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Longitudinal analysis of transplant candidates with primary sclerosing cholangitis in an Asian liver transplant center. Eur J Gastroenterol Hepatol 2023; 35:480-487. [PMID: 36719819 DOI: 10.1097/meg.0000000000002516] [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] [Indexed: 02/01/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a rare disease in Asia, and few studies have investigated the disease in this ethnicity, particularly in wait-listed patients for liver transplantation (LT). We aimed to investigate the prognostic factors and outcomes of wait-listed patients with PSC in an Asian transplant center. METHODS Survival was retrospectively analyzed. RESULTS Eighteen (10 male and 8 female) wait-listed patients with PSC, with a median age at diagnosis of 44.5 years, were included. Compared with men, women had significantly higher aspartate aminotransferase to platelet ratio index scores (3.28 vs. 1.13; P = 0.012) and bilirubin levels (7.68 vs. 4.03 mg/dl; P = 0.043) and more often presented with decompensating events, including ascites [5 (63%) vs. 1 (10%); P = 0.043] and splenomegaly [8 (100%) vs. 4 (40%); P = 0.013]. Compared with the non-LT group, the LT group exhibited a superior survival rate for women ( P = 0.004) but not for men. In the univariable analysis, significant risk factors associated with overall survival included malignancies with a hazard ratio (95% confidence interval) of 5.53 (1.00-30.51) and esophageal varices (EV) [4.18 (1.05-16.61)], whereas female gender [25.00 (1.49-500.00)], LT [0.09 (0.01-0.80)] and EV [39.03 (2.92-521.96)] were indicated in the multivariable analysis. CONCLUSIONS For Asian wait-listed patients with PSC, EV and female gender were the risk factors related to overall survival, and LT was the protective factor. Our experiences suggested that LT brings more benefits in female patients. Strategies are needed to provide equivalent transplant benefits.
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Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, Schramm C, Trauner M. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761-806. [PMID: 35738507 DOI: 10.1016/j.jhep.2022.05.011] [Citation(s) in RCA: 146] [Impact Index Per Article: 48.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/16/2022] [Indexed: 02/07/2023]
Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
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Bhat P, Aabakken L. Role of Endoscopy in Primary Sclerosing Cholangitis. Clin Endosc 2020; 54:193-201. [PMID: 32380796 PMCID: PMC8039754 DOI: 10.5946/ce.2020.019-iden] [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: 01/07/2020] [Accepted: 03/23/2020] [Indexed: 11/24/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a progressive disease of the bile ducts that usually results in chronic liver disease often requiring liver transplantation. Endoscopy remains crucial to the care of these patients, although magnetic resonance cholangiopancreatography has replaced endoscopic retrograde cholangiopancreatography (ERCP) as the primary imaging modality for diagnosis. For detection of dysplasia or cholangiocarcinoma, ERCP with intraductal sampling remains compulsory. Moreover, dominant strictures play an important part in the disease development, and management by balloon dilatation or stenting could contribute to long-term prognosis. In addition, endoscopy offers management for adverse events such as bile leaks and anastomotic strictures after liver transplantation. Finally, the special phenotype of inflammatory bowel disease associated with PSC as well as the frequent occurrence of portal hypertension mandates close follow-up with colonoscopy and upper endoscopy. With the emergence of novel techniques, the endoscopist remains a key member of the multidisciplinary team caring for PSC patients.
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Affiliation(s)
- Purnima Bhat
- Gastroenterology and Hepatology Unit, Canberra Hospital, Canberra, Australia.,College of Health and Medicine, Australian National University, Canberra, Australia
| | - Lars Aabakken
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
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Duah A, Nkrumah KN, Tachi K. Non-invasive markers as predictors of oesophageal varices in cirrhotic patient in a teaching hospital in Ghana. Ghana Med J 2019; 53:142-149. [PMID: 31481810 PMCID: PMC6697776 DOI: 10.4314/gmj.v53i2.9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Introduction Oesophageal variceal (OV) bleeding is a potentially fatal consequence of portal hypertension in patients with liver cirrhosis. Upper GI endoscopy is recommended for screening for varices in cirrhotics for early detection and treatment, however, this is invasive. The purpose of this study was to assess the predictive values of the noninvasive tests in detecting the presence of OV. Methods A cross-sectional hospital-based study involving 149 patients with liver cirrhosis was carried out at the Korle-Bu Teaching Hospital from 1st November 2015 to 25th November 2016. Relevant clinical parameters assessed included Child-Pugh class, ascites and splenomegaly. Full blood count and liver function tests, abdominal ultrasound and gastroscopy were done for all the participants. Receiver operating characteristic curve was generated to determine the cut-off values for the best sensitivity, specificity, negative and positive predictive values of the variables (serum albumin, platelet count (PC), aspartate aminotransferase (AST)/alanine aminotransferase (ALT), PC/Spleen diameter( SD)) with regard to the presence of OV. Results On gastroscopy, 135 (90.60%) had OV and 14 patients (9.40%) had no OV. One hundred and eleven of the varices (82.22%) were large varices and the rest (17.78%) small varices. The overall mean of serum albumin, PC and PC/SD were not significant predictors of the presence of OV. However, the overall mean of AST/ALT significantly predicted the presence of OV. A PC/SD cut off value of ≤833.3 had 72.62% diagnostic accuracy for diagnosing all OV. Conclusion PC/SD cut-off could be used to screen cirrhotics for OV and treatment initiated in geographical areas lacking endoscopy facilities Funding None declared
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Affiliation(s)
- Amoako Duah
- Department of Medicine, St. Dominic Hospital, Akwatia, Ghana
| | - Kofi N Nkrumah
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Science, University of Ghana
| | - Kenneth Tachi
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Science, University of Ghana
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Chapman MH, Thorburn D, Hirschfield GM, Webster GGJ, Rushbrook SM, Alexander G, Collier J, Dyson JK, Jones DE, Patanwala I, Thain C, Walmsley M, Pereira SP. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut 2019; 68:1356-1378. [PMID: 31154395 PMCID: PMC6691863 DOI: 10.1136/gutjnl-2018-317993] [Citation(s) in RCA: 172] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 02/21/2019] [Accepted: 03/24/2019] [Indexed: 12/11/2022]
Abstract
These guidelines on the management of primary sclerosing cholangitis (PSC) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included medical representatives from hepatology and gastroenterology groups as well as patient representatives from PSC Support. The guidelines aim to support general physicians, gastroenterologists and surgeons in managing adults with PSC or those presenting with similar cholangiopathies which may mimic PSC, such as IgG4 sclerosing cholangitis. It also acts as a reference for patients with PSC to help them understand their own management. Quality of evidence is presented using the AGREE II format. Guidance is meant to be used as a reference rather than for rigid protocol-based care as we understand that management of patients often requires individual patient-centred considerations.
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Affiliation(s)
- Michael Huw Chapman
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Liver Unit, Royal Free London NHS Foundation Trust, London, UK
| | | | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, University Health Network and University of Toronto, Toronto, Canada
| | | | - Simon M Rushbrook
- Department of Hepatology, Norfolk and Norwich University Hospitals NHS Trust, Norwich, UK
| | | | | | - Jessica K Dyson
- Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - David Ej Jones
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - Imran Patanwala
- Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
- University of Liverpool, Liverpool, UK
| | | | | | - Stephen P Pereira
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Institute for Liver & Digestive Health, University College London, London, UK
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Non-Invasive Prediction of High-Risk Varices in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis. Am J Gastroenterol 2019; 114:446-452. [PMID: 30315285 DOI: 10.1038/s41395-018-0265-7] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Baveno-VI guidelines recommend that patients with compensated cirrhosis with liver stiffness by transient elastography (LSM-TE) <20 kPa and platelets >150,000/mm(3) do not need an esophagogastroduodenoscopy (EGD) to screen for varices, since the risk of having varices needing treatment (VNT) is <5%. It remains uncertain if this tool can be used in patients with cholestatic liver diseases (ChLDs): primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These patients may have a pre-sinusoidal component of portal hypertension that could affect the performance of this rule. In this study we evaluated the performance of Baveno-VI, expanded Baveno-VI (LSM-TE <25 kPa and platelets >110,000/mm(3)), and other criteria in predicting the absence of VNT. METHODS This was a multicenter cross-sectional study in four referral hospitals. We retrospectively analyzed data from 227 patients with compensated advanced chronic liver disease (cACLD) due to PBC (n = 147) and PSC (n = 80) that had paired EGD and LSM-TE. We calculated false negative rate (FNR) and number of saved endoscopies for each prediction rule. RESULTS Prevalence of VNT was 13%. Baveno-VI criteria had a 0% FNR in PBC and PSC, saving 39 and 30% of EGDs, respectively. In PBC the other LSM-TE-based criteria resulted in FNRs >5%. In PSC the expanded Baveno criteria had an adequate performance. In both conditions LSM-TE-independent criteria resulted in an acceptable FNR but saved less EGDs. CONCLUSIONS Baveno-VI criteria can be applied in patients with cACLD due to ChLDs, which would result in saving 30-40% of EGDs. Expanded criteria in PBC would lead to FNRs >5%.
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El Din Mohamed Abdo A, Mahmoud Mohy El Din K, El Din Saeed Bedewy E, Abdel Haleem Abo Elwafa R, Adel Abdel Aziz M. Plasma soluble CD 163 level as a marker of oesophageal varices in cirrhotic patients. ALEXANDRIA JOURNAL OF MEDICINE 2018. [DOI: 10.1016/j.ajme.2017.08.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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Tabibian JH, Ali AH, Lindor KD. Primary Sclerosing Cholangitis, Part 1: Epidemiology, Etiopathogenesis, Clinical Features, and Treatment. Gastroenterol Hepatol (N Y) 2018; 14:293-304. [PMID: 29991937 PMCID: PMC6034608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, idiopathic cholangiopathy that can progress to cirrhosis, end-stage liver disease, hepatobiliary cancer, and/or colorectal cancer. The course of PSC is often complicated by portal hypertension, symptoms of cholestasis, and recurrent bacterial cholangitis, among other conditions, with a consequent decrease in survival (median, approximately 20 years) and quality of life. The etiopathogenesis of PSC remains poorly understood, and, as such, pharmacotherapy has yet to be definitively established. Despite its rarity, PSC is the fifth leading indication for liver transplantation (LT) in the United States. Although the only intervention known to extend survival of patients with PSC, LT is costly and invasive, and recurrent PSC affects approximately 30% of LT recipients. Over the past several years, owing in part to progress in the understanding of PSC, novel pharmacotherapeutics have been developed, some of which are currently in the PSC clinical trial pipeline. Here, in the first of a 2-part series, we provide a review and update of the epidemiology, etiopathogenesis, clinical features, and treatment of PSC. The second part of the series will focus on cancer risk, prevention, and surveillance of PSC.
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Affiliation(s)
- James H Tabibian
- Dr Tabibian is an associate professor in the Geffen School of Medicine at UCLA in Los Angeles, California and director of endoscopy in the Department of Medicine at Olive View-UCLA Medical Center in Sylmar, California. Dr Ali is a research fellow in the Division of Gastroenterology and Hepatology at Mayo Clinic in Phoenix, Arizona. Dr Lindor is a professor of medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic and senior advisor to the provost at Arizona State University in Phoenix, Arizona
| | - Ahmad H Ali
- Dr Tabibian is an associate professor in the Geffen School of Medicine at UCLA in Los Angeles, California and director of endoscopy in the Department of Medicine at Olive View-UCLA Medical Center in Sylmar, California. Dr Ali is a research fellow in the Division of Gastroenterology and Hepatology at Mayo Clinic in Phoenix, Arizona. Dr Lindor is a professor of medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic and senior advisor to the provost at Arizona State University in Phoenix, Arizona
| | - Keith D Lindor
- Dr Tabibian is an associate professor in the Geffen School of Medicine at UCLA in Los Angeles, California and director of endoscopy in the Department of Medicine at Olive View-UCLA Medical Center in Sylmar, California. Dr Ali is a research fellow in the Division of Gastroenterology and Hepatology at Mayo Clinic in Phoenix, Arizona. Dr Lindor is a professor of medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic and senior advisor to the provost at Arizona State University in Phoenix, Arizona
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Noninvasive Methods of Predicting Large Esophageal Varices in Children With Intrahepatic Portal Hypertension. J Pediatr Gastroenterol Nutr 2018; 66:442-446. [PMID: 29176477 DOI: 10.1097/mpg.0000000000001841] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Esophageal variceal bleeding is a severe complication of portal hypertension. The standard diagnostic screening test and therapeutic procedure for esophageal varices (EV) is endoscopy, which is invasive in pediatric patients. This study aimed to evaluate the role of noninvasive parameters as predictors of large varices in children with intrahepatic portal hypertension. METHODS Participants included in this cross-sectional study underwent a screening endoscopy. Variceal size, red marks, and portal gastropathy were assessed and rated. Patients were classified into two groups: Group 1 (G1) with small or no varices and Group 2 (G2) with large varices. The population consisted of 98 children with no history of gastrointestinal (GI) bleeding, with a mean age of 8.9 ± 4.7 years. The main outcome evaluated was the presence of large varices. RESULTS The first endoscopy session revealed the presence of large varices in 32 children. The best noninvasive predictors for large varices were platelets (Area under the ROC Curve [AUROC] 0.67; 95% CI 0.57-0.78), the Clinical Prediction Rule (CPR; AUROC 0.65; 95% CI 0.54-0.76), and risk score (AUROC 0.66; 95% CI 0.56-0.76). The logistic regression model showed that children with a CPR value under 114 were 8.59 times more likely to have large varices. Risk scores higher than -1.2 also increased the likelihood of large varices (OR 6.09; P = 0.014), as did a platelet count/spleen size z score lower than 25 (OR 3.99; P = 0.043). The combination of these three tests showed a high negative predictive value. CONCLUSIONS The CPR, the risk score, and the platelet count/spleen size z score could be helpful in identifying cirrhotic children who may be eligible for endoscopy.
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Isayama H, Tazuma S, Kokudo N, Tanaka A, Tsuyuguchi T, Nakazawa T, Notohara K, Mizuno S, Akamatsu N, Serikawa M, Naitoh I, Hirooka Y, Wakai T, Itoi T, Ebata T, Okaniwa S, Kamisawa T, Kawashima H, Kanno A, Kubota K, Tabata M, Unno M, Takikawa H. Clinical guidelines for primary sclerosing cholangitis 2017. J Gastroenterol 2018; 53:1006-1034. [PMID: 29951926 PMCID: PMC8930933 DOI: 10.1007/s00535-018-1484-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 06/11/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is relatively rare disease and pathogenesis and methods of treatments were still not established. Then, we had conducted the making clinical guidelines to manage patients with PSC based on the literature review and expert opinions. These clinical guidelines were made for the medical doctors on the management of PSC, except child case of PSC. METHODS We had employed modified Delphi method. The production committee decided guidelines, strength of recommendations and evidence level after reviewed literatures systematically, and The Expert panel evaluated those. The Scientific Committee of the Japan Biliary Association (JBA) evaluated revised guidelines, and the Public comments were collected on web site of JBA. RESULTS We had made 16 guidelines about epidemiology/pathophysiology, diagnostics, therapy and prognosis. Also, we had made both diagnostic and therapeutic flow chart. CONCLUSIONS We hope that these guidelines will contribute to the improvement and development of the medical care of PSC.
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Affiliation(s)
- Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Susumu Tazuma
- Department of General Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Toshio Tsuyuguchi
- Department of Medicine and Gastroenterology, Chiba University, Chiba, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Suguru Mizuno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Yoshiki Hirooka
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinji Okaniwa
- Department of Gastroenterology, Iida Municipal Hospital, Nagano, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Komagome Metropolitan Hospital, Tokyo, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Atsushi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi Japan
| | - Keiichi Kubota
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Masami Tabata
- Department of Surgery, Matsusaka Central General Hospital, Matsusaka, Mie Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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Deneau MR, El-Matary W, Valentino PL, Abdou R, Alqoaer K, Amin M, Amir AZ, Auth M, Bazerbachi F, Broderick A, Chan A, Cotter J, Doan S, El-Youssef M, Ferrari F, Furuya KN, Gottrand M, Gottrand F, Gupta N, Homan M, Kamath BM, Kim KM, Kolho KL, Konidari A, Koot B, Iorio R, Ledder O, Mack C, Martinez M, Miloh T, Mohan P, O'Cathain N, Papadopoulou A, Ricciuto A, Saubermann L, Sathya P, Shteyer E, Smolka V, Tanaka A, Varier R, Venkat V, Vitola B, Vos MB, Woynarowski M, Yap J, Jensen MK. The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration. Hepatology 2017; 66:518-527. [PMID: 28390159 DOI: 10.1002/hep.29204] [Citation(s) in RCA: 139] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 02/07/2017] [Accepted: 04/04/2017] [Indexed: 12/14/2022]
Abstract
UNLABELLED There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518-527).
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Affiliation(s)
| | | | | | - Reham Abdou
- State University of New York Buffalo, Buffalo, NY
| | - Khaled Alqoaer
- Prince Salman North West Armed Forces Hospital, Tabuk, Saudi Arabia
| | - Mansi Amin
- University of California San Francisco, San Francisco, CA, and Texas Children's Hospital, Houston, TX
| | - Achiya Z Amir
- The Dana-Dwek Children's Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | - Marcus Auth
- Alder Hey Children's Hospital, Liverpool, UK
| | | | | | - Albert Chan
- University of Rochester Medical Center, Rochester, NY
| | | | | | | | | | - Katryn N Furuya
- Mayo Clinic, Rochester, MN.,Nemours Alfred I duPont Hospital For Children, Wilmington, DE
| | | | | | - Nitika Gupta
- Emory University School of Medicine, Atlanta, GA
| | | | | | | | | | - Anastasia Konidari
- University of Liverpool, Liverpool, and University of Manchester, Manchester, UK
| | - Bart Koot
- Academic Medical Centre, Amsterdam, The Netherlands
| | | | - Oren Ledder
- Shaare Zedek Medical Center, Jerusalem, Israel
| | - Cara Mack
- University of Colorado School of Medicine, Aurora, CO
| | - Mercedes Martinez
- Columbia University College of Physicians and Surgeons, New York, NY
| | - Tamir Miloh
- Texas Children's Hospital, Houston, TX, and Phoenix Children's Hospital, Phoenix, AZ
| | | | | | | | | | | | - Pushpa Sathya
- Memorial University, St. John's, Newfoundland and Labrador, Canada
| | | | | | | | - Raghu Varier
- Northwest Pediatric Gastroenterology LLC, Portland, OR
| | - Veena Venkat
- University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Miriam B Vos
- Emory University School of Medicine, Atlanta, GA
| | | | - Jason Yap
- University of Alberta, Edmonton, Alberta, Canada
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Colli A, Gana JC, Yap J, Adams‐Webber T, Rashkovan N, Ling SC, Casazza G. Platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices in people with chronic liver disease or portal vein thrombosis. Cochrane Database Syst Rev 2017; 4:CD008759. [PMID: 28444987 PMCID: PMC6478276 DOI: 10.1002/14651858.cd008759.pub2] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Current guidelines recommend screening of people with oesophageal varices via oesophago-gastro-duodenoscopy at the time of diagnosis of hepatic cirrhosis. This requires that people repeatedly undergo unpleasant invasive procedures with their attendant risks, although half of these people have no identifiable oesophageal varices 10 years after the initial diagnosis of cirrhosis. Platelet count, spleen length, and platelet count-to-spleen length ratio are non-invasive tests proposed as triage tests for the diagnosis of oesophageal varices. OBJECTIVES Primary objectives To determine the diagnostic accuracy of platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices of any size in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology. To investigate the accuracy of these non-invasive tests as triage or replacement of oesophago-gastro-duodenoscopy. Secondary objectives To compare the diagnostic accuracy of these same tests for the diagnosis of high-risk oesophageal varices in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology.We aimed to perform pair-wise comparisons between the three index tests, while considering predefined cut-off values.We investigated sources of heterogeneity. SEARCH METHODS The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, the Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), and Science Citation Index - Expanded (Web of Science) (14 June 2016). We applied no language or document-type restrictions. SELECTION CRITERIA Studies evaluating the diagnostic accuracy of platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices via oesophago-gastro-duodenoscopy as the reference standard in children or adults of any age with chronic liver disease or portal vein thrombosis, who did not have variceal bleeding. DATA COLLECTION AND ANALYSIS Standard Cochrane methods as outlined in the Cochrane Handbook for Diagnostic Test of Accuracy Reviews. MAIN RESULTS We included 71 studies, 67 of which enrolled only adults and four only children. All included studies were cross-sectional and were undertaken at a tertiary care centre. Eight studies reported study results in abstracts or letters. We considered all but one of the included studies to be at high risk of bias. We had major concerns about defining the cut-off value for the three index tests; most included studies derived the best cut-off values a posteriori, thus overestimating accuracy; 16 studies were designed to validate the 909 (n/mm3)/mm cut-off value for platelet count-to-spleen length ratio. Enrolment of participants was not consecutive in six studies and was unclear in 31 studies. Thirty-four studies assessed enrolment consecutively. Eleven studies excluded some included participants from the analyses, and in only one study, the time interval between index tests and the reference standard was longer than three months. Diagnosis of varices of any size. Platelet count showed sensitivity of 0.71 (95% confidence interval (CI) 0.63 to 0.77) and specificity of 0.80 (95% CI 0.69 to 0.88) (cut-off value of around 150,000/mm3 from 140,000 to 150,000/mm3; 10 studies, 2054 participants). When examining potential sources of heterogeneity, we found that of all predefined factors, only aetiology had a role: studies including participants with chronic hepatitis C reported different results when compared with studies including participants with mixed aetiologies (P = 0.036). Spleen length showed sensitivity of 0.85 (95% CI 0.75 to 0.91) and specificity of 0.54 (95% CI 0.46 to 0.62) (cut-off values of around 110 mm, from 110 to 112.5 mm; 13 studies, 1489 participants). Summary estimates for detection of varices of any size showed sensitivity of 0.93 (95% CI 0.83 to 0.97) and specificity of 0.84 (95% CI 0.75 to 0.91) in 17 studies, and 2637 participants had a cut-off value for platelet count-to-spleen length ratio of 909 (n/mm3)/mm. We found no effect of predefined sources of heterogeneity. An overall indirect comparison of the HSROCs of the three index tests showed that platelet count-to-spleen length ratio was the most accurate index test when compared with platelet count (P < 0.001) and spleen length (P < 0.001). Diagnosis of varices at high risk of bleeding. Platelet count showed sensitivity of 0.80 (95% CI 0.73 to 0.85) and specificity of 0.68 (95% CI 0.57 to 0.77) (cut-off value of around 150,000/mm3 from 140,000 to 160,000/mm3; seven studies, 1671 participants). For spleen length, we obtained only a summary ROC curve as we found no common cut-off between studies (six studies, 883 participants). Platelet count-to-spleen length ratio showed sensitivity of 0.85 (95% CI 0.72 to 0.93) and specificity of 0.66 (95% CI 0.52 to 0.77) (cut-off value of around 909 (n/mm3)/mm; from 897 to 921 (n/mm3)/mm; seven studies, 642 participants). An overall indirect comparison of the HSROCs of the three index tests showed that platelet count-to-spleen length ratio was the most accurate index test when compared with platelet count (P = 0.003) and spleen length (P < 0.001). DIagnosis of varices of any size in children. We found four studies including 277 children with different liver diseases and or portal vein thrombosis. Platelet count showed sensitivity of 0.71 (95% CI 0.60 to 0.80) and specificity of 0.83 (95% CI 0.70 to 0.91) (cut-off value of around 115,000/mm3; four studies, 277 participants). Platelet count-to-spleen length z-score ratio showed sensitivity of 0.74 (95% CI 0.65 to 0.81) and specificity of 0.64 (95% CI 0.36 to 0.84) (cut-off value of 25; two studies, 197 participants). AUTHORS' CONCLUSIONS Platelet count-to-spleen length ratio could be used to stratify the risk of oesophageal varices. This test can be used as a triage test before endoscopy, thus ruling out adults without varices. In the case of a ratio > 909 (n/mm3)/mm, the presence of oesophageal varices of any size can be excluded and only 7% of adults with varices of any size would be missed, allowing investigators to spare the number of oesophago-gastro-duodenoscopy examinations. This test is not accurate enough for identification of oesophageal varices at high risk of bleeding that require primary prophylaxis. Future studies should assess the diagnostic accuracy of this test in specific subgroups of patients, as well as its ability to predict variceal bleeding. New non-invasive tests should be examined.
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Affiliation(s)
- Agostino Colli
- A Manzoni Hospital ASST LeccoDepartment of Internal MedicineVia dell'Eremo, 9/11LeccoItaly23900
| | - Juan Cristóbal Gana
- Division of Pediatrics, Escuela de Medicina, Pontificia Universidad Católica de ChileGastroenterology and Nutrition Department85 LiraSantiagoRegion MetropolitanaChile8330074
| | - Jason Yap
- University of AlbertaDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Dept. of Pediatrics, Stollery Children's Hospital, Faculty of MedicineAberhart Centre 111402 University AveEdmontonABCanadaT6G 2J3
| | | | - Natalie Rashkovan
- Sunnybrook Health Sciences CentreDepartment of Neurology2075 Bayview ave., room A448TorontoONCanadaM4N 3M5
| | - Simon C Ling
- The Hospital for Sick ChildrenDivision of Gastroenterology, Hepatology and Nutrition555 University AvenueTorontoONCanadaM5G 1X8
| | - Giovanni Casazza
- Università degli Studi di MilanoDipartimento di Scienze Biomediche e Cliniche "L. Sacco"via GB Grassi 74MilanItaly20157
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Karsdal MA, Manon-Jensen T, Genovese F, Kristensen JH, Nielsen MJ, Sand JMB, Hansen NUB, Bay-Jensen AC, Bager CL, Krag A, Blanchard A, Krarup H, Leeming DJ, Schuppan D. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2015; 308:G807-30. [PMID: 25767261 PMCID: PMC4437019 DOI: 10.1152/ajpgi.00447.2014] [Citation(s) in RCA: 179] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Accepted: 03/04/2015] [Indexed: 02/06/2023]
Abstract
Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to 1) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies, 2) discuss selected pathological posttranslational modifications of ECM proteins resulting in altered functional (signaling) properties from the original structural proteins, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behavior. Key ECM components and their posttranslational modifications often harbor multiple domains with different signaling potential, in particular when modified during inflammation or wound healing. This signaling by the ECM should be considered a paracrine/endocrine function, as it affects cell phenotype, function, fate, and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and antifibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases.
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Affiliation(s)
- Morten A. Karsdal
- 1Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark; ,2University of Southern Denmark, SDU, Odense, Denmark;
| | | | | | | | | | | | | | | | | | - Aleksander Krag
- 3Department of Gastroenterology and Hepatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark;
| | - Andy Blanchard
- 4GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, United Kingdom;
| | - Henrik Krarup
- 5Section of Molecular Biology, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark;
| | | | - Detlef Schuppan
- 6Institute of Translational Immunology and Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany; ,7Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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Peñaloza-Posada MA, Pérez-Torres E, Pérez-Hernández JL, Higuera-de la Tijera F. Non-invasive parameters as predictors of high risk of variceal bleeding in cirrhotic patients. REVISTA MÉDICA DEL HOSPITAL GENERAL DE MÉXICO 2014. [DOI: 10.1016/j.hgmx.2014.09.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Abstract
Primary sclerosing cholangitis is the classic hepatobiliary manifestation of inflammatory bowel disease and is generally chronic and progressive. Patients frequently present with asymptomatic, anicteric cholestasis, but many develop progressive biliary strictures with time, leading to recurrent cholangitis, biliary cirrhosis, and end-stage liver disease. Medical treatment does not slow the progression of disease, and many patients need liver transplantation, after which recurrent disease is a risk. The increased incidence of hepatobiliary cancer, which is not related to the underlying severity of biliary fibrosis, is of particular concern. Risk of colorectal cancer is also increased in patients with coexistent inflammatory bowel disease. Mechanistic insights have arisen from studies of secondary sclerosing cholangitis, in which a similar clinical profile is associated with a specific cause, and genomic studies have elucidated potential disease-initiating pathways in the primary form. The close association between inflammatory bowel disease and primary sclerosing cholangitis underscores the need to further understand the role of environmental factors in generation of lymphocytes that are postulated to be retargeted, deleteriously, to the biliary tree. Treatment of primary sclerosing cholangitis is confined to supportive measures, but advances in pathobiology suggest that new stratified approaches will soon be available.
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Affiliation(s)
- Gideon M Hirschfield
- Centre for Liver Research, National Institute for Health Research Biomedical Research Unit, University of Birmingham, Birmingham, UK.
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Adami MR, Ferreira CT, Kieling CO, Hirakata V, Vieira SMG. Noninvasive methods for prediction of esophageal varices in pediatric patients with portal hypertension. World J Gastroenterol 2013; 19:2053-2059. [PMID: 23599624 PMCID: PMC3623982 DOI: 10.3748/wjg.v19.i13.2053] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2012] [Revised: 12/19/2012] [Accepted: 01/12/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate clinical and laboratory parameters for prediction of bleeding from esophageal varices (EV) in children with portal hypertension.
METHODS: Retrospective study of 103 children (mean age: 10.1 ± 7.7 years), 95.1% with intrahepatic portal hypertension. All patients had no history of bleeding and underwent esophagogastroduodenoscopy for EV screening. We recorded variceal size (F1, F2 and F3), red-color signs and portal gastropathy, according to the Japanese Research Society for Portal Hypertension classification. Patients were classified into two groups: with and without EV. Seven noninvasive markers were evaluated as potential predictors of EV: (1) platelet count; (2) spleen size z score, expressed as a standard deviation score relative to normal values for age; (3) platelet count to spleen size z score ratio; (4) platelets count to spleen size (cm) ratio; (5) the clinical prediction rule (CPR); (6) the aspartate aminotransferase to platelet ratio index (APRI); and (7) the risk score.
RESULTS: Seventy-one children had EV on first endoscopy. On univariate analysis, spleen size, platelets, CPR, risk score, APRI, and platelet count to spleen size z score ratio showed significant associations. The best noninvasive predictors of EV were platelet count [area under the receiver operating characteristic curve (AUROC) 0.82; 95%CI: 0.73-0.91], platelet: spleen size z score (AUROC 0.78; 95%CI: 0.67-0.88), CPR (AUROC 0.77; 95%CI: 0.64-0.89), and risk score (AUROC 0.77; 95%CI: 0.66-0.88). A logistic regression model was applied with EV as the dependent variable and corrected by albumin, bilirubin and spleen size z score. Children with a CPR < 114 were 20.7-fold more likely to have EV compared to children with CPR > 114. A risk score > -1.2 increased the likelihood of EV (odds ratio 7.47; 95%CI: 2.06-26.99).
CONCLUSION: Children with portal hypertension with a CPR below 114 and a risk score greater than -1.2 are more likely to have present EV. Therefore, these two tests can be helpful in selecting children for endoscopy.
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Hall P, Cash J. What is the real function of the liver 'function' tests? THE ULSTER MEDICAL JOURNAL 2012; 81:30-6. [PMID: 23536736 PMCID: PMC3609680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 08/24/2011] [Indexed: 11/09/2022]
Abstract
Liver enzymes are commonly used in the evaluation of patients with a range of diseases. Classically they are used to give information on whether a patient's primary disorder is hepatitic or cholestatic in origin. However, knowledge of enzyme ratios and pattern recognition allow much more information to be derived from these simple tests. This paper offers an insight to generalists on how to extractgreater information from these tests in order to improve theinvestigation and management of liver disease.
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Abstract
Current guidelines recommend that all cirrhotic patients should undergo screening endoscopy at diagnosis to identify patients with varices at high risk of bleeding who will benefit from primary prophylaxis. This approach places a heavy burden upon endoscopy units and the repeated testing over time may have a detrimental effect on patient compliance. Noninvasive identification of patients at highest risk for oesophageal varices would limit investigation to those most likely to benefit. Upper GI endoscopy is deemed to be the gold standard against which all other tests are compared, but is not without its limitations. Multiple studies have been performed assessing clinical signs and variables relating to liver function, variables relating to liver fibrosis, and also to portal hypertension and hypersplenism. Whilst some tests are clearly preferable to patients, none appear to be as accurate as upper GI endoscopy in the diagnosis of oesophageal varices. The search for noninvasive tests continues.
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Current world literature. Curr Opin Rheumatol 2010; 23:125-30. [PMID: 21124095 DOI: 10.1097/bor.0b013e3283422cce] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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