seems that the patients with IBD and PSC have a distinct phenotype. IBD with coexisting PSC is more extensive and is characterized by milder activity compared to IBD alone. The coexistence of PSC increases the risk for colorectal cancer in IBD patients and lifelong annual surveillance colonoscopy is recommended. Also, liver transplantation (LT) for PSC may affect the course of IBD. In addition, the management of IBD after LT includes many specific problems. On the other hand, the effect of IBD on the natural history of PSC appears to be milder. However, IBD may increase the risk of postsurgical complications after LT and is a risk factor for recurrent PSC after LT. Overall, the coexistence of IBD with PSC changes the management, natural history and prognosis of both diseases.
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Affiliation(s)
- Fotios S. Fousekis
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Vasileios I. Theopistos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Ioannis V. Mitselos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Alexandros Skamnelos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Athanasios Kavvadias
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Konstantinos H. Katsanos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Dimitrios K. Christodoulou
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
- Corresponding Author: Dimitrios K. Christodoulou, Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina 45100, Greece.
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7
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Shen B. Pathogenesis of Pouchitis. POUCHITIS AND ILEAL POUCH DISORDERS 2019:129-146. [DOI: 10.1016/b978-0-12-809402-0.00011-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Trivedi PJ, Reece J, Laing RW, Slaney E, Cooney R, Gunson BK, Kamarajah SK, Pinkney T, Thompson F, Muiesan P, Schlegel A, Hirschfield GM, Iqbal T, Ferguson J. The impact of ileal pouch-anal anastomosis on graft survival following liver transplantation for primary sclerosing cholangitis. Aliment Pharmacol Ther 2018; 48:322-332. [PMID: 29882252 DOI: 10.1111/apt.14828] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 03/25/2018] [Accepted: 05/08/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Liver transplantation is the only life-extending intervention for primary sclerosing cholangitis (PSC). Given the co-existence with colitis, patients may also require colectomy; a factor potentially conferring improved post-transplant outcomes. AIM To determine the impact of restorative surgery via ileal pouch-anal anastomosis (IPAA) vs retaining an end ileostomy on liver-related outcomes post-transplantation. METHODS Graft survival was evaluated across a prospectively accrued transplant database, stratified according to colectomy status and type. RESULTS Between 1990 and 2016, 240 individuals with PSC/colitis underwent transplantation (cumulative 1870 patient-years until first graft loss or last follow-up date), of whom 75 also required colectomy. A heightened incidence of graft loss was observed for the IPAA group vs those retaining an end ileostomy (2.8 vs 0.4 per 100 patient-years, log-rank P = 0.005), whereas rates between IPAA vs no colectomy groups were not significantly different (2.8 vs 1.7, P = 0.1). In addition, the ileostomy group experienced significantly lower graft loss rates vs. patients retaining an intact colon (P = 0.044). The risks conferred by IPAA persisted when taking into account timing of colectomy as related to liver transplantation via time-dependent Cox regression analysis. Hepatic artery thrombosis and biliary strictures were the principal aetiologies of graft loss overall. Incidence rates for both were not significantly different between IPAA and no colectomy groups (P = 0.092 and P = 0.358); however, end ileostomy appeared protective (P = 0.007 and 0.031, respectively). CONCLUSION In PSC, liver transplantation, colectomy + IPAA is associated with similar incidence rates of hepatic artery thrombosis, recurrent biliary strictures and re-transplantation compared with no colectomy. Colectomy + end ileostomy confers more favourable graft outcomes.
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Affiliation(s)
- P J Trivedi
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.,Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.,Centre for Rare Diseases, Institute of Translational Medicine, University of Birmingham, Birmingham, UK
| | - J Reece
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - R W Laing
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - E Slaney
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - R Cooney
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - B K Gunson
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - S K Kamarajah
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - T Pinkney
- Department of Colorectal Surgery, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - F Thompson
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.,Centre for Rare Diseases, Institute of Translational Medicine, University of Birmingham, Birmingham, UK
| | - P Muiesan
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - A Schlegel
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.,Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland
| | - G M Hirschfield
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.,Centre for Rare Diseases, Institute of Translational Medicine, University of Birmingham, Birmingham, UK
| | - T Iqbal
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - J Ferguson
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.,Centre for Rare Diseases, Institute of Translational Medicine, University of Birmingham, Birmingham, UK
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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: 6] [Impact Index Per Article: 0.8] [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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10
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Khosa K, Clarke K. Management of ulcerative colitis pre- and post-liver transplant for primary sclerosing cholangitis: two case reports and review of literature. Int J Colorectal Dis 2014; 29:1313-20. [PMID: 24990353 DOI: 10.1007/s00384-014-1945-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/22/2014] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Management of ulcerative colitis (UC) pre- and post-liver transplant for primary sclerosing cholangitis (PSC) can be challenging and complex. There are no formal guidelines, but there is a plethora of data regarding the use of medical and surgical treatment options, mainly from case series, retrospective data, and experience from transplant centers. DISCUSSION We present two cases of UC-PSC with variable severity of liver disease and discuss the available data on the management of UC pre- and post-liver transplant. A PubMed search was conducted using various keyword combinations looking for studies involving patients with UC-PSC pre- and post-liver transplant. We reviewed and summarized the available literature on the course of UC in patients with PSC-related cirrhosis pre- and post-transplant and risk of colorectal neoplasia post-transplant. Finally, we summarize the available data on the medical and surgical management of UC pre- and post-liver transplant and the effect of transplant on pouchitis. Current literature supports the use of medical therapies, including immunomodulators and biologic agents, following liver transplant. There is also literature supporting surgical management including total colectomy. A multidisciplinary, patient-centered approach is important when managing UC pre- and post-liver transplantation.
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Affiliation(s)
- Kiranpreet Khosa
- Division of Gastroenterology, Allegheny General Hospital, Allegheny Health Network, 1301 Federal North Street, Suite 301, Pittsburgh, PA, 15212, USA
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11
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Abstract
The interaction between inflammatory bowel disease (IBD) and hepatobiliary manifestations represents a classic example of liver-gut crosstalk. The importance of liver-gut crosstalk in IBD is demonstrated in the pathogenesis and outcome of primary sclerosing cholangitis (PSC) in IBD patients. Immunoglobulin G4-associated cholangitis (IAC), which has recently been described in UC patients, may also illustrate the significance of gut-liver interaction in these patients. Presence of these hepatobiliary manifestations influences the outcome of associated IBD, in particular ulcerative colitis (UC), and vice versa. The pathogenesis of PSC is postulated to be related to gut inflammation in IBD that results in inflammation in the portal tracts (the 'leaky gut'). Enterohepatic circulation of lymphocytes from the gut to the liver is also of potential relevance to PSC pathogenesis and outcomes. The presence of PSC and gut inflammation in IBD influences the course and outcomes of both diseases. Further research is required, to understand the mutual effect of liver-gut crosstalk in the outcomes of UC patients, and highlights the importance of an interdisciplinary approach-involving gastroenterologists, hepatologists, advanced endoscopists and liver transplant surgeons-in the management of these patients.
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Affiliation(s)
- Udayakumar Navaneethan
- Department of Gastroenterology/Hepatology, Digestive Disease Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
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12
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Indriolo A, Ravelli P. Clinical management of inflammatory bowel disease in the organ recipient. World J Gastroenterol 2014; 20:3525-3533. [PMID: 24707135 PMCID: PMC3974519 DOI: 10.3748/wjg.v20.i13.3525] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
There was estimated a higher incidence of de novo inflammatory bowel disease (IBD) after solid organ transplantation than in the general population. The onset of IBD in the organ transplant recipient population is an important clinical situation which is associated to higher morbidity and difficulty in the medical therapeutic management because of possible interaction between anti-reject therapy and IBD therapy. IBD course after liver transplantation (LT) is variable, but about one third of patients may worsen, needing an increase in medical therapy or a colectomy. Active IBD at the time of LT, discontinuation of 5-aminosalicylic acid or azathioprine at the time of LT and use of tacrolimus-based immunosuppression may be associated with an unfavorable outcome of IBD after LT. Anti-tumor necrosis factor alpha (TNFα) therapy for refractory IBD may be an effective and safe therapeutic option after LT. The little experience of the use of biological therapy in transplanted patients, with concomitant anti-rejection therapy, suggests there be a higher more careful surveillance regarding the risk of infectious diseases, autoimmune diseases, and neoplasms. An increased risk of colorectal cancer (CRC) is present also after LT in IBD patients with primary sclerosing cholangitis (PSC). An annual program of endoscopic surveillance with serial biopsies for CRC is recommended. A prophylactic colectomy in selected IBD/PSC patients with CRC risk factors could be a good management strategy in the CRC prevention, but it is used infrequently in the majority of LT centers. About 30% of patients develop multiple IBD recurrence and 20% of patients require a colectomy after renal transplantation. Like in the liver transplantation, anti-TNFα therapy could be an effective treatment in IBD patients with conventional refractory therapy after renal or heart transplantation. A large number of patients are needed to confirm the preliminary observations. Regarding the higher clinical complexity of this subgroup of IBD patients, a close multidisciplinary approach between an IBD dedicated gastroenterologist and surgeon and an organ transplantation specialist is necessary in order to have the best clinical management of IBD after transplantation.
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13
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Abstract
: Restorative proctocolectomy with ileal pouch-anal anastomosis is commonly used in the management of ulcerative colitis. Inflammation of the ileal pouch reservoir, or pouchitis, is a common complication of ileal pouch-anal anastomosis that is incompletely understood. Risk factors including nonsmoker status and primary sclerosing cholangitis have been linked with pouchitis development, but the etiopathogenesis of pouchitis remains poorly defined. Pouchitis is more commonly a complication of ileal pouch-anal anastomosis performed in patients with ulcerative colitis, and similar to ulcerative colitis, chronic pouchitis is associated with extraintestinal manifestations and other diseases of immune origin, suggesting overlap in the disease pathogenesis. It is becoming apparent that pouchitis encompasses clinically distinct subtypes based on the response or lack of response to antibiotic therapy. There is also emerging evidence of the role of autoimmunity in a subgroup of patients with pouchitis, including patients with concurrent primary sclerosing cholangitis, seropositivity for immunoglobulin G4, or infiltration of immunoglobulin G4-expressing plasma cells in the pouch mucosa. The identification of underlying autoimmunity may have important clinical implications in the diagnosis, subclassification, and management of pouchitis.
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Singh S, Loftus EV, Talwalkar JA. Inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Am J Gastroenterol 2013; 108:1417-25. [PMID: 23896954 DOI: 10.1038/ajg.2013.163] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 04/23/2013] [Indexed: 02/07/2023]
Abstract
The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complex, with several IBD-, PSC-, and transplant-related factors interplaying with each other. Approximately one-third of patients with known IBD improve, and one-third paradoxically worsen, after LT for PSC. Active IBD, discontinuation of 5-aminosalicylates (5-ASA) at time of LT and tacrolimus-based immunosuppression may be associated with an unfavorable course of IBD after LT. Approximately 14-30% patients with PSC may develop de novo IBD 10 years after LT. LT confers a high risk of pouchitis after ileal pouch-anal anastomosis, although it may not be higher than baseline rates for PSC patients. The risk of colorectal cancer continues to be high after LT for PSC, and is higher in this cohort of patients with PSC-IBD, compared with patients undergoing LT for other indications. IBD does not adversely affect patient survival after LT, although the risk of recurrent PSC in the allograft may be higher in patients with IBD and an intact colon at time of LT. Standard therapy with 5-ASA and/or azathioprine may be appropriate for treatment of active IBD after LT and maintenance of remission. Anti-tumor necrosis factor-α agents are effective, but should be used with caution because of high risk of adverse events. The management of IBD after LT requires close coordination between transplant hepatologists and IBD experts.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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15
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Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) has been shown to increase the risk for chronic pouchitis. However, the association between PSC and Crohn's disease (CD) of the pouch has not been studied. METHODS Consecutive inflammatory bowel disease patients undergoing proctocolectomy with ileal pouch-anal anastomosis in our Pouchitis Registry from 2002 to 2012 were studied. Cases consisted of patients with CD of the pouch. Both univariable and multivariable analyses were performed. RESULTS A total of 1425 patients met the inclusion criteria, including 265 (18.6%) with CD of the pouch and 78 (5.5%) with PSC. In the whole cohort, 799 patients (56.1%) were male and the mean ages at the time of diagnosis of inflammatory bowel disease and at pouch surgery were 25.5 ± 12.3 years and 35.4 ± 13.9 years, respectively. Patients with PSC had a longer duration from inflammatory bowel disease diagnosis to pouch construction (P < 0.001). Fewer patients with PSC had toxic megacolon at the time of colectomy (P = 0.009), but more patients with PSC had neoplasia as the indication for colectomy (P < 0.001), concurrent autoimmune disorders (P < 0.001), and liver transplantation (P = 0.001). In the multivariate analysis, the presence of PSC was shown to be inversely associated with the risk for the development of CD of the pouch, with a hazard ratio of 0.39 (95% confidence interval: 0.16 to 0.95, P = 0.038). However, no significant difference in terms of the distribution of phenotypes of CD of the pouch between patients with and without PSC was identified (P = 0.59). CONCLUSIONS The presence of PSC is inversely associated with the development of CD of the pouch.
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16
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Obusez EC, Lian L, Shao Z, Navaneethan U, O'Shea R, Kiran RP, Shen B. Impact of ileal pouch-anal anastomosis on the surgical outcome of orthotopic liver transplantation for primary sclerosing cholangitis. J Crohns Colitis 2013; 7:230-8. [PMID: 22789675 DOI: 10.1016/j.crohns.2012.06.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2011] [Revised: 05/15/2012] [Accepted: 06/02/2012] [Indexed: 01/19/2023]
Abstract
BACKGROUND The definitive treatment for patients with primary sclerosing cholangitis (PSC) is orthotopic liver transplantation (OLT), while the surgical treatment of choice for UC is restorative protocolectomy with ileal pouch-anal anastomosis (IPAA). While studies to date show that OLT may impact the outcome of IPAA, the effect of IPAA on the surgical outcome of OLT is not known. METHODS All eligible patients (those with PSC and OLT) from our prospectively maintained OLT and Pouch Databases were included. Patient and OLT graft survivals along with surgical outcomes were assessed. Univariable and multivariable analyses were performed. RESULTS Seventy-nine patients with OLT for PSC were studied, including those with UC (PSC+OLT+UC, n=27) or without UC (PSC+OLT, n=30), and with UC and IPAA (PSC+OLT+UC+IPAA, n=22). In the PSC+OLT+UC group, 23 (85.2%) had UC before OLT and 4 (14.8%) had UC diagnosed after OLT. In the PSC+OLT+UC+IPAA group, 9 (40.9%) had IPAA-then-OLT and 13 (59.1%) had OLT-then-IPAA, while 21 (95.5%) had UC before OLT and 1 (4.5%) had UC diagnosed after OLT. Kaplan-Meier survival curve showed no statistical differences in patient and graft survivals between the 3 groups. In univariable analysis, there was no statistical difference for acute and chronic rejection, hepatic artery thrombosis, stricture, bile leak and acute and chronic renal failure for the 3 groups. In multivariable analysis, no factors were found to be associated with bacteremia or intra-abdominal abscess. CONCLUSIONS The presence of the IPAA in OLT for PSC patients appears not to have a negative impact on patient and graft survivals and post-operative complications.
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Affiliation(s)
- Emmanuel C Obusez
- Lerner College of Medicine, Department of Gastroenterology and Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA
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Trivedi PJ, Chapman RW. PSC, AIH and overlap syndrome in inflammatory bowel disease. Clin Res Hepatol Gastroenterol 2012; 36:420-36. [PMID: 22306055 DOI: 10.1016/j.clinre.2011.10.007] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Revised: 10/08/2011] [Accepted: 10/14/2011] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disorder characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include pruritus, fatigue and in advanced cases ascending cholangitis, cirrhosis and end-stage hepatic failure. Patients are at an increased risk of malignancy arising from the bile ducts, gallbladder, liver and colon. The majority (>80%) of Northern European patients with PSC also have inflammatory bowel disease (IBD), usually ulcerative colitis (UC). IBD commonly presents before the onset of PSC, although the opposite can occur and the onset of both conditions can be separated by many years. The colitis associated with PSC is characteristically mild although frequently involves the whole colon. Despite the majority of patients having relatively inactive colonic disease, paradoxically the risk of colorectal malignancy is substantially increased. Patients may also develop dominant, stenotic lesions of the biliary tree which may be difficult to differentiate from cholangiocarcinoma and the coexistence of IBD may influence the development of this complication. Ursodeoxycholic acid may offer a chemoprotective effect against colorectal malignancy and improve liver biochemical indices. Evidence of any beneficial effect on histological progression of hepatobiliary disease is less clear. High doses (∼25-30 mg/kg/d) may be harmful and should be avoided. Autoimmune hepatitis (AIH) is less common in patients with IBD than PSC, however, an association has been observed. A small subgroup may have an overlap syndrome between AIH and PSC and management should be individualised dependant on liver histology, serum immunoglobulin levels, autoantibodies, degree of biochemical cholestasis and cholangiography.
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Affiliation(s)
- P J Trivedi
- Centre for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Wolfson Drive, Edgbaston, Birmingham, B15 2TT United Kingdom.
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18
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Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis has become the procedure of choice for the majority of patients with ulcerative colitis who require surgical treatment. Pouchitis, the most common long-term complication of the procedure, involves a spectrum of disease processes with heterogeneous risk factors, clinical features, disease courses and prognoses. In addition, clinical symptoms of pouchitis are not specific and often overlap with those of other inflammatory and functional pouch disorders, such as Crohn's disease of the pouch and irritable pouch syndrome. Pouchoscopy and biopsy, along with laboratory and radiographic evaluations, are often required for accurate diagnosis in patients with symptoms indicative of pouchitis. Dysbiosis has been implicated as a triggering factor for pouchitis, and concurrent infection with pathogens, such as Clostridium difficile, might contribute to disease relapse and exacerbation. Antibiotic therapy is the main treatment modality. However, the management of antibiotic-dependent and antibiotic-refractory pouchitis remains challenging. Secondary causes of pouchitis, such as ischaemia, NSAID use, the presence of concurrent primary sclerosing cholangitis and other systemic immune-mediated disorders, should be evaluated and properly managed.
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Shen B, Bennett AE, Navaneethan U, Lian L, Shao Z, Kiran RP, Fazio VW, Remzi FH. Primary sclerosing cholangitis is associated with endoscopic and histologic inflammation of the distal afferent limb in patients with ileal pouch-anal anastomosis. Inflamm Bowel Dis 2011; 17:1890-900. [PMID: 21830267 DOI: 10.1002/ibd.21594] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2010] [Accepted: 11/03/2010] [Indexed: 12/16/2022]
Abstract
BACKGROUND We hypothesized that patients with primary sclerosing cholangitis (PSC) may have a higher risk for prepouch ileitis in the setting of ileal pouch-anal anastomosis (IPAA). The aim of this study was to compare endoscopic and histologic inflammation in the afferent limb (prepouch ileum) and pouch between IPAA patients with and without PSC. METHODS In all, 39 consecutive inflammatory bowel disease (IBD) and IPAA patients with PSC (study group) were identified and 91 IBD and IPAA patients without PSC (control group) were randomly selected with a 1:2 ratio. Demographic, clinical, endoscopic, and histologic variables were analyzed. RESULTS There were no significant differences in age, gender, and nonsteroidal antiinflammatory drug use between the study and control groups. Twelve (30.8%) patients in the IPAA-PSC group had coexisting autoimmune disorders, in contrast to five (5.5%) patients in the IPAA control group (P < 0.001). More patients in the study group had endoscopic inflammation as demonstrated by the higher Pouchitis Disease Activity Index (PDAI) endoscopic scores of the afferent limb and pouch body than those in the control group (P = 0.02 and P < 0.001, respectively). In addition, more patients with PSC had higher PDAI histologic scores of the afferent limb than those without PSC (P < 0.001). Multivariate analysis showed higher PDAI endoscopy and histology subscores were associated with risk for PSC, with odds ratio 1.34 (95% confidence interval [CI]: 1.34, 3.79) and 1.61 (95% CI: 1.00, 2.58), respectively. CONCLUSIONS Concurrent PSC appears to be associated with a significant prepouch ileitis on endoscopy and histology in patients with IPAA. Pouch patients with long segment of ileitis should be evaluated for PSC.
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Affiliation(s)
- Bo Shen
- Department of Gastroenterology, the Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
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20
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Abstract
One of typical examples of liver-gut cross talk is the interaction and impact of inflammatory bowel disease (IBD) and hepatobiliary (HB) abnormalities on each other's disease course. There are several layers of association between IBD and HB diseases: (i) HB diseases and IBD share pathogenetic mechanisms; (ii) HB diseases parallel structural and pathophysiological changes seen with IBD; and (iii) hepatic toxicity is associated with medical therapy for IBD. Interdisciplinary approach, involving gastroenterologists, hepatologists and, in advanced cases, general, colorectal, and liver transplant surgeons, is advocated.
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Affiliation(s)
- Preethi Gk Venkatesh
- Department of Gastroenterology/Hepatology, Digestive Disease Institute, the Cleveland Clinic Foundation, Cleveland, Ohio, USA
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21
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Rahman M, Desmond P, Mortensen N, Chapman RW. The clinical impact of primary sclerosing cholangitis in patients with an ileal pouch-anal anastomosis for ulcerative colitis. Int J Colorectal Dis 2011; 26:553-9. [PMID: 21279368 DOI: 10.1007/s00384-011-1140-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/16/2011] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Primary sclerosing cholangitis (PSC), a chronic inflammatory disease affecting the liver, is associated with ulcerative colitis (UC) in up to 75% of Northern European patients. These patients are at increased risk for the development of colorectal cancer, and the operation of choice is restorative proctocolectomy with an ileal pouch-anal anastomosis. However, complications such as pouchitis can occur, and studies have suggested that PSC is an independent risk factor for the development of pouchitis. AIM The aim of this study is to review and discuss the available literature on the effect of PSC on clinical outcomes of patients who undergo pouch surgery for UC. The outcomes reviewed comprise the incidence of pouchitis and pouch dysplasia/cancer and quality of life, including sexual function in UC patients with or without PSC. METHODS Pubmed/Medline and Embase searches were undertaken to obtain papers in English between 1966 and 2008. The keywords used were primary sclerosing cholangitis, ulcerative colitis, ileal pouch-anal anastomosis, quality of life, sexual function, dysplasia or cancer, pouchitis and orthotopic liver transplantation. RESULTS The incidence of pouchitis, pouch mucosal atrophy and risk of dysplasia appear to be greater in patients with associated PSC than in UC patients without PSC. Quality of life does not appear to be worse than in patients without PSC. Sexual function has not been studied in this subgroup of patients. CONCLUSION Pouchitis appears to be more common in the subset of UC patients with PSC, although there is clearly a need for further well-designed studies.
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Affiliation(s)
- Monira Rahman
- Department of Gastroenterology, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
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22
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Karlsen TH, Schrumpf E, Boberg KM. Primary sclerosing cholangitis. Best Pract Res Clin Gastroenterol 2010; 24:655-66. [PMID: 20955968 DOI: 10.1016/j.bpg.2010.07.005] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2010] [Revised: 07/15/2010] [Accepted: 07/16/2010] [Indexed: 01/31/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic bile duct disease leading to fibrotic biliary strictures and liver cirrhosis. The patient population is heterogeneous with regard to disease progression and the presence of co-morbidities, complicating the practical handling of patients as well as studies of pathogenetic mechanisms. The aetiology of PSC is unknown, but the recent findings of several robust susceptibility genes emphasise the importance of genetic risk factors. There is no effective medical treatment available to delay the disease progression, but endoscopic therapy of biliary stenoses may be indicated. Follow-up of patients includes management of the inflammatory bowel disease that is found in the majority of cases along with investigations aimed at the early detection of cholangiocarcinoma and colorectal cancer, which also occur at increased frequencies. In the present review, we aim to summarise the present knowledge of PSC with a particular emphasis on the possible basis of disease variability.
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Affiliation(s)
- Tom H Karlsen
- Norwegian PSC Research Center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway.
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Navaneethan U, Shen B. Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease. Inflamm Bowel Dis 2010; 16:1598-619. [PMID: 20198712 DOI: 10.1002/ibd.21219] [Citation(s) in RCA: 145] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Diseases involving the hepatopancreatobiliary (HPB) system are frequently encountered in patients with inflammatory bowel disease (IBD). Hepatobiliary manifestations constitute some of the most common extraintestinal manifestations of IBD. They appear to occur with similar frequency in patients with Crohn's disease or ulcerative colitis. HPB manifestations may occur in following settings: 1) disease possibly associated with a shared pathogenetic mechanism with IBD including primary sclerosing cholangitis (PSC), small-duct PSC/pericholangitis and PSC/autoimmune hepatitis overlap, acute and chronic pancreatitis related to IBD; 2) diseases which parallel structural and physiological changes seen with IBD, including cholelithiasis, portal vein thrombosis, and hepatic abscess; and 3) diseases related to adverse effects associated with treatment of IBD, including drug-induced hepatitis, pancreatitis (purine-based agents), or liver cirrhosis (methotrexate), and reactivation of hepatitis B, and biologic agent-associated hepatosplenic lymphoma. Less common HPB manifestations that have been described in association with IBD include autoimmune pancreatitis (AIP), IgG4-associated cholangitis (IAC), primary biliary cirrhosis (PBC), fatty liver, granulomatous hepatitis, and amyloidosis. PSC is the most significant hepatobiliary manifestation associated with IBD and poses substantial challenges in management requiring a multidisciplinary approach. The natural disease course of PSC may progress to cirrhosis and ultimately require liver transplantation in spite of total proctocolectomy with ileal-pouch anal anastomosis. The association between AIP, IAC, and elevated serum IgG4 in patients with PSC is intriguing. The recently reported association between IAC and IBD may open the door to investigate these complex disorders. Further studies are warranted to help understand the pathogenesis of HPB manifestations associated with IBD, which would help clinicians better manage these patients. An interdisciplinary approach, involving gastroenterologists, hepatologists, and, in advanced cases, general, colorectal, and transplant surgeons is advocated.
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Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for most patients with ulcerative colitis who require surgery. Although the surgical procedure offers a cure in some patients, postoperative inflammatory and noninflammatory complications are common. Pouchitis is the most common long-term complication of the procedure. Pouchitis represents a spectrum of disease processes with heterogeneous risk factors, clinical phenotypes, natural history, and prognosis. Accurate diagnosis and classification are important for proper treatment and prognosis.
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Affiliation(s)
- Hao Wu
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China
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25
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Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for most patients with ulcerative colitis who require surgery. Although the surgical procedure offers a cure in some patients, postoperative inflammatory and noninflammatory complications are common. Pouchitis is the most common long-term complication of the procedure. Pouchitis represents a spectrum of disease processes with heterogeneous risk factors, clinical phenotypes, natural history, and prognosis. Accurate diagnosis and classification are important for proper treatment and prognosis.
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Affiliation(s)
- Hao Wu
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China
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26
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Shen B, Remzi FH, Nutter B, Bennett AE, Lashner BA, Lavery IC, Brzezinski A, Bambrick ML, Queener E, Fazio VW. Association between immune-associated disorders and adverse outcomes of ileal pouch-anal anastomosis. Am J Gastroenterol 2009; 104:655-64. [PMID: 19262522 DOI: 10.1038/ajg.2008.76] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Autoimmune disorders (ADs) frequently coexist with inflammatory bowel disease. The aim of the study was to determine whether coexisting AD in patients with ileal pouches increases the risk for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch. METHODS A total of 622 patients seen in our Pouchitis Clinic were enrolled. We compared the prevalence of adverse outcomes of the pouch (including CARP, Crohn's disease of the pouch, and pouch failure) in patients with or without concurrent AD and assessed the factors for these adverse outcomes. RESULTS There were seven pouch disease categories: normal (N=60), irritable pouch syndrome (N=112), active pouchitis (N=131), CARP (N=67), Crohn's disease (N=131), cuffitis (N=83), surgical complications (N=36), and anismus (N=2). The prevalence of AD in these pouch disease categories was 4.5%, 12.5%, 9.2%, 13.4%, 10.7%, 3.8%, 1.5%, and 0%, respectively. The presence of at least one AD at time of pouch surgery was shown to be associated with a twofold increase in the risk for CARP (hazard ratio=2.29; 95% CI: 1.52, 3.46; P<0.001) and for pouch-associated hospitalization (hazard ratio=2.39; 95% CI: 1.59, 3.58; P<0.001). The presence of AD was not associated with increased risk for irritable pouch syndrome, active pouchitis, Crohn's disease, cuffitis, surgical complications, or pouch failure. Patients with Crohn's disease of the pouch had a 2.42 times higher risk for pouch failure (P=0.042) than these without. Active smoking or a history of smoking was shown to be associated with an increased risk for pouch-associated hospitalization and pouch failure. CONCLUSIONS AD appears to be associated with an increased risk for CARP, and the presence of the association between these AD and pouch disorders may stimulate further research on the link of these organ systems on an immunological basis.
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Affiliation(s)
- Bo Shen
- Pouchitis Clinic, Digestive Disease Institute, Cleveland Clinic, Ohio 44195, USA.
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Abstract
PURPOSE OF REVIEW Advances in conventional therapy, novel targets and therapeutic goals are the highlights of treatment for ulcerative colitis in the last year. There have also been disappointments. This review summarizes the highs and lows, with an emphasis on strategy as opposed to seeking the newest treatment option. RECENT FINDINGS In conventional therapy, once daily therapy for 5-aminosalicylic acid is generally sufficient. Furthermore, a new 5-aminosalicylic acid (mesalamine MMX) has been released that effectively induces and maintains remission. There have been reappraisals of immunomodulators and further evaluation of (yes, now conventional!) infliximab for ulcerative colitis. Opportunistic infections, long-term outcomes and the burden of disease are being characterized. New therapeutic targets included an antibody against T cells (anti-CD3), but trials on visilizumab for acute severe colitis have been suspended. T-cell costimulation, phosphatidylcholine to promote barrier function, new anti-tumour necrosis factor agents, B-cell (anti-CD20) depletion and complementary therapies represent new therapeutic horizons. International agreement is needed on activity indices, definitions of remission, therapeutic goals (including mucosal healing) and outcomes that matter to patients, so that trials can be compared. SUMMARY Advances will take time to alter mainstream practice, but 2007-2008 is the year of organized strategies, with European, American and British guidelines on ulcerative colitis published or in press. These should be the platform for better outcomes for patients.
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