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Wakil A, Muzahim Y, Awadallah M, Kumar V, Mazzaferro N, Greenberg P, Pyrsopoulos N. Trends of autoimmune liver disease inpatient hospitalization and mortality from 2011 to 2017: A United States nationwide analysis. World J Hepatol 2024; 16:1029-1038. [PMID: 39086532 PMCID: PMC11287613 DOI: 10.4254/wjh.v16.i7.1029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 05/23/2024] [Accepted: 06/25/2024] [Indexed: 07/26/2024] Open
Abstract
BACKGROUND Autoimmune liver diseases (AiLD) encompass a variety of disorders that target either the liver cells (autoimmune hepatitis, AIH) or the bile ducts [(primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC)]. These conditions can progress to chronic liver disease (CLD), which is characterized by fibrosis, cirrhosis, and hepatocellular carcinoma. Recent studies have indicated a rise in hospitalizations and associated costs for CLD in the US, but information regarding inpatient admissions specifically for AiLD remains limited. AIM To examine the trends and mortality of inpatient hospitalization of AiLD from 2011 to 2017. METHODS This study is a retrospective analysis utilizing the National Inpatient Sample (NIS) databases. All subjects admitted between 2011 and 2017 with a diagnosis of AiLD (AIH, PBC, PSC) were identified using the International Classification of Diseases (ICD-9) and ICD-10 codes. primary AiLD admission was defined if the first admission code was one of the AiLD codes. secondary AiLD admission was defined as having the AiLD diagnosis anywhere in the admission diagnosis (25 diagnoses). Subjects aged 21 years and older were included. The national estimates of hospitalization were derived using sample weights provided by NIS. χ 2 tests for categorical data were used. The primary trend characteristics were in-hospital mortality, hospital charges, and length of stay. RESULTS From 2011 to 2017, hospitalization rates witnessed a significant decline, dropping from 83263 admissions to 74850 admissions (P < 0.05). The patients hospitalized were predominantly elderly (median 53% for age > 65), mostly female (median 59%) (P < 0.05), and primarily Caucasians (median 68%) (P < 0.05). Medicare was the major insurance (median 56%), followed by private payer (median 27%) (P < 0.05). The South was the top geographical distribution for these admissions (median 33%) (P < 0.05), with most admissions taking place in big teaching institutions (median 63%) (P < 0.05). Total charges for admissions rose from 66031 in 2011 to 78987 in 2017 (P < 0.05), while the inpatient mortality rate had a median of 4.9% (P < 0.05), rising from 4.67% in 2011 to 5.43% in 2017. The median length of stay remained relatively stable, changing from 6.94 days (SD = 0.07) in 2011 to 6.51 days (SD = 0.06) in 2017 (P < 0.05). Acute renal failure emerged as the most common risk factor associated with an increased death rate, affecting nearly 68% of patients (P < 0.05). CONCLUSION AiLD-inpatient hospitalization showed a decrease in overall trends over the studied years, however there is a significant increase in financial burden on healthcare with increasing in-hospital costs along with increase in mortality of hospitalized patient with AiLD.
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Affiliation(s)
- Ali Wakil
- Department of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
| | - Yasameen Muzahim
- Department of Gastroenterology and Hepatology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United States
| | - Mina Awadallah
- Department of Gastroenterology and Hepatology, Rutgers the New Jersey Medical School, Newark, NJ 07103, United States
| | - Vikash Kumar
- Department of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
| | - Natale Mazzaferro
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, United States
| | - Patricia Greenberg
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, United States
| | - Nikolaos Pyrsopoulos
- Department of Gastroenterology and Hepatology, Rutgers the New Jersey Medical School, Newark, NJ 07103, United States.
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Momayez Sanat Z, Vahedi H, Malekzadeh R, Fanni Z. A systematic review and meta-analysis of extra-intestinal manifestation of inflammatory bowel disease in the Eastern Mediterranean Region (EMRO) countries. Ann Med Surg (Lond) 2024; 86:2892-2899. [PMID: 38694357 PMCID: PMC11060319 DOI: 10.1097/ms9.0000000000001543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/17/2023] [Indexed: 05/04/2024] Open
Abstract
Background Inflammatory bowel disease which is subgrouped mainly to ulcerative colitis and Crohn's disease is thought to be a multi-organ disease. Most organs can be involved in the disease course in addition to gastrointestinal tract involvement. In this systematic review we aimed to assess the prevalence of these manifestations in Eastern Mediterranean Regional Office (EMRO) countries. Method The present systematic review and meta-analysis study was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline. Joanna Briggs Institute (JBI) Critical Appraisal Checklist was admired for the quality evaluation of the included studies. For determining the heterogeneity, we used Cochran test and I2 statistics. Result Finally, 12 studies were included in our study. Based on the results of our study the prevalence of arthritis in ulcerative colitis and Crohn's disease patients was 7.1% (95% CI: 2.6-18.2%) and 13.5% (95% CI: 2.6-47.3%), respectively. Prevalence of arthralgia in ulcerative colitis patients was 18.4% (95% CI: 14.3-23.3%). skin involvement prevalence was 9.9% (95% CI 4.7-19.6%) in inflammatory bowel disease (IBD) patients. ocular involvement prevalence was 7.2% (95% CI 17-25.8%) in IBD patients. PSC prevalence in ulcerative colitis and Crohn's disease patients was 3.5% (95% CI: 1.7-7.3%) and 2.7% (95% CI: 1.3-5.5%), respectively. Conclusion Based on the results of this study arthralgia and arthritis were the most common extra-intestinal manifestation of IBD followed by dermatologic and ocular involvements. This extra-intestinal manifestation can challenge the patients' management and identifying their pattern is important during the disease course.
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Affiliation(s)
- Zahra Momayez Sanat
- Tehran University of Medical Sciences
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Homayoon Vahedi
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Tow CY, Chung E, Kaul B, Bhalla A, Fortune BE. Diagnostic Tests in Primary Sclerosing Cholangitis: Serology, Elastography, Imaging, and Histology. Clin Liver Dis 2024; 28:157-169. [PMID: 37945157 DOI: 10.1016/j.cld.2023.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the biliary tree leading to biliary strictures, cholangitis, and cirrhosis. Early in presentation, patients may have normal liver tests, though over time develop a cholestatic pattern of liver injury. Diagnosis is made radiographically with magnetic resonance or endoscopic cholangiography. While several autoantibodies are associated with PSC, none have proven to have adequate diagnostic utility. Liver biopsy is rarely recommended unless to evaluate for small-duct PSC or overlap syndrome. Elastography, in various forms, is an effective, non-invasive modality to evaluate liver fibrosis in PSC.
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Affiliation(s)
- Clara Y Tow
- Division of Hepatology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA; Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
| | - Erica Chung
- Division of Gastroenterology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA
| | - Bindu Kaul
- Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA; Department of Radiology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA
| | - Amarpreet Bhalla
- Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA; Department of Pathology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA
| | - Brett E Fortune
- Division of Hepatology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA; Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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Ahmed W, Joshi D, Huggett MT, Everett SM, James M, Menon S, Oppong KW, On W, Paranandi B, Trivedi P, Webster G, Hegade VS. Update on the optimisation of endoscopic retrograde cholangiography (ERC) in patients with primary sclerosing cholangitis. Frontline Gastroenterol 2024; 15:74-83. [PMID: 38487565 PMCID: PMC10935540 DOI: 10.1136/flgastro-2023-102491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 08/28/2023] [Indexed: 03/17/2024] Open
Affiliation(s)
- Wafaa Ahmed
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Deepak Joshi
- Gastroenterology, King's College Hospital Liver Unit, London, UK
| | - Matthew T Huggett
- Gastroenterology, St James's University Hospital, The Leeds Teaching Hospitals NHS Foundation Trust, Leeds, UK
| | - Simon M Everett
- Gastroenterology, St James's University Hospital NHS Trust, Leeds, UK
| | - Martin James
- Gastroenterology, Nottingham University, Nottingham, UK
| | - Shyam Menon
- Department of Hepatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - Wei On
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Bharat Paranandi
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Palak Trivedi
- National Institute for Health Research, Centre for Liver Research, University Hospitals Birmingham, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - George Webster
- Department of Gastroenterology, University College London Hospital NHS Foundation Trust, London, UK
| | - Vinod S Hegade
- Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Harputluoglu M, Calgin MZ, Ataman E, Tikici D, Kutluturk K, Kutlu R, Efe CS, Yilmaz S. Outcomes of patients with primary sclerosing cholangitis after liver transplantation in a predominantly living donor liver transplant center. JOURNAL OF LIVER TRANSPLANTATION 2023; 12:100186. [DOI: 10.1016/j.liver.2023.100186] [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: 01/11/2025] Open
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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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Almujarkesh MK, Damughatla AR, Bathla J, Sugg K, LaBuda D, Alkassis S, Al Hallak MN. Primary Squamous Cell Biliary Carcinoma With Liver Metastasis Is Rare but Malicious. Gastroenterology Res 2023; 16:276-279. [PMID: 37937226 PMCID: PMC10627356 DOI: 10.14740/gr1637] [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: 05/29/2023] [Accepted: 09/12/2023] [Indexed: 11/09/2023] Open
Abstract
Primary squamous cell carcinoma (SCC) of the liver is quite rare, and to our knowledge, very few cases have been reported in the literature. The exact pathogenesis of the disease is unestablished; however, it is mostly reported to be associated with hepatic cyst, Caroli's disease, hepatolithiasis, hepatic cirrhosis, and hepatic teratoma. We report a case of a 50-year-old woman with no prior medical history initially, who presented with postprandial epigastric and right upper quadrant pain that continued to worsen and was associated with early satiety, nausea, and weight loss of 25 pounds over 2 months, which prompted further evaluation by her primary care physician. Magnetic resonance imaging (MRI) examination a month later revealed a large heterogeneous area measuring 8.5 × 2.4 × 7.4 cm in the inferior right hepatic lobe with heterogeneous enhancement and involvement of the gallbladder, concerning for cholangiocarcinoma. Given radiographic findings, she underwent a computed tomography (CT)-guided core biopsy of the liver, which showed a necrotic malignant tumor favoring adenocarcinoma and was also found to have germline BRCA mutation. A positron emission tomography (PET) scan revealed a large partially necrotic fluorodeoxyglucose (FDG) avid mass, possibly arising from the gallbladder fossa with an invasion of both lobes of the liver and probable involvement of a portion of the ascending colon. There was no gross evidence of distant metastatic disease. The patient underwent staging laparoscopy prior to initiating chemotherapy, and another biopsy was done, which returned in favor of SCC, with immunohistochemical stains being positive for cytokeratin (CK)19, Ber-EP4 (epithelial antigen recognized by Ber-EP4 antibody), and P40 (DeltaNp63); while negative for CK7, CK20, caudal-type homeobox 2 (CDX-2), paired box 8 (PAX-8), and mucicarmine. The patient started platinum-based chemotherapy due to germline BRCA mutation. However, due to complications associated with therapy and the progression of the disease, the patient eventually chose hospice. Primary SSC remains an unexplored aggressive malignancy that carries an overall poor prognosis. Diagnosis can be challenging and requires high clinical suspicion due to the scarcity in specific laboratory workup. Pathological diagnosis remains the gold standard; however, it also carries its own challenges. Treatment is usually case-oriented, and definitive protocols have yet to be established.
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Affiliation(s)
| | - Anirudh R. Damughatla
- Department of Internal Medicine, Wayne State University & Detroit Medical Center, Detroit, MI, USA
| | - Jasdeep Bathla
- Department of Internal Medicine, Wayne State University & Detroit Medical Center, Detroit, MI, USA
| | - Kyle Sugg
- Department of Internal Medicine, Wayne State University & Detroit Medical Center, Detroit, MI, USA
| | - Dana LaBuda
- School of Medicine, Wayne State University, Detroit, MI, USA
| | - Samer Alkassis
- Department of Oncology, University of California, Los Angeles, CA, USA
| | - Mohammed Najeeb Al Hallak
- Department of Internal Medicine, Wayne State University & Detroit Medical Center, Detroit, MI, USA
- Department of Oncology, Karmanos Cancer Institute, Detroit, MI, USA
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Jamil OK, Shaw D, Deng Z, Dinardi N, Fillman N, Khanna S, Krugliak Cleveland N, Sakuraba A, Weber CR, Cohen RD, Dalal S, Jabri B, Rubin DT, Pekow J. Inflammation in the proximal colon is a risk factor for the development of colorectal neoplasia in inflammatory bowel disease patients with primary sclerosing cholangitis. Therap Adv Gastroenterol 2023; 16:17562848231184985. [PMID: 37692199 PMCID: PMC10486214 DOI: 10.1177/17562848231184985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 06/12/2023] [Indexed: 09/12/2023] Open
Abstract
Background Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have an increased risk of developing colorectal neoplasia (CRN) in the proximal colon. Objectives To evaluate whether duration and severity of inflammation are linked to the development of CRN in this population. Design Retrospective, case-control chart review of patients with PSC and IBD at a tertiary care center. Methods Disease activity was scored per colonic segment at each colonoscopy prior to the first instance of observed CRN using a modified Mayo endoscopic sub-score and histologic assessment. Patients in the CRN-positive group were compared to controls that did not. Results In all, 72 PSC-IBD patients with no history of CRN were identified, 13 of whom developed CRN after at least one colonoscopy at our institution. Patients in the CRN-positive group had significantly more endoscopic (p < 0.01) and histologic (p < 0.01) inflammation in the right compared to the control group prior to the development of dysplasia. There was significantly greater endoscopic inflammation in the segment of the colon with a dysplastic lesion than other segments of the colon (p = 0.018). Patients with moderate/severe lifetime endoscopic (p = 0.02) or histologic inflammation (p = 0.04) score had a lower probability of remaining free of dysplasia during follow-up. Nearly half of the patients with dysplasia had invisible lesions found on random biopsy. Conclusions Endoscopic and histologic inflammation in the proximal colon are risk factors for CRN in patients with PSC-IBD. PSC-IBD patients frequently have subclinical inflammation, and these findings support the practice of regular assessment of disease activity and random biopsy of inflamed and uninflamed areas in patients with PSC with the goal of reducing inflammation to prevent the development of CRN.
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Affiliation(s)
- Omar K. Jamil
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Dustin Shaw
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA Digestive Diseases Research Core Center, University of Chicago Medicine, Chicago, IL, USA
| | - Zifeng Deng
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Nicholas Dinardi
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Natalie Fillman
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Shivani Khanna
- Department of Allergy and Immunology, Johns Hopkins University, Baltimore, MD, USA
| | | | - Atsushi Sakuraba
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | | | - Russell D. Cohen
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Sushila Dalal
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Bana Jabri
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA Digestive Diseases Research Core Center, University of Chicago Medicine, Chicago, IL, USA
| | - David T. Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Joel Pekow
- Inflammatory Bowel Disease Center, University of Chicago Medicine, 900 East 57th Street, MB #9, Chicago, IL 60637, USA
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Rinaldi L, Giorgione C, Mormone A, Esposito F, Rinaldi M, Berretta M, Marfella R, Romano C. Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review. Viruses 2023; 15:1730. [PMID: 37632072 PMCID: PMC10459581 DOI: 10.3390/v15081730] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/04/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
Transient elastography by FibroScan® (Echosens, Paris, France) is a non-invasive method that can provide a reliable measurement of liver fibrosis through the evaluation of liver stiffness. Despite its limitations and risks, liver biopsy has thus far been the only procedure able to provide data to quantify fibrosis. Scientific evidence and clinical practice have made it possible to use FibroScan® in the diagnostic work-up of several liver diseases to monitor patients' long-term treatment response and for complication prevention. For these reasons, this procedure is widely used in clinical practice and is still being investigated for further applications. The aim of this narrative review is to provide a comprehensive overview of the main applications of transient elastography in the current clinical practice.
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Affiliation(s)
- Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Chiara Giorgione
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Andrea Mormone
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Francesca Esposito
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Michele Rinaldi
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, “Federico II” University of Naples, 80131 Naples, Italy;
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, University of Messina, 98121 Messina, Italy;
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Ciro Romano
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
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Lakkasani S, Kogilathota Jagirdhar GS, Qirem M, Digiacomo SW, Pantula S. A Rare Case of Primary Sclerosing Cholangitis Overlapped With Autoimmune Hepatitis and Ulcerative Colitis. Cureus 2023; 15:e43403. [PMID: 37706140 PMCID: PMC10495695 DOI: 10.7759/cureus.43403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/13/2023] [Indexed: 09/15/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a liver disease of idiopathic origin, displaying a diverse and varied nature, which leads to cholestasis. It is characterized by continuous, advancing inflammation and fibrosis in the bile ducts. PSC is closely linked with inflammatory bowel disease and poses a risk for colon, bile duct, and gallbladder cancer. Unfortunately, there is currently no effective medical treatment available for this condition. In some cases, the disease may progress to end-stage liver failure, making liver transplantation a possible necessity for affected individuals. PSC association with autoimmune hepatitis (AIH) is very rare. This is a case of PSC that is overlapped with AIH. Screening colonoscopy showed colitis, and a biopsy was consistent with ulcerative colitis without any colitis symptoms, emphasizing the need for ruling out any other associated conditions, which respond well to the effective treatment to avoid morbidity and mortality in PSC.
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Affiliation(s)
| | | | - Murad Qirem
- Medical Education, Saint Michael's Medical Center, Newark, USA
| | - Scott W Digiacomo
- Gastroenterology and Hepatology, Saint Michael's Medical Center, Newark, USA
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11
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Lee SH, Moon SJ, Woo SH, Ahn G, Kim WK, Lee CH, Hwang JH. CrebH protects against liver injury associated with colonic inflammation via modulation of exosomal miRNA. Cell Biosci 2023; 13:116. [PMID: 37370191 DOI: 10.1186/s13578-023-01065-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Hepatic liver disease, including primary sclerosing cholangitis (PSC), is a serious extraintestinal manifestations of colonic inflammation. Cyclic adenosine monophosphate (cAMP)-responsive element-binding protein H (CrebH) is a transcription factor expressed mostly in the liver and small intestine. However, CrebH's roles in the gut-liver axis remain unknown. METHODS Inflammatory bowel disease (IBD) and PSC disease models were established in wild-type and CrebH-/- mice treated with dextran sulfate sodium, dinitrobenzene sulfonic acid, and diethoxycarbonyl dihydrocollidine diet, respectively. RNA sequencing were conducted to investigate differential gene expression. Exosomes were isolated from plasma and culture media. miRNA expression profiling was performed using the NanoString nCounter Mouse miRNA Panel. Effects of miR-29a-3p on adhesion molecule expression were investigated in bEnd.3 brain endothelial cells. RESULTS CrebH-/- mice exhibited accelerated liver injury without substantial differences in the gut after administration of dextran sulfate sodium (DSS), and had similar features to PSC, including enlarged bile ducts, enhanced inflammation, and aberrant MAdCAM-1 expression. Furthermore, RNA-sequencing analysis showed that differentially expressed genes in the liver of CrebH-/- mice after DSS overlapped significantly with genes changed in PSC-liver. Analysis of plasma exosome miRNA isolated from WT and CrebH-/- mice indicates that CrebH can contribute to the exosomal miRNA profile. We also identified miR-29a-3p as an effective mediator for MAdCAM-1 expression. Administration of plasma exosome from CrebH-/- mice led to prominent inflammatory signals in the liver of WT mice with inflammatory bowel disease (IBD). CONCLUSIONS CrebH deficiency led to increased susceptibility to IBD-induced liver diseases via enhanced expression of adhesion molecules and concomitant infiltration of T lymphocytes. Exosomes can contribute to the progression of IBD-induced liver injury in CrebH-/- mice. These study provide novel insights into the role of CrebH in IBD-induced liver injury.
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Affiliation(s)
- Sang-Hee Lee
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseoung-gu, Daejeon, 34141, Korea
- Department of Biology, Daejeon University, 62 Daehak-ro, Dong-gu, Daejeon, 34520, Korea
| | - Sung-Je Moon
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseoung-gu, Daejeon, 34141, Korea
- KRIBB School of Bioscience, University of Science and Technology (UST), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Korea
| | - Seung Hee Woo
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseoung-gu, Daejeon, 34141, Korea
- Department of Biology and Microbiology, Changwon National University, 20 Chanwondaehak-ro, Uichan-gu, Chanwon-si, Gyeonsangnam-do, 51140, Korea
| | - Gwangsook Ahn
- Department of Biology, Daejeon University, 62 Daehak-ro, Dong-gu, Daejeon, 34520, Korea
| | - Won Kon Kim
- KRIBB School of Bioscience, University of Science and Technology (UST), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Korea
- Metabolic Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseoung-gu, Daejeon, 34141, Korea
| | - Chul-Ho Lee
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseoung-gu, Daejeon, 34141, Korea.
- KRIBB School of Bioscience, University of Science and Technology (UST), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Korea.
| | - Jung Hwan Hwang
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseoung-gu, Daejeon, 34141, Korea.
- KRIBB School of Bioscience, University of Science and Technology (UST), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Korea.
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12
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Shaw DG, Aguirre-Gamboa R, Vieira MC, Gona S, DiNardi N, Wang A, Dumaine A, Gelderloos-Arends J, Earley ZM, Meckel KR, Ciszewski C, Castillo A, Monroe K, Torres J, Shah SC, Colombel JF, Itzkowitz S, Newberry R, Cohen RD, Rubin DT, Quince C, Cobey S, Jonkers IH, Weber CR, Pekow J, Wilson PC, Barreiro LB, Jabri B. Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis. Nat Med 2023; 29:1520-1529. [PMID: 37322120 PMCID: PMC10287559 DOI: 10.1038/s41591-023-02372-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 04/26/2023] [Indexed: 06/17/2023]
Abstract
Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.
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Affiliation(s)
- Dustin G Shaw
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Raúl Aguirre-Gamboa
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA
| | - Marcos C Vieira
- Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA
| | - Saideep Gona
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA
| | - Nicholas DiNardi
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Anni Wang
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Anne Dumaine
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA
| | - Jody Gelderloos-Arends
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Zachary M Earley
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | | | - Cezary Ciszewski
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Anabella Castillo
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kelly Monroe
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Joana Torres
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
- Division of Gastroenterology, Hospital Luz, Lisboa, Portugal
- Faculty of Medicine, Universidade de Lisboa, Lisboa, Portugal
| | - Shailja C Shah
- Division of Gastroenterology, University of California San Diego, San Diego, CA, USA
- Jennifer Moreno VA San Diego Healthcare System, San Diego, CA, USA
| | - Jean-Frédéric Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Steven Itzkowitz
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Rodney Newberry
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Russell D Cohen
- University of Chicago Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - David T Rubin
- University of Chicago Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - Christopher Quince
- Organisms and Ecosystems, Earlham Institute, Norwich, NR4 7UZ, UK
- Warwick Medical School, University of Warwick, Coventry, CV4 7HL, UK
- Gut Microbes and Health, Quadram Institute, Norwich, NR4 7UQ, UK
| | - Sarah Cobey
- Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA
| | - Iris H Jonkers
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | | | - Joel Pekow
- University of Chicago Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - Patrick C Wilson
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Section of Rheumatology, University of Chicago, Chicago, IL, USA
| | - Luis B Barreiro
- Committee on Immunology, University of Chicago, Chicago, IL, USA.
- Department of Medicine, University of Chicago, Chicago, IL, USA.
- Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA.
| | - Bana Jabri
- Committee on Immunology, University of Chicago, Chicago, IL, USA.
- Department of Medicine, University of Chicago, Chicago, IL, USA.
- Department of Pathology, University of Chicago, Chicago, IL, USA.
- Department of Pediatrics, University of Chicago, Chicago, IL, USA.
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Kruk B, Milkiewicz M, Raszeja-Wyszomirska J, Milkiewicz P, Krawczyk M. A common variant in the hepatobiliary phospholipid transporter ABCB4 modulates liver injury in PBC but not in PSC: prospective analysis in 867 patients. Orphanet J Rare Dis 2022; 17:419. [PMID: 36397154 PMCID: PMC9670364 DOI: 10.1186/s13023-022-02565-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 10/30/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The ATP-binding cassette subfamily B member 4 (ABCB4) gene encodes the hepatic phospholipid transporter. Variants in the ABCB4 gene are associated with various cholestatic phenotypes, some of which progress to liver fibrosis and cirrhosis. The aim of our study was to investigate the role of the cholestasis-associated variant ABCB4 c.711A > T (p.I237I, rs2109505) in patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). RESULTS Two cohorts of Polish patients took part in this study. The Szczecin cohort comprised 196 patients with PBC (174 females, 38% with cirrhosis) and 135 patients with PSC (39 females, 39% with cirrhosis). The Warsaw cohort consisted of 260 patients with PBC (241 females, 44% with cirrhosis) and 276 patients with PSC (97 females, 33% with cirrhosis). Two control cohorts-150 healthy blood donors and 318 patients without liver disease, were recruited in Szczecin and in Warsaw, respectively. The ABCB4 c.711A > T polymorphism was genotyped using TaqMan assay. In both PBC cohorts, carriers of the risk variant presented more frequently with cirrhosis (Szczecin: OR = 1.841, P = 0.025; Warsaw: OR = 1.528, P = 0.039). The risk allele was associated with increased serum AST, GGT and ALP (all P < 0.05) at inclusion. During the follow-up, patients in both cohorts significantly improved their laboratory results, independently of their ABCB4 c.711A > T genotype (P > 0.05). During 8 ± 4 years follow-up, a total of 22 patients in the Szczecin PBC group developed cirrhosis, and this risk was higher among carriers of the risk variant (OR = 5.65, P = 0.04). In contrast to PBC, we did not detect any association of ABCB4 c.711A > T with a liver phenotype in PSC cohorts. CONCLUSIONS The frequent pro-cholestatic variant ABCB4 c.711A > T modulates liver injury in PBC, but not in PSC. In particular, carriers of the major allele are at increased risk of progressive liver scarring.
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Affiliation(s)
- Beata Kruk
- grid.13339.3b0000000113287408Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Malgorzata Milkiewicz
- grid.107950.a0000 0001 1411 4349Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Joanna Raszeja-Wyszomirska
- grid.13339.3b0000000113287408Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Milkiewicz
- grid.13339.3b0000000113287408Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland ,grid.107950.a0000 0001 1411 4349Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Marcin Krawczyk
- grid.13339.3b0000000113287408Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland ,grid.411937.9Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
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Berberine Ursodeoxycholate for the Treatment of Primary Sclerosing Cholangitis: The Search for the Elusive Pharmacologic Holy Grail Will Need to Continue. Am J Gastroenterol 2022; 117:1762-1763. [PMID: 36327435 DOI: 10.14309/ajg.0000000000001999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 08/23/2022] [Indexed: 11/06/2022]
Abstract
Effective pharmacologic treatment of primary sclerosing cholangitis (PSC) remains elusive. Ursodeoxycholic acid (UDCA) is known to improve liver biochemistry, specifically serum alkaline phosphatase, in patients with PSC but has not been shown to favourably alter the natural history. Similarly, many immunomodulatory medications have been studied for the treatment of PSC, but none has been demonstrated to be of unequivocal benefit. In this issue of the Journal, a pilot study of a ursodeoxycholate berberine salt vs placebo is reported. Although improvement in serum alkaline phosphatase is reported, without a control arm with UDCA monotherapy, it is not possible to determine whether this study drug is beneficial over UDCA by itself. More study in the PSC therapeutic arena is needed.
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15
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Efficacy and safety of immune-modulating therapy for primary sclerosing cholangitis: A systematic review and meta-analysis. Pharmacol Ther 2022; 237:108163. [DOI: 10.1016/j.pharmthera.2022.108163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 02/23/2022] [Accepted: 02/28/2022] [Indexed: 11/17/2022]
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16
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Park JK, Kim D, Lee JM, Lee KH, Lee KT, Park JK, Lee JK. Clinical Utility of Personalized Serum IgG Subclass Ratios for the Differentiation of IgG4-Related Sclerosing Cholangitis (IgG4-SC) from Primary Sclerosing Cholangitis (PSC) and Cholangiocarcinoma (CCA). J Pers Med 2022; 12:jpm12060855. [PMID: 35743640 PMCID: PMC9225113 DOI: 10.3390/jpm12060855] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/10/2022] [Accepted: 05/21/2022] [Indexed: 11/16/2022] Open
Abstract
Background: The differential diagnosis of immunoglobulin G4-sclerosing cholangitis (IgG4-SC) from primary sclerosing cholangitis (PSC) or cholangiocarcinoma (CCA) is important. In this study, we aimed to find the best combinations of serum IgG subclasses and IgG4 levels for differentiating IgG4-SC from PSC or CCA. Methods: In total, 31 patients with IgG4-SC, 27 patients with PSC, and 40 patients with CCA were enrolled from 2003 to 2017 at a single tertiary referral center. We retrospectively assessed the IgG4, IgG4/IgG1, IgG4/(IgG1+IgG3), and (IgG4+IgG2)/(IgG1+IgG3) in each of the patients. ROC curves were established to obtain the optimal cutoff value for each parameter. McNemar’s test was used to compare the sensitivities, specificities, and accuracies of diagnostic algorithms. Results: In differentiating IgG4-SC from PSC, the accuracies of IgG4/IgG1 ≥ 0.087 and of IgG4/(IgG1+IgG3) ≥ 0.081 were significantly higher than that of IgG4 ≥ 135 mg/dL alone (78% vs. 66%, p = 0.025). Serum IgG4 ≥ 52 mg/dL showed the best accuracy for differentiation of IgG4-SC from CCA, with a sensitivity and specificity of 80% and 82%, respectively, but this was statistically not significant (p = 0.405). Conclusions: The serum IgG4/IgG1 or IgG4/(IgG1+IgG3) level may help to differentiate IgG4-SC from PSC. IgG4 alone is the most accurate serologic marker for the differentiation of IgG4-SC from CCA.
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Affiliation(s)
- Jae Keun Park
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441, Korea;
| | - Dongwuk Kim
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
| | - Jeong Min Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
| | - Kwang Hyuck Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul 16419, Korea
| | - Kyu Taek Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
| | - Joo Kyung Park
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
| | - Jong Kyun Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (D.K.); (J.M.L.); (K.H.L.); (K.T.L.); (J.K.P.)
- Correspondence:
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Quinn KP, Urquhart SA, Janssens LP, Lennon RJ, Chedid VG, Raffals LE. Primary Sclerosing Cholangitis-Associated Pouchitis: A Distinct Clinical Phenotype. Clin Gastroenterol Hepatol 2022; 20:e964-e973. [PMID: 33549866 DOI: 10.1016/j.cgh.2021.02.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 01/20/2021] [Accepted: 02/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with primary sclerosing cholangitis (PSC) commonly undergo ileal pouch-anal anastomosis (IPAA) for medically-refractory ulcerative colitis (UC) or colorectal dysplasia. Pouchitis develops more frequently in patients with PSC, potentially leading to increased morbidity. We aimed to assess clinical characteristics and treatment outcomes for pouchitis in patients with PSC compared to a matched, non-PSC cohort. METHODS All patients with PSC who underwent IPAA and were diagnosed with pouchitis (PSC-pouchitis) were identified. A matched cohort composed of non-PSC patients who underwent IPAA for UC and subsequently developed pouchitis (UC-pouchitis) was developed. Relevant demographic, clinical, endoscopic, histologic, and treatment data were collected and compared between groups. RESULTS Of those with PSC-pouchitis (n=182), 53.9% and 46.1% underwent IPAA for medically-refractory disease and dysplasia, respectively, compared to 88.7% and 11.3% in the UC-pouchitis group (P < .001). Patients with PSC-pouchitis were more likely to develop chronic pouchitis (68.1% vs 34.1%; P < .001), have moderate-to-severe pouch inflammation (54.9% vs 32.4%; P < .001), and prepouch ileitis (34.1% vs 11.5%; P < .001) compared to UC-pouchitis. Of those with PSC-pouchitis, 50.6% and 17.6% developed chronic antibiotic-dependent or antibiotic-refractory pouchitis, respectively, compared to 25.8% and 7.7% with UC-pouchitis. There was no difference in treatment response between the two groups with use of thiopurines, anti-tumor necrosis factor agents, and newer biologics. CONCLUSIONS PSC-associated pouchitis presents with a unique clinical phenotype, characterized by increased risk of chronic pouchitis, moderate-to-severe pouch inflammation, prepouch ileitis, and less response to conventional antimicrobial therapy.
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Affiliation(s)
- Kevin P Quinn
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Siri A Urquhart
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | | | - Ryan J Lennon
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Victor G Chedid
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Laura E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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18
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Ferrigno B, Barba R, Medina-Morales E, Trivedi H, Patwardhan V, Bonder A. Cholestatic Liver Disease and Pregnancy: A Systematic Review and Meta-Analysis. J Clin Med 2022; 11:1068. [PMID: 35207342 PMCID: PMC8875982 DOI: 10.3390/jcm11041068] [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] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/08/2022] [Accepted: 02/16/2022] [Indexed: 02/01/2023] Open
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two types of chronic cholestatic liver disease (CCLD). Little is known regarding the relationship between these conditions and pregnancy. We performed a systematic review and meta-analysis regarding the maternal and fetal outcomes amongst patients with a known diagnosis of PBC and PSC undergoing pregnancy. Our analysis shows that patients with PBC and PSC who undergo pregnancy are at an increased risk of pre-term delivery, as well as the development of new or worsening pruritus during pregnancy. Additionally, patients with PBC are at higher risk of undergoing a biochemical disease flare during the postpartum period compared to during pregnancy. However, there were no documented cases of maternal mortality or development of decompensated cirrhosis during pregnancy or the postpartum period.
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Affiliation(s)
- Bryan Ferrigno
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA;
| | - Romelia Barba
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; (R.B.); (E.M.-M.); (H.T.); (V.P.)
| | - Esli Medina-Morales
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; (R.B.); (E.M.-M.); (H.T.); (V.P.)
| | - Hirsh Trivedi
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; (R.B.); (E.M.-M.); (H.T.); (V.P.)
| | - Vilas Patwardhan
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; (R.B.); (E.M.-M.); (H.T.); (V.P.)
| | - Alan Bonder
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; (R.B.); (E.M.-M.); (H.T.); (V.P.)
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19
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Acher AW, Rahnemai-Azar AA, Weber SM, Pawlik TM. Surgical Approach to Pancreas, Liver, Biliary Physiologic Impairment. THE IASGO TEXTBOOK OF MULTI-DISCIPLINARY MANAGEMENT OF HEPATO-PANCREATO-BILIARY DISEASES 2022:31-49. [DOI: 10.1007/978-981-19-0063-1_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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20
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Araz M, Akkuş P, Baltacioglu MH, Soydal C, Kır KM. Diffuse increased uptake in intrahepatic biliary ducts on 18F-FDG PET/CT in a case with primary sclerosing cholangitis. Rev Esp Med Nucl Imagen Mol 2022; 41 Suppl 1:S4-S5. [DOI: 10.1016/j.remnie.2020.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 09/24/2020] [Indexed: 11/27/2022]
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21
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Alborzi F, Ebrahimi Daryani N, Deihim T, Azizi Z, Azmoudeh Ardalan F, Teimouri A, Taslimi R, Roshan N, Mami M, Mirzade M, Aletaha N. Colonic Mucosal Infiltration of IgG4 Plasma Cells and Ulcerative Colitis: Determinant of Presence, Activity, Extension, and Duration of Disease. Middle East J Dig Dis 2021; 13:287-293. [PMID: 36606008 PMCID: PMC9489443 DOI: 10.34172/mejdd.2021.237] [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: 01/21/2021] [Accepted: 06/11/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Infiltration of IgG4 positive plasma cells has been detected in the colonic mucosa of patients with ulcerative colitis (UC). The aim of the study was to investigate the association between colonic mucosal infiltration of IgG4 plasma cells and the presence, activity, extension, and duration of UC. METHODS In this case-control study (2009-2014), 102 subjects (84 with UC/18 controls) were enrolled. Clinical records and rectosigmoid biopsies of UC patients were selected, and biopsies were stained with IgG4 monoclonal antibodies. IgG4 positive plasma cells were counted by a single pathologist. RESULTS Amongst 84 patients with UC, 73.8% had UC without primary sclerosing cholangitis (PSC), and 26.2% had UC with PSC. IgG4 plasma cells were seen in 35 (41.7%) patients with UC and 0% of controls (p = 0.001). The mean amount of IgG4 containing plasma cells was significantly different between active and inactive patients with UC, although it was not significantly different between UC patients with and without PSC. The presence of IgG4 infiltration was significantly associated with the extension and duration of the disease. Furthermore, IgG4 count had a sensitivity/specificity of 78.6%/83.3% for the diagnosis of UC. CONCLUSION Our study revealed the diagnostic role of IgG4 plasma cells in the colonic mucosa of patients with UC and its association with activity, extension, and duration of disease.
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Affiliation(s)
- Foroogh Alborzi
- Assistant Professor of Gastroenterology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi Daryani
- Professor of Gastroenterology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Tina Deihim
- Internal Medicine Resident, Internal Medicine Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Azizi
- Researcher, Iran University of Medical Sciences, Tehran, Iran
| | | | - Azam Teimouri
- Assistant Professor of Gastroenterology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Taslimi
- Assistant Professor of Gastroenterology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Nader Roshan
- Associate Professor of Gastroenterology, Tehran University of Medical Sciences, Tehran, Iran
| | - Masood Mami
- Assistant Professor of Gastroenterology, Ilam University of Medical Sciences, Ilam, Iran
| | - Monirsadat Mirzade
- Resident of Community Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Najmeh Aletaha
- Associate Professor of Gastroenterology, Tehran University of Medical Sciences, Tehran, Iran
,Corresponding Author: Najmeh Aletaha,MD Gastroentrology and Hepatology Ward, Imam Khomeini Hospital, Tehran university of Medical Science, Tehran, Iran Tel: + 98 21 88799446 Fax: + 98 21 88799840
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Han S, Kahaleh M, Sharaiha RZ, Tarnasky PR, Kedia P, Slivka A, Chennat JS, Joshi V, Sejpal DV, Sethi A, Shah RJ. Probe-based confocal laser endomicroscopy in the evaluation of dominant strictures in patients with primary sclerosing cholangitis: results of a U.S. multicenter prospective trial. Gastrointest Endosc 2021; 94:569-576.e1. [PMID: 33798541 DOI: 10.1016/j.gie.2021.03.027] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/21/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Patients with primary sclerosing cholangitis (PSC) and dominant biliary strictures carry increased risk for the development of cholangiocarcinoma. Although ERCP-based techniques including brush cytology and intraductal biopsy sampling represent first-line tissue sampling methods for dominant strictures, sensitivity is low. Probe-based confocal laser endomicroscopy (pCLE) offers microscopic-level imaging of subepithelial biliary mucosa. Because data regarding the use of pCLE in PSC are limited, we aimed to investigate its diagnostic performance in dominant strictures. METHODS This was a multicenter prospective study involving PSC patients with dominant strictures. ERCP with pCLE was performed with use of the Miami classification (2+ criteria for malignant diagnosis) and Paris classification. Final malignant diagnoses required histopathologic confirmation, and benign diagnoses required a minimum of 1 year of follow-up without development of cancer. RESULTS Fifty-nine patients (mean age, 49 years; 59% men) with 63 strictures were included in the study. Stricture locations included the common bile duct (31.7%), bifurcation (22.2%), and common hepatic duct (19%). Seven patients (11.9%) were found to have cholangiocarcinoma. The sensitivity and specificity of pCLE was 85.7% (95% confidence interval [CI], 42.1-99.6) and 73.1% (95% CI, 58.9-84.4), respectively. Within specific stricture locations, the highest sensitivity was seen at the bifurcation (100%; 95% CI, 2.5-100) and the right hepatic duct (100%; 95% CI, 29.2-100). The lowest sensitivities were seen at the common bile duct (25%; 95% CI, 5.5-57.2) and the left hepatic duct (28.6%; 95% CI, 3.7-70.9). CONCLUSIONS In this prospective multicenter study, pCLE had a high sensitivity in detecting cholangiocarcinoma, but technical aspects of the probe may limit evaluation in the common bile duct and left hepatic duct. Further evaluation is needed to elucidate the role of pCLE in the algorithm of excluding neoplasia in biliary strictures associated with PSC. (Clinical trial registration number: NCT02736708.).
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Affiliation(s)
- Samuel Han
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Michel Kahaleh
- Division of Gastroenterology, Rutgers Robert Wood Johnson University Hospital, New Brunswick, New Jersey, USA
| | - Reem Z Sharaiha
- Division of Gastroenterology, Weill Cornell Medical Center, New York, New York, USA
| | - Paul R Tarnasky
- Division of Gastroenterology, Dallas Methodist Medical Center, Dallas, Texas, USA
| | - Prashant Kedia
- Division of Gastroenterology, Dallas Methodist Medical Center, Dallas, Texas, USA
| | - Adam Slivka
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jennifer S Chennat
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Virendra Joshi
- Division of Gastroenterology, Louisiana State University Health Center, New Orleans, Louisiana, USA
| | - Divyesh V Sejpal
- Division of Gastroenterology, Northwell Health, Manhasset, New York, USA
| | - Amrita Sethi
- Division of Gastroenterology, Columbia University Medical Center, New York, New York, USA
| | - Raj J Shah
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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23
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Bozward AG, Ronca V, Osei-Bordom D, Oo YH. Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy. Front Immunol 2021; 12:711217. [PMID: 34512631 PMCID: PMC8425300 DOI: 10.3389/fimmu.2021.711217] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 08/09/2021] [Indexed: 12/12/2022] Open
Abstract
The tight relationship between the gut and liver on embryological, anatomical and physiological levels inspired the concept of a gut-liver axis as a central element in the pathogenesis of gut-liver axis diseases. This axis refers to the reciprocal regulation between these two organs causing an integrated system of immune homeostasis or tolerance breakdown guided by the microbiota, the diet, genetic background, and environmental factors. Continuous exposure of gut microbiome, various hormones, drugs and toxins, or metabolites from the diet through the portal vein adapt the liver to maintain its tolerogenic state. This is orchestrated by the combined effort of immune cells network: behaving as a sinusoidal and biliary firewall, along with a regulatory network of immune cells including, regulatory T cells and tolerogenic dendritic cells (DC). In addition, downregulation of costimulatory molecules on hepatic sinusoids, hepatocytes and biliary epithelial cells as well as regulating the bile acids chain also play a part in hepatic immune homeostasis. Recent evidence also demonstrated the link between changes in the gut microbiome and liver resident immune cells in the progression of cirrhosis and the tight correlation among primary sclerosing cholangitis (PSC) and also checkpoint induced liver and gut injury. In this review, we will summarize the most recent evidence of the bidirectional relationship among the gut and the liver and how it contributes to liver disease, focusing mainly on PSC and checkpoint induced hepatitis and colitis. We will also focus on completed therapeutic options and on potential targets for future treatment linking with immunology and describe the future direction of this research, taking advantage of modern technologies.
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Affiliation(s)
- Amber G. Bozward
- Centre for Liver and Gastrointestinal Research and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- Liver Transplant and Hepatobiliary Unit, Queen Elizabeth Hospital, University Hospital of Birmingham NHS Foundation Trust, Birmingham, United Kingdom
- Centre for Rare Diseases, European Reference Network - Rare Liver Centre, Birmingham, United Kingdom
- Birmingham Advanced Cellular Therapy Facility, University of Birmingham, Birmingham, United Kingdom
| | - Vincenzo Ronca
- Centre for Liver and Gastrointestinal Research and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- Liver Transplant and Hepatobiliary Unit, Queen Elizabeth Hospital, University Hospital of Birmingham NHS Foundation Trust, Birmingham, United Kingdom
- Centre for Rare Diseases, European Reference Network - Rare Liver Centre, Birmingham, United Kingdom
| | - Daniel Osei-Bordom
- Centre for Liver and Gastrointestinal Research and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- Queen Elizabeth Hospital, University Hospital of Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Ye Htun Oo
- Centre for Liver and Gastrointestinal Research and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- Liver Transplant and Hepatobiliary Unit, Queen Elizabeth Hospital, University Hospital of Birmingham NHS Foundation Trust, Birmingham, United Kingdom
- Centre for Rare Diseases, European Reference Network - Rare Liver Centre, Birmingham, United Kingdom
- Birmingham Advanced Cellular Therapy Facility, University of Birmingham, Birmingham, United Kingdom
- Queen Elizabeth Hospital, University Hospital of Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
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Rodrigues T, Boike JR. Biliary Strictures: Etiologies and Medical Management. Semin Intervent Radiol 2021; 38:255-262. [PMID: 34393335 DOI: 10.1055/s-0041-1731086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Biliary strictures have several etiologies that can broadly be classified into benign and malignant causes. The clinical presentation is variable with strictures identified incidentally on imaging or during the evaluation of routine laboratory abnormalities. Symptoms and cholangitis lead to imaging that can diagnose biliary strictures. The diagnosis and medical management of biliary strictures will be discussed in this article.
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Affiliation(s)
- Terrance Rodrigues
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Justin R Boike
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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25
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McClure T, Cui W, Asadi K, John T, Testro A. Case of nivolumab-induced sclerosing cholangitis: lessons from long-term follow-up. BMJ Open Gastroenterol 2021; 7:bmjgast-2020-000487. [PMID: 32912846 PMCID: PMC7484867 DOI: 10.1136/bmjgast-2020-000487] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 08/18/2020] [Accepted: 08/19/2020] [Indexed: 12/19/2022] Open
Abstract
Nivolumab is an immune checkpoint inhibitor used to treat multiple solid-organ malignancies. While many of its immune-related adverse events are well established, nivolumab-induced sclerosing cholangitis remains poorly characterised, with no defined diagnostic criteria. Moreover, data regarding long-term outcomes are particularly lacking. We present a biopsy-proven case of nivolumab-induced sclerosing cholangitis, which uniquely captures 18 months of follow-up post-treatment. Our case highlights key features of intrahepatic subtype sclerosing cholangitis and suggests durable response to corticosteroid therapy.
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Affiliation(s)
- Tess McClure
- Gastroenterology, Austin Health, Heidelberg, Victoria, Australia .,Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Wanyuan Cui
- Medicine, The University of Melbourne, Melbourne, Victoria, Australia.,Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Khashayar Asadi
- Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia
| | - Thomas John
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Adam Testro
- Gastroenterology, Austin Health, Heidelberg, Victoria, Australia.,Medicine, The University of Melbourne, Melbourne, Victoria, Australia
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26
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Ferreira MTGB, Ribeiro IB, de Moura DTH, McCarty TR, da Ponte Neto AM, Farias GFA, de Miranda Neto AA, de Oliveira PVAG, Bernardo WM, de Moura EGH. Stent versus Balloon Dilation for the Treatment of Dominant Strictures in Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis. Clin Endosc 2021; 54:833-842. [PMID: 34192839 PMCID: PMC8652153 DOI: 10.5946/ce.2021.052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Accepted: 02/02/2021] [Indexed: 11/17/2022] Open
Abstract
Background/Aims The endoscopic management of primary sclerosing cholangitis (PSC)-associated dominant strictures remains challenging. This systematic review and meta-analysis aimed to compare balloon dilation and stent placement in the treatment of dominant strictures among PSC patients.
Methods Literature searches on MEDLINE, EMBASE, Cochrane CENTRAL and Lilacs/Bireme were performed for studies published until December 2020. Measured outcomes included clinical efficacy, stricture recurrence, cumulative recurrencefree rate, transplant rate, 5-year survival rate, and adverse events (i.e., pancreatitis, cholangitis, bleeding, perforation and death).
Results A total of 5 studies (n=467) were included. Based on pooled analyses, there were no differences in clinical efficacy (risk difference [RD], -0.13; 95% confidence interval [CI], -0.58 to 0.33; I2=93%) or transplant rates (RD, -0.09; 95% CI, -0.19 to 0.01; I2=0%); however, the risk of occurrence of adverse events was lower with balloon dilatation than with stent placement (RD,-0.34; 95% CI, -0.45 to -0.23; I2=61%). Among the types of adverse events reported, only the rates of cholangitis/bacteremia were significantly lower in balloon dilation patients (RD, -0.19; 95% CI, -0.25 to -0.13; I2=51%).
Conclusions Compared to balloon dilation, stent placement for dominant strictures in PSC appeared to have higher complication rates without significant differences in efficacy.
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Affiliation(s)
| | - Igor Braga Ribeiro
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HC/FMUSP, São Paulo, SP, Brazil
| | - Diogo Turiani Hourneaux de Moura
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HC/FMUSP, São Paulo, SP, Brazil
| | - Thomas R McCarty
- Division of Gasteoenterology, Hepatology and Endoscopy - Brigham and Women's Hospital - Harvard Medical School, Boston, MA, USA
| | - Alberto Machado da Ponte Neto
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HC/FMUSP, São Paulo, SP, Brazil
| | - Galileu Ferreira Ayala Farias
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HC/FMUSP, São Paulo, SP, Brazil
| | - Antônio Afonso de Miranda Neto
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HC/FMUSP, São Paulo, SP, Brazil
| | - Pedro Victor Aniz Gomes de Oliveira
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HC/FMUSP, São Paulo, SP, Brazil
| | - Wanderley Marques Bernardo
- Gastrointestinal Endoscopy Unity, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HC/FMUSP, São Paulo, SP, Brazil
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27
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The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies. Int J Mol Sci 2021; 22:ijms22136975. [PMID: 34203536 PMCID: PMC8268159 DOI: 10.3390/ijms22136975] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/18/2021] [Accepted: 06/21/2021] [Indexed: 02/08/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It is associated with high rates of progression to end-stage liver disease as well as a significant risk of cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Currently, no effective medical treatment with an impact on the overall survival is available, and liver transplantation is the only curative treatment option. Emerging evidence indicates that gut microbiota is associated with disease pathogenesis. Several studies analyzing fecal and mucosal samples demonstrate a distinct gut microbiome in individuals with PSC compared to healthy controls and individuals with inflammatory bowel disease (IBD) without PSC. Experimental mouse and observational human data suggest that a diverse set of microbial functions may be relevant, including microbial metabolites and bacterial processing of pharmacological agents, bile acids, or dietary compounds, altogether driving the intrahepatic inflammation. Despite critical progress in this field over the past years, further functional characterization of the role of the microbiota in PSC and related malignancies is needed. In this review, we discuss the available data on the role of the gut microbiome and elucidate important insights into underlying pathogenic mechanisms and possible microbe-altering interventions.
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28
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Araz M, Akkuş P, Baltacioglu MH, Soydal C, Kır KM. Diffuse increased uptake in intrahepatic biliary ducts on 18F-FDG PET/CT in a case with primary sclerosing cholangitis. Rev Esp Med Nucl Imagen Mol 2021; 41:S2253-654X(20)30194-3. [PMID: 34167931 DOI: 10.1016/j.remn.2020.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 09/23/2020] [Accepted: 09/24/2020] [Indexed: 11/25/2022]
Affiliation(s)
- M Araz
- Nuclear Medicine Department, Ankara University Medical School, Ankara, Turquía.
| | - P Akkuş
- Nuclear Medicine Department, Ankara University Medical School, Ankara, Turquía
| | - M H Baltacioglu
- Nuclear Medicine Department, Ankara University Medical School, Ankara, Turquía
| | - C Soydal
- Nuclear Medicine Department, Ankara University Medical School, Ankara, Turquía
| | - K M Kır
- Nuclear Medicine Department, Ankara University Medical School, Ankara, Turquía
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29
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Abstract
Chronic liver disease in pregnancy is rare. Historically, many chronic liver diseases were considered contraindications to pregnancy; however, with current monitoring and treatment strategies, pregnancy may be considered in many cases. Preconception and initial antepartum consultation should focus on disease activity, medication safety, risks of pregnancy, as well as the need for additional monitoring during pregnancy. In most cases, a multidisciplinary approach is necessary to ensure optimal maternal and fetal outcomes. Despite improving outcomes, pregnancy in women with the chronic liver disease remains high risk.
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30
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Rabiee A, Silveira MG. Primary sclerosing cholangitis. Transl Gastroenterol Hepatol 2021; 6:29. [PMID: 33824933 DOI: 10.21037/tgh-20-266] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/19/2020] [Indexed: 12/15/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.
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Affiliation(s)
- Anahita Rabiee
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Marina G Silveira
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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31
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McCain JD, Chascsa DM, Lindor KD. Assessing and managing symptom burden and quality of life in primary sclerosing cholangitis patients. Expert Opin Orphan Drugs 2021. [DOI: 10.1080/21678707.2021.1898370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Josiah D. McCain
- Department of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA
| | - David M. Chascsa
- Department of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA
- Department of Transplant Center, Mayo Clinic, Phoenix, Arizona, USA
| | - Keith D. Lindor
- Office of University Provost, Arizona State University, Arizona, USA
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Palmer M, Regev A, Lindor K, Avigan MI, Dimick‐Santos L, Treem W, Marcinak JF, Lewis JH, Anania FA, Seekins D, Shneider BL, Chalasani N. Consensus guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury occurring during clinical trials in adults with chronic cholestatic liver disease. Aliment Pharmacol Ther 2020; 51:90-109. [PMID: 31762074 PMCID: PMC6972572 DOI: 10.1111/apt.15579] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 07/03/2019] [Accepted: 10/19/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Improved knowledge of the molecular pathophysiology and immunopathogenesis of cholestatic liver diseases in recent years has led to an increased interest in developing novel therapies. Patients with cholestatic liver disease often require different approaches to assessment and management of suspected drug-induced liver injury (DILI) compared to those with healthy livers and those with parenchymal liver diseases. At present, there are no regulatory guidelines or society position papers, that systematically address best practices pertaining to detection of DILI in these patients. AIMS To outline best practices for detection, assessment and management of suspected acute DILI during clinical trials in adults with the cholestatic liver diseases - Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC). METHODS This is one of the several papers developed by the IQ DILI Initiative, which is comprised of members from 16 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. The contents are the result of an extensive literature review, as well as in-depth discussions among industry, regulatory and academic DILI experts, to achieve consensus recommendations on DILI-related issues occurring during clinical trials for cholestatic liver diseases. RESULTS Recommended best practices are outlined pertaining to hepatic eligibility criteria, monitoring of liver tests, approach to a suspected DILI signal, and hepatic discontinuation rules. CONCLUSIONS This paper provides a framework for the approach to detection, assessment and management of suspected acute DILI occurring during clinical trials in adults with cholestatic liver disease.
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Distinct Disease Phenotype of Ulcerative Colitis in Patients With Coincident Primary Sclerosing Cholangitis: Evidence From a Large Retrospective Study With Matched Cohorts. Dis Colon Rectum 2019; 62:1494-1504. [PMID: 31725582 DOI: 10.1097/dcr.0000000000001496] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis is a classical extraintestinal manifestation in patients with ulcerative colitis. However, the impact of primary sclerosing cholangitis on the disease course is incompletely understood. OBJECTIVE This study aimed to assess the impact of primary sclerosing cholangitis on disease phenotype and its course in patients with ulcerative colitis. DESIGN This is a retrospective study with 3:1 matched cohorts. SETTINGS Tertiary care center's electronic database was used for data analysis from 2000 and 2018. PATIENTS Of 782 patients with ulcerative colitis, 77 patients who had coincident primary sclerosing cholangitis were included. MAIN OUTCOME MEASURES The primary outcomes evaluated were disease characteristics including colonic disease activity, temporal change of disease course, colorectal neoplasia, and colectomy rates. RESULTS Disease activity during acute flares, assessed by the complete Mayo score, was significantly lower in patients with primary sclerosing cholangitis (6.2 vs 7.3; p < 0.001). In addition, disease activity in patients with primary sclerosing cholangitis was decreased, especially within the first 10 years after disease onset, and biological therapy with anti-tumor necrosis factor and anti-integrin agents was commenced less frequently (22% vs 35%; p = 0.043) and later (10-year risk: 17.4% vs 27.8%; p = 0.034). Patients with primary sclerosing cholangitis were younger at colitis diagnosis (23.3 vs 29.3 years; p < 0.001) and had more extensive disease (75% vs 46%; p < 0.001). Colorectal cancer was more frequently detected in patients with coincident primary sclerosing cholangitis (6/77 vs 16/705; p = 0.016). Colectomy rates did not differ between both groups (14.3% vs 14.5%; p = 0.56). In contrast, patients with ulcerative colitis had to undergo surgery more frequently because of therapy-refractant inflammation, whereas surgery due to neoplasia development was increased in patients with coincident primary sclerosing cholangitis (p = 0.013). LIMITATIONS The study was limited by its retrospective design. CONCLUSION Patients who have ulcerative colitis with coincident primary sclerosing cholangitis develop a distinct disease course characterized by an earlier disease onset and lower disease activity, but more frequent extensive disease manifestation and higher risk for colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B45. FENOTIPO DE ENFERMEDAD DISTINTIVO DE LA COLITIS ULCERATIVA EN PACIENTES CON COLANGITIS ESCLEROSANTE PRIMARIA CONCOMITANTE: EVIDENCIA DE UN ESTUDIO RETROSPECTIVO GRANDE CON COHORTES EMPAREJADAS: La colangitis esclerosante primaria es una manifestación extraintestinal clásica en pacientes con colitis ulcerativa. Sin embargo, el impacto de la colangitis esclerosante primaria en el curso de la enfermedad no es comprendido completamente.Evaluar el impacto de la colangitis esclerosante primaria en el fenotipo y curso de la enfermedad en pacientes con colitis ulcerativa.Este es un estudio retrospectivo con cohortes emparejadas 3:1.La base de datos electrónica de un centro de atención terciaria se utilizó para el análisis de datos de 2000 a 2018.782 pacientes con colitis ulcerativa, 77 padecían colangitis esclerosante primaria concomitante y fueron incluidos.Se evaluaron las características de la enfermedad, incluida la actividad de enfermedad colónica, el cambio temporal del curso de la enfermedad, la neoplasia colorrectal y las tasas de colectomía.La actividad de la enfermedad durante los brotes agudos, evaluada por la puntuación completa de Mayo, fue significativamente menor en pacientes con colangitis esclerosante primaria (6.2 vs 7.3; p < 0.001). Además, la actividad de la enfermedad en pacientes con colangitis esclerosante primaria se redujo especialmente en los primeros 10 años después del inicio de la enfermedad, y la terapia biológica con agentes anti-TNF y anti-integrina se inició con menos frecuencia (22% vs 35%; p = 0.043) y más tarde (riesgo a 10 años: 17.4% vs 27.8%; p = 0.034). Los pacientes con colangitis esclerosante primaria eran más jóvenes en el momento del diagnóstico de colitis (23.3 vs 29.3 años; p < 0.001) y tenían enfermedad más extensa (75% vs 46%; p < 0.001). El cáncer colorrectal se detectó con mayor frecuencia en pacientes con colangitis esclerosante primaria concomitante (6/77 vs 16/705; p = 0.016). Las tasas de colectomía no fueron diferentes entre ambos grupos (14.3% vs 14.5%; p = 0.56). En contraste, los pacientes con colitis ulcerativa tuvieron que someterse a cirugía con mayor frecuencia debido a inflamación refractaria a la terapia, mientras que el desarrollo de neoplasia se incrementó en pacientes con colangitis esclerosante primaria concomitante (p = 0.013).El estudio estuvo limitado por su diseño retrospectivo.Los pacientes con colitis ulcerativa con colangitis esclerosante primaria concomitante desarrollan un curso de enfermedad distintivo caracterizado por un inicio temprano de la enfermedad y una menor actividad de la enfermedad, pero con manifestación de enfermedad extensa más frecuente y un mayor riesgo de cáncer colorrectal. Vea el resumen en video en http://links.lww.com/DCR/B45.
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Zhang C, Hussaini T, Yoshida EM. Review of pharmacotherapeutic treatments for primary sclerosing cholangitis. CANADIAN LIVER JOURNAL 2019; 2:58-70. [PMID: 35990218 PMCID: PMC9202752 DOI: 10.3138/canlivj-2018-0016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 08/15/2018] [Indexed: 11/13/2023]
Abstract
BACKGROUND The objective of this review was to evaluate pharmacotherapeutic treatments for primary sclerosing cholangitis (PSC) through a literature search of current published data. A review of the current clinical data for each treatment is discussed. METHODS We conducted a systematic literature search for articles using EMBASE (1980 to April 1, 2018), and MEDLINE (1948 to April 1, 2018) using Ovid, to identify studies investigating various therapies in PSC. Search terms included the following: primary sclerosing cholangitis, cholangitis, sclerosing cholangitis; ursodeoxycholic acid, glucocorticoids, cyclosporine, tacrolimus, methotrexate, azathioprine, 6-mercaptopurine, penicillamine, anti-TNF, antibiotics, and probiotics. We also performed a review of current clinical trials using ClinicalTrials.gov. We considered for review relevant studies published in English, pilot studies, and randomized controlled trials involving human subjects. RESULTS Therapies that have been investigated in the management of PSC include those used in search terms and others that were not included in our search parameters. Analysis of published data involving each therapy was explored and none have shown any sustained, significant benefit in the treatment of PSC. In terms of relevance to patient care and clinical practice, this review evaluates and compares various pharmacotherapeutic treatments for PSC where liver transplantation remains the only definitive treatment. CONCLUSIONS To date, no clinical study of any drug has demonstrated effectiveness in terms of survival benefit or a decreased need for liver transplantation. More clinical studies are needed, and patients need to be adequately informed before any medical therapy for PSC is undertaken.
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Affiliation(s)
- Chaoran Zhang
- Internal Medicine Residency Training Program, Department of Medicine, University of British Columbia, Vancouver, British Columbia;
| | - Trana Hussaini
- Department of Pharmaceutical Sciences Medicine, Vancouver General Hospital, Vancouver, British Columbia;
| | - Eric M Yoshida
- Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia
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Menon S, Holt A. Large-duct cholangiopathies: aetiology, diagnosis and treatment. Frontline Gastroenterol 2019; 10:284-291. [PMID: 31288256 PMCID: PMC6583582 DOI: 10.1136/flgastro-2018-101098] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 12/06/2018] [Accepted: 12/09/2018] [Indexed: 02/04/2023] Open
Abstract
Cholangiopathies describe a group of conditions affecting the intrahepatic and extrahepatic biliary tree. Impairment to bile flow and chronic cholestasis cause biliary inflammation, which leads to more permanent damage such as destruction of the small bile ducts (ductopaenia) and biliary cirrhosis. Most cholangiopathies are progressive and cause end-stage liver disease unless the physical obstruction to biliary flow can be reversed. This review considers large-duct cholangiopathies, such as primary sclerosing cholangitis, ischaemic cholangiopathy, portal biliopathy, recurrent pyogenic cholangitis and Caroli disease.
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Affiliation(s)
- Shyam Menon
- Department of Hepatology and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK,Department of Gastroenterology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | - Andrew Holt
- Department of Hepatology and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Van Haele M, Snoeck J, Roskams T. Human Liver Regeneration: An Etiology Dependent Process. Int J Mol Sci 2019; 20:ijms20092332. [PMID: 31083462 PMCID: PMC6539121 DOI: 10.3390/ijms20092332] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 05/06/2019] [Accepted: 05/09/2019] [Indexed: 02/07/2023] Open
Abstract
Regeneration of the liver has been an interesting and well-investigated topic for many decades. This etiology and time-dependent mechanism has proven to be extremely challenging to investigate, certainly in human diseases. A reason for this challenge is found in the numerous interactions of different cell components, of which some are even only temporarily present (e.g., inflammatory cells). To orchestrate regeneration of the epithelial cells, their interaction with the non-epithelial components is of utmost importance. Hepatocytes, cholangiocytes, liver progenitor cells, and peribiliary glands have proven to be compartments of regeneration. The ductular reaction is a common denominator in virtually all liver diseases; however, it is predominantly found in late-stage hepatic and biliary diseases. Ductular reaction is an intriguing example of interplay between epithelial and non-epithelial cells and encompasses bipotential liver progenitor cells which are able to compensate for the loss of the exhausted hepatocytes and cholangiocytes in biliary and hepatocytic liver diseases. In this manuscript, we focus on the etiology-specific damage that is observed in different human diseases and how the liver regulates the regenerative response in an acute and chronic setting. Furthermore, we describe the importance of morphological keynotes in different etiologies and how spatial information is of relevance for every basic and translational research of liver regeneration.
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Affiliation(s)
- Matthias Van Haele
- Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, 3000 Leuven, Belgium.
| | - Janne Snoeck
- Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, 3000 Leuven, Belgium.
| | - Tania Roskams
- Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, 3000 Leuven, Belgium.
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Abstract
Chronic liver disease (CLD) is a global health problem with chronic viral hepatitis, alcohol-related liver disease, and nonalcoholic fatty liver disease being important causes of mortality. Besides its clinical burden, patients with CLD also suffer from impairment of their health-related quality of life and other patient-reported outcomes (PRO). In this context, a combination of both clinical and PROs will allow assessment of the comprehensive burden of liver disease on patients. PROs cannot be observed directly and must be assessed by validated questionnaires or tools. Various tools have been developed to accurately measure PROs in patients with CLD, including generic and disease-specific questionnaires such as Short Form-36, Chronic Liver Disease Questionnaire and its subtypes. It is important to note that PRO instruments can be used to appreciate the impact of the natural history of CLD or of treatment on patients' experiences. This review summarizes PRO assessment in different types of liver disease and different tools useful to investigators and clinicians who are interested in this aspect of patients' experience.
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Abstract
Hepatobiliary disorders are commonly encountered in patients with inflammatory bowel disease (IBD). Although primary sclerosing cholangitis is the stereotypical hepatobiliary disorder associated with IBD, other diseases, including autoimmune hepatitis and nonalcoholic fatty liver disease, also are encountered in this population. Several agents used for treatment of IBD may cause drug-induced liver injury, although severe hepatotoxicity occurs infrequently. Furthermore, reactivation of hepatitis B virus infection may occur in patients with IBD treated with systemic corticosteroids and biologic agents.
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Affiliation(s)
- Mahmoud Mahfouz
- Department of Internal Medicine, Mount Sinai Medical Center, 4300 Alton Road, Suite 301, Miami Beach, FL 33140, USA
| | - Paul Martin
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 Northwest 14 Street #1115, Miami, FL 33136, USA.
| | - Andres F Carrion
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 Northwest 14 Street #1115, Miami, FL 33136, USA
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Koga A, Toda K, Tatsushima K, Matsuubayashi S, Tamura N, Imamura M, Kawai K. Portal hypertension in prolonged anorexia nervosa with laxative abuse: A case report of three patients. Int J Eat Disord 2019; 52:211-215. [PMID: 30636007 PMCID: PMC6590132 DOI: 10.1002/eat.23007] [Citation(s) in RCA: 6] [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: 05/30/2018] [Revised: 11/07/2018] [Accepted: 12/08/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE There has been no report on portal hypertension related to anorexia nervosa (AN). METHOD We describe three cases of portal hypertension manifesting with collateral circulation represented by gastroesophageal varices in prolonged AN with laxative abuse and self-vomiting. These women, in their 20s to 50s, were diagnosed as having AN binging and purging type (AN-BP) that included self-induced vomiting and abuse of irritating laxatives (more than 100 tablets daily). RESULTS Case 1 showed prominent ascites and a gastro-renal shunt on computed tomography scanning. Case 2 showed gastroesophageal varices on endoscopic examination. Case 3 showed gastroesophageal varices on computed tomography scanning and endoscopic examination. We performed liver biopsies in all patients and found only slight pericellular fibrosis. Our patients showed typical symptoms of portal hypertension, although liver cirrhosis was not present. DISCUSSION We speculated that abnormal eating and purging behaviors were involved in the development of portal hypertension. We hypothesized that long-term laxative abuse, dehydration, and abnormal eating behavior are involved in the development of portal hypertension, considering these were common features in our patients. Portal hypertension and gastroesophageal varices should be considered as one of the potentially existing complications in prolonged AN-BP with self-induced vomiting and abuse of irritating laxatives.
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Affiliation(s)
- Aiko Koga
- Department of Psychosomatic MedicineKohnodai Hospital, National Center for Global Health MedicineIchikawa CityChibaJapan
| | - Kenta Toda
- Department of Psychosomatic MedicineKohnodai Hospital, National Center for Global Health MedicineIchikawa CityChibaJapan
| | - Keita Tatsushima
- Department of Psychosomatic MedicineKohnodai Hospital, National Center for Global Health MedicineIchikawa CityChibaJapan
| | - Sunao Matsuubayashi
- Department of Psychosomatic MedicineFukuoka Tokusyuukai HospitalKasuga CityFukuokaJapan
| | - Naho Tamura
- Department of Psychosomatic MedicineKohnodai Hospital, National Center for Global Health MedicineIchikawa CityChibaJapan
| | - Masatoshi Imamura
- Department of Gastroenterology and HepatologyKohnodai Hospital, National Center for Global Health MedicineIchikawa CityChibaJapan
| | - Keisuke Kawai
- Department of Psychosomatic MedicineKohnodai Hospital, National Center for Global Health MedicineIchikawa CityChibaJapan
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Sarkisian AM, Sharaiha RZ. Malignant Biliary Obstruction of the Hilum and Proximal Bile Ducts. ERCP 2019:385-393.e3. [DOI: 10.1016/b978-0-323-48109-0.00040-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Khoshpouri P, Ameli S, Ghasabeh MA, Pandey A, Zarghampour M, Varzaneh FN, Jacob A, Pandey P, Luo Y, Kamel IR. Correlation between quantitative liver and spleen volumes and disease severity in primary sclerosing cholangitis as determined by Mayo risk score. Eur J Radiol 2018; 108:254-260. [PMID: 30396665 DOI: 10.1016/j.ejrad.2018.10.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 08/29/2018] [Accepted: 10/05/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To correlate total and lobar liver and spleen volume with disease severity in primary sclerosing cholangitis (PSC) as determined by Mayo risk score. METHODS This HIPAA-compliant single center retrospective study included 147 PSC patients with available imaging studies (MRCP/CT) and laboratory data between January 2003 and January 2018. Total and lobar (right, left and caudate) liver volume and spleen volume were measured. ANOVA test was performed to assess the differences in volumes between low, intermediate and high-risk groups (Mayo risk score <0, >0 and <2, >2, respectively). Correlations between volumes and Mayo risk score were calculated. ROC analysis was performed to assess the accuracy of the variable with the strongest correlation to PSC severity to predict Mayo risk score. P value <0.05 was considered statistically significant. RESULTS The mean age of this cohort was 45 ± 17 years; 58% were men. Absolute volumes of left lobe, caudate and spleen and volume ratios of left lobe and caudate to total liver volume of the high-risk group were significantly higher compared to those of low and intermediate risk groups (p < 0.05). Left lobe to total liver volume ratio had the highest correlation to Mayo risk score (Pearson correlation coefficient 0.61, p < 0.05) and on ROC analysis it had 84.4% accuracy in detecting high-risk PSC. CONCLUSIONS In this single institution large cohort study, the left lobe to total liver volume ratio was the best quantifiable volumetric biomarker to correlate with severity of PSC as identified by Mayo risk score.
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Affiliation(s)
- Pegah Khoshpouri
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA
| | - Sanaz Ameli
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA
| | - Mounes Aliyari Ghasabeh
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA
| | - Ankur Pandey
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA
| | - Manijeh Zarghampour
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA
| | - Farnaz Najmi Varzaneh
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA
| | - Angela Jacob
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA
| | - Pallavi Pandey
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA
| | - Yan Luo
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA
| | - Ihab R Kamel
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD, 21287, USA.
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Wijarnpreecha K, Panjawatanan P, Mousa OY, Cheungpasitporn W, Pungpapong S, Ungprasert P. Association between appendectomy and risk of primary sclerosing cholangitis: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2018; 42:436-442. [PMID: 29655526 DOI: 10.1016/j.clinre.2018.03.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 03/01/2018] [Accepted: 03/15/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND/OBJECTIVES Recent epidemiologic studies have suggested that appendectomy could be a risk factor for primary sclerosing cholangitis (PSC) although the results were inconsistent. This systematic review and meta-analysis was conducted to summarize all available evidence. METHODS A comprehensive literature review was conducted using MEDLINE and EMBASE database through January 2018 to identify all studies that reported the risk of PSC among individuals who had appendectomy versus those with no history of appendectomy. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS A total of 6 case-control studies with 2432 participants met the eligibility criteria and were included in the meta-analysis. The risk of PSC in individuals who had appendectomy was significantly higher than those with no history of appendectomy with the pooled odds ratio of 1.37 (95% CI: 1.15-1.63). The statistical heterogeneity was insignificant with an I2 of 0%. CONCLUSIONS A significantly increased risk of PSC among individuals who had a history of appendectomy was found in this study.
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Affiliation(s)
- Karn Wijarnpreecha
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY, USA.
| | | | - Omar Y Mousa
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Wisit Cheungpasitporn
- Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Surakit Pungpapong
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Virani S, Akers A, Stephenson K, Smith S, Kennedy L, Alpini G, Francis H. Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma. JOURNAL OF LIVER 2018; 7:231. [PMID: 30613437 PMCID: PMC6319937 DOI: 10.4172/2167-0889.1000231] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cholestatic liver injury is characterized by damage induced on the biliary tree and cholangiocytes, the cells lining the biliary tree, thus they are termed "cholangiopathies". Cholangiopathies include diseases such as Primary Biliary Cholangitis, Primary Sclerosing Cholangitis, Biliary Atresia and Cholangiocarcinoma. These pathologies lack viable therapies and most patients are diagnosed during late stage disease progression (with the exception of Biliary Atresia, which is found shortly after birth). The lack of therapies for these diseases has put a significant burden on the need for liver transplantation as this is the only indicative "cure" for cholangiopathies. The molecular mechanisms for cholangiopathies have been extensively studied; however, and unfortunately, the lack of effective biomarkers and therapeutics remains. In this review article we highlight the latest studies to investigate the molecular mechanisms regulating cholangiopathies and the potential therapeutics that might be discovered.
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Affiliation(s)
- Shohaib Virani
- Department of Medical Physiology, College of Medicine Texas A&M Health Science Center, Temple, Texas, USA
| | - Austin Akers
- Department of Internal Medicine, Baylor Scott & White Health, Texas, USA
| | - Kristen Stephenson
- Department of Internal Medicine, Baylor Scott & White Health, Texas, USA
| | - Steven Smith
- Department of Internal Medicine, Baylor Scott & White Health, Texas, USA
| | - Lindsey Kennedy
- Department of Medical Physiology, College of Medicine Texas A&M Health Science Center, Temple, Texas, USA
| | - Gianfranco Alpini
- Research, Central Texas Veterans Health Care System, Texas, USA
- Department of Medical Physiology, College of Medicine Texas A&M Health Science Center, Temple, Texas, USA
| | - Heather Francis
- Research, Central Texas Veterans Health Care System, Texas, USA
- Department of Medical Physiology, College of Medicine Texas A&M Health Science Center, Temple, Texas, USA
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Chua D, Chiow AKH, Ang TL, Wang LM. Malignant Transformation Arising Within Unusual and Rare Hepatic Lesions: Fibropolycystic Disease Form of Ductal Plate Malformation and Biliary Adenofibroma. Int J Surg Pathol 2018; 26:542-550. [PMID: 29464972 DOI: 10.1177/1066896918758172] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Cholangiocarcinoma is the second most common hepatobiliary cancer following hepatocellular carcinoma, and 20% to 25% are intrahepatic. We describe 2 cases of intrahepatic cholangiocarcinoma arising within unusual and rare hepatic lesions, fibropolycystic liver disease form of ductal plate malformation and biliary adenofibroma, whose association with malignancy is rarely reported in the literature.
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Affiliation(s)
- Darren Chua
- 1 Changi General Hospital SingHealth, Singapore, Singapore
| | | | | | - Lai Mun Wang
- 1 Changi General Hospital SingHealth, Singapore, Singapore
- 2 Ludwig Institute, University of Oxford Nuffield Department of Medicine, Oxford, England
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PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC. PLoS One 2018; 13:e0202942. [PMID: 30161167 PMCID: PMC6117000 DOI: 10.1371/journal.pone.0202942] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 08/13/2018] [Indexed: 02/07/2023] Open
Abstract
Background The adiponutrin (PNPLA3) p.I148M and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K variants represent major genetic risk factors for progressive liver injury in nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD) and chronic viral hepatitis. The aim of this study was to find out whether these variants have a detrimental impact on the progression of chronic liver disease in patients with prolonged cholestasis induced by primary sclerosing cholangitis (PSC). Methods We prospectively recruited 178 PSC patients (112 male, age range 17–75 years, 55 with liver cirrhosis, 94 with ulcerative colitis, 48 transplanted during follow-up). PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms were genotyped using dedicated TaqMan assays. Associations between genotypes, biochemical and clinical phenotypes were analyzed using contingency tables. Results Allele and genotype distribution of both variants were consistent with Hardy-Weinberg equilibrium. No significant differences in the genotype distribution of PNPLA3 (P = 0.90) or TM6SF2 (P = 0.72) were observed between patients with cirrhosis and patients without cirrhosis. Serum liver enzyme activities were not modified by the presence of PNPLA3 (ALT P = 0.88, AST P = 0.77) or TM6SF2 (ALT P = 0.92, AST P = 0.49) risk variants. Increasing number of risk alleles had no impact on serum liver enzyme activities, as demonstrated by a separate analysis of patients carrying 0 (n = 99), 1 (n = 64), 2 (n = 12) or 3 (n = 3) risk alleles (P>0.05). No impact of PNPLA3 or TM6SF2 risk variants was detectable in patients with PSC and ulcerative colitis, and none of the variants increased the odds of transplantation. Conclusions Neither PNPLA3 nor TM6SF2 polymorphisms seem to contribute significantly towards an increased risk for deterioration of liver function in patients with PSC. These results underscore the divergent mechanisms of liver damage in cholestatic conditions as compared to metabolic and viral liver diseases.
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Tse CS, Deepak P, De La Fuente J, Bledsoe AC, Larson JJ, Murray JA, Papadakis KA. Phenotype and Clinical Course of Inflammatory Bowel Disease With Co-existent Celiac Disease. J Crohns Colitis 2018; 12:973-980. [PMID: 29741603 DOI: 10.1093/ecco-jcc/jjy061] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 05/06/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Inflammatory bowel diseases, principally Crohn's disease and ulcerative colitis, and celiac disease are among the most common immune-mediated gastrointestinal diseases. We aim to elucidate the clinical course and outcomes of patients with concomitant inflammatory bowel disease and celiac disease, a unique population that remains scarcely studied to date. METHODS A retrospective matched case-control study of adults with co-existent inflammatory bowel disease [IBD] and celiac disease was performed at a tertiary referral institution in North America. Logistic regression and Kaplan-Meier curves compared disease characteristics and clinical outcomes of the two groups. RESULTS A total of 342 inflammatory bowel disease patients were included in this study, of whom 114 had co-existent celiac disease and 228 did not. Patients with co-existent inflammatory bowel disease and celiac disease had higher rates of primary sclerosing cholangitis [19.3% vs 5.7%; odds ratio, 4.4; 95% confidence interval, 2.1-9.4; p <0.001], extensive ulcerative colitis [78.1% vs 59.0%; odds ratio, 2.8; 95% confidence interval, 1.5-5.5; p =0.002], and family history of celiac disease [10.5% vs 3.5%; odds ratio 3.2; 95% confidence interval, 1.3-8.2; p =0.01], compared with patients without concomitant celiac disease. CONCLUSIONS Patients with inflammatory bowel disease with concomitant celiac disease have unique phenotypic features compared with non-celiac inflammatory bowel disease, with higher risks for colitis-related hospitalisations, extensive colitis, and primary sclerosing cholangitis. Increased recognition of co-existent IBD and celiac disease can prompt clinicians to investigate for concomitant disease sooner, particularly in patients with seemingly refractory disease.
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Affiliation(s)
- Chung Sang Tse
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Parakkal Deepak
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.,Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | | | - Adam C Bledsoe
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Joseph J Larson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Yang BR, Choi NK, Kim MS, Chun J, Joo SH, Kim H, Lee J. Prevalence of extraintestinal manifestations in Korean inflammatory bowel disease patients. PLoS One 2018; 13:e0200363. [PMID: 29990326 PMCID: PMC6039042 DOI: 10.1371/journal.pone.0200363] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 06/25/2018] [Indexed: 12/18/2022] Open
Abstract
Background The prevalence of inflammatory bowel disease (IBD) in South Korea is increasing. Although extraintestinal manifestations (EIMs) are an important factor in the clinical outcomes of IBD patients, EIMs have not yet been investigated in Korea. Thus, we conducted a cross-sectional study to assess the prevalence of EIMs in Korean IBD patients. Methods The 2014 claims data from the National Health Insurance System (NHIS) of Korea were used. IBD patients were identified by codes for Crohn disease (CD) and ulcerative colitis (UC) in the NHIS registration system for rare or intractable diseases. International Classification of Diseases, Tenth Edition codes were used to identify EIM cases. To estimate the prevalence of EIMs in the general population of Korea, we used national sample data. Standardized prevalence ratios (SPRs) were calculated to compare the prevalence rates of EIMs among IBD patients to those among the general population of Korea. Results A total of 13,925 CD patients and 29,356 UC patients were identified. CD and UC patients were different in terms of demographics and utilization of medication. Among the 17 EIMs investigated, pyoderma gangrenosum, osteomalacia, Sweet syndrome, and scleritis were observed in very few patients. The SPRs were greater than 1 for all EIMs. Aphthous stomatitis, rheumatoid arthritis, and osteoporosis were highly prevalent in both CD and UC patients, but the SPRs of the EIMs were not high. Conclusion The study confirmed that EIMs are more prevalent among IBD patients than among the general population of Korea. The prevalence of EIMs in IBD patients suggests the need for greater attention and effort in clinical practice.
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Affiliation(s)
- Bo Ram Yang
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Nam-Kyong Choi
- Department of Health Convergence, Ewha Womans University, Seoul, Republic of Korea
| | - Mi-Sook Kim
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jaeyoung Chun
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Joo
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyesung Kim
- Medical Affairs, Janssen Korea, Seoul, Republic of Korea
| | - Joongyub Lee
- School of Medicine, Inha University, Incheon, Republic of Korea
- Department of Prevention and Management, Inha University Hospital, Incheon, Republic of Korea
- * E-mail:
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Tse CS, Loftus EV, Raffals LE, Gossard AA, Lightner AL. Effects of vedolizumab, adalimumab and infliximab on biliary inflammation in individuals with primary sclerosing cholangitis and inflammatory bowel disease. Aliment Pharmacol Ther 2018; 48:190-195. [PMID: 29808485 DOI: 10.1111/apt.14829] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 03/28/2018] [Accepted: 05/08/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic biliary disease associated with inflammatory bowel disease (IBD) with no known cure. AIM To evaluate the effect of biological therapies on PSC progression in IBD patients. METHODS We performed a retrospective cohort study of 88 cases (75 unique patients with 12 patients treated >1 biologics) of IBD (48 ulcerative colitis, 24 Crohn's disease and 3 indeterminate colitis) with concomitant PSC who received biological therapy (42 infliximab, 19 adalimumab, 27 vedolizumab) between June 2002 and October 2017. Hepatic biochemistries were compared using the paired t-test (patients served as their own controls) ≤3 months before and 6-8 and 12-14 months after biological initiation. Radiographic information of biliary stenosis and liver fibrosis were obtained via abdominal ultrasound, abdominal magnetic resonance imaging and magnetic resonance elastography. RESULTS Use of adalimumab was associated with a significant decrease in alkaline phosphatase (ALP) after 6-8 months (P = 0.03; mean change -70 U/L, standard deviation [SD] 88 U/L) compared to vedolizumab (mean change +50 U/L, SD 142 U/L) or infliximab (mean change +37 U/L, SD 183 U/L) but the change was not significant after 12-14 months (P = 0.24). No significant decreases were observed with AST, ALT, total or direct bilirubin, elastography score or radiographic imaging of biliary tree dilation/strictures with any biological therapy after 6-8 or 12-14 months. CONCLUSIONS Current evidence suggests that biological therapies used for the treatment of IBD are not effective treatments for PSC. Further study is needed to elucidate any potential beneficial effect of adalimumab on PSC.
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Affiliation(s)
- C S Tse
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - E V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - L E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - A A Gossard
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - A L Lightner
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
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Tabibian JH, Bowlus CL. WITHDRAWN: Primary sclerosing cholangitis: A review and update. LIVER RESEARCH 2018. [DOI: 10.1016/j.livres.2017.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Fousekis FS, Theopistos VI, Katsanos KH, Tsianos EV, Christodoulou DK. Hepatobiliary Manifestations and Complications in Inflammatory Bowel Disease: A Review. Gastroenterology Res 2018; 11:83-94. [PMID: 29707074 PMCID: PMC5916631 DOI: 10.14740/gr990w] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Accepted: 03/12/2018] [Indexed: 12/12/2022] Open
Abstract
Liver and biliary track diseases are common extraintestinal manifestations of inflammatory bowel disease (IBD), reported both in Crohn’s disease and ulcerative colitis, and may occur at any time during the natural course of the disease. Their etiology is mainly related to pathophysiological changes induced by IBD, and secondary, due to drugs used in IBD. Fatty liver is considered as the most frequent hepatobiliary manifestation in IBD, while primary sclerosing cholangitis (PSC) is the most correlated hepatobiliary disorder and is more prevalent in patients with ulcerative colitis. PSC can cause serious complications from the liver, biliary tree, and gallbladder and can lead to liver failure. Less frequently, IBD-associated hepatobiliary manifestations include cholelithiasis, granulomatous hepatitis, portal vein thrombosis, IgG4-related cholangiopathy, pyogenic liver abscess, hepatic amyloidosis and primary biliary cirrhosis. Most of the drugs used for IBD treatment may cause liver toxicity. Methotrexate and thiopurines carry the higher risk for hepatotoxicity, and in many cases, dose adjustment may normalize the liver biochemical tests. Reactivation of hepatitis B and C virus during immunosuppressive use, especially during use of biological agents, is a major concern, and adequate screening, vaccination and prophylactic treatment is warranted.
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Affiliation(s)
- Fotios S Fousekis
- Department of Gastroenterology and Hepatology, Medical School of Ioannina, Greece
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