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1
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Meng X, Peng J, Wei H. Etiology and Clinical Features of Secondary Sclerosing Cholangitis: A Single-Center Retrospective Study From 2016 to 2024. JGH Open 2025; 9:e70122. [PMID: 39989845 PMCID: PMC11845274 DOI: 10.1002/jgh3.70122] [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: 12/10/2024] [Revised: 02/05/2025] [Accepted: 02/09/2025] [Indexed: 02/25/2025]
Abstract
Aims Secondary sclerosing cholangitis (SSC) is a rare progressive biliary disease. We aimed to analyze the underlying causes, treatment approaches, and prognosis of SSC in order to enhance awareness of this disease. Methods A retrospective analysis was conducted on patients diagnosed with SSC in a single tertiary center in China between October 2016 and March 2024, focusing on the etiology, treatment modalities, and follow-up outcomes. Clinical outcomes were compared to patients with primary sclerosing cholangitis during the same period. Results A total of 21 patients were included in the study, with a median age of 42 (interquartile range 34, 57). The primary causes of SSC included surgical injury (seven cases, 33.3%) and drug-induction (six cases, 28.6%). Eight patients (38.1%) underwent ERCP, six patients (28.6%) received PTCD, and two patients (9.5%) underwent choledochoscopic bile duct dilation or stone extraction.Median follow-up time was 13 (interquartile range 10, 35) months, during which five patients (23.8%) died and five patients (23.8%) underwent liver transplants.Comparison of patients who received biliary decompression interventions and patients who did not revealed no significant difference in prognosis (p = 0.45). The median time of transplant-free survival was 35 months in the SSC group compared with 67 months in the PSC group. A trend toward a worse prognosis was observed in SSC compared to PSC (p = 0.13). Conclusions SSC is a complex disease with varied etiologies and poor prognosis, particularly when caused by bile duct surgical trauma. Bile duct decompression like ERCP does not offer long-term survival benefits. SSC exhibited a trend towards a less favorable prognosis compared to PSC.
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Affiliation(s)
- Xiangchen Meng
- Department of Gastroenterology, Beijing Friendship HospitalCapital Medical UniversityBeijingChina
| | - Jiafei Peng
- Department of Gastroenterology, Beijing Friendship HospitalCapital Medical UniversityBeijingChina
- Capital Medical UniversityBeijingChina
| | - Hongtao Wei
- Department of Gastroenterology, Beijing Friendship HospitalCapital Medical UniversityBeijingChina
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2
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Alsharif NM, Souleiman MM, Gunaseelan L, Big C. AIDS-Associated Cryptosporidial and Cytomegalovirus Cholangiopathy. Cureus 2024; 16:e63963. [PMID: 39104976 PMCID: PMC11299468 DOI: 10.7759/cureus.63963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2024] [Indexed: 08/07/2024] Open
Abstract
Acquired immune deficiency syndrome (AIDS)-associated cholangiopathy is a biliary tract condition seen in AIDS patients who are severely immunosuppressed, contributing to significant mortality in this population, even in developed countries with access to highly active antiretroviral therapy (HAART). We discuss a thirty-six-year-old human immunodeficiency virus (HIV)-positive male, non-compliant with HAART therapy, who presented with a one-year history of weight loss, persistent fatigue, and chronic diarrhea, which had worsened significantly in the past few weeks. Routine laboratory studies on presentation indicated elevated liver enzymes and alkaline phosphatase, a CD4 count of 2 cells/mm3, and a high HIV RNA count of 8.8 million. Imaging via CT of the abdomen and pelvis and ultrasound of the abdomen both displayed thickening and edema in the gallbladder without evidence of gallstones, raising concerns of acalculous cholecystitis. The patient subsequently decompensated, requiring intravenous vasopressors to maintain hemodynamic stability, broad-spectrum antibiotics, and resumption of antiretroviral therapy. Biliary fluid drainage was performed, and Cryptosporidium and cytomegalovirus (CMV) were detected via polymerase chain reaction (PCR) testing. The diagnosis of AIDS cholangiopathy was established; however, the patient's diarrhea worsened upon the introduction of tube feeds. Despite ongoing antimicrobial treatment, the patient developed a fever of 101.4°F, became asystolic and subsequently passed away. This case highlights the diagnostic, management, and therapeutic challenges of AIDS cholangiopathy. Also, it underscores the importance of thorough investigation into even mild or intermittent diarrhea and abnormal liver function tests in all HIV-infected patients, particularly in severely immunosuppressed patients. AIDS cholangiopathy should be considered in AIDS patients with diarrhea and abnormal liver function tests, irrespective of age, due to its associated morbidity across all age groups. Laboratory investigations often reveal markedly elevated alkaline phosphatase, gamma-glutamyltransferase, and mild to moderate liver enzyme elevations as hallmark findings of AIDS cholangiopathy. Ultrasonography is the first-line screening modality of AIDS cholangiopathy. Cryptosporidium parvum is the most common infectious etiology of AIDS cholangiopathy and can be identified by DNA-based polymerase chain reaction (PCR) testing of the stool or biliary fluid or acid-fast staining of stool specimens. Early detection of HIV infection and the prompt initiation and adherence to highly active antiretroviral therapy (HAART), which helps with maintaining a normal CD4 count and a low HIV viral load through HAART therapy, thereby significantly reducing the risk of developing AIDS cholangiopathy in HIV patients.
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Affiliation(s)
- Nada M Alsharif
- Internal Medicine, Corewell Health Dearborn Hospital, Dearborn, USA
| | | | | | - Cecilia Big
- Infectious Disease, Corewell Health Dearborn Hospital, Dearborn, USA
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3
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Mínguez A, Conde I, Montón C, Gonzalez L, Pascual S, Antón MD, Palau A, Forés A, Gisbert C, Ojeda A, Girona E, Di Maira T, Berenguer M. Primary Sclerosing Cholangitis: Gender Effects in Valencia's Low-Prevalence Region. Dig Dis Sci 2024; 69:1863-1871. [PMID: 38517562 DOI: 10.1007/s10620-024-08368-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 02/22/2024] [Indexed: 03/24/2024]
Abstract
BACKGROUND AND AIMS Recent studies point out to epidemiological changes in primary sclerosing cholangitis (PSC). Our aims were to determine in PSC patients followed in several centers in a Mediterranean geographic area: (i) changes in baseline features and (ii) effect of gender on clinical course. METHODS Retrospective multicenter study of PSC patients treated in 8 hospitals in a Mediterranean area between 2000 and 2021. Charts were reviewed compiling demographic, clinical, radiological, and histological variables. RESULTS Cohort of 112 PSC patients included, 42% women, 70% diagnosed after 2010. Women were increasingly diagnosed in recent cohorts. The median time from diagnosis to the combined endpoint liver transplantation (Lt) and/or death was 6.9 years. Asthenia at diagnosis (p = 0.009) was associated with lower transplant-free survival, while diagnosis before 2005 was associated with greater LT-free survival (p < 0.001). By Cox regression, LT-free survival was not influenced by age, sex, or cirrhosis at the time of diagnosis. Women were found to have less jaundice at diagnosis (2 vs 14%; p = 0.013), higher prevalence of ANA antibodies (43.9 vs 15.7%; p = 0.003), and lower GGT levels at diagnosis (GGT 123 vs 209U/L; p = 0.014) than men. CONCLUSION In an area traditionally considered to have low prevalence, the prevalence of affected women surpasses expectations based on existing literature. There appear to be gender-related variations in the presentation of the condition, highlighting the need for confirmation through larger-scale studies.
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Affiliation(s)
- Alejandro Mínguez
- Universitary and Politecnic Hospital La Fe, 46007, Valencia, CP, Spain.
| | - Isabel Conde
- Universitary and Politecnic Hospital La Fe, 46007, Valencia, CP, Spain
- Hepatology and Liver Transplant Unit, IIS La Fe & CIBER-EHD, Universitary and Politecnic Hospital La Fe, Valencia, Spain
| | - Cristina Montón
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, 46410, Valencia, Spain
| | - Lara Gonzalez
- General University Hospital of Valencia, Valencia, Spain
| | - Sonia Pascual
- Hepatology and Liver Transplant Unit/HGU Dr. Balmis, Alicante, Spain
| | | | - Antonio Palau
- General University Hospital of Castellón, Castellon de La Plana, Spain
| | - Ana Forés
- General University Hospital of Castellón, Castellon de La Plana, Spain
| | - Concha Gisbert
- Digestive Medicine Hospital Arnau de Vilanova, Valencia, Spain
| | - Asunción Ojeda
- Digestive Medicine, General University Hospital of Elche, Alicante, Spain
| | - Eva Girona
- Digestive Medicine, General University Hospital of Elche, Alicante, Spain
| | - Tommaso Di Maira
- Universitary and Politecnic Hospital La Fe, 46007, Valencia, CP, Spain
- Hepatology and Liver Transplant Unit, IIS La Fe & CIBER-EHD, Universitary and Politecnic Hospital La Fe, Valencia, Spain
| | - Marina Berenguer
- Universitary and Politecnic Hospital La Fe, 46007, Valencia, CP, Spain
- Hepatology and Liver Transplant Unit, IIS La Fe & CIBER-EHD, Universitary and Politecnic Hospital La Fe, Valencia, Spain
- Department of Medicina, University of Valencia, Valencia, Spain
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Horwich BH, Dieterich DT. Phenotypes of Primary Sclerosing Cholangitis and Differential Diagnosis. Clin Liver Dis 2024; 28:143-155. [PMID: 37945155 DOI: 10.1016/j.cld.2023.07.006] [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 is a heterogenous immune-mediated disorder characterized by chronic inflammation and stricturing of the bile ducts. Though the driving pathophysiologic mechanisms remain elusive, there are several observed clinical phenotypes of the disease. The distribution of bile duct involvement, presence of concomitant inflammatory bowel disease, significant infiltration of IgG4-positive plasma cells, and overlapping features with other autoimmune disease has significant implications for prognosis and treatment. As there remains no pathognomonic finding for primary sclerosing cholangitis, a broad differential diagnosis and extensive evaluation of other underlying causes is critical to appropriate management.
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Affiliation(s)
- Brian H Horwich
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, PO Box 1076, New York, NY 10029, USA
| | - Douglas T Dieterich
- Division of Liver Diseases, Institute for Liver Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, Annenberg 5-04, New York, NY 10029, USA.
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5
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Ceccherini E, Michelucci E, Signore G, Coco B, Zari M, Bellini M, Brunetto MR, Cecchettini A, Rocchiccioli S. The Clinical Utility of the Saliva Proteome in Rare Diseases: A Pilot Study for Biomarker Discovery in Primary Sclerosing Cholangitis. J Clin Med 2024; 13:544. [PMID: 38256678 PMCID: PMC10816894 DOI: 10.3390/jcm13020544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/08/2024] [Accepted: 01/16/2024] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory liver disease characterized by biliary strictures and cholestasis. Due to the lack of effective serological indicators for diagnosis and prognosis, in the present study, we examined the potentiality of the saliva proteome to comprehensively screen for novel biomarkers. METHODS Saliva samples of PSC patients and healthy controls were processed and subsequently analyzed using a liquid chromatography-tandem mass spectrometry technique. A bioinformatic approach was applied to detect the differentially expressed proteins, their related biological functions and pathways, and the correlation with the clinical evidence in order to identify a possible marker for the PSC group. RESULTS We identified 25 differentially expressed proteins in PSC patients when compared to the healthy control group. Among them, eight proteins exhibited area under the curve values up to 0.800, suggesting these saliva proteins as good discriminators between the two groups. Multiple positive correlations were also identified between the dysregulated salivary proteins and increased serum alkaline phosphatase levels and the presence of ulcerative colitis. Pathway analysis revealed significant enrichments in the immune system, neutrophil degranulation, and in the interleukine-17 signaling pathway. CONCLUSION We demonstrated the potentiality of saliva as a useful biofluid to obtain a fingerprint of the pathology, suggesting disulfide-isomerase A3 and peroxiredoxin-5 as the better discriminating proteins in PSC patients. Hence, analysis of saliva proteins could become, in future, a useful tool in the screening of patients with suspected PSC.
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Affiliation(s)
- Elisa Ceccherini
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
| | - Elena Michelucci
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
- Institute of Chemistry of Organometallic Compounds, National Research Council, 56124 Pisa, Italy
| | - Giovanni Signore
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
- Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy
| | - Barbara Coco
- Hepatology Unit, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy; (B.C.); (M.R.B.)
| | - Michela Zari
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy; (M.Z.); (M.B.)
| | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy; (M.Z.); (M.B.)
| | - Maurizia Rossana Brunetto
- Hepatology Unit, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy; (B.C.); (M.R.B.)
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Antonella Cecchettini
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Silvia Rocchiccioli
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
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Stahl K, Klein F, Voigtländer T, Großhennig A, Book T, Müller T, Wree A, Kuellmer A, Weigt J, Dechene A, Wedi E, Kandulski A, Lange CM, Holzwart D, von Witzendorff D, Ringe KI, Wedemeyer H, Heidrich B. BISCIT: Biliary interventions in critically ill patients with secondary sclerosing cholangitis-a study protocol for a multicenter, randomized, controlled parallel group trial. Trials 2023; 24:247. [PMID: 37004078 PMCID: PMC10067228 DOI: 10.1186/s13063-023-07260-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 03/17/2023] [Indexed: 04/03/2023] Open
Abstract
BACKGROUND Progress of cholangitis to cholangiosepsis is a frequent observation in patients with secondary sclerosing cholangitis in critically ill patients (SSC-CIP). Adequate biliary drainage may reduce episodes of cholangiosepsis and therefore stabilize liver function and improve survival. The primary objective of the BISCIT study is to demonstrate that scheduled biliary interventions will reduce incidence of cholangiosepsis, liver transplantation, or death in patients with SSC-CIP. METHODS A total of 104 patients will be randomized at ten study sites. Patients with SSC-CIP, confirmed by endoscopic retrograde cholangiography (ERC), will be randomized 1:1 either in the intervention group which will be treated with scheduled biliary interventions (i.e., therapeutic ERC) every 8 weeks for 6 months or in the control group which will receive standard of care. The randomization will be stratified by center. The composite primary efficacy endpoint is defined as (1) occurrence of death, (2) necessity of liver transplantation, or (3) occurrence of cholangiosepsis within 6 months following randomization. DISCUSSION Prospective evaluation of endoscopic treatment procedures is urgently needed to establish an evidence-based therapeutic treatment algorithm in SSC-CIP. A positive trial result could change the current standard of care for patients with SSC-CIP. The results of this study will be disseminated through presentations at international congresses, workshops, and peer-reviewed publications. TRIAL REGISTRATION The trial was registered at ClinicalTrials.gov (NCT05396755, date of registration: May 31, 2022, last update: May 31, 2022).
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Affiliation(s)
- Klaus Stahl
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Strasse 1, 30625, Hannover, Germany.
| | - Friederike Klein
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Strasse 1, 30625, Hannover, Germany
| | - Torsten Voigtländer
- Department of Gastroenterology, Clementinenkrankenhaus Hannover, Hannover, Germany
| | - Anika Großhennig
- Department of Biostatistics, Hannover Medical School, Hannover, Germany
| | - Thorsten Book
- Department of Gastroenterology, Clementinenkrankenhaus Hannover, Hannover, Germany
| | - Tobias Müller
- Department of Hepatology and Gastroenterology, Charite University Medicine Berlin, Campus Charite Mitte/Campus Virchow Clinic, Berlin, Germany
| | - Alexander Wree
- Department of Hepatology and Gastroenterology, Charite University Medicine Berlin, Campus Charite Mitte/Campus Virchow Clinic, Berlin, Germany
| | - Armin Kuellmer
- Clinic for Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, University Hospital Freiburg, Freiburg, Germany
| | - Jochen Weigt
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
| | - Alexander Dechene
- Department of Gastroenterology and Endocrinology, Hospital Nurnberg, Nurnberg, Germany
| | - Edris Wedi
- Department of Gastroenterology, Gastro-Oncology and Interventional Endoscopy, Sana Hospital Offenbach, Offenbach, Germany
| | - Arne Kandulski
- Department of Gastroenterology, Endocrinology, Infectious Diseases and Rheumatology, University Hospital Regensburg, Regensburg, Germany
| | - Christian M Lange
- Department of Gastroenterology and Hepatology, University Hospital Munich (LMU), Munich, Germany
| | - Dennis Holzwart
- Department of Biostatistics, Hannover Medical School, Hannover, Germany
| | - Dorothee von Witzendorff
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Strasse 1, 30625, Hannover, Germany
| | - Kristina I Ringe
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
- Zentrum Klinische Studien (ZKS), Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Strasse 1, 30625, Hannover, Germany
| | - Benjamin Heidrich
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Strasse 1, 30625, Hannover, Germany
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7
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Takahashi K, Ohyama H, Takiguchi Y, Sekine Y, Toyama S, Yamada N, Sugihara C, Kan M, Ouchi M, Nagashima H, Iino Y, Kusakabe Y, Okitsu K, Ohno I, Kato N. Secondary Sclerosing Cholangitis After Emphysematous Cholecystitis. ACG Case Rep J 2023; 10:e01016. [PMID: 36968126 PMCID: PMC10036046 DOI: 10.14309/crj.0000000000001016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 02/21/2023] [Indexed: 03/24/2023] Open
Abstract
A 64-year-old woman was diagnosed with emphysematous cholecystitis. An open cholecystectomy was performed immediately. After the cholecystectomy, jaundice and multiple bile duct strictures that were not present preoperatively appeared. The patient was diagnosed with sclerosing cholangitis secondary to emphysematous cholecystitis. Endoscopic biliary stenting and endoscopic biliary balloon dilatation were performed. However, jaundice did not improve. She developed candidemia 75 days after cholecystectomy. The patient died of multiple organ failures 92 days after cholecystectomy. Although rare, secondary sclerosing cholangitis occurred after emphysematous cholecystitis, and endoscopic treatment was ineffective in this case.
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Affiliation(s)
- Koji Takahashi
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
- Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroshi Ohyama
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yuichi Takiguchi
- Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yu Sekine
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shodai Toyama
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Nana Yamada
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Chihei Sugihara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Motoyasu Kan
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Mayu Ouchi
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroki Nagashima
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yotaro Iino
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yuko Kusakabe
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kohichiroh Okitsu
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Izumi Ohno
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
- Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
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8
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Morgan MA, Khot R, Sundaram KM, Ludwig DR, Nair RT, Mittal PK, Ganeshan DM, Venkatesh SK. Primary sclerosing cholangitis: review for radiologists. Abdom Radiol (NY) 2023; 48:136-150. [PMID: 36063181 PMCID: PMC9852001 DOI: 10.1007/s00261-022-03655-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/13/2022] [Accepted: 08/15/2022] [Indexed: 01/22/2023]
Abstract
Primary sclerosing cholangitis is a rare chronic inflammatory disease affecting the bile ducts, which can eventually result in bile duct strictures, cholestasis and cirrhosis. Patients are often asymptomatic but may present with clinical features of cholestasis. Imaging plays an important role in the diagnosis and management. This review covers the pathophysiology, clinical features, imaging findings as well as methods of surveillance and post-transplant appearance.
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Affiliation(s)
- Matthew A. Morgan
- Department of Radiology, University of Pennsylvania Health System, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA, USA
| | - Rachita Khot
- Radiology and Medical Imaging, University of Virginia Health, 1215 Lee Street, Charlottesville, VA, USA
| | - Karthik M. Sundaram
- Department of Radiology, University of Pennsylvania Health System, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA, USA
| | - Daniel R. Ludwig
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, Saint Louis, MO, USA
| | - Rashmi T. Nair
- Department of Radiology, University of Kentucky, 800 Rose Street, Room HX 313B, Lexington, KY 40536-0293, USA
| | - Pardeep K. Mittal
- Medical College of Georgia at Augusta University, 1120 15th street BA −1411, Augusta, GA 30912, USA
| | - Dhakshina M. Ganeshan
- The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Unit 1473, Houston, TX 77030, USA
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Ludwig DR, Anderson MA, Itani M, Sharbidre KG, Lalwani N, Paspulati RM. Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis. Abdom Radiol (NY) 2023; 48:151-165. [PMID: 35585354 PMCID: PMC9116710 DOI: 10.1007/s00261-022-03551-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 05/01/2022] [Accepted: 05/02/2022] [Indexed: 01/21/2023]
Abstract
Sclerosing cholangitis is a chronic cholestatic disease characterized by stricturing, beading, and obliterative fibrosis of the bile ducts. Sclerosing cholangitis is considered primary (PSC) if no underlying etiology is identified or secondary (SSC) if related to another identifiable cause. In this article, we will review the clinical features, pathogenesis, diagnosis, and imaging findings of PSC and SSC, with an emphasis on features that may aid in the distinction of these entities. We will also discuss various etiologies of SSC including recurrent pyogenic cholangitis, other infectious etiologies, ischemic damage, toxic insults, and immunologic, congenital, and miscellaneous causes, highlighting the unique imaging findings and clinical context of each diagnosis.
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Affiliation(s)
- Daniel R. Ludwig
- grid.4367.60000 0001 2355 7002Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, Saint Louis, MO 63110 USA
| | - Mark A. Anderson
- grid.38142.3c000000041936754XDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA
| | - Malak Itani
- grid.4367.60000 0001 2355 7002Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, Saint Louis, MO 63110 USA
| | - Kedar G. Sharbidre
- grid.265892.20000000106344187Department of Radiology, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Neeraj Lalwani
- grid.224260.00000 0004 0458 8737Department of Radiology, Virginia Commonwealth University, Richmond, VA USA
| | - Raj M. Paspulati
- grid.67105.350000 0001 2164 3847Department of Radiology, Case Western Reserve University, Cleveland, OH USA
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10
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Wongtanasarasin W. Cholestatic liver injury: A rare but fatal complication during and after COVID-19 infection. World J Virol 2022; 11:435-442. [PMID: 36483106 PMCID: PMC9724201 DOI: 10.5501/wjv.v11.i6.435] [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: 08/09/2022] [Revised: 09/21/2022] [Accepted: 10/19/2022] [Indexed: 11/23/2022] Open
Abstract
The 2019 coronavirus disease (COVID-19), resulting from the severe acute respiratory syndrome 2 virus, has transformed our globe and provided a new perspective on respiratory tract infections. However, COVID-19 would not be recognized as a condition restricted to only pneumonia. This narrative review was conducted by searching manuscripts in several databases, including PubMed/ MEDLINE, Web of Science, and Reference Citation Analysis, from December 2019 to July 2022. Many studies have revealed a broad spectrum of potential systemic symptoms, including biliary complications. Although biliary injury has been observed in a very low proportion of COVID-19 patients, it is associated with increased mortalities and long-term morbidities. We identify a cholangiopathy condition in individuals during infection and after recovering from severe COVID-19, defined by a significant increase in serum alkaline phosphatase and signs of bile duct injury. Understanding the pathogeneses behind this condition would help us develop new techniques to prevent these complications. This review thoroughly discusses and summarizes the current information regarding COVID-19-associated cholangiopathy. In addition, the possible explanations for COVID-19-associated cholangiopathy are presented. Since the exact pathogenesis may not be concluded, this review could provide relevant information to encourage additional investigations shortly.
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Affiliation(s)
- Wachira Wongtanasarasin
- Department of Emergency Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Emergency Medicine, UC Davis School of Medicine, Sacramento, CA 95817, United States
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Interleukin-33 deficiency prevents biliary injuries and repairments caused by Clonorchis sinensis via restraining type 2 cytokines. Parasit Vectors 2022; 15:386. [PMID: 36271450 PMCID: PMC9587592 DOI: 10.1186/s13071-022-05490-6] [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: 02/15/2022] [Accepted: 09/16/2022] [Indexed: 11/10/2022] Open
Abstract
Background Clonorchiasis caused by Clonorchis sinensis is a zoonotic parasitic disease characterized by cholangitis, biliary proliferation, biliary fibrosis, and even cholangiocarcinoma. Our previous study showed that the expression of interleukin (IL)-33 is increased in both humans and mice infected by C. sinensis, suggesting that IL-33 is potentially involved in the pathogenesis of clonorchiasis. However, the roles and potential mechanism of IL-33 underlying remain unknown. Methods Wild-type (WT) and IL-33 knockout (KO) mice (BALB/c female mice) were orally infected with 45 metacercariae of C. sinensis for 8 weeks. Biliary injuries and fibrosis were extensively evaluated. Hepatic type II cytokines (IL-4, IL-13, and IL-10) were detected by ELISA. Results For wild-type mice, we found that the mice infected with C. sinensis showed severe biliary injuries and fibrosis compared with the normal mice that were free from worm infection. In addition, the levels of type II cytokines such as IL-4, IL-13, and IL-10 in infected wild-type mice were significantly higher than in the control mice without infection (P < 0.05). However, IL-33 deficiency (IL-33 KO) prevents the augmentation of biliary injuries and fibrosis caused by C. sinensis infection. Furthermore, the increased levels of these type II cytokines induced by worm infection were also reversed in IL-33 KO mice. Conclusion Our present study demonstrates that IL-33 contributes to the pathogenesis of C. sinensis-induced biliary injuries and repair, which can potentially orchestrate type 2 responses. These findings highlight the pathophysiological role of IL-33 in the progression of clonorchiasis. Supplementary Information The online version contains supplementary material available at 10.1186/s13071-022-05490-6.
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12
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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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13
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Holm M, Joenväärä S, Saraswat M, Tohmola T, Saarela T, Tenca A, Arola J, Renkonen R, Färkkilä M. Quantitative bile and serum proteomics for the screening and differential diagnosis of primary sclerosing cholangitis. PLoS One 2022; 17:e0272810. [PMID: 36006970 PMCID: PMC9409575 DOI: 10.1371/journal.pone.0272810] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 07/26/2022] [Indexed: 11/19/2022] Open
Abstract
Background
Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by biliary strictures, cholestasis, and a markedly increased risk of cholangiocarcinoma. New markers for the screening and differential diagnosis of PSC are needed. In this pilot study, we have analyzed both the bile and serum proteomic profiles of 80 PSC patients and non-PSC controls (n = 6 for bile and n = 18 for serum).
Aim
The aim of this study was to discover candidates for new biomarkers for the differential diagnosis of PSC.
Methods
Bile and serum samples were processed and subsequently analyzed using ultra performance liquid chromatography-ultra definition mass spectrometry (UPLC-UDMSE). Further analysis included statistical analyses such as receiver operating characteristic curve analysis as well as pathway analysis using Ingenuity Pathway Analysis.
Results and conclusions
In bile, we discovered 64 proteins with significantly different levels between the groups, with fold changes of up to 129. In serum, we discovered 112 proteins with significantly different levels. Receiver operating characteristic curve analysis found multiple proteins with high area under the curve values, up to 0.942, indicating that these serum proteins are of value as new non-invasive classifiers of PSC. Pathway analysis revealed multiple canonical pathways that were enriched in the dataset, which have roles in bile homeostasis and metabolism. We present several serum proteins that could serve as new blood-based markers for the diagnosis of PSC after further validation. The measurement of serum levels of these proteins could be of use in the screening of patients with suspected PSC.
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Affiliation(s)
- Matilda Holm
- Transplantation Laboratory, Haartman Institute, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- * E-mail:
| | - Sakari Joenväärä
- Transplantation Laboratory, Haartman Institute, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- HUSLAB, Helsinki University Hospital, Helsinki, Finland
| | - Mayank Saraswat
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Tiialotta Tohmola
- Transplantation Laboratory, Haartman Institute, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Toni Saarela
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Andrea Tenca
- Clinic of Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Johanna Arola
- HUSLAB, Helsinki University Hospital, Helsinki, Finland
| | - Risto Renkonen
- Transplantation Laboratory, Haartman Institute, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- HUSLAB, Helsinki University Hospital, Helsinki, Finland
| | - Martti Färkkilä
- Clinic of Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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14
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Pria HD, Torres US, Faria SC, Velloni FG, Caiado AH, Tiferes DA, D'Ippolito G. Practical Guide for Radiological Diagnosis of Primary and Secondary Sclerosing Cholangitis. Semin Ultrasound CT MR 2022; 43:490-509. [DOI: 10.1053/j.sult.2022.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Gulati S, Goyal A, Sharma R. Mimics of cholangiocarcinoma-exploring beneath the surface! Abdom Radiol (NY) 2022; 47:1507-1508. [PMID: 35218382 DOI: 10.1007/s00261-022-03459-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 02/15/2022] [Accepted: 02/16/2022] [Indexed: 11/24/2022]
Affiliation(s)
- Shrea Gulati
- Department of Radiodiagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Ankur Goyal
- Department of Radiodiagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, 110029, India.
| | - Raju Sharma
- Department of Radiodiagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, 110029, India
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16
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Di Giorgio A, Vergani D, Mieli-Vergani G. Cutting edge issues in juvenile sclerosing cholangitis. Dig Liver Dis 2022; 54:417-427. [PMID: 34289942 DOI: 10.1016/j.dld.2021.06.028] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 06/08/2021] [Accepted: 06/23/2021] [Indexed: 12/11/2022]
Abstract
Sclerosing cholangitis (SC) is a rare chronic disorder characterised by inflammation and progressive obliterative fibrosis of the intrahepatic and/or extrahepatic bile ducts. Diagnosis is based on cholangiogram showing bile duct dilatation, narrowing and obliteration of the biliary tree, and histologically, on the presence of inflammatory bile duct damage leading to periductal fibrosis. In children the most common SC is associated with strong autoimmune features, overlapping with those of autoimmune hepatitis (AIH); this form is known as autoimmune sclerosing cholangitis, ASC. Conversely, primary SC (PSC), a condition in which the term "primary" indicates that aetiology and pathogenesis are unknown, is rare in paediatrics. Secondary SC (SSC) defines a cholangiopathy associated with an identifiable aetiology such as immunodeficiencies, infections or haematological disorders. ASC and PSC are strongly associated with inflammatory bowel disease (IBD). ASC responds biochemically well to immunosuppressive drugs and ursodeoxycholic acid (UDCA). Primary forms are exclusively managed with oral UDCA, while in the secondary forms the medical treatment depends on the underlying aetiology. Despite treatment, SC often progresses to biliary cirrhosis and end-stage liver disease requiring liver transplantation. The disease can recur after transplant. Better understanding of pathogenic mechanisms and better treatment modalities are needed to improve the prognosis of this invalidating hepatic disorder.
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Affiliation(s)
- Angelo Di Giorgio
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy.
| | - Diego Vergani
- King's College London Faculty of Life Sciences and Medicine, Institute of Liver Studies, Mowat Labs King's College Hospital, London, United Kingdom
| | - Giorgina Mieli-Vergani
- King's College London Faculty of Life Sciences and Medicine, Institute of Liver Studies, Mowat Labs King's College Hospital, London, United Kingdom; Paediatric Liver, Gastrointestinal, and Nutrition Centre, King's College Hospital, London, United Kingdom
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17
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Devarapalli UV, Sarma MS, Mathiyazhagan G. Gut and liver involvement in pediatric hematolymphoid malignancies. World J Gastrointest Oncol 2022; 14:587-606. [PMID: 35321282 PMCID: PMC8919016 DOI: 10.4251/wjgo.v14.i3.587] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/22/2021] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
Hematolymphoid malignancies are common neoplasms in childhood. The involvement of the gastrointestinal (GI) tract, liver, biliary system, pancreas, and peritoneum are closely interlinked and commonly encountered. In leukemias, lymphomas, and Langerhans cell histiocytosis (LCH), the manifestations result from infiltration, compression, overwhelmed immune system, and chemotherapy-induced drug toxicities. In acute leukemias, major manifestations are infiltrative hepatitis, drug induced gastritis, neutropenic typhlitis and chemotherapy related pancreatitis. Chronic leukemias are rare. Additional presentation in lymphomas is cholestasis due to infiltration or biliary obstruction by lymph nodal masses. Presence of ascites needs a thorough workup for the underlying pathophysiology that may modify the therapy and affect the outcome. Uncommon hematolymphoid malignancies are primary hepatic, hepatosplenic, and GI lymphomas which have strict definitions. In advanced diseases with extensive spread, it may be impossible to distinguish these diseases from the primary site of origin. LCH produces biliary strictures that mimic as sclerosing cholangitis. Liver infiltration is associated with poor liver recovery even after chemotherapy. The heterogeneity of gut and liver manifestations in hematolymphoid malignancies has a clinical impact on their management. Though chemotherapy is the mainstay of therapy in all hematolymphoid malignancies, debulking surgery and radiotherapy have an adjuvant role in specific clinical scenarios. Rare situations presenting as liver failure or end-stage liver disease require liver transplantation. At their initial presentation to a primary care physician, given the ambiguity in clinical manifestations and the prognostic difference with time-bound management, it is vital to recognize them early for optimal outcomes. Pooled data from robust registries across the world is required for better understanding of these complications.
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Affiliation(s)
- Umeshreddy V Devarapalli
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Moinak S Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Gopinathan Mathiyazhagan
- Department of Hematology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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18
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Diagnosis of Primary Sclerosing Cholangitis Beyond Childhood is Associated with Worse Outcomes. J Clin Exp Hepatol 2022; 12:110-117. [PMID: 35068791 PMCID: PMC8766535 DOI: 10.1016/j.jceh.2021.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 03/16/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND The elucidation of differences between adult and pediatric-onset primary sclerosing cholangitis (PSC) may inform clinical decision making, and whether results of adult PSC clinical trials can be extrapolated to pediatric subjects. METHODS A single-center retrospective analysis of PSC subjects diagnosed during the epoch 2000-13 was conducted. Demographic, clinical, and laboratory data were compared between PSC subjects diagnosed between 0-18 (pediatric) and 19+ (adult) years of age. An adverse outcome was defined as PSC-related death, liver transplant, or malignancy. Survival without any of these was defined as event-free survival. RESULTS Analyses of 28 pediatric-diagnosed and 59 adult-diagnosed subjects revealed that incidence of early portal hypertension (PHT; P = 0.2), laboratory parameters of liver disease severity, and fibrosis grade at diagnosis were comparable between adult and pediatric PSC subjects. Adult-diagnosed PSC subjects had higher incidences of adverse outcomes compared to pediatric-diagnosed PSC subjects (P = 0.02). The age group 0-18 years (n = 30) had significantly better event-free survival compared to the age group more than 40 years (n = 25; P = 0.03). The prevalence of PHT in adult PSC subjects was 2.6 that of pediatric PSC subjects. PHT adversely affected outcomes in both adult (P < 0.001) and pediatric (P = 0.01) subjects. Adult PSC subjects were more likely to develop biliary complications (BCs; P = 0.001), ascites (P = 0.004), and variceal bleed (P = 0.03). Adult PSC subjects were more likely to have extra-hepatic co-morbidities (P < 0.001). Adult subjects had a longer follow-up duration compared to pediatric subjects (P = 0.06). CONCLUSION Despite having a comparable clinical, laboratory, and histologic biomarkers of liver disease severity at the time of diagnosis, adult PSC subjects had a worse outcome compared to pediatric PSC subjects. Possible reasons for this finding include higher incidence of PHT, BCs, extra-hepatic co-morbidities, and longer duration of follow-up.
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Key Words
- AIH, autoimmune hepatitis
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- ERCP, endoscopic cholangiopancreatography
- GGT, gamma-glutamyl transferase
- GI, gastrointestinal
- IBD, inflammatory bowel disease
- INR, international normalized ratio
- MR imaging, magnetic resonance imaging
- MRCP, magnetic resonance cholangiopancreatography
- PHT, portal hypertension
- PSC, primary sclerosing cholangitis
- age
- cholangitis
- outcome
- primary
- sclerosing
- x ULN, times upper limit of normal
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19
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Chazouillères O, Potier P, Bouzbib C, Hanslik B, Heurgue A, NGuyen-Khac E, Gournay J, Tanne F, Bureau C, Bourlière M, Ganne-Carrié N, de Lédinghen V. Non-invasive diagnosis and follow-up of primary sclerosing cholangitis. Clin Res Hepatol Gastroenterol 2022; 46:101775. [PMID: 34332142 DOI: 10.1016/j.clinre.2021.101775] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 07/23/2021] [Indexed: 02/04/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a rare and chronic cholestatic liver disease of unknown cause commonly associated with inflammatory bowel disease (IBD) and characterized by progressive obliterative fibro-inflammation of the biliary tree. Although the natural course is highly variable, PSC is often progressive, leading to biliary cirrhosis and its complications. In addition, PSC is a condition harbouring broad neoplastic potential with increased susceptibility for the development of both biliary and colon cancer. As in other chronic liver diseases, non-invasive methods play a major role in the diagnosis and monitoring of PSC. MR cholangiography is the key exam for the diagnosis and has replaced diagnostic endoscopic retrograde cholangiopancreatography (ERCP). A strict and standardised protocol for carrying out MR cholangiography is recommended. Liver stiffness measured by FibroScan® correlates with the degree of liver fibrosis, has a prognostic value and should be repeated during follow-up. Invasive methods still play an important role, especially ERCP which is indicated for therapeutic purposes or for endo-biliary sample collection in suspected cholangiocarcinoma (following discussion in a multidisciplinary team meeting) and total colonoscopy which is recommended at the initial diagnosis of any PSC and annually in patients with IBD.
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Affiliation(s)
- Olivier Chazouillères
- Service d'hépato-gastroentérologie, Hôpital Saint Antoine, APHP, 184 Rue du Faubourg Saint-Antoine, 75012 Paris, France.
| | - Pascal Potier
- Service d'hépato-gastroentérologie et oncologie digestive, CHR Orléans, Orléans, France
| | - Charlotte Bouzbib
- Service d'Hépatologie, Hopital Pitié Salpêtrière, APHP, Paris, France
| | - Bertrand Hanslik
- Centre Montpelliérain des maladies du foie et de l'appareil digestif, Montpellier, France
| | - Alexandra Heurgue
- Service d'hépato-gastroentérologie et cancérologie digestive, CHU Reims, Reims, France
| | - Eric NGuyen-Khac
- Service d'hépato-gastroentérologie, CHU Amiens-Picardie, Amiens, France
| | - Jérôme Gournay
- Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle, CHU Nantes, Nantes, France
| | - Florence Tanne
- Service d'hépato-gastro-entérologie, CHRU Brest Cavale Blanche, Brest, France
| | - Christophe Bureau
- Service d'hépatologie, Hôpital Rangueil, CHU Toulouse, Toulouse, France
| | - Marc Bourlière
- Service d'hépato-gastroentérologie, Hôpital Saint Joseph & INSERM UMR 1252 IRD SESSTIM Aix Marseille Université, Marseille, France
| | - Nathalie Ganne-Carrié
- Service d'hépatologie, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, INSERM UMR 1138, Centre de Recherche des Cordeliers, Université de Paris, Bobigny, France
| | - Victor de Lédinghen
- Service d'hépato-gastroentérologie, Hôpital Haut-Lévêque, CHU Bordeaux, pessac & INSERM U1053, Université de Bordeaux, Bordeaux, France
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20
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Ponsioen CY, Assis DN, Boberg KM, Bowlus CL, Deneau M, Thorburn D, Aabakken L, Färkkilä M, Petersen B, Rupp C, Hübscher SG. Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process. Gastroenterology 2021; 161:1764-1775.e5. [PMID: 34384749 DOI: 10.1053/j.gastro.2021.07.046] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 07/29/2021] [Indexed: 12/24/2022]
Affiliation(s)
- Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, the Netherlands
| | - David N Assis
- Department of Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
| | - Kirsten M Boberg
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine, and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; ERN RARE Liver, Hamburg, Germany
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, California
| | - Mark Deneau
- University of Utah and Intermountain Primary Children's Hospital, Salt Lake City, Utah
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free Hospital and Institute for Liver and Digestive Health, University College London, London, United Kingdom; ERN RARE Liver, Hamburg, Germany
| | - Lars Aabakken
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine, and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; ERN RARE Liver, Hamburg, Germany
| | - Martti Färkkilä
- Abdominal Center, Helsinki University Hospital, Helsinki, Finland; ERN RARE Liver, Hamburg, Germany
| | - Bret Petersen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Christian Rupp
- Department of Internal Medicine IV, Gastroenterology, and Hepatology, University Hospital Heidelberg, Heidelberg, Germany
| | - Stefan G Hübscher
- Institute of Immunology and Immunotherapy, University of Birmingham and, Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, United Kingdom
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21
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Klatskin-Mimicking Lesions. Diagnostics (Basel) 2021; 11:diagnostics11111944. [PMID: 34829291 PMCID: PMC8622290 DOI: 10.3390/diagnostics11111944] [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: 09/27/2021] [Revised: 10/14/2021] [Accepted: 10/15/2021] [Indexed: 11/17/2022] Open
Abstract
Altemeier-Klatskin tumor is a perihilar cholangiocarcinoma that occurs within 2 cm of the confluence of the right and left hepatic duct at the hepatic hilum and accounts for 50-70% of all cholangiocarcinomas cases. Although imaging techniques have come very far today, this entity can still be very challenging to diagnose as there are many lesions that can mimic Klatskin tumor. In this review, we will present the most common Klatskin-mimicking lesions.
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22
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Nair AV, Macdonald DB, Kelly EM, Satheesh S, Venugopalan P, Soman DK. Utility of MRCP in surveillance of primary sclerosing cholangitis associated hepatobiliary malignancy: 15 year experience at a single institution in Ontario, Canada. Clin Imaging 2021; 81:47-53. [PMID: 34598005 DOI: 10.1016/j.clinimag.2021.08.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 08/18/2021] [Accepted: 08/23/2021] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Magnetic resonance cholangiopancreatography (MRCP) is used for the surveillance of primary sclerosing cholangitis (PSC) and its associated complications. The time interval gap for subsequent follow-up MRCP is variable depending on clinical practice patterns, therefore this study was done to assess the MRCP follow-up strategy used in our institution for screening PSC-associated hepatobiliary malignancies. MATERIALS AND METHODS This retrospective observational cohort included MRCP studies in adult patients, with clinical and radiological diagnosis of PSC over the past 15-year period between January 1, 2003 to December 31, 2018. The study population was grouped based on the presence and absence of PSC-associated malignancy. The frequency of MRCP follow-up was compared between the groups to look for MRI ordering trends in surveillance for PSC-associated complications. RESULTS The overall median interval follow-up with MRCP was 14 months. The median follow-up interval in cases with PSC-associated malignancy was 6.0 months, compared to 13.1 months in the PSC group without malignancy (p 0.013). During the study period, the PSC-associated malignancy group had a median number of 7.5 scans, while the no malignancy group had a median number of 4 scans. Three patients (3/10, 30%) developed hepatobiliary malignancies within the first year of clinical diagnosis of PSC. The most common malignancy associated with PSC was cholangiocarcinoma (4.6%,7/10). Other PSC-associated malignancies included carcinoma gallbladder (1.3%,2/10), and hepatocellular carcinoma (0.6%,1/10). The median age of PSC associated malignancies was 56 (IQR 15) and higher compared to median age of PSC group without malignancies 46 (IQR 25.5), p 0.035. CONCLUSION The median interval for subsequent follow-up MRCP in our study cohort was 14 months. One-third of PSC-associated hepato-biliary malignancies developed within the first year of clinical diagnosis of PSC, and the risk of PSC-associated hepato-biliary malignancy is constant after the first year.
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Affiliation(s)
| | - D Blair Macdonald
- Dept of Medical Imaging, The Ottawa Hospital Research Institute, Ottawa, Canada
| | - Erin M Kelly
- Dept of Gastro-enterology, The Ottawa Hospital, University of Ottawa, Canada
| | - Soumya Satheesh
- Dept of Pathology, VPS Lakeshore Hospital, Kochi, Kerala, India
| | - Prasanna Venugopalan
- Dept of Obstetrics and Gynaecology, Travancore Medical College, Kollam, Kerala, India
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23
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Pötter-Lang S, Ba-Ssalamah A, Bastati N, Messner A, Kristic A, Ambros R, Herold A, Hodge JC, Trauner M. Modern imaging of cholangitis. Br J Radiol 2021; 94:20210417. [PMID: 34233488 PMCID: PMC9327751 DOI: 10.1259/bjr.20210417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/09/2021] [Accepted: 06/21/2021] [Indexed: 12/07/2022] Open
Abstract
Cholangitis refers to inflammation of the bile ducts with or without accompanying infection. When intermittent or persistent inflammation lasts 6 months or more, the condition is classified as chronic cholangitis. Otherwise, it is considered an acute cholangitis. Cholangitis can also be classified according to the inciting agent, e.g. complete mechanical obstruction, which is the leading cause of acute cholangitis, longstanding partial mechanical blockage, or immune-mediated bile duct damage that results in chronic cholangitis.The work-up for cholangitis is based upon medical history, clinical presentation, and initial laboratory tests. Whereas ultrasound is the first-line imaging modality used to identify bile duct dilatation in patients with colicky abdominal pain, cross-sectional imaging is preferable when symptoms cannot be primarily localised to the hepatobiliary system. CT is very useful in oncologic, trauma, or postoperative patients. Otherwise, magnetic resonance cholangiopancreatography is the method of choice to diagnose acute and chronic biliary disorders, providing an excellent anatomic overview and, if gadoxetic acid is injected, simultaneously delivering morphological and functional information about the hepatobiliary system. If brush cytology, biopsy, assessment of the prepapillary common bile duct, stricture dilatation, or stenting is necessary, then endoscopic ultrasound and/or retrograde cholangiography are performed. Finally, when the pathologic duct is inaccessible from the duodenum or stomach, percutaneous transhepatic cholangiography is an option. The pace of the work-up depends upon the severity of cholestasis on presentation. Whereas sepsis, hypotension, and/or Charcot's triad warrant immediate investigation and management, chronic cholestasis can be electively evaluated.This overview article will cover the common cholangitides, emphasising our clinical experience with the chronic cholestatic liver diseases.
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Affiliation(s)
- Sarah Pötter-Lang
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Ahmed Ba-Ssalamah
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Nina Bastati
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Alina Messner
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Antonia Kristic
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Raphael Ambros
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Alexander Herold
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Jacqueline C. Hodge
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Mawardi M, Alalwan A, Fallatah H, Abaalkhail F, Hasosah M, Shagrani M, Alghamdi MY, Alghamdi AS. Cholestatic liver disease: Practice guidelines from the Saudi Association for the Study of Liver diseases and Transplantation. Saudi J Gastroenterol 2021; 27:S1-S26. [PMCID: PMC8411950 DOI: 10.4103/sjg.sjg_112_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/26/2021] [Accepted: 05/16/2021] [Indexed: 11/04/2022] Open
Abstract
Cholestatic liver diseases (CLDs) are a group of diseases characterized by jaundice and cholestasis as the main presentation with different complications, which have considerable impact on the liver and can lead to end-stage liver disease, cirrhosis, and liver-related complications. In the last few years, tremendous progress has been made in understanding the pathophysiology, diagnosis, and treatment of patients with these conditions. However, several aspects related to the management of CLDs remain deficient and unclear. Due to the lack of recommendations that can help in the management, treatment of those conditions, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) has created a task force group to develop guidelines related to CLDs management in order to provide a standard of care for patients in need. These guidelines provide general guidance for health care professionals to optimize medical care for patients with CLDs for both adult and pediatric populations, in association with clinical judgments to be considered on a case-by-case basis. These guidelines describe common CLDs in Saudi Arabia, with recommendations on the best approach for diagnosis and management of different diseases based on the Grading of Recommendation Assessment (GRADE), combined with a level of evidence available in the literature.
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Affiliation(s)
- Mohammad Mawardi
- Department of Medicine, Gastroenterology Section, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia
| | - Abduljaleel Alalwan
- Department of Hepatobiliary Sciences and Liver Transplantation, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Hind Fallatah
- Department of Medicine, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Gastroenterology Section, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Mohammed Hasosah
- Department of Pediatrics, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Mohammad Shagrani
- Department of Liver and Small Bowel Transplantation, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Mohammed Y Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Abdullah S Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad General Hospital, Jeddah, Saudi Arabia
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25
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Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications. Am J Gastroenterol 2021; 116:1414-1425. [PMID: 33993134 DOI: 10.14309/ajg.0000000000001264] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 03/12/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.
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26
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Talbot S, MacLaren V, Lafferty H. Sclerosing cholangitis in a patient treated with nivolumab. BMJ Case Rep 2021; 14:14/5/e241700. [PMID: 34049893 DOI: 10.1136/bcr-2021-241700] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
A 69-year-old retired miner with stage 4 non-small-cell lung cancer presented with a 2-month history of obstructive liver function tests following nivolumab immunotherapy. His case had not responded to high dose prednisolone or mycophenolate and he was admitted for investigation. MR cholangiopancreatography demonstrated areas of intrahepatic biliary tree beading and stricturing, in keeping with sclerosing cholangitis. Prednisolone and mycophenolate were stopped and ursodeoxycholic acid commenced with subsequent partial improvement of the patient's liver function tests.
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Affiliation(s)
- Sam Talbot
- Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Vivienne MacLaren
- Clinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK
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27
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Mínguez Sabater A, Conde Amiel I, Ladrón Abia P, Martínez Delgado S, Camarasa Pérez Á, Berenguer M. Characteristics and impact of sex in a cohort of patients with primary sclerosing cholangitis: Experience of a transplant center in the Mediterranean basin. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:177-185. [PMID: 34052401 DOI: 10.1016/j.gastrohep.2021.03.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 03/02/2021] [Accepted: 03/29/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease that typically affects middle-aged men with ulcerative colitis (UC). However, recent studies point out to epidemiological changes. Our aim was to determine if the epidemiology, clinical course and outcome of patients with PSC followed at a reference hepatology center resemble what is described in the literature. PATIENTS AND METHOD Retrospective search of patients with a diagnosis of PSC treated in our center between 2000 and 2019. RESULTS Cohort of 55 patients (mean age: 37 years), 44% women. Most were large duct type (79%). Most diagnoses were made after 2011. At time of diagnosis, 63% of patients were asymptomatic. The median time from suspicion to diagnosis was 2 years. After a mean follow-up time of 7 years, one third developed cirrhosis, and 25% required liver transplantation (LT); among these, the disease recurred in almost half. Inflammatory bowel disease (IBD) was present in 45%, especially UC. Although statistical significance was not reached, PSC in women was characterized by higher rate of asymptomatic presentation and more frequent association with UC versus other forms of IBD. Women also had more frequently cirrhosis at diagnosis and required LT more often than men. CONCLUSION The epidemiology of PSC is changing. The number of women affected is greater than what was expected from the literature, with a recent increase in incidence. There seems to be differences between sexes in the form of presentation and disease course that should be confirmed in subsequent studies.
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Affiliation(s)
- Alejandro Mínguez Sabater
- Departamento de Gastroenterología, Hepatología y Unidad de Trasplante Hepático, Hospital Universitari y Politècnic La Fe, Valencia, España.
| | - Isabel Conde Amiel
- Departamento de Gastroenterología, Hepatología y Unidad de Trasplante Hepático, Hospital Universitari y Politècnic La Fe, Valencia, España; Instituto de Investigación Sanitaria La Fe, Valencia, España
| | - Pablo Ladrón Abia
- Departamento de Gastroenterología, Hepatología y Unidad de Trasplante Hepático, Hospital Universitari y Politècnic La Fe, Valencia, España
| | - Sara Martínez Delgado
- Departamento de Gastroenterología, Hepatología y Unidad de Trasplante Hepático, Hospital Universitari y Politècnic La Fe, Valencia, España
| | - Ángel Camarasa Pérez
- Cirugía General y del Aparato Digestivo, Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Tenerife, España
| | - Marina Berenguer
- Departamento de Gastroenterología, Hepatología y Unidad de Trasplante Hepático, Hospital Universitari y Politècnic La Fe, Valencia, España; Instituto de Investigación Sanitaria La Fe, Valencia, España; Centro de Investigación Biomédica en Red del Área de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, España; Departamento de Medicina, Universitat de València, Valencia, España
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28
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Klindt C, Jensen B, Brandenburger T, Feldt T, Killer A, Schimmöller L, Antoch G, Senff T, Hauka S, Timm J, Bahners BH, Seidl M, Esposito I, Luedde T, Bode JG, Keitel V. Secondary sclerosing cholangitis as a complication of severe COVID-19: A case report and review of the literature. Clin Case Rep 2021; 9:e04068. [PMID: 34084492 PMCID: PMC8142800 DOI: 10.1002/ccr3.4068] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 02/25/2021] [Accepted: 03/01/2021] [Indexed: 12/24/2022] Open
Abstract
This case of secondary sclerosing cholangitis (SSC-CIP) emphasizes the need to provide follow-up care for patients that have recovered from COVID-19 in order to understand the complexity of SARS-CoV-2 associated sequela.
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Affiliation(s)
- Caroline Klindt
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
| | - Björn‐Erik Jensen
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
| | - Timo Brandenburger
- Department of AnaesthesiologyMedical FacultyHeinrich‐Heine UniversitätDüsseldorfGermany
| | - Torsten Feldt
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
| | - Alexander Killer
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
| | - Lars Schimmöller
- Department of Diagnostic and Interventional RadiologyHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
| | - Gerald Antoch
- Department of Diagnostic and Interventional RadiologyHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
| | - Tina Senff
- Institute of VirologyHeinrich Heine UniversityUniversity HospitalDüsseldorfGermany
| | - Sandra Hauka
- Institute of VirologyHeinrich Heine UniversityUniversity HospitalDüsseldorfGermany
| | - Jörg Timm
- Institute of VirologyHeinrich Heine UniversityUniversity HospitalDüsseldorfGermany
| | - Bahne Hendrik Bahners
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
| | - Maximilian Seidl
- Institute of PathologyHeinrich‐Heine University and University HospitalDüsseldorfGermany
| | - Irene Esposito
- Institute of PathologyHeinrich‐Heine University and University HospitalDüsseldorfGermany
| | - Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
| | - Johannes G. Bode
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
| | - Verena Keitel
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesHeinrich‐Heine‐University DüsseldorfDüsseldorfGermany
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29
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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: 30] [Impact Index Per Article: 7.5] [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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30
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Shimomura T, Nakajima T, Nakashima T, Morimoto Y, Yamaoka J, Shibuya A, Ohno T, Yoshida N, Kishimoto M, Konishi E, Tanaka H, Moriguchi M, Itoh Y. Eosinophilic Cholangitis with Poor Prognosis after Corticosteroid- and Ursodeoxycholic Acid-Related Remission of Peripheral and Peribiliary Eosinophilia. Case Rep Gastroenterol 2021; 15:232-243. [PMID: 33790710 PMCID: PMC7989825 DOI: 10.1159/000512420] [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: 10/08/2020] [Accepted: 10/16/2020] [Indexed: 12/04/2022] Open
Abstract
A 79-year-old man presented with high fever, marked eosinophilia, altered biochemical liver function tests (LFT) with predominance of biliary enzymes, and severe wall thickening of the gallbladder. Magnetic resonance cholangiopancreatography (MRCP) suggested cholecystitis, without signs of biliary strictures. Laparoscopic cholecystectomy and exploratory liver excision revealed eosinophilic cholangitis and cholecystitis, complicated with hepatitis and portal phlebitis. Prednisolone monotherapy rapidly improved peripheral eosinophilia, but not LFT. Liver biopsy showed that infiltrating eosinophils were replaced by lymphocytes and plasma cells. Treatment with ursodeoxycholic acid improved LFT abnormalities. Nevertheless, after 2 months, transaminase-dominant LFT abnormalities appeared. Transient prednisolone dose increase improved LFT, but biliary enzymes' levels re-elevated and jaundice progressed. The second and third MRCP within a 7-month interval showed rapid progression of biliary stricture. The repeated liver biopsy showed lymphocytic, not eosinophilic, peribiliary infiltration and hepatocellular reaction to cholestasis. Eighteen months after the first visit, the patient died of hepatic failure. Autopsy specimen of the liver showed lymphocyte-dominant peribiliary infiltration and bridging fibrosis due to cholestasis. Though eosinophil-induced biliary damage was an initial trigger, repeated biopsy suggested that lymphocytes played a key role in progression of the disease. Further studies are needed to elucidate the relationship between eosinophils and lymphocytes in eosinophilic cholangitis.
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Affiliation(s)
- Takahito Shimomura
- Department of Internal Medicine, Saiseikai Kyoto Hospital, Nagaoka-Kyo, Japan
| | - Tomoki Nakajima
- Department of Internal Medicine, Saiseikai Kyoto Hospital, Nagaoka-Kyo, Japan
| | - Toshiaki Nakashima
- Department of Internal Medicine, Saiseikai Kyoto Hospital, Nagaoka-Kyo, Japan
| | - Yasutaka Morimoto
- Department of Internal Medicine, Saiseikai Kyoto Hospital, Nagaoka-Kyo, Japan
| | - Junko Yamaoka
- Department of Internal Medicine, Saiseikai Kyoto Hospital, Nagaoka-Kyo, Japan
| | - Akiko Shibuya
- Department of Internal Medicine, Saiseikai Kyoto Hospital, Nagaoka-Kyo, Japan
| | - Tomoyuki Ohno
- Department of Internal Medicine, Saiseikai Kyoto Hospital, Nagaoka-Kyo, Japan
| | - Norimasa Yoshida
- Department of Internal Medicine, Saiseikai Kyoto Hospital, Nagaoka-Kyo, Japan
| | - Mitsuo Kishimoto
- Department of Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Eiichi Konishi
- Department of Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hideo Tanaka
- Department of Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Michihisa Moriguchi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshito Itoh
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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31
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Yoshikawa Y, Imamura M, Yamaoka K, Kosaka Y, Murakami E, Morio K, Fujino H, Nakahara T, Okamoto W, Yamauchi M, Kawaoka T, Tsuge M, Hiramatsu A, Hayes CN, Aikata H, Fujitaka K, Arihiro K, Hattori N, Chayama K. A case with life-threatening secondary sclerosing cholangitis caused by nivolumab. Clin J Gastroenterol 2020; 14:283-287. [PMID: 33200345 DOI: 10.1007/s12328-020-01287-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023]
Abstract
Immune checkpoint inhibitor (ICI) therapy has potent anti-cancer effects but is associated with immune-related adverse events (irAEs). We present a case who developed secondary sclerosing cholangitis following treatment with nivolumab for non-small cell lung cancer who did not respond to immunosuppressive treatments and died of liver failure. A 75 year-old male with lung cancer who had been treated with nivolumab for non-small cell lung cancer developed Grade 3 liver injury with significant elevation of hepatobiliary enzymes. Magnetic resonance cholangiopancreatography (MRCP) revealed diffuse dilatation of the common bile duct and multifocal stenosis with prestenotic dilatation from the perihilar to intrahepatic bile duct, consistent with sclerosing cholangitis. Histological findings represented an infiltration of mainly CD8-positive T cells around the bile ducts in the liver. Despite treatments with ursodeoxycholic acid, prednisolone, and mycophenolate mofetil, the sclerosing cholangitis did not improve, and the patient died due to liver failure and aggravation of lung cancer. These findings suggest that immune checkpoint inhibitors may lead to resistance to immunosuppressive treatment as well as pose a risk of life-threatening sclerosing cholangitis.
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Affiliation(s)
- Yuki Yoshikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenji Yamaoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yumi Kosaka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Eisuke Murakami
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Wataru Okamoto
- Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan
| | - Masami Yamauchi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masataka Tsuge
- Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.,Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Clair Nelson Hayes
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kazunori Fujitaka
- Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kouji Arihiro
- Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan
| | - Noboru Hattori
- Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan. .,Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. .,RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
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32
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Pembrolizumab-induced sclerosing cholangitis in a lung adenocarcinoma patient with a remarkable response to chemotherapy: a case report. Clin J Gastroenterol 2020; 13:1310-1314. [PMID: 32643124 DOI: 10.1007/s12328-020-01178-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 06/25/2020] [Indexed: 12/24/2022]
Abstract
A 68-year-old man with advanced lung adenocarcinoma was admitted to our department because of high levels of alkaline phosphatase (ALP) after 4 courses of chemotherapy, including pembrolizumab. An imaging study showed findings of sclerosing cholangitis in the intrahepatic bile duct. Liver histology revealed infiltration of CD8-positive T cells into the portal tract. Corticosteroid and ursodeoxycholic acid were administered, and the ALP levels and findings of sclerosing cholangitis gradually improved. Furthermore, his lung carcinoma was remarkably decreased by chemotherapy, and he did not show progression of cancer without treatment. Our case suggests that early treatment before developing jaundice may be effective for sclerosing cholangitis in the intrahepatic bile duct due to immune checkpoint inhibitors.
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33
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Dumonceau JM, Delhaye M, Charette N, Farina A. Challenging biliary strictures: pathophysiological features, differential diagnosis, diagnostic algorithms, and new clinically relevant biomarkers - part 1. Therap Adv Gastroenterol 2020; 13:1756284820927292. [PMID: 32595761 PMCID: PMC7298429 DOI: 10.1177/1756284820927292] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 04/16/2020] [Indexed: 02/04/2023] Open
Abstract
It is frequently challenging to make the correct diagnosis in patients with biliary strictures. This is particularly important as errors may have disastrous consequences. Benign-appearing strictures treated with stents may later be revealed to be malignant and unnecessary surgery for benign strictures carries a high morbidity rate. In the first part of the review, the essential information that clinicians need to know about diseases responsible for biliary strictures is presented, with a focus on the most recent data. Then, the characteristics and pitfalls of the methods used to make the diagnosis are summarized. These include serum biomarkers, imaging studies, and endoscopic modalities. As tissue diagnosis is the only 100% specific tool, it is described in detail, including techniques for tissue acquisition and their yields, how to prepare samples, and what to expect from the pathologist. Tricks to increase diagnostic yields are described. Clues are then presented for the differential diagnosis between primary and secondary sclerosing cholangitis, IgG4-related sclerosing cholangitis, cholangiocarcinoma, pancreatic cancer, autoimmune pancreatitis, and less frequent diseases. Finally, algorithms that will help to achieve the correct diagnosis are proposed.
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Affiliation(s)
- Jean-Marc Dumonceau
- Department of Gastroenterology, Charleroi
University Hospitals, Chaussée de Bruxelles 140, Charleroi, 6042,
Belgium
| | - Myriam Delhaye
- Department of Gastroenterology,
Hepatopancreatology and GI Oncology, Erasme University Hospital, Brussels,
Belgium
| | - Nicolas Charette
- Department of Gastroenterology, Charleroi
University Hospitals, Charleroi, Belgium
| | - Annarita Farina
- Department of Medicine, Geneva University,
Geneva, Switzerland
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Intrahepatic biliary strictures after liver transplantation are morphologically similar to primary sclerosing cholangitis but immunologically distinct. Eur J Gastroenterol Hepatol 2020; 32:276-284. [PMID: 31895887 DOI: 10.1097/meg.0000000000001649] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Biliary strictures are an important cause of morbidity and mortality in primary hepatic disease and after liver transplantation (LT). We aimed to characterize inflammatory cytokines in biliary fluids in biliary strictures to investigate their immunological origin. METHODS We conducted a retrospective study on 72 patients with strictures after LT, eight patients with primary sclerosing cholangitis (PSC) and 15 patients with secondary sclerosing cholangitis (SSC). We measured cytokines interleukin (IL)-2, -4, -6, -10, -17, monocyte chemoattractant protein (MCP)-1, fibroblast growth factor (FGF)-2 and interferon (IFN)-γ as well as biochemical components such as protein and phospholipids in biliary fluid obtained from endoscopic retrograde cholangiography (ERC). Cell viability assays were performed on human cholangiocytes (H69) after being treated with IL-6, IL-4 and IFN-γ. RESULTS Bile of patients with diffuse strictures after LT or due to SSC showed low values of all measured cytokines except for IL-6 levels, which were largely elevated in patients with diffuse strictures after LT. Patients high in biliary IL-6 showed an increase in profibrotic markers FGF-2 and MCP-1. In contrast, PSC bile was dominated by a Th1/Th17 profile with elevated IL-2, IL-17 and IFN-γ. In LT patients with biliary strictures, biliary IL-6 negatively predicted retransplantation-free survival after ERC. CONCLUSION PSC patients showed a biliary Th1/Th17 cytokine profile, while SSC and diffuse strictures showed low values of cytokines except IL-6. In diffuse intrahepatic strictures after LT, biliary IL-6 is strongly associated with retransplantation-free survival after ERC.
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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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Multimethodological Approach to Gastrointestinal Microsporidiosis in HIV-Infected Patients. Acta Parasitol 2019; 64:658-669. [PMID: 31286356 DOI: 10.2478/s11686-019-00095-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 06/14/2019] [Indexed: 12/24/2022]
Abstract
PURPOSE Microsporidiosis is an opportunistic infection that produces chronic diarrhoea and cholangiopathy in patients with AIDS, mainly caused by two species of microsporidia, Enterocytozoon bieneusi and Encephalitozon intestinalis. The aim of this work was to develop an integral system for the diagnosis of microsporidiosis of the intestine and biliary tract in HIV-infected patients, comprising microscopic and molecular techniques. METHODS The study population comprised 143 adult patients of both sexes with diagnosis of HIV infection, with chronic diarrhoea, and with or without HIV-associated cholangiopathy. Stool studies for microsporidia identification of spores were performed on each patient. A video esofagogastroduodenoscopy with biopsy collection was also carried out for routine histology and semi-thin sections stained with Azure II. Species identification was carried out by transmission electron microscopy and/or polymerase chain reaction for the species E. bieneusi and E. intestinalis. RESULTS Out of the 143 patients a total of 12.6% (n = 18) were infected with microsporidia. Microsporidia species identified in most cases was E. bieneusi (16/18 cases), followed by E. intestinalis (4/18), all of these last ones in coinfection with E. bieneusi. CONCLUSIONS Clinical, imaging, microscopic and molecular analyses, when applied in a systematic and integrated approach, allow diagnosis and identification of microsporidia at species level in AIDS patients with chronic diarrhoea, and with or without HIV-associated cholangiopathy.
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Shaikh H, Umar S, Sial M, Christou A, Kulkarni A. A Case of Secondary Sclerosing Cholangitis in the setting of Non-Hodgkin's Lymphoma. Cureus 2019; 11:e4707. [PMID: 31355067 PMCID: PMC6650171 DOI: 10.7759/cureus.4707] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Sclerosing cholangitis represents a spectrum of cholestatic liver disease characterized by inflammation, fibrosis, and stricture of the bile ducts. A 67-year-old Caucasian female with a history of breast cancer in remission, presented with jaundice and an exophytic mass at the base of the tongue. Laboratory data revealed cholestasis with alkaline phosphatase 953 U/L, total bilirubin 7.7 mg/dL, direct bilirubin 6.4 mg/dL, and gamma-glutamyltransferase 3369 U/L. Computed tomography (CT) scan showed widespread lymphadenopathy in the chest, abdomen, and pelvis concerning for lymphoma, acute pancreatitis and biliary dilation with hyperenhancement of the common bile duct wall. Diffuse intrahepatic biliary ductal dilatation and narrowing with multifocal stenosis of the proximal and distal aspects of the common bile duct was seen on magnetic resonance cholangiopancreatography (MRCP). Findings were consistent with sclerosing cholangitis. Pathology of the oral lesion revealed activin receptor-like kinase 1 (ALK1) positive anaplastic large cell lymphoma. Chemotherapy was initiated with cyclophosphamide, doxorubicin, adriamycin, vincristine, etoposide, and prednisone (CHOEP-14) regimen, which resulted in significant clinical improvement along with a remarkable decrease in the liver function tests. Non-Hodgkin's lymphoma (NHL) has only rarely been reported in the literature as a cause of secondary sclerosing cholangitis, i.e., only 0.2% to 2.0% of patients with NHL present with biliary tract obstruction. It is essential for gastroenterologists, oncologists, and radiologists to recognize sclerosing cholangitis occurring secondary to a systemic disease because early initiation of treatment can improve clinical outcome, as manifested by our case.
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Affiliation(s)
- Hira Shaikh
- Internal Medicine, Allegheny Health Network, Pittsburgh, USA
| | - Shifa Umar
- Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, USA
| | - Moaz Sial
- Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, USA
| | | | - Abhijit Kulkarni
- Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, USA
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Kono M, Sakurai T, Okamoto K, Masaki S, Nagai T, Komeda Y, Kamata K, Minaga K, Yamao K, Takenaka M, Watanabe T, Nishida N, Kudo M. Efficacy and Safety of Chemotherapy Following Anti-PD-1 Antibody Therapy for Gastric Cancer: A Case of Sclerosing Cholangitis. Intern Med 2019; 58:1263-1266. [PMID: 30626829 PMCID: PMC6543221 DOI: 10.2169/internalmedicine.1981-18] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Accepted: 08/28/2018] [Indexed: 12/16/2022] Open
Abstract
Immunotherapy targeting programmed cell death-1 (PD-1) signaling is becoming the standard of care for advanced gastric cancer. We herein report a patient with gastric adenocarcinoma with peritoneal dissemination who was treated with nab-paclitaxel and ramucirumab following nivolumab and developed sclerosing cholangitis. Endoscopic retrograde cholangiography showed irregular narrowing and widening of the entire intrahepatic biliary system. Intriguingly, the patient receiving second-line chemotherapy with nab-paclitaxel plus ramucirumab prior to being administered nivolumab, however, he had experienced progressive disease. Thereafter, the administration of fourth-line chemotherapy with nab-paclitaxel and ramucirumab following nivolumab resulted in a clinical response. Nivolumab may enhance the efficacy of the subsequent chemotherapy regimens but also induce sclerosing cholangitis.
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Affiliation(s)
- Masashi Kono
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Toshiharu Sakurai
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Kazuki Okamoto
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Shou Masaki
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Tomoyuki Nagai
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Yoriaki Komeda
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Kosuke Minaga
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Kentarou Yamao
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Mamoru Takenaka
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Tomohiro Watanabe
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Naoshi Nishida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
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Novikov A, Kowalski TE, Loren DE. Practical Management of Indeterminate Biliary Strictures. Gastrointest Endosc Clin N Am 2019; 29:205-214. [PMID: 30846149 DOI: 10.1016/j.giec.2018.12.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Indeterminate biliary strictures pose a diagnostic and therapeutic challenge. Although underlying malignancy is a primary concern, biliary strictures may result from benign processes. An accurate diagnosis is paramount to define the treatment strategy and minimize morbidity. The limitations of traditional endoscopic retrograde cholangiopancreatography-based tissue acquisition with cytology brushings are well-documented. Endoscopic retrograde cholangiopancreatography is generally unable to determine a stricture's etiology. Complementary advanced endoscopic imaging and multimodal tissue acquisition have evolved. Careful consideration of the clinical presentation, location of the stricture, and interpretation of imaging constitute the most optimal approach for diagnosis and management.
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Affiliation(s)
- Aleksey Novikov
- Division of Gastroenterology and Hepatology, Thomas Jefferson University, 132 South 10th Street, 585 Main Building, Philadelphia, PA 19107, USA
| | - Thomas E Kowalski
- Division of Gastroenterology and Hepatology, Thomas Jefferson University, 132 South 10th Street, 585 Main Building, Philadelphia, PA 19107, USA
| | - David E Loren
- Division of Gastroenterology and Hepatology, Thomas Jefferson University, 132 South 10th Street, 585 Main Building, Philadelphia, PA 19107, USA.
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[Immune-mediated cholangiopathies : Diagnostic and therapeutic challenges]. Radiologe 2019; 59:348-356. [PMID: 30874827 DOI: 10.1007/s00117-019-0513-x] [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: 10/27/2022]
Abstract
BACKGROUND Immune-mediated cholangiopathies comprise primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and IgG4-associated cholangitis (IAC). A common feature is the progressive destruction of bile ducts leading to cholestasis with fibrosis and cirrhosis of the liver over time. The diseases are mostly identified during routine laboratory testing. Clinical signs and symptoms such as pruritus, fatigue or jaundice are infrequent in the early stage. DIAGNOSIS The diagnostic work-up involves the patient's history, physical examination, serological tests, abdominal ultrasonography, magnetic resonance cholangiopancreatography (MRCP) and, where necessary, liver biopsy and genetic testing. THERAPY Ursodeoxycholic acid (UDCA) is an effective treatment of PBC. Second-line therapies in addition to UDCA for incomplete UDCA responders are obeticholic acid (OCA) and bezafibrate, whereby only OCA has received approval for this indication from American (Federal Drug Administration) and European (European Medicines Agency) authorities. In PSC, UDCA improves prognostic markers; dominant bile duct strictures are treated with endoscopic balloon dilatation. Despite therapy, liver transplantation is frequently necessary for PSC. The risk of developing cholangiocarcinoma, colon cancer, and gallbladder cancer is increased for patients with PSC. In contrast to PBC and PSC, IAC responds well to corticosteroids. Disease relapse, however, is common, making long-term treatment with low-dose prednisolone or azathioprine necessary.
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Yen YH, Kuo FY, Kee KM, Chang KC, Tsai MC, Hu TH, Lu SN, Wang JH, Hung CH, Chen CH. Diabetes is associated with advanced fibrosis and fibrosis progression in non-genotype 3 chronic hepatitis C patients. Dig Liver Dis 2019; 51:142-148. [PMID: 30076015 DOI: 10.1016/j.dld.2018.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 07/01/2018] [Accepted: 07/04/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Diabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted. AIMS We investigated whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients. METHODS A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC was studied. After excluding patients with biopsy-proven or ultrasound-identified cirrhosis, there were 684 patients without cirrhosis. All 684 patients underwent hepatocellular carcinoma surveillance using ultrasound every 6 months, with a median duration of follow-up evaluation of 102.4 months. During the follow-up period, 60 patients developed cirrhosis according to ultrasound findings. RESULTS For the subgroup of 684 patients without cirrhosis, Kaplan-Meier survival analyses showed no significantly different cumulative incidences of cirrhosis (log-rank test; P = 0.71) among the patients with diabetes as compared to those without. However, after making adjustments for age, gender, fibrosis, steatosis, sustained virological response status, and obesity using Cox's proportional hazard model, diabetes was found to be an independent predictor for cirrhosis (HR = 1.9; 95% CI = 1.05-3.43, P = 0.03). CONCLUSIONS Diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.
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Affiliation(s)
- Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Fang-Ying Kuo
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chin Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Kerkar N, Chan A. Autoimmune Hepatitis, Sclerosing Cholangitis, and Autoimmune Sclerosing Cholangitis or Overlap Syndrome. Clin Liver Dis 2018; 22:689-702. [PMID: 30266157 DOI: 10.1016/j.cld.2018.06.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Autoimmune hepatitis (AIH) is characterized by elevated serum aminotransferases, immunoglobulin G, autoantibodies, and interface hepatitis, in the absence of a known diagnosis. Presentation is varied. Therapy is with immunosuppression. There is inflammation of the intrahepatic and/or extrahepatic bile ducts in Sclerosing cholangitis (SC) and when associated with inflammatory bowel disease, it is known as primary SC, with Ursodeoxycholic acid used for therapy. The overlap of clinical, biochemical and histological features of AIH and PSC is known as autoimmune sclerosing cholangitis (ASC) or overlap syndrome. Liver transplantation is performed when medical treatment fails and both AIH and PSC may recur post-transplantation.
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Affiliation(s)
- Nanda Kerkar
- Division of Gastroenterology, Hepatology and Nutrition, Golisano Children's Hospital, University of Rochester Medical Center, 601 Elmwood Avenue, Box 667, Rochester, NY 14642, USA.
| | - Albert Chan
- Division of Gastroenterology, Hepatology and Nutrition, Golisano Children's Hospital, University of Rochester Medical Center, 601 Elmwood Avenue, Box 667, Rochester, NY 14642, USA; Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Florida, PO Box 100296, Gainesville, FL 32610, USA
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Autoimmune sclerosing cholangitis: Evidence and open questions. J Autoimmun 2018; 95:15-25. [PMID: 30366655 DOI: 10.1016/j.jaut.2018.10.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 10/13/2018] [Indexed: 02/06/2023]
Abstract
Juvenile sclerosing cholangitis is a rare chronic hepatobiliary disorder characterized by inflammation of the intra- and/or extrahepatic bile ducts, bile duct dilatation, narrowing and obliteration, and, histologically, by inflammatory bile duct damage leading to periductular fibrosis. The diagnosis is based on endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. In children, it may be associated to a variety of systemic and hepatic conditions: thus, the term "primary" sclerosing cholangitis should be reserved for the rare cases without a known cause. Small duct disease is diagnosed in the presence of histological features diagnostic of sclerosing cholangitis and normal cholangiography. Autoimmune sclerosing cholangitis (ASC) is a form of sclerosing cholangitis with strong autoimmune features overlapping with those of autoimmune hepatitis (AIH). It is a well-recognized nosological entity in paediatrics, where it accounts for the majority of sclerosing cholangitis cases. It is as prevalent as AIH in children, is equally frequent in males and females, half of the patients have concomitant inflammatory bowel disease, virtually all patients have raised immunoglobulin G levels and positive anti-nuclear and/or anti-smooth muscle antibodies. Half of the ASC patients respond well to standard immunosuppressive treatment for AIH with the addition of ursodeoxycholic acid, but the transplant rate is higher than in AIH, and post-transplant recurrence is frequent. A number of open questions remain: are ASC and AIH distinct entities or different manifestations of the same condition? What is the role of histology? Is small duct disease a specific entity? What is the relationship between ASC and adult primary sclerosing cholangitis? What is the role of inflammatory bowel disease? In addition, validated diagnostic criteria for ASC are needed.
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Herta T, Verheij J, Beuers U. IgG4-assoziierte Cholangitis – klinische Präsentation eines lange übersehenen Krankheitsbildes. Internist (Berl) 2018; 59:560-566. [DOI: 10.1007/s00108-018-0431-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Secondary sclerosing cholangitis in critically ill patients after a traffic accident-a new entity that should be considered in death classification. Int J Legal Med 2018; 132:1729-1732. [PMID: 29484493 DOI: 10.1007/s00414-018-1801-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 02/14/2018] [Indexed: 10/17/2022]
Abstract
A 49-year-old female sustained a polytrauma after being hit by a vehicle in a traffic accident. Following the incident, the woman had various surgical interventions and underwent intensive care over a 6-week period. Eight months later, she died after developing secondary sclerosing cholangitis (SSC). Autopsy revealed liver failure and hepatic encephalopathy due to SSC caused by the polytrauma and the subsequent intensive care. Prior to the accident, there was no evidence of a pre-existing liver or biliary system disease. The death of the patient was classified as non-natural as a causal consequence of the traffic accident. SSC has been clinically described as a complication of intensive care. Since it has a high mortality rate, it is important that forensics and pathologists are aware of the condition.
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Chen JH, Deshpande V. Inflammatory Nodules Identify Steroid-Responsive Primary Sclerosing Cholangitis. Int J Surg Pathol 2018; 26:402-409. [PMID: 29464971 DOI: 10.1177/1066896918758451] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a cholangiopathy-usually associated with inflammatory bowel disease-that leads to cirrhosis and liver failure. Based on a multitude of clinical trials, there is general consensus that PSC progression is unchanged by current therapies, including steroids. However, there are scattered reports in the literature of PSC patients responsive to steroids. Recently, several steroid-responsive PSC mimics have been described, most notably immunoglobulin G4-related sclerosing cholangitis. Following these discoveries, many assume that cases in the literature previously reported as steroid-responsive PSC would now be classified as one of these mimics. We reviewed liver biopsies and the medical histories of patients diagnosed with PSC with documented response to steroids. We identified 3 cases of steroid-responsive PSC in patients with inflammatory bowel disease that do not fit criteria of known PSC mimics. All 3 were adults (age range = 18-44 years) with inflammatory bowel disease, and included 2 males and 1 female. All 3 patients had abnormal liver function tests that normalized on prednisone. Histologically, these 3 cases share a common feature, hepatic fibroinflammatory nodules in a collagen-rich background. They lacked clinical, serologic, and histologic features of immunoglobulin G4-related sclerosing cholangitis. These cases suggest that fibroinflammatory nodules may identify a unique subset of PSC patients who are responsive to steroids.
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Affiliation(s)
- Jonathan H Chen
- 1 Massachusetts General Hospital, Boston, MA, USA.,2 Harvard Medical School, Boston, MA, USA
| | - Vikram Deshpande
- 1 Massachusetts General Hospital, Boston, MA, USA.,2 Harvard Medical School, Boston, MA, USA
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Trivedi PJ, Scalera I, Slaney E, Laing RW, Gunson B, Hirschfield GM, Schlegel A, Ferguson J, Muiesan P. Clinical outcomes of donation after circulatory death liver transplantation in primary sclerosing cholangitis. J Hepatol 2017; 67:957-965. [PMID: 28690174 DOI: 10.1016/j.jhep.2017.06.027] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 06/23/2017] [Accepted: 06/27/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIM Primary sclerosing cholangitis (PSC) is a progressive fibro-inflammatory cholangiopathy for which liver transplantation is the only life-extending intervention. These patients may benefit from accepting liver donation after circulatory death (DCD), however their subsequent outcome is unknown. The aim of this study was to determine the clinical impact of using DCD liver grafts in patients specifically undergoing transplantation for PSC. METHODS Clinical outcomes were prospectively evaluated in PSC patients undergoing transplantation from 2006 to 2016 stratified by donor type (DCD, n=35 vs. donation after brainstem death [DBD], n=108). RESULTS In liver transplantation for PSC; operating time, days requiring critical care support, total ventilator days, incidence of acute kidney injury, need for renal replacement therapy (RRT) or total days requiring RRT were not significantly different between DCD vs. DBD recipients. Although the incidence of ischaemic-type biliary lesions was greater in the DCD group (incidence rate [IR]: 4.4 vs. 0 cases/100-patient-years; p<0.001) there was no increased risk of post-transplant biliary strictures overall (hazard ratio [HR]: 1.20, 0.58-2.46; p=0.624), or in sub-analysis specific to anastomotic strictures or recurrent PSC, between donor types. Graft loss and mortality rates were not significantly different following transplantation with DCD vs. DBD livers (IR: 3.6 vs. 3.1 cases/100-patient-years, p=0.34; and 3.9 vs. 4.7, p=0.6; respectively). DCD liver transplantation in PSC did not impart a heightened risk of graft loss (HR: 1.69, 0.58-4.95, p=0.341) or patient mortality (0.75, 0.25-2.21, p=0.598). CONCLUSION Transplantation with DCD (vs. DBD) livers in PSC patients does not impact graft loss or patient survival. In an era of organ shortage, DCD grafts represent a viable therapeutic option for liver transplantation in PSC patients. Lay summary: This study examines the impact of liver transplantation in primary sclerosing cholangitis (PSC) with organs donated after circulatory death (DCD), compared to donation after brainstem death (DBD). We show that in appropriately selected patients, the outcomes for DCD transplantation mirror those using DBD livers, with no significant differences in complication rate, patient survival or transplanted liver survival. In an era of organ shortage and increasing wait-list times, DCD livers represent a potential treatment option for transplantation in PSC.
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Affiliation(s)
- Palak J Trivedi
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Irene Scalera
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Emma Slaney
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Richard W Laing
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Bridget Gunson
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Gideon M Hirschfield
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Andrea Schlegel
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK; Department of Surgery and Transplantation, University Hospital Zürich, Zürich, Switzerland
| | - James Ferguson
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK.
| | - Paolo Muiesan
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK; Department of Liver Surgery, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
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48
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Björnsson ES. Primary sclerosing cholangitis: best practices for diagnosis. Expert Opin Orphan Drugs 2017. [DOI: 10.1080/21678707.2017.1358163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Einar S. Björnsson
- Department of Internal Medicine, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Division of Gastroenterology and Hepatology, The National University Hospital of Iceland
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Resolution of Diffuse Intrahepatic Biliary Strictures after Chemotherapy for Metastatic Ovarian Cancer. ACG Case Rep J 2017; 4:e77. [PMID: 28620623 PMCID: PMC5464395 DOI: 10.14309/crj.2017.77] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 04/17/2017] [Indexed: 12/12/2022] Open
Abstract
Sclerosing cholangitis and cholestatic jaundice secondary to metastatic disease is a rare complication. We report a rare case of secondary sclerosing cholangitis (SSC) due to lymphatic spread from ovarian cancer with complete resolution after chemotherapy. The diagnosis of SSC from metastatic ovarian cancer was clinically challenging, as endoscopic retrograde cholangiopancreatography revealed irregular hepatic ducts consistent with sclerosing cholangitis, but it did not identify any malignant cells. The final diagnosis was made with liver biopsy revealing high-grade metastatic Mullerian carcinoma. The patient responded well to chemotherapy and is in remission. A timely diagnosis is important and can lead to complete resolution of the disease.
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Aabakken L, Karlsen TH, Albert J, Arvanitakis M, Chazouilleres O, Dumonceau JM, Färkkilä M, Fickert P, Hirschfield GM, Laghi A, Marzioni M, Fernandez M, Pereira SP, Pohl J, Poley JW, Ponsioen CY, Schramm C, Swahn F, Tringali A, Hassan C. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline. J Hepatol 2017; 66:1265-1281. [PMID: 28427764 DOI: 10.1016/j.jhep.2017.02.013] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 02/14/2017] [Indexed: 02/06/2023]
Abstract
This guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE) and of the European Association for the Study of the Liver (EASL) on the role of endoscopy in primary sclerosing cholangitis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations.
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