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Kulkarni C, Cholankeril G, Fardeen T, Rathkey J, Khan S, Murag S, Lerrigo R, Kamal A, Mannalithara A, Jalal P, Ahmed A, Vierling J, Goel A, Sinha SR. Statin Use Is Associated With Protection Against Acute Cholangitis in Patients With Primary Sclerosing Cholangitis: A Multicenter Retrospective Cohort Study. Clin Transl Gastroenterol 2025; 16:e00816. [PMID: 40272937 PMCID: PMC12020706 DOI: 10.14309/ctg.0000000000000816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 12/22/2024] [Indexed: 01/22/2025] Open
Abstract
INTRODUCTION Patients with primary sclerosing cholangitis (PSC) are at increased risk of acute cholangitis. The epidemiological risks of cholangitis are poorly studied despite the high morbidity associated with this infection. The aim of this study was to understand the impact of statins on acute cholangitis in PSC. METHODS This multicenter, retrospective cohort study assessed data from 294 patients with PSC at Stanford Medical Center, Baylor Medical Center, and Valley Medical Center. Clinical factors associated with the development of cholangitis were identified using multivariable Cox regression. RESULTS The patients were predominantly male (68.7%) with a median age at enrollment of 48 years (interquartile range [IQR]: 31.0-60.8). Fifty patients (17.0%) were prescribed statins. The median follow-up time was 6 years (IQR: 2.0-12.0), in which 29.6% (n = 87) developed cholangitis. In multivariable analysis, statins were associated with an 81% reduction in cholangitis (HR 0.19, 95% confidence interval 0.03-0.64). Statins were associated with a lower adjusted incidence of cholangitis at 36 months compared with patients not on statin therapy (incidence of 2.8% vs 12.2%, P < 0.001). Statins were also associated with increased time-to-stricture ( P = 0.004), an outcome known to be associated with PSC complications. DISCUSSION Statin therapy is associated with reduced risk of cholangitis in PSC, possibly by delaying the time to develop dominant or high-grade strictures. In patients with PSC, use of statin therapy may be a beneficial modality to prevent the development of cholangitis and warrants further investigation.
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Affiliation(s)
- Chiraag Kulkarni
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - George Cholankeril
- Section of Gastroenterology & Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Touran Fardeen
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Joseph Rathkey
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Samir Khan
- Section of Gastroenterology & Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Soumya Murag
- Santa Clara Valley Medical Center, Santa Clara, California, USA
| | - Robert Lerrigo
- Santa Clara Valley Medical Center, Santa Clara, California, USA
| | - Ahmad Kamal
- Santa Clara Valley Medical Center, Santa Clara, California, USA
| | - Ajitha Mannalithara
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Prasun Jalal
- Section of Gastroenterology & Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Aijaz Ahmed
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - John Vierling
- Section of Gastroenterology & Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Aparna Goel
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Sidhartha R. Sinha
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
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Helmke S, Kittelson J, Imperial JC, McRae MP, Everson GT. The Oral Cholate Challenge Test Quantifies Risk for Liver-Related Clinical Outcomes in Primary Sclerosing Cholangitis. GASTRO HEP ADVANCES 2024; 3:944-953. [PMID: 39286620 PMCID: PMC11403427 DOI: 10.1016/j.gastha.2024.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 07/09/2024] [Indexed: 09/19/2024]
Abstract
Background and Aims We quantified hepatic functional impairment using quantitative function tests and linked severity of functional impairment to liver-related complications and outcome in primary sclerosing cholangitis. Methods Forty-seven patients had baseline testing, and 40 were retested after 1 year. For each test, cholates labeled with cold, nonradioactive isotopes were administered orally (DuO, SHUNT tests) and intravenously (SHUNT test), and blood was analyzed at 20 and 60 minutes (DuO), or 0, 5, 20, 45, 60, and 90 minutes (SHUNT). Disease severity index (DSI), hepatic reserve (HR%), and portal-systemic shunting (SHUNT%) were calculated. Results Three subgroups with low, moderate, and high disease severity were defined from the age-adjusted results for DSI, HR%, and SHUNT%. Standard laboratory tests, clinical scores, cytokine levels, and clinical outcome correlated with these subgroups. In univariate analysis of baseline tests, SHUNT% was a strong predictor of clinical outcome (n = 13 of 47; areas under the receiver operating characteristic curve, 0.84DuO, 0.90SHUNT). A model combining SHUNT%, DSI (or HR%), platelet count, and changes from baseline was most predictive of outcome (n = 10 of 40; areas under the receiver operating characteristic curve, 0.95DuO, 0.96SHUNT). Conclusion DSI, HR%, and SHUNT% identified subgroups of primary sclerosing cholangitis based on the age-related severity of hepatic impairment that predicted risk for liver-related clinical outcome. Further study is warranted to confirm and validate these intriguing findings both in studies of natural progression of primary sclerosing cholangitis and in clinical trials. DuO enhances the utility of quantitative liver function testing.
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Affiliation(s)
- Steve Helmke
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
- HepQuant LLC, Denver, Colorado
| | - John Kittelson
- Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | | | | | - Gregory T Everson
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
- HepQuant LLC, Denver, Colorado
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Alsakarneh S, Ahmed M, Jaber F, Zulqarnain M, Karagozian R, Francis F, Farraye FA, Hashash JG. Does Timing of Ileal Pouch-Anal Anastomosis Matter in Patients With Primary Sclerosing Cholangitis and Orthotopic Liver Transplantation? A Systematic Review and Meta-analysis. CROHN'S & COLITIS 360 2024; 6:otae036. [PMID: 38974606 PMCID: PMC11224914 DOI: 10.1093/crocol/otae036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Indexed: 07/09/2024] Open
Abstract
Introduction Pouchitis is the most common complication in patients with ileal pouch-anal anastomosis (IPAA), which can develop in up to 66% of patients. There is limited data on the effect of orthoptic liver transplantation (OLT) on the risk of developing pouchitis. We aimed to objectively assess whether OLT itself significantly modifies the risk of developing pouchitis in patients with overlap PSC and inflammatory bowel disease (IBD). Method We searched Medline, Scopus, and Embase databases from inception through September 2023 for studies that describe the outcomes of IPAA in patients with PSC and IBD who also have a history of OLT. Pooled proportions, Odds Ratio (OR), and 95% confidence intervals (CI) for data were calculated utilizing a random effects model. Using the Freeman-Turkey double arcsine transformation (FTT) method, the pooled weight-adjusted estimate of event rates for clinical outcomes in each group was also calculated. Heterogeneity between studies was assessed using the Cochrane Q statistic (I2). Results Seven studies with a total of 291 patients with a history of PSC, IBD, and OLT were identified. The pooled overall risk of pouchitis in PSC/IBD patients with a history of OLT was 65% (95% CI: 0.57-0.72), with no heterogeneity observed in the analysis (I2 = 0%). In a subgroup analysis of patients who had IPAA followed by OLT, 3 studies with 28 patients were included; the pooled risk of pouchitis after IPAA and OLT was 83% (95% CI: 0.71-0.94; I2 = 0%), which was significantly higher (P < .001) than the OLT followed by IPAA group (59%; 95 CI: 0.48-0.71; I2 = 0%). There was no difference in the risk of pouchitis between OLT and non-OLT groups (OR = 1.36; 95% CI: 0.37-5.0). Conclusions Our meta-analysis revelaed that pouchitis is common in patients who underwent OLT for PSC, especially in those who had IPAA before the OLT. OLT before IPAA may reduce the risk of pouchitis. Further larger studies are warranted to reproduce this and investigate the reason behind this difference.
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Affiliation(s)
- Saqr Alsakarneh
- Department of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Mohamed Ahmed
- Department of Gastroenterology and Hepatology, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Fouad Jaber
- Department of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Mir Zulqarnain
- Department of Gastroenterology and Hepatology, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Raffi Karagozian
- Department of Transplant Hepatology, Tufts University, Medford, MA, USA
| | - Fadi Francis
- Department of Transplant Hepatology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Francis A Farraye
- Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Jana G Hashash
- Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
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Taghavi SA, Safarpour AR, Ghahramani S, Moghadam SM, Shahramian I, Sivandzadeh GR, Nikeghbalian S, Tahani M, Saeian S, Malek-Hosseini SA. Study of Risk Factors Associated With Recurrent Primary Sclerosing Cholangitis After Liver Transplantation in Shiraz >From 2011 to 2021. EXP CLIN TRANSPLANT 2024; 22:531-539. [PMID: 39223811 DOI: 10.6002/ect.2024.0085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
OBJECTIVES Primary sclerosing cholangitis is an autoimmune illness affecting the intrahepatic and/or extrahepatic bile ducts that has a varying clinical history and no clear therapy. Recurrence of primary sclerosing cholangitis after transplantation can cause recurring liver failure, decreased survival, and the necessity for retransplant. Here, we explored the incidence of recurrence while also identifying the risk factors of primary sclerosing cholangitis. MATERIALS AND METHODS In this retrospective cohort study, we collected demographic and clinical data from patients with a history of primary sclerosing cholangitis after liver transplant between 2011 and 2021. With SPSS software, we compared results in 2 groups of patients (with and without recurrent sclerosing biliary cholangitis) in terms of demographic and clinical variables. RESULTS The study included 408 patients. Lower donor age and the occurrence of acute cellularrejection were shown to be key risk factors for recurrence of primary sclerosing cholangitis. Acute cellularrejection showed the best likelihood of predicting primary sclerosing cholangitis recurrence. As the number of acute cellular rejection episodes increased, so did the chance of primary sclerosing cholangitis. Death rate of patients with recurrence of primary sclerosing cholangitis was 40.8% (n = 20 patients) compared with 18.9% (n = 68 patients) in those without recurrence (significant at P < .001). CONCLUSIONS The recurrence of primary sclerosing cholangitis had a detrimental effect on survival after liver transplant. Modifiable risk variables have the potentialto affecttherapies on care and prevention of primary sclerosing cholangitis recurrence. Donor age and acute cellular rejection were risk factors for decreased survival and higher primary sclerosing cholangitis recurrence. The use of mycophenolate (Cellcept) increased recurrence, but tacrolimus reduced mortality.
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Affiliation(s)
- Seyed Alireza Taghavi
- >From the Gastroenterohepatology Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Dar FS, Abbas Z, Ahmed I, Atique M, Aujla UI, Azeemuddin M, Aziz Z, Bhatti ABH, Bangash TA, Butt AS, Butt OT, Dogar AW, Farooqi JI, Hanif F, Haider J, Haider S, Hassan SM, Jabbar AA, Khan AN, Khan MS, Khan MY, Latif A, Luck NH, Malik AK, Rashid K, Rashid S, Salih M, Saeed A, Salamat A, Tayyab GUN, Yusuf A, Zia HH, Naveed A. National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma. World J Gastroenterol 2024; 30:1018-1042. [PMID: 38577184 PMCID: PMC10989497 DOI: 10.3748/wjg.v30.i9.1018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/03/2024] [Accepted: 01/29/2024] [Indexed: 03/06/2024] Open
Abstract
A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
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Affiliation(s)
- Faisal Saud Dar
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Zaigham Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Dr. Ziauddin University Hospital, Karachi 75600, Sindh, Pakistan
| | - Irfan Ahmed
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
- University of Aberdeen, Aberdeen B24 3FX, United Kingdom
| | - Muhammad Atique
- Department of Pathology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Usman Iqbal Aujla
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | | | - Zeba Aziz
- Department of Oncology, Hameed Latif Hospital, Lahore 54000, Pakistan
| | - Abu Bakar Hafeez Bhatti
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Tariq Ali Bangash
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Amna Subhan Butt
- Department of Medicine, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Osama Tariq Butt
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Abdul Wahab Dogar
- Department of Liver Transplant, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | - Javed Iqbal Farooqi
- Department of Medicine & Gastroenterology, Lifecare Hospital and Research Centre, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan
| | - Faisal Hanif
- Department of Hepatopancreatobiliary & Liver Transplant, Bahria International Hospital, Lahore 54000, Pakistan
| | - Jahanzaib Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Siraj Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Syed Mujahid Hassan
- Department of Gastroenterology, Hepatology & Nutrition, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | | | - Aman Nawaz Khan
- Department of Radiology, Rehman Medical Institute, Peshawar 25000, Pakistan
| | - Muhammad Shoaib Khan
- Army Liver Transplant Unit, Pak Emirates Military Hospital, Rawalpindi 46000, Pakistan
| | - Muhammad Yasir Khan
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amer Latif
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Nasir Hassan Luck
- Department of Gastroenterology, Sindh Institute of Urology and Transplantation, Karachi 75500, Pakistan
| | - Ahmad Karim Malik
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Kamran Rashid
- Rashid Nursing Home and Cancer Clinic, Rashid Nursing Home and Cancer Clinic, Rawalpindi 46000, Pakistan
| | - Sohail Rashid
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Mohammad Salih
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Abdullah Saeed
- Department of Radiology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amjad Salamat
- Department of Gastroenterology and Hepatology, Quaid-e-Azam International Hospital, Rawalpindi 44000, Pakistan
| | - Ghias-un-Nabi Tayyab
- Department of Gastroenterology and Hepatology, Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Aasim Yusuf
- Department of Internal Medicine, Division of Gastroenterology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore 54000, Pakistan
| | - Haseeb Haider Zia
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Ammara Naveed
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
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Catanzaro E, Gringeri E, Burra P, Gambato M. Primary Sclerosing Cholangitis-Associated Cholangiocarcinoma: From Pathogenesis to Diagnostic and Surveillance Strategies. Cancers (Basel) 2023; 15:4947. [PMID: 37894314 PMCID: PMC10604939 DOI: 10.3390/cancers15204947] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/09/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC), accounting for 2-8% of cases and being the leading cause of death in these patients. The majority of PSC-associated CCAs (PSC-CCA) develop within the first few years after PSC diagnosis. Older age and male sex, as well as concomitant inflammatory bowel disease (IBD) or high-grade biliary stenosis, are some of the most relevant risk factors. A complex combination of molecular mechanisms involving inflammatory pathways, direct cytopathic damage, and epigenetic and genetic alterations are involved in cholangiocytes carcinogenesis. The insidious clinical presentation makes early detection difficult, and the integration of biochemical, radiological, and histological features does not always lead to a definitive diagnosis of PSC-CCA. Surveillance is mandatory, but current guideline strategies failed to improve early detection and consequently a higher patient survival rate. MicroRNAs (miRNAs), gene methylation, proteomic and metabolomic profile, and extracellular vesicle components are some of the novel biomarkers recently applied in PSC-CCA detection with promising results. The integration of these new molecular approaches in PSC diagnosis and monitoring could contribute to new diagnostic and surveillance strategies.
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Affiliation(s)
- Elisa Catanzaro
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Center, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Patrizia Burra
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Martina Gambato
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
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Longitudinal analysis of transplant candidates with primary sclerosing cholangitis in an Asian liver transplant center. Eur J Gastroenterol Hepatol 2023; 35:480-487. [PMID: 36719819 DOI: 10.1097/meg.0000000000002516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a rare disease in Asia, and few studies have investigated the disease in this ethnicity, particularly in wait-listed patients for liver transplantation (LT). We aimed to investigate the prognostic factors and outcomes of wait-listed patients with PSC in an Asian transplant center. METHODS Survival was retrospectively analyzed. RESULTS Eighteen (10 male and 8 female) wait-listed patients with PSC, with a median age at diagnosis of 44.5 years, were included. Compared with men, women had significantly higher aspartate aminotransferase to platelet ratio index scores (3.28 vs. 1.13; P = 0.012) and bilirubin levels (7.68 vs. 4.03 mg/dl; P = 0.043) and more often presented with decompensating events, including ascites [5 (63%) vs. 1 (10%); P = 0.043] and splenomegaly [8 (100%) vs. 4 (40%); P = 0.013]. Compared with the non-LT group, the LT group exhibited a superior survival rate for women ( P = 0.004) but not for men. In the univariable analysis, significant risk factors associated with overall survival included malignancies with a hazard ratio (95% confidence interval) of 5.53 (1.00-30.51) and esophageal varices (EV) [4.18 (1.05-16.61)], whereas female gender [25.00 (1.49-500.00)], LT [0.09 (0.01-0.80)] and EV [39.03 (2.92-521.96)] were indicated in the multivariable analysis. CONCLUSIONS For Asian wait-listed patients with PSC, EV and female gender were the risk factors related to overall survival, and LT was the protective factor. Our experiences suggested that LT brings more benefits in female patients. Strategies are needed to provide equivalent transplant benefits.
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Allograft liver failure awaiting liver transplantation in Japan. J Gastroenterol 2022; 57:495-504. [PMID: 35648201 DOI: 10.1007/s00535-022-01880-w] [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: 02/01/2022] [Accepted: 05/14/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Following liver transplantation (LT), allograft liver failure can be developed by various causes and requires re-LT. Hence, this study aimed to clarify the characteristics and prognostic factors of patients with allograft liver failure awaiting deceased donor LT (DDLT) in Japan. METHODS Of the 2686 DDLT candidates in Japan between 2007 and 2016, 192 adult patients listed for re-LT were retrospectively enrolled in this study. Factors associated with waitlist mortality were assessed using the Cox proportional hazards model. The transplant-free survival probabilities were evaluated using the Kaplan-Meier analysis and log-rank test. RESULTS The median period from the previous LT to listing for re-LT was 1548 days (range, 4-8449 days). Primary sclerosing cholangitis (PSC), which was a primary indication, showed a higher listing probability for re-LT as compared with other primary etiologies. Recurrent liver disease was a leading cause of allograft failure and was more frequently observed in the primary indication of hepatitis C virus (HCV) infection and PSC in contrast with other etiologies. Multivariate analysis identified the following independent risk factors associated with waitlist mortality: age, Child-Turcotte-Pugh (CTP) score, mode for end-stage liver disease (MELD) score, alanine aminotransferase (ALT), and causes of allograft failure. CONCLUSIONS Recurrent HCV and PSC were major causes of allograft liver failure in Japan. In addition to CTP and MELD scores, either serum ALT levels or causes of allograft failure should be considered as graft liver allocation measures.
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Alamoudi JA, Li W, Gautam N, Olivera M, Meza J, Mukherjee S, Alnouti Y. Bile acid indices as biomarkers for liver diseases II: The bile acid score survival prognostic model. World J Hepatol 2021; 13:543-556. [PMID: 34131469 PMCID: PMC8173345 DOI: 10.4254/wjh.v13.i5.543] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/21/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cholestatic liver diseases are characterized by an accumulation of toxic bile acids (BA) in the liver, blood and other tissues which lead to progressive liver injury and poor prognosis in patients. AIM To discover and validate prognostic biomarkers of cholestatic liver diseases based on the urinary BA profile. METHODS We analyzed urine samples by liquid chromatography-tandem mass spectrometry and investigated the use of the urinary BA profile to develop survival models that can predict the prognosis of hepatobiliary diseases. The urinary BA profile, a set of non-BA parameters, and the adverse events of liver transplant and/or death were monitored in 257 patients with cholestatic liver diseases for up to 7 years. The BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, formation of secondary BA, and toxicity of the BA profile. We have developed and validated the bile-acid score (BAS) model (a survival model based on BA indices) to predict the prognosis of cholestatic liver diseases. RESULTS We have developed and validated a survival model based on BA (the BAS model) indices to predict the prognosis of cholestatic liver diseases. Our results demonstrate that the BAS model is more accurate and results in higher true-positive and true-negative prediction of death compared to both non-BAS and model for end-stage liver disease (MELD) models. Both 5- and 3-year survival probabilities markedly decreased as a function of BAS. Moreover, patients with high BAS had a 4-fold higher rate of death and lived for an average of 11 mo shorter than subjects with low BAS. The increased risk of death with high vs low BAS was also 2-4-fold higher and the shortening of lifespan was 6-7-mo lower compared to MELD or non-BAS. Similarly, we have shown the use of BAS to predict the survival of patients with and without liver transplant (LT). Therefore, BAS could be used to define the most seriously ill patients, who need earlier intervention such as LT. This will help provide guidance for timely care for liver patients. CONCLUSION The BAS model is more accurate than MELD and non-BAS models in predicting the prognosis of cholestatic liver diseases.
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Affiliation(s)
- Jawaher Abdullah Alamoudi
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-6025, United States
| | - Wenkuan Li
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-6025, United States
| | - Nagsen Gautam
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-6025, United States
| | - Marco Olivera
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Jane Meza
- Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE 68198-4375, United States
| | - Sandeep Mukherjee
- Department of Internal Medicine, Creighton University Medical Center, Omaha, NE 68124, United States
| | - Yazen Alnouti
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-6025, United States.
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10
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Alamoudi JA, Li W, Gautam N, Olivera M, Meza J, Mukherjee S, Alnouti Y. Bile acid indices as biomarkers for liver diseases I: Diagnostic markers. World J Hepatol 2021; 13:433-455. [PMID: 33959226 PMCID: PMC8080550 DOI: 10.4254/wjh.v13.i4.433] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/11/2021] [Accepted: 03/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis. AIM To discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile. METHODS We analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical analysis. The BA profile was characterized using BA indices, which quantifies the composition, metabolism, hydrophilicity, and toxicity of the BA profile. BA indices have much lower inter- and intra-individual variability compared to absolute concentrations of BA. In addition, BA indices demonstrate high area under the receiver operating characteristic curves, and changes of BA indices are associated with the risk of having a liver disease, which demonstrates their use as diagnostic biomarkers for cholestatic liver diseases. RESULTS Total and individual BA concentrations were higher in all patients. The percentage of secondary BA (lithocholic acid and deoxycholic acid) was significantly lower, while the percentage of primary BA (chenodeoxycholic acid, cholic acid, and hyocholic acid) was markedly higher in patients compared to controls. In addition, the percentage of taurine-amidation was higher in patients than controls. The increase in the non-12α-OH BA was more profound than 12α-OH BA (cholic acid and deoxycholic acid) causing a decrease in the 12α-OH/ non-12α-OH ratio in patients. This trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic decompensation. The percentage of sulfation was also higher in patients with more severe forms of liver diseases. CONCLUSION BA indices have much lower inter- and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the risk of developing liver diseases.
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Affiliation(s)
- Jawaher Abdullah Alamoudi
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Wenkuan Li
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Nagsen Gautam
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Marco Olivera
- Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Jane Meza
- Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Sandeep Mukherjee
- Department of Internal Medicine, College of Medicine, Creighton University Medical Center, Omaha, NE 68124, United States
| | - Yazen Alnouti
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States.
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11
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Osiecki M, Kierkuś J, Pawłowska J, Woźniak M, Jankowska I, Teisseyre M, Dądalski M, Jarzębicka D, Stefanowicz M, Czubkowski P. The Course of Ulcerative Colitis After Pediatric Liver Transplantation for Sclerosing Cholangitis. Transplant Proc 2020; 53:244-249. [PMID: 33162100 DOI: 10.1016/j.transproceed.2020.09.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 08/30/2020] [Accepted: 09/20/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC) are often associated with ulcerative colitis (UC). The impact on the course of UC remains unclear, and up-to-date evidence in pediatric populations is scarce. The aim of the study was to analyze the course of UC in pediatric patients transplanted owing to PSC or ASC. MATERIAL AND METHODS We retrospectively reviewed data from children with PSC/ASC and UC who underwent orthotopic liver transplantation (OLT). In all patients UC diagnosis was based on clinical presentation, endoscopy, and histology. RESULTS Seventeen patients (9 female) with PSC or ASC underwent OLT from deceased donors at a median age of 16.8 years (range = 11.5-18.2 years). In 15 patients, UC was diagnosed before OLT (median age of diagnosis = 10.6 years; range = 6.6-18.0 years), and 2 patients developed UC after OLT. Ten patients (59%) presented with pancolitis on initial endoscopy. Disease activity was severe in 9 patients (53%) and most patients improved after initial treatment with steroids. Before OLT only 2 patients (13%) had severe disease activity. After OLT, 4 patients developed flares of the disease. These patients were successfully treated and remained in remission at the end of the posttransplant follow-up period (median = 3.76 years; range = 0.4-15.5 years). None of the patients developed colorectal cancer or underwent colectomy during 3.7 years of post-OLT follow-up. CONCLUSION In our experience, the course of UC was not aggravated by OLT for PSC, and UC did not adversely affect patient or graft survival.
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Affiliation(s)
- Marcin Osiecki
- Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland.
| | - Jarosław Kierkuś
- Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Joanna Pawłowska
- Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Małgorzata Woźniak
- Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Irena Jankowska
- Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Mikołaj Teisseyre
- Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Maciej Dądalski
- Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Dorota Jarzębicka
- Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Marek Stefanowicz
- Department of Paediatric Surgery and Organ Transplantation, The Children's Memorial Health Institute, Warsaw, Poland
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland
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12
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Perino A, Demagny H, Velazquez-Villegas L, Schoonjans K. Molecular Physiology of Bile Acid Signaling in Health, Disease, and Aging. Physiol Rev 2020; 101:683-731. [PMID: 32790577 DOI: 10.1152/physrev.00049.2019] [Citation(s) in RCA: 249] [Impact Index Per Article: 49.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Over the past two decades, bile acids (BAs) have become established as important signaling molecules that enable fine-tuned inter-tissue communication from the liver, their site of production, over the intestine, where they are modified by the gut microbiota, to virtually any organ, where they exert their pleiotropic physiological effects. The chemical variety of BAs, to a large extent determined by the gut microbiome, also allows for a complex fine-tuning of adaptive responses in our body. This review provides an overview of the mechanisms by which BA receptors coordinate several aspects of physiology and highlights new therapeutic strategies for diseases underlying pathological BA signaling.
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Affiliation(s)
- Alessia Perino
- Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne (EPFL), Switzerland
| | - Hadrien Demagny
- Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne (EPFL), Switzerland
| | - Laura Velazquez-Villegas
- Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne (EPFL), Switzerland
| | - Kristina Schoonjans
- Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne (EPFL), Switzerland
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13
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Dekkers N, Westerouen van Meeteren M, Wolterbeek R, Farina Sarasqueta A, Laleman W, Inderson A, Desschans B, van Hoek B, Sebib Korkmaz K, Vermeire S, Maljaars J. Does mucosal inflammation drive recurrence of primary sclerosing cholangitis in liver transplantion recipients with ulcerative colitis? Dig Liver Dis 2020; 52:528-533. [PMID: 32147286 DOI: 10.1016/j.dld.2020.02.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 01/20/2020] [Accepted: 02/05/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Liver transplantation remains the only effective evidence based treatment for advanced primary sclerosing cholangitis. However, recurrence of disease occurs in approximately 18%. AIMS This study aimed to assess risk factors of recurrence of primary sclerosing cholangitis. METHODS A retrospective cohort study was performed on patients undergoing transplantation for recurrence of primary sclerosing cholangitis in two academic centers (Leuven, Belgium and Leiden, The Netherlands). Besides other risk factors, the degree of mucosal inflammation was assessed as a potential risk factor using histological Geboes scores. RESULTS 81 patients were included, of which 62 (76.5%) were diagnosed with ulcerative colitis. Seventeen patients (21.0%) developed rPSC during a median follow-up time of 5.2 years. In a subset of 42 patients no association was found between the degree of mucosal inflammation and recurrence, using both original Geboes scores and multiple cut-off points. In the total cohort, cytomegaloviremia post-transplantation (HR: 4.576, 95%CI 1.688-12.403) and younger receiver age at time of liver transplantation (HR: 0.934, 95%CI 0.881-0.990) were independently associated with an increased risk of recurrence of disease. CONCLUSION This study found no association between the degree of mucosal inflammation and recurrence of primary sclerosing cholangitis. An association with recurrence was found for cytomegaloviremia post-liver transplantation and younger age at time of liver transplantation.
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Affiliation(s)
- Nik Dekkers
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands.
| | - Menso Westerouen van Meeteren
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
| | - Ron Wolterbeek
- Leiden University Medical Centre, Department of Medical Statistics, LUMC, Leiden, The Netherlands
| | - Arantza Farina Sarasqueta
- Leiden University Medical Centre, Department of Pathology, LUMC, Leiden, The Netherlands; Amsterdam University Medical Centre, Department of Pathology, AUMC, Amsterdam, The Netherlands
| | - Wim Laleman
- University Hospitals Leuven, Department of Gastroenterology-Hepatology, Division of Liver and Biliopancreatic Disorders, KU Leuven, Leuven, Belgium; KU Leuven, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), Leuven, Belgium; University Hospitals Leuven, Department of Abdominal Transplant Surgery & Transplant Coordination, KU Leuven, Belgium
| | - Akin Inderson
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
| | - Bruno Desschans
- University Hospitals Leuven, Department of Gastroenterology-Hepatology, Division of Liver and Biliopancreatic Disorders, KU Leuven, Leuven, Belgium
| | - Bart van Hoek
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
| | - Kerem Sebib Korkmaz
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
| | - Severine Vermeire
- KU Leuven, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology-Hepatology, KU Leuven, Belgium
| | - Jeroen Maljaars
- Leiden University Medical Centre, Department of Gastroenterology-hepatology, LUMC: Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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14
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Biodegradable versus multiple plastic stent implantation in benign biliary strictures: A systematic review and meta-analysis. Eur J Radiol 2020; 125:108899. [DOI: 10.1016/j.ejrad.2020.108899] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 02/04/2020] [Accepted: 02/11/2020] [Indexed: 12/12/2022]
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15
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Singhi AD, Nikiforova MN, Chennat J, Papachristou GI, Khalid A, Rabinovitz M, Das R, Sarkaria S, Ayasso MS, Wald AI, Monaco SE, Nalesnik M, Ohori NP, Geller D, Tsung A, Zureikat AH, Zeh H, Marsh JW, Hogg M, Lee K, Bartlett DL, Pingpank JF, Humar A, Bahary N, Dasyam AK, Brand R, Fasanella KE, McGrath K, Slivka A. Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures. Gut 2020; 69:52-61. [PMID: 30971436 PMCID: PMC6943248 DOI: 10.1136/gutjnl-2018-317817] [Citation(s) in RCA: 112] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 03/25/2019] [Accepted: 03/27/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.
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Affiliation(s)
- Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - Marina N Nikiforova
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - Jennifer Chennat
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | - Asif Khalid
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | - Rohit Das
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Savreet Sarkaria
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - M Samir Ayasso
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Abigail I Wald
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - Sara E Monaco
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - Michael Nalesnik
- Department of Pathology, Division of Transplant Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - N Paul Ohori
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - David Geller
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Allan Tsung
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Herbert Zeh
- Department of Clinical Sciences, Surgery, University of Texas Southwestern, Dallas, Texas, USA
| | - J Wallis Marsh
- Department of Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA
| | - Melissa Hogg
- Department of Surgery, NorthShore University Health System, Evanston, Illinois, USA
| | - Kenneth Lee
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - David L Bartlett
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - James F Pingpank
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Abhinav Humar
- Department of Transplant, Thomas E Starzl Transplant Instiute University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Nathan Bahary
- Division of Hematology and Oncology, UPMC Cancer Centers, Pittsburgh, Pennsylvania, USA
| | - Anil K Dasyam
- Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Randall Brand
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kenneth E Fasanella
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kevin McGrath
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Adam Slivka
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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16
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Black DD, Mack C, Kerkar N, Miloh T, Sundaram SS, Anand R, Gupta A, Alonso E, Arnon R, Bulut P, Karpen S, Lin CH, Rosenthal P, Ryan M, Squires RH, Valentino P, Elsea SH, Shneider BL. A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis. Hepatol Commun 2019; 3:1482-1495. [PMID: 31701072 PMCID: PMC6824074 DOI: 10.1002/hep4.1421] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 07/27/2019] [Indexed: 12/15/2022] Open
Abstract
Ursodeoxycholic acid (UDCA) is commonly used to treat several liver disorders in adults and children, including primary sclerosing cholangitis (PSC) for which it is not U.S. Food and Drug Administration approved. UDCA treatment has an uncertain impact on disease outcomes and has been reported in high doses to be associated with worse outcome in adults with PSC. In this context, controlled withdrawal and reintroduction of UDCA in children with PSC were studied. Prior to study initiation, participants were required to have alanine aminotransferase (ALT) and gamma‐glutamyl transpeptidase (GGT) <2 times the upper limit of normal on stable UDCA dosing. The study included four phases: I (stable dosing), II (50% UDCA reduction), III (UDCA discontinuation), IV (UDCA reintroduction), with a primary endpoint of change in ALT and GGT between phases I and III. We enrolled 27 participants (22 completed) between March 2011 and June 2016. Changes in mean ALT and GGT between phases I and III were ALT, +29.5 IU/L (P = 0.105) and GGT, +60.4 IU/L (P = 0.003). In 7 participants, ALT and GGT ≤29 IU/L did not rise above 29 IU/L (null response group). Eight participants had increases of ALT or GGT >100 IU/L (flare group). None developed elevated bilirubin. All flares responded to UDCA reinstitution. Serum GGT, interleukin‐8, and tumor necrosis factor α levels were higher in the flare group at baseline. Liver biochemistries increased in children with PSC during controlled UDCA withdrawal; one third increased above 100 IU/L and one third remained normal during UDCA withdrawal. Conclusion: The impact of prolonged UDCA use in childhood PSC and the significance of a biochemical flare are unclear. Further studies of the natural history and treatment of pediatric PSC and UDCA use are needed.
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Affiliation(s)
- Dennis D Black
- Pediatrics University of Tennessee Health Science Center Memphis TN
| | - Cara Mack
- Pediatrics University of Colorado School of Medicine Aurora CO
| | - Nanda Kerkar
- Pediatrics University of Rochester Medical Center Rochester NY.,Pediatrics Keck School of Medicine of University of Southern California Los Angeles CA
| | - Tamir Miloh
- Pediatrics Baylor College of Medicine Houston TX
| | | | | | | | - Estella Alonso
- Pediatrics Northwestern University College of Medicine Chicago IL
| | - Ronen Arnon
- Pediatrics Mount Sinai Icahn School of Medicine New York NY
| | - Pinar Bulut
- Pediatrics Phoenix Children's Hospital Phoenix AZ
| | - Saul Karpen
- Pediatrics Emory University School of Medicine Atlanta GA
| | - Chuan-Hao Lin
- Pediatrics Keck School of Medicine of University of Southern California Los Angeles CA
| | - Philip Rosenthal
- Pediatrics School of Medicine University of California, San Francisco San Francisco CA
| | - Matthew Ryan
- Pediatrics Children's Hospital of Philadelphia Philadelphia PA
| | - Robert H Squires
- Pediatrics University of Pittsburgh School of Medicine Pittsburgh PA
| | | | - Sarah H Elsea
- Molecular and Human Genetics Baylor College of Medicine Houston TX
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17
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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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18
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Mohajeri S, Bezabeh T, Ijare OB, King SB, Thomas MA, Minuk G, Lipschitz J, Kirkpatrick I, Micflikier AB, Summers R, Smith ICP. In vivo 1 H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune-mediated disease versus bile acid-induced injury. NMR IN BIOMEDICINE 2019; 32:e4065. [PMID: 30735273 DOI: 10.1002/nbm.4065] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Revised: 12/11/2018] [Accepted: 12/12/2018] [Indexed: 06/09/2023]
Abstract
Primary sclerosing cholangitis (PSC) has been considered to be either an "autoimmune disease" or a "bile acid-induced injury." In vitro MRS studies on PSC patients have limitations due to the contamination of bile with contrast agent (commonly administered during endoscopic retrograde cholangiopancreatography) and/or the use of patient cohorts with other diseases as controls. The objective of this study was to quantify biliary metabolites using in vivo 1 H MRS and gain insight into the pathogenesis of PSC. Biliary metabolites in 10 PSC patients and 14 healthy controls were quantified in vivo using 1 H MRS on a 3 T MR scanner. The concentrations of total bile acids plus cholesterol, glycine-conjugated bile acids, taurine-conjugated bile acids, and choline-containing phospholipids (chol-PLs) were compared between the two groups. There were statistically significant decreases in the levels of the above mentioned biliary metabolites in the PSC patients compared with controls. The reduction in bile acid secretion in bile of PSC patients indicates accumulation of bile acids in hepatocytes. Moreover, reduction in the levels of chol-PLs in bile may increase the toxic effects of bile acids. Our findings suggest that the bile duct injury in PSC patients is most likely due to "bile acid-induced injury."
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Affiliation(s)
| | - Tedros Bezabeh
- University of Winnipeg, Winnipeg, Manitoba, Canada
- University of Guam, Mangilao, Guam, USA
| | | | - Scott B King
- National Research Council of Canada, Winnipeg, Manitoba, Canada
| | | | - Gerald Minuk
- University of Manitoba, Winnipeg, Manitoba, Canada
| | | | | | | | - Randy Summers
- National Research Council of Canada, Winnipeg, Manitoba, Canada
| | - Ian C P Smith
- University of Manitoba, Winnipeg, Manitoba, Canada
- University of Winnipeg, Winnipeg, Manitoba, Canada
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19
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Abstract
Cholangiocarcinoma is a rare malignancy and accounts for 2% of all malignancies. Incidence is on the increase in the Western world. Cholangiocarcinoma arises from the malignant growth of the epithelial lining of the bile ducts and can be found all along the biliary tree. It can be classified into subtypes based on location: intrahepatic (arising from the intrahepatic biliary tract in the hepatic parenchyma), perihilar (at the hilum of the liver involving the biliary confluence) and distal (extrahepatic, often in the head of the pancreas). Margin status and locoregional lymph node metastases are the most important determinants of postsurgical outcomes.
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Affiliation(s)
- Adeel S Khan
- Section of Abdominal Transplant Surgery, Washington University St Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO 63110, USA.
| | - Leigh Anne Dageforde
- Division of Transplant Surgery, Massachusetts General Hospital, 55 Fruit Street, White 511, Boston, MA 02114, USA
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20
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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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21
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Akulkina LA, Brovko MY, Sholomova VI, Rozina TP, Yanakayeva AS, Frantsuzevich LY, Lebedeva MV, Fomin VV. Variety of lung involvement in autoimmune liver diseases. TERAPEVT ARKH 2018. [DOI: 10.26442/terarkh2018908107-112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The primary autoimmune liver diseases conventionally include primary biliary cholangitis, primary sclerosing cholangitis and autoimmune hepatitis. Despite of primary autoimmune affection of different parts of the hepatobiliary system, in the recent decades, a lot of data has emerged indicating the presence of extrahepatic manifestations of these diseases, in particular, lung lesions, such as nodular and interstitial changes with possible progression and development of fibrosis and respiratory failure. In case of lungs disease, both pulmonary parenchyma and lung vessels, pleura, and intrathoracic lymph nodes can be involved. The most sensitive and specific procedure to assess the extent of the lung lesions and their evolution is high-resolution computed tomography. Due to the possibility of long-term asymptomatic course of the pulmonary disease with development of irreversible changes in patients with autoimmune liver diseases, it seems reasonable to conduct screening studies aimed at early detection and treatment of lung lesions in this population.
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Ferrari F, Ranucci G, Aloi M, Della Volpe L, Viola F, Miele E, Cucchiara S, Iorio R. A promising medium-term follow-up of pediatric sclerosing cholangitis: Mild phenotype or early diagnosis? Hepatol Res 2018; 48:556-565. [PMID: 29316057 DOI: 10.1111/hepr.13059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 01/02/2018] [Accepted: 01/05/2018] [Indexed: 12/24/2022]
Abstract
AIM Sclerosing cholangitis (SC) is a chronic cholestatic liver disease that is being increasingly diagnosed in childhood. The long-term course and prognosis of pediatric SC are poorly described. METHODS We reviewed data of pediatric SC patients, followed in two referral centers, during a period of up to 20 years. We aimed to evaluate long-term outcomes according to SC phenotype. RESULTS Among 45 patients (median age, 10.4 years; male patients, 73.4%) 29 (64.4%) were asymptomatic at presentation. Twenty patients (44%) had a concomitant inflammatory bowel disease (SC/IBD). Autoimmune features were found in 20 patients (44%). Liver biopsy showed severe fibrosis or cirrhosis in 32% of cases. Patients with SC alone had a higher rate of interface hepatitis at liver biopsy than SC/IBD patients. All children received ursodeoxycholic acid at diagnosis, and 17 received steroids and/or azathioprine. After a mean follow-up of 8.7 ± 5.6 years, all patients were alive and seven developed at least one liver-related complication. At the end of follow-up, 10 patients stopped immunosuppressants and two had no therapy. Only two patients underwent liver transplantation. Complication-free survival did not differ between SC/IBD and SC patients, but survival was longer in patients without autoimmune features. CONCLUSIONS In our early diagnosed cohort, the 9-year survival with native liver was better than that reported in other studies. Approximately 15% of patients developed liver-related disease complications, less than previously reported. The long-term course of SC was negatively influenced by the presence of autoimmune features, but not by concomitant IBD.
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Affiliation(s)
- Federica Ferrari
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Italy
| | - Giusy Ranucci
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Marina Aloi
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Italy
| | - Luca Della Volpe
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Franca Viola
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Italy
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Salvatore Cucchiara
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Italy
| | - Raffaele Iorio
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
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Thakare R, Alamoudi JA, Gautam N, Rodrigues AD, Alnouti Y. Species differences in bile acids I. Plasma and urine bile acid composition. J Appl Toxicol 2018; 38:1323-1335. [DOI: 10.1002/jat.3644] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 04/11/2018] [Accepted: 04/11/2018] [Indexed: 12/20/2022]
Affiliation(s)
- Rhishikesh Thakare
- Department of Pharmaceutical Sciences, College of Pharmacy; University of Nebraska Medical Center; Omaha NE 68198 USA
| | - Jawaher Abdullah Alamoudi
- Department of Pharmaceutical Sciences, College of Pharmacy; University of Nebraska Medical Center; Omaha NE 68198 USA
| | - Nagsen Gautam
- Department of Pharmaceutical Sciences, College of Pharmacy; University of Nebraska Medical Center; Omaha NE 68198 USA
| | - A. David Rodrigues
- Pharmacokinetics, Pharmacodynamics & Metabolism, Medicine Design, Pfizer Inc.; Groton CT 06340 USA
| | - Yazen Alnouti
- Department of Pharmaceutical Sciences, College of Pharmacy; University of Nebraska Medical Center; Omaha NE 68198 USA
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Wu J, Zhu P, Zhang Z, Zhang B, Shu C, Chen L, Feng R, Mba'nbo Koumpa AA, Li G, Ge Q. A new tumor-associated antigen prognostic scoring system for spontaneous ruptured hepatocellular carcinoma after partial hepatectomy. Cancer Biol Med 2018; 15:415-424. [PMID: 30766751 PMCID: PMC6372911 DOI: 10.20892/j.issn.2095-3941.2018.0095] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objective: Spontaneous hepatocellular carcinoma (HCC) rupture can be fatal, and hepatic resection could achieve a favorable long-term survival among all strategies of tumor rupture. However, there is no available prognostic scoring system for patients with ruptured HCC who underwent partial hepatectomy. Methods: From January 2005 to May 2015, 129 patients with spontaneous HCC rupture underwent partial hepatectomy. Preoperative clinical data were collected and analyzed. Independent risk factors affecting overall survival (OS) were used to develop the new scoring system. Harrell’s C statistics, Akaike information criterion (AIC), the relative likelihood, and the log likelihood ratio were calculated to measure the homogeneity and discriminatory ability of a prognostic system. Results: In the multivariable Cox regression analysis, three factors, including tumor size, preoperative α-fetoprotein level, and alkaline phosphatase level, were chosen for the new tumor-associated antigen (TAA) prognostic scoring system. The 1-year OS rates were 88.1%, 43.2%, and 30.2% for TAA scores of 0–5 points (low-risk group), 6–9 points (moderate-risk group), and 10–13 points (high-risk group), respectively. The TAA scoring system had superior homogeneity and discriminatory ability (Harrell’s C statistics, 0.693 vs. 0.627 and 0.634; AIC, 794.79 vs. 817.23 and 820.16; relative likelihood, both < 0.001; and log likelihood ratio, 45.21 vs. 22.77 and 21.84) than the Barcelona Clinic Liver Cancer staging system and the Cancer of the Liver Italian Program in predicting OS. Similar results were found while predicting disease-free survival (DFS).
Conclusions: The new prognostic scoring system is simple and effective in predicting both OS and DFS of patients with spontaneous ruptured HCC.
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Affiliation(s)
| | - Peng Zhu
- Department of Hepatic Surgery Center
| | | | | | - Chang Shu
- Department of Hepatic Surgery Center
| | - Lin Chen
- Department of Hepatic Surgery Center
| | - Renjie Feng
- Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China
| | | | - Ganxun Li
- Department of Hepatic Surgery Center
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Majeed A, Castedal M, Arnelo U, Söderdahl G, Bergquist A, Said K. Optimizing the detection of biliary dysplasia in primary sclerosing cholangitis before liver transplantation. Scand J Gastroenterol 2018; 53:56-63. [PMID: 28990806 DOI: 10.1080/00365521.2017.1385840] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Patients with primary sclerosing cholangitis (PSC) have increased risk of cholangiocarcinoma (CCA). We evaluated pre-transplant work-up in PSC patients, to search for the most effective strategy for the detection of biliary dysplasia or early CCA. METHODS Two hundred and twenty five consecutive PSC patients undergoing liver transplantation (LTx) in Sweden between 1999 and 2013 were studied. Patients with CCA or dysplasia in the explanted liver were compared with those with benign histopathology. Measures of test performance were calculated for patients having brush cytology on one endoscopic retrograde cholangiopancreaticography (ERCP) occasion, for those having repeated examinations with or without cholangioscopy, and for fluorescence in situ hybridization (FISH). Survival after LTx was analyzed. RESULTS Brush cytology on a single ERCP occasion had moderate sensitivity (57%) and high specificity (94%) for the detection of CCA/high grade dysplasia (HGD) in the explanted liver. The corresponding sensitivity and specificity for FISH were 84% and 90%, respectively. Utilizing repeated ERCP and brush cytology to confirm the initial finding improved sensitivity to 82%. Using single operator cholangioscopy (SOC) for targeted examination at the second ERCP improved sensitivity (100%) and specificity (97%) significantly. Mortality rate in patients with incidentally discovered CCA (n = 16) in the explanted liver was significantly higher than in patients with HGD or benign histopathology (HR 16.0; 95% CI, 5.6-45.4; p < .001). CONCLUSIONS Repeated brush cytology especially when combined with targeted examination under SOC guidance is superior to single brush examinations. This strategy improves the detection of malignancy in PSC and is of importance for selection of patients for LTx.
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Affiliation(s)
- Ammar Majeed
- a Center for Digestive Disease, Karolinska University Hospital, Karolinska Institutet , Stockholm , Sweden.,b Department of Medical Epidemiology and Biostatistics , Karolinska Institutet , Stockholm , Sweden.,c Central Clinical School, Monash University, Alfred Hospital , Melbourne , Australia
| | - Maria Castedal
- d Transplant Institute, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Urban Arnelo
- a Center for Digestive Disease, Karolinska University Hospital, Karolinska Institutet , Stockholm , Sweden.,e Department of Clinical Science, Division of Surgery , Intervention and Technology (CLINTEC), Karolinska Institutet , Stockholm , Sweden
| | - Gunnar Söderdahl
- a Center for Digestive Disease, Karolinska University Hospital, Karolinska Institutet , Stockholm , Sweden.,f Department of Transplantation Surgery , Karolinska Institutet and Karolinska University Hospital , Huddinge , Sweden
| | - Annika Bergquist
- a Center for Digestive Disease, Karolinska University Hospital, Karolinska Institutet , Stockholm , Sweden
| | - Karouk Said
- a Center for Digestive Disease, Karolinska University Hospital, Karolinska Institutet , Stockholm , Sweden
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Mizuno S, Isayama H, Hirano K, Watanabe T, Takahara N, Kogure H, Matsubara S, Nakai Y, Tada M, Koike K. Factors predictive of the efficacy of bezafibrate therapy in patients with primary sclerosing cholangitis. Hepatol Res 2017; 47:1102-1107. [PMID: 27874998 DOI: 10.1111/hepr.12846] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 11/17/2016] [Accepted: 11/20/2016] [Indexed: 12/13/2022]
Abstract
AIM Primary sclerosing cholangitis (PSC) is a rare cholestatic disease. We previously reported the effects of bezafibrate on elevated hepatobiliary enzyme levels in patients with this disease both retrospectively and prospectively. In this study, we assessed factors predictive of bezafibrate efficacy. METHODS Twenty-five patients with PSC, who underwent bezafibrate therapy (400 mg per day) from November 2006 to June 2015, were evaluated. Treatment was judged as being effective if the levels of all of the hepatobiliary enzymes decreased after 12 weeks. We investigated the patients' characteristics, disease history, concomitant medications, liver function, and liver stiffness. RESULTS The efficacy rate of bezafibrate was 60% (15/25 patients). The efficacy rate in patients graded as Child-Pugh class A was significantly higher (75% [15/20]) than that in patients graded as class B (0% [0/5], P < 0.01). Non-responders had higher liver stiffness values (18.0 vs. 8.8 kPa, P = 0.19), and concomitantly used ursodeoxycholic acid more frequently (100% vs. 73%, P = 0.12) than responders. CONCLUSIONS We could not elucidate the factors predictive for bezafibrate efficacy for the treatment of PSC. However, bezafibrate was more effective for patients with preserved liver function (Child-Pugh class A) when it was prescribed before progression of liver fibrosis and failure of ursodeoxycholic acid therapy.
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Affiliation(s)
- Suguru Mizuno
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kenji Hirano
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Takeo Watanabe
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Naminatsu Takahara
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hirofumi Kogure
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Saburo Matsubara
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Minoru Tada
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Hall C, Ehrlich L, Meng F, Invernizzi P, Bernuzzi F, Lairmore TC, Alpini G, Glaser S. Inhibition of microRNA-24 increases liver fibrosis by enhanced menin expression in Mdr2 -/- mice. J Surg Res 2017; 217:160-169. [PMID: 28602220 PMCID: PMC5760243 DOI: 10.1016/j.jss.2017.05.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 04/03/2017] [Accepted: 05/03/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Liver transplantation remains the primary treatment for primary sclerosing cholangitis (PSC). Mdr2-/- mice provide a reliable in vivo model of PSC and develop characteristic biliary inflammation and fibrosis. We tested the hypothesis that the tumor suppressor protein menin is implicated in the progression of liver fibrosis and that menin expression can be regulated in the liver via microRNA-24 (miR-24). MATERIALS AND METHODS Menin expression was measured in human PSC and Mdr2-/- mice. Twelve-week-old FVB/NJ wild-type (WT) and Mdr2-/- mice were treated with miR-24 Vivo-Morpholino to knockdown miR-24 expression levels. Liver fibrosis was evaluated by Sirius Red staining and quantitative polymerase chain reaction (qPCR) for genes associated with liver fibrosis, such as fibronectin 1, collagen type 1 alpha 1, transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin. Studies were also performed in vitro using immortalized murine cholangiocyte lines treated with miR-24 hairpin inhibitor and mimic. RESULTS Menin gene expression was increased in Mdr2-/- mice and late-stage human PSC samples. Treatment of FVB/NJ WT and Mdr2-/- mice with miR-24 Vivo-Morpholino increased menin expression, which correlated with increased expression of fibrosis genes. In vitro, inhibition of miR-24 also significantly increased the expression of fibrosis genes. CONCLUSIONS Inhibition of miR-24 increases menin and TGF-β1 expression, subsequently increasing hepatic fibrosis in FVB/NJ WT and Mdr2-/- mice. Modulation of the menin/miR-24 axis may provide novel targeted therapies to slow the progression of hepatic fibrosis into cirrhosis in PSC patients by altering TGF-β1 expression.
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Affiliation(s)
- Chad Hall
- Department of Surgery, Baylor Scott & White Health and Texas A&M University Health Science Center, Temple, Texas
| | - Laurent Ehrlich
- Department of Surgery, Baylor Scott & White Health and Texas A&M University Health Science Center, Temple, Texas; Department of Medicine, Baylor Scott & White Health and Texas A&M University Health Science Center, Temple, Texas
| | - Fanyin Meng
- Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, Texas
| | - Pietro Invernizzi
- Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Francesca Bernuzzi
- Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Terry C Lairmore
- Department of Surgery, Baylor Scott & White Health and Texas A&M University Health Science Center, Temple, Texas
| | - Gianfranco Alpini
- Department of Medicine, Baylor Scott & White Health and Texas A&M University Health Science Center, Temple, Texas; Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, Texas; Research, Central Texas Veterans Health Care System, Temple, Texas
| | - Shannon Glaser
- Department of Medicine, Baylor Scott & White Health and Texas A&M University Health Science Center, Temple, Texas; Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, Texas; Research, Central Texas Veterans Health Care System, Temple, Texas.
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Lammert C, Vuppalanchi R. Future Therapies for Primary Sclerosing Cholangitis. PRIMARY SCLEROSING CHOLANGITIS 2017:153-166. [DOI: 10.1007/978-3-319-40908-5_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kuzu UB, Ödemiş B, Suna N, Yıldız H, Parlak E, Dişibeyaz S, Torun S, Akpınar MY, Coşkun O, Turhan N, Yüksel M, Kayaçetin E. The Detection of Cholangiocarcinoma in Primary Sclerosing Cholangitis Patients: Single Center Experience. J Gastrointest Cancer 2016; 47:8-14. [PMID: 26537791 DOI: 10.1007/s12029-015-9777-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. Cholangiocarcinoma (CCA) is one of the feared complications of PSC. In our study, we aim to establish the success of brush cytology and CA 19-9 in putting the diagnosis of CCA. METHODS The data of 30 PSC patients was retrospectively screened whom had brush cytology performed due to dominant strictures. The definitive diagnosis was established by histopathological examination or via radiological/clinic follow-up for at least 12 months. RESULTS A total of four patients were excluded from the study. Twenty-six patients diagnosed with PSC, six of which were also diagnosed with CCA, were included in the study. The sensitivity and the specificity of the brush cytology in the diagnosis of CCA in PSC patients were 66.7 and 95%, respectively. CA 19-9 had high correlation with bilirubin level. The optimal level of CA 19-9 in the diagnosis of CCA was determined to be 138.5 U/ml. Superiority of Ramage scoring over CA 19-9 in the diagnosis of CCA in PSC patients was not established (sensitivity and specificity were 50%, 94.7% and 83.3%, 85%, respectively). CONCLUSION Brush cytology has moderate sensitivity in differentiating strictures in PSC patients. CA 19-9 has high sensitivity but bilirubin level can affect the CA 19-9. Therefore, advanced techniques and parameters are needed for detecting CCA in PSC patients.
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Affiliation(s)
- Ufuk Barış Kuzu
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey.
| | - Bülent Ödemiş
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Nuretdin Suna
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Hakan Yıldız
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Erkan Parlak
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Selçuk Dişibeyaz
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Serkan Torun
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Muhammet Yener Akpınar
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Orhan Coşkun
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Nesrin Turhan
- Department of Pathology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Mahmut Yüksel
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Ertuğrul Kayaçetin
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
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Abstract
Cholangiocarcinomas are neoplasms that involve the epithelial cells of the bile duct, also known as cholangiocytes. This disease is difficult to diagnose early, as most symptoms present late in the disease. In addition, the specific anatomic position can cause periductal extension and result in a very low radical excision rate and a very poor prognosis. Improved understanding of the features underlying the onset of cholangiocarcinoma and its carcinogenic mechanism may lead to early diagnosis and better prognosis. With the development of molecular biology, much has been learned about oncogenes, tumor-suppressor genes, DNA methylation, microRNAs, and the molecular mechanisms of tumor invasion and metastasis. Based on our research and others, this review article will discuss the current status and prospects of early diagnosis of cholangiocarcinoma.
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Affiliation(s)
- Xiao-Fang Liu
- Department of Hepatobiliary Surgery, Affiliated Yantai Yuhuangding Hospital, Qingdao University Medical College, Yantai, China
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Primary sclerosing cholangitis associated with inflammatory bowel disease: an observational study in a Southern Europe population focusing on new therapeutic options. Eur J Gastroenterol Hepatol 2016; 28:508-13. [PMID: 26872110 DOI: 10.1097/meg.0000000000000596] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with a strong association with inflammatory bowel disease (IBD). Medical treatment for PSC is still disappointing, whereas immunomodulators and biologics have been proven to be effective in IBD. AIMS This study aimed to analyze (i) the natural history of patients with PSC with or without IBD and (ii) the long-term efficacy of biologics in patients with PSC and concomitant IBD or rheumatological disorders. PATIENTS AND METHODS This study included 92 consecutive PSC patients, 50 (54.3%) men and 42 (45.7%) women, with a mean age of 32.0±14.3 years at diagnosis and a mean follow-up duration of 103.8±86 months. Forty-nine (53.3%) patients had associated IBD (38 ulcerative colitis, 10 Crohn's disease, one indeterminate colitis). RESULTS No significant differences were found between PSC patients with and without associated IBD in terms of liver transplantation, cancer, and death rates. Cholangiocarcinoma was only identified among patients with PSC alone, whereas other cancers (hepatocellular carcinoma, colorectal, and gallbladder cancer) were found only in the group with associated IBD. Five PSC patients were treated with biologic agents: three with adalimumab and one with infliximab for IBD or for rheumatoid arthritis, and one patient with rituximab for rheumatoid arthritis. Adalimumab decreased alkaline phosphatase in two of three patients after 6 and 12 months, infliximab reduced γ-glutamyltransferase after 6 and 12 months, but liver function tests tended to deteriorate thereafter. Cholangiography changes remained stable in all patients. CONCLUSION Biologic agents may improve liver function tests in PSC patients, but may be associated with adverse events including deterioration of liver function.
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Fevery J, Van Steenbergen W, Van Pelt J, Laleman W, Hoffman I, Geboes K, Vermeire S, Nevens F. Patients with large-duct primary sclerosing cholangitis and Crohn's disease have a better outcome than those with ulcerative colitis, or without IBD. Aliment Pharmacol Ther 2016; 43:612-20. [PMID: 26748470 DOI: 10.1111/apt.13516] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Revised: 04/17/2015] [Accepted: 12/13/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Approximately 20% of primary sclerosing cholangitis (PSC) patients with concomitant inflammatory bowel disease (IBD) have Crohn's disease (CD). AIM To compare PSC/CD with other PSC patients. METHODS Retrospective study of 240 PSC patients diagnosed between 1975 and 2012 (median follow-up 12 years). Activity of PSC at diagnosis was assessed by liver biopsy, Mayo risk and ERC scores. Survival without liver transplantation, number of transplantations and liver-related death were endpoints. RESULTS Sixty-three per cent of patients had IBD: 105 UC, 32 CD and 14 IBD unclassified (IBDu). IBD was diagnosed before PSC in 50%. The yearly development of PSC after diagnosing IBD was similar in UC, CD or IBDu. Small-duct PSC was present in 28% of PSC/CD compared to 3% of PSC/UC. Small-duct PSC had a markedly better survival than large-duct PSC: no patient developed cholangiocarcinoma or liver-related death, but colorectal cancer occurred in three patients. In large-duct PSC, a more favourable outcome was evident in patients with CD. The liver disease was less progressive: one patient underwent liver transplantation compared to 28% and liver-related deaths were absent compared to 7% in the other PSC groups. CONCLUSIONS The prevalence of PSC with concomitant Crohn's disease is relatively rare, but the outcome is more benign than PSC with UC or without IBD. Approximately one-fourth has small-duct PSC. In large-duct PSC/CD, liver disease is less aggressive and the outcome is much better. The outcome of PSC patients with UC resembled that of PSC without IBD.
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Affiliation(s)
- J Fevery
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - W Van Steenbergen
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - J Van Pelt
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - W Laleman
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - I Hoffman
- Paediatric Gastroenterology, Department of Clinical and Experimental Medicine, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - K Geboes
- Pathology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - S Vermeire
- Gastroenterology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - F Nevens
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
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Kubitz R, Dröge C, Kluge S, Stross C, Walter N, Keitel V, Häussinger D, Stindt J. Autoimmune BSEP disease: disease recurrence after liver transplantation for progressive familial intrahepatic cholestasis. Clin Rev Allergy Immunol 2016; 48:273-84. [PMID: 25342496 DOI: 10.1007/s12016-014-8457-4] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Severe cholestasis may result in end-stage liver disease with the need of liver transplantation (LTX). In children, about 10 % of LTX are necessary because of cholestatic liver diseases. Apart from bile duct atresia, three types of progressive familial intrahepatic cholestasis (PFIC) are common causes of severe cholestasis in children. The three subtypes of PFIC are defined by the involved genes: PFIC-1, PFIC-2, and PFIC-3 are due to mutations of P-type ATPase ATP8B1 (familial intrahepatic cholestasis 1, FIC1), the ATP binding cassette transporter ABCB11 (bile salt export pump, BSEP), or ABCB4 (multidrug resistance protein 3, MDR3), respectively. All transporters are localized in the canalicular membrane of hepatocytes and together mediate bile salt and phospholipid transport. In some patients with PFIC-2 disease, recurrence has been observed after LTX, which mimics a PFIC phenotype. It could be shown by several groups that inhibitory anti-BSEP antibodies emerge, which most likely cause disease recurrence. The prevalence of severe BSEP mutations (e.g., splice site and premature stop codon mutations) is very high in this group of patients. These mutations often result in the complete absence of BSEP, which likely accounts for an insufficient auto-tolerance against BSEP. Although many aspects of this "new" disease are not fully elucidated, the possibility of anti-BSEP antibody formation has implications for the pre- and posttransplant management of PFIC-2 patients. This review will summarize the current knowledge including diagnosis, pathomechanisms, and management of "autoimmune BSEP disease."
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Affiliation(s)
- Ralf Kubitz
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany,
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Kerkar N, Yanni G. ‘De novo’ and ‘recurrent’ autoimmune hepatitis after liver transplantation: A comprehensive review. J Autoimmun 2016; 66:17-24. [DOI: 10.1016/j.jaut.2015.08.017] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 08/23/2015] [Indexed: 02/08/2023]
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Nakanishi Y, Saxena R. Nonneoplastic Hepatobiliary Disease. ESSENTIALS OF ANATOMIC PATHOLOGY 2016:1969-2030. [DOI: 10.1007/978-3-319-23380-2_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Geramizadeh B, Ghavvas R, Kazemi K, Shamsaeefar A, Nikeghbalian S, Malekhosseini SA. Cholangiocarcinoma Secondary to Primary Sclerosing Cholangitis in Explanted Livers: A Single-Center Study in the South of Iran. HEPATITIS MONTHLY 2015; 15:e33626. [PMID: 26977169 PMCID: PMC4779251 DOI: 10.5812/hepatmon.33626] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 11/24/2015] [Accepted: 11/28/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic disease, characterized by chronic inflammation and fibrosis of bile duct epithelial cells. This is a significant contributory factor to the development of malignancy, most commonly cholangiocarcinoma (CCA), which is the second most common malignant liver tumor. OBJECTIVES For the first time in Iran, we intend to describe our experience with cases of PSC, with and without CCA, in explanted livers, and compare our results with those found in other areas of the world. PATIENTS AND METHODS The study population comprised 181 individuals with a diagnosis of PSC who had undergone liver transplantation in the main liver transplant center of Iran, the largest center of hepatobiliary surgery in the south of that country, over a 3-year period between 2012 and 2014. All explanted livers, with and without CCA, were evaluated. RESULTS Of the 181 patients, 16 were found to have CCA, two of whom had been diagnosed after pathologic study of the explanted livers. Therefore it appeared that 8.8% of the patients with PSC in our center had developed CCA before liver transplantation. CONCLUSIONS A comparison of our results with those obtained from other centers in both Western and Asian countries (which reported CCA in 3.6% - 36.5% of patients with PSC), shows that the incidence of CCA in the patients we studied is intermediate.
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Affiliation(s)
- Bita Geramizadeh
- Department of Pathology, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Roshanak Ghavvas
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Kurosh Kazemi
- Department of Hepatobiliary and Liver Transplant Surgery, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Alireza Shamsaeefar
- Department of Hepatobiliary and Liver Transplant Surgery, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Saman Nikeghbalian
- Department of Hepatobiliary and Liver Transplant Surgery, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Seyed-Ali Malekhosseini
- Department of Hepatobiliary and Liver Transplant Surgery, Shiraz University of Medical Sciences, Shiraz, IR Iran
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Ravikumar R, Tsochatzis E, Jose S, Allison M, Athale A, Creamer F, Gunson B, Iyer V, Madanur M, Manas D, Monaco A, Mirza D, Owen N, Roberts K, Sen G, Srinivasan P, Wigmore S, Fusai G, Fernando B, Burroughs A. Risk factors for recurrent primary sclerosing cholangitis after liver transplantation. J Hepatol 2015; 63:1139-46. [PMID: 26186988 DOI: 10.1016/j.jhep.2015.07.005] [Citation(s) in RCA: 95] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 06/13/2015] [Accepted: 07/02/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is well recognised. However, the relationship between IBD and recurrent PSC (rPSC) is less well understood. We assessed the prevalence of rPSC and analysed the factors associated with rPSC post-liver transplantation and its influence on graft and patient survival. METHODS This is a UK multicentre observational cohort study across six of the seven national liver transplant units. All patients undergoing a first liver transplant for PSC between January 1 1990 and December 31 2010 were included. Prospectively collected liver transplant data was obtained from NHSBT and colitis data was retrospectively collected from individual units. RESULTS There were 679 (8.8%) first transplants for PSC. 347 patients (61.4%) had IBD, of which 306 (88.2%) had ulcerative colitis (UC). 81 (14.3%) patients developed rPSC and 37 (48.7%) of them developed graft failure from rPSC. Presence of UC post-liver transplant (HR=2.40, 95% CI 1.44-4.02) and younger age (HR=0.78, 95% CI 0.66-0.93) were the only factors significantly associated with rPSC. rPSC was associated with over a 4-fold increase in the risk of death (HR=4.71, 95% CI 3.39, 6.56) with 1, 5, and 10-year graft survival rates of 98%, 84%, and 56% respectively compared to 95%, 88%, and 72% in patients who did not develop rPSC. CONCLUSION The presence of UC post-liver transplant is associated with a significantly increased risk of rPSC. Furthermore, the presence of rPSC increases the rate of graft failure and death, with higher re-transplantation rates.
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Affiliation(s)
- Reena Ravikumar
- Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Sophie Jose
- Research Department of Infection and Population Health, University College London, UK
| | - Michael Allison
- Cambridge Transplant Unit, Cambridge University Hospitals, Cambridge, UK
| | - Anuja Athale
- Institute of Liver Studies, Kings College Hospital, London, UK
| | - Felicity Creamer
- Department of HPB and Liver Transplant Surgery, Royal Infirmary of Edinburgh, UK
| | | | - Vikram Iyer
- The Liver Unit, University Hospital Birmingham, UK
| | - Mansoor Madanur
- Institute of Liver Studies, Kings College Hospital, London, UK
| | - Derek Manas
- Institute of Transplantation, Freeman Hospital, Newcastle, UK
| | - Andrea Monaco
- Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Darius Mirza
- The Liver Unit, University Hospital Birmingham, UK
| | - Nicola Owen
- Cambridge Transplant Unit, Cambridge University Hospitals, Cambridge, UK
| | | | - Gourab Sen
- Institute of Transplantation, Freeman Hospital, Newcastle, UK
| | | | - Stephen Wigmore
- Institute of Transplantation, Freeman Hospital, Newcastle, UK
| | - Giuseppe Fusai
- Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Bimbi Fernando
- Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Andrew Burroughs
- Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
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Nakanishi Y, Saxena R. Pathophysiology and Diseases of the Proximal Pathways of the Biliary System. Arch Pathol Lab Med 2015; 139:858-66. [PMID: 26125426 DOI: 10.5858/arpa.2014-0229-ra] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
CONTEXT Diseases of the proximal pathways of the biliary system can be divided into those that affect the interlobular bile ducts and those that affect the bile canaliculi. The former include primary biliary cirrhosis, small-duct variant of primary sclerosing cholangitis, graft-versus-host disease, and drug-induced liver injury, whereas the latter include progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis, intrahepatic cholestasis of pregnancy, and drug-induced liver injury. OBJECTIVE To summarize the current state of knowledge of diseases of the proximal pathways of the biliary system, with special emphasis on clinical presentation, pathological features, and differential diagnosis. DATA SOURCES Clinicopathological information was extracted from pertinent published literature. CONCLUSIONS Care of the patient with cholestasis hinges on identifying the etiology. Diagnostic steps in cholestatic conditions comprise a thorough patient history, abdominal imaging, distinct serological studies, and liver biopsy. Primary biliary cirrhosis is characterized by distinctive serological and histological findings. The small-duct variant of primary sclerosing cholangitis is very rare and difficult to diagnose; imaging of the bile ducts is not helpful. Graft-versus-host disease is characterized by damage and loss of intrahepatic bile ducts. Drugs can cause injury variably at the level of bile canaliculus or the interlobular bile duct. Loss of bile ducts may be seen with primary biliary cirrhosis, primary sclerosing cholangitis, graft-versus-host disease, and drug-induced liver injury. Progressive familial intrahepatic cholestasis and progressive familial intrahepatic cholestasis represent 2 extreme ends of the spectrum of abnormalities in transporters responsible for bile formation. Intrahepatic cholestasis of pregnancy has a variable incidence in different parts of the world and may be due to abnormalities in transporter molecules.
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Affiliation(s)
| | - Romil Saxena
- From the Department of Pathology, Indiana University School of Medicine, Indianapolis
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Abedi SH, Ghassami M, Molaei M, Mohsenifar Z, Mohammad Alizadeh AH. Secondary Sclerosing Cholangitis and Hodgkin's Lymphoma. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2015; 8:83-7. [PMID: 26380560 PMCID: PMC4560457 DOI: 10.4137/ccrep.s23665] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 03/09/2015] [Accepted: 03/16/2015] [Indexed: 12/24/2022]
Abstract
CONTEXT Liver damage is relatively common in patients affected by HL, but paraneoplastic cholestasis is an uncommon presenting symptom in HL. CASE REPORT We report the case of a 38-year-old man who came to our hospital with jaundice, pruritis, nausea, vomiting, weight loss, and recurrent episodes of fever without any hepatosplenomegaly or lymphadenopathy. Laboratory findings showed abnormal liver functioning with mixed hepatocellular and cholestatic patterns. Sonographic evaluation of the biliary tract was normal. We ruled out viral infections, autoimmune process, and hemochromatosis. The patient was put on ursobile and NAC (N-acetyl-systeine) and prednisolone treatment. In magnetic resonance cholangiopancreatography examination, there were multiple strictures in the intrahepatic and extrahepatic bile ducts with mild dilatation. Histologic finding of liver biopsy was compatible with sclerosing cholangitis or drug-induced cholestasis. General condition and laboratory examination results of the patient became better, but we found lymph-adenopathy on monthly follow-up examination. Histological finding of the lymph node was compatible with HL. CONCLUSION This report emphasizes that HL can be presented with different paraneoplastic symptoms and that one of them is secondary sclerosing cholangitis. It has better prognosis than vanishing bile duct syndrome, and perhaps steroid treatment can be suggested.
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Affiliation(s)
- Seyed Hassan Abedi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Ghassami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Molaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zhaleh Mohsenifar
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Houshang Mohammad Alizadeh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Haapamäki J, Tenca A, Sintonen H, Barner-Rasmussen N, Färkkilä MA. Health-related quality of life among patients with primary sclerosing cholangitis. Liver Int 2015; 35:2194-201. [PMID: 25546575 DOI: 10.1111/liv.12775] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Accepted: 12/17/2014] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS To assess health-related quality of life (HRQoL) of patients with primary sclerosing cholangitis (PSC), and to compare it with that of the general population. Also, to examine changes in HRQoL in newly diagnosed PSC patients at a follow-up 1-2 years later, and to compare their HRQoL with HRQoL of newly diagnosed inflammatory bowel disease (IBD) patients. Furthermore, sources of and need for disease-related information among PSC patients were surveyed. METHODS Primary sclerosing cholangitis patients filled in the survey questionnaire when attending an endoscopic retrograde cholangiography examination. The 15D served as a general HRQoL instrument. The follow-up questionnaire was mailed to the newly diagnosed patients 1-2 years later. RESULTS No significant difference was seen in 15D scores between PSC patients and general population, but the dimensions of excretion (P < 0.001), depression (P = 0.003), distress (P = 0.003) and vitality (P = 0.005) were significantly lower in PSC. Age and symptoms affected HRQoL but severity of biliary changes did not. Those with newly diagnosed IBD had lower 15D scores than those with PSC. No significant changes were observed in 15D scores of new PSC patients in the follow-up. Many patients were dissatisfied with information received. CONCLUSION Newly diagnosed PSC patients have better HRQoL than do IBD patients, and no significant HRQoL changes were observed in the mean follow-up of 1.58 years after PSC diagnosis. ERC findings did not correlate with HRQoL or symptoms. HRQoL of PSC patients was mostly comparable with that of general population, but special attention should be paid to patients' psychological well-being.
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Affiliation(s)
- Johanna Haapamäki
- Department of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland
| | - Andrea Tenca
- Department of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland.,Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Harri Sintonen
- Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland
| | - Nina Barner-Rasmussen
- Department of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland
| | - Martti A Färkkilä
- Department of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland.,Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland
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Nakanuma Y, Sasaki M, Harada K. Autophagy and senescence in fibrosing cholangiopathies. J Hepatol 2015; 62:934-45. [PMID: 25435435 DOI: 10.1016/j.jhep.2014.11.027] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 11/08/2014] [Accepted: 11/16/2014] [Indexed: 12/16/2022]
Abstract
Fibrosing cholangiopathy such as primary sclerosing cholangitis (PSC) and biliary atresia (BA) is characterized by biliary epithelial injuries and concentric fibrous obliteration of the biliary tree together with inflammatory cell infiltration. In these diseases, inappropriate innate immunity is reported to contribute more to bile duct pathology as compared with various aspects of "classical" autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by chronic cholangitis with bile duct loss and classical autoimmune features. Cellular senescence of cholangiocytes and a senescence-associated secretory phenotype lead to the production of proinflammatory cytokines and chemokines that may modify the milieu of the bile duct and then trigger fibroinflammatory responses in PSC and PBC. Furthermore, deregulated autophagy might be involved in cholangiocyte senescence and possibly in the autoimmune process in PBC, and the deregulated innate immunity against enteric microbes or their products that is associated with cholangiocyte senescence might result in the fibrosing cholangitis that develops in PBC and PSC. In BA, innate immunity against double-stranded RNA viruses might be involved in cholangiocyte apoptosis and also in the development of the epithelial-mesenchymal transition of cholangiocytes that results in fibrous obliteration of bile ducts. These recent advances in the understanding of immune-mediated biliary diseases represent a paradigm shift: the cholangiocyte is no longer viewed merely as a passive victim of injury; it is now also considered to function as a potential effector in bile duct pathology.
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Affiliation(s)
- Yasuni Nakanuma
- Department of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan; Department of Pathology, Kanazawa University Graduate School of Medical Science, Japan.
| | - Motoko Sasaki
- Department of Pathology, Kanazawa University Graduate School of Medical Science, Japan
| | - Kenichi Harada
- Department of Pathology, Kanazawa University Graduate School of Medical Science, Japan
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Carrasco-Avino G, Schiano TD, Ward SC, Thung SN, Fiel MI. Primary sclerosing cholangitis: detailed histologic assessment and integration using bioinformatics highlights arterial fibrointimal hyperplasia as a novel feature. Am J Clin Pathol 2015; 143:505-13. [PMID: 25780002 DOI: 10.1309/ajcpvkfviprbxqr2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES Liver biopsy diagnosis of primary sclerosing cholangitis (PSC) is difficult. We performed a detailed histologic analysis of PSC cases using novel bioinformatics analysis to identify histologic features that may be useful in its diagnosis. METHODS PSC liver explants were examined and compared with primary biliary cirrhosis and hepatitis C explants to act as controls. Demographic, macroscopic, and histologic variables were analyzed using both conventional statistics and an integrative bioinformatics approach, significance analysis of microarrays (SAM), and hierarchical clustering analysis (HCA). RESULTS The PSC group was younger and had distinctive PSC features, including bile duct scars, onion-skin fibrosis, and arterial fibrointimal hyperplasia. SAM allowed the integration of variables by comparing PSC and control groups, whereas HCA was able to correctly categorize each group. CONCLUSIONS This study demonstrates characteristic PSC histology as well as arterial hyperplasia to be distinctive features that may aid in PSC diagnosis and be confirmed by bioinformatics.
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Affiliation(s)
| | - Thomas D. Schiano
- Division of Liver Diseases and Recanati-Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Stephen C. Ward
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Swan N. Thung
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - M. Isabel Fiel
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY
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Matsushita H, Miyake Y, Takaki A, Yasunaka T, Koike K, Ikeda F, Shiraha H, Nouso K, Yamamoto K. TLR4, TLR9, and NLRP3 in biliary epithelial cells of primary sclerosing cholangitis: relationship with clinical characteristics. J Gastroenterol Hepatol 2015; 30:600-8. [PMID: 25160604 DOI: 10.1111/jgh.12711] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/03/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Inappropriate innate immune responses have been suggested to contribute to the pathogenesis of primary sclerosing cholangitis (PSC). We evaluated the associations of expressions of toll-like receptor (TLR) 4, TLR9, and nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 (NLRP3) in the biliary epithelial cells (BECs) with clinical features of PSC patients. METHODS We retrospectively evaluated the expressions of TLR4, TLR9, and NLRP3 in the intrahepatic BECs by immunohistochemical staining in 21 PSC patients and 10 normal controls. In PSC, 17 patients underwent liver biopsy, and, in the other four patients, liver specimens were obtained at the time of liver transplantation. RESULTS TLR9 expressions in BECs were higher in PSC patients than in normal controls. TLR9 expressions were correlated with Ludwig fibrosis scores in PSC patients. TLR4 and NLRP3 expressions were similar between PSC patients and normal controls. Seventeen PSC patients undergoing liver biopsy were followed up during a median period of 55.7 months. Four reached to liver transplantation and four developed cholangiocarcinoma. Patients developing cholangiocarcinoma showed lower NLRP3 expressions than the others. Patients reaching to liver transplantation showed higher TLR9 expressions. Expression levels of TLR9 and NLRP3 were not correlated with liver biochemical tests and Mayo risk scores. CONCLUSIONS In PSC, excessive immune responses through TLR9 signaling may be associated with the disease progression. Insufficient immune response through NLRP3 signaling may be associated with the development of cholangiocarcinoma. Evaluation of TLR9 and NLRP3 expressions in BECs may be useful for predicting the prognosis as an auxiliary marker.
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Affiliation(s)
- Hiroshi Matsushita
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Abstract
Liver biopsy (LB) is still the criterion standard procedure for obtaining liver tissue for histopathological examination and a valuable tool in the diagnosis, prognosis, and management of many parenchymal liver diseases. The aim of this position paper is to summarise the present practice of paediatric LB and make recommendations about its performance. Although histological evaluation of the liver is important in assessing prognosis and exploring treatment, noninvasive techniques (ie, imaging, laboratory markers) may replace use of liver histology. The indications for LB are changing as present knowledge of aetiologies, pathomechanism, and therapeutic options in paediatric liver disease is evolving. Adult and paediatric literature was reviewed to assess the existing clinical practice of LB with focus on the technique, indications, risk of complications, and contraindications in paediatrics. This position paper presents types of LB, indications, complications, contraindications, and an essential checklist for paediatric LB.
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Rapid Progression of Primary Sclerosing Cholangitis Complicated with Ulcerative Colitis. Case Rep Gastrointest Med 2015; 2015:125718. [PMID: 25694833 PMCID: PMC4324808 DOI: 10.1155/2015/125718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Accepted: 01/10/2015] [Indexed: 11/21/2022] Open
Abstract
Primary sclerosing cholangitis is a cholestatic condition with unknown etiology and long-standing, progressive course, leading to cirrhosis and requiring orthotropic liver transplant. In approximately 80%, primary sclerosing cholangitis is accompanied by inflammatory bowel disease, and in most cases the recognition of bowel disease precedes the diagnosis of primary sclerosing cholangitis. We describe a case of 22-year-old male diagnosed simultaneously with primary sclerosing cholangitis and ulcerative colitis, with a medical history suggesting uncommon prior development of the liver disease. Five months after the initial diagnosis, we observed advanced lesions of bile tree due to progression of primary sclerosing cholangitis, which led to the unusually fast necessity for the orthotopic liver transplant.
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Primary biliary tract malignancies: MRI spectrum and mimics with histopathological correlation. ACTA ACUST UNITED AC 2014; 40:1520-57. [DOI: 10.1007/s00261-014-0300-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Matsubayashi H, Igarashi K, Kishida Y, Yoshida Y, Sasaki K, Ono H. Sclerosing cholangitis with thumbprint appearance and incomplete steroid response. J Dig Dis 2014; 15:578-82. [PMID: 25060539 DOI: 10.1111/1751-2980.12176] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Abstract
Hepatic involvement is often encountered in gastrointestinal (GI) diseases, in part because of the close anatomic and physiologic relations between the liver and GI tract. Drainage of the mesenteric blood supply to the portal vein permits absorbed and/or translocated nutrients, toxins, bacterial elements, cytokines, and immunocytes to gain hepatic access. Liver problems in digestive disorders may range from nonspecific hepatocellular enzyme elevations to significant pathologic processes that may progress to end-stage liver disease. Hepatobiliary manifestations of primary GI diseases in childhood and adolescence are not uncommon and include several well-described associations, such as sclerosing cholangitis with inflammatory bowel disease. Liver damage may also result from the effects of drugs used to treat GI diseases, for example, the hepatotoxicity of immunomodulatory therapies. This review highlights the important features of the hepatic and biliary abnormalities associated with 3 common pediatric GI conditions: inflammatory bowel disease, celiac disease, and cystic fibrosis.
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Affiliation(s)
- Hanh D Vo
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital at Downstate, SUNY-Downstate Medical Center, Brooklyn, NY
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Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, Mazariegos GV. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Hepatology 2014; 60:362-98. [PMID: 24782219 DOI: 10.1002/hep.27191] [Citation(s) in RCA: 142] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 04/22/2014] [Indexed: 12/16/2022]
Affiliation(s)
- Robert H Squires
- Department of Pediatrics, University of Pittsburgh School of Medicine; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA
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Ahmad Z, Idrees R, Fatima S, Arshad H, Din NU, Memon A, Minhas K, Ahmed A, Fatima SS, Arif M, Ahmed R, Haroon S, Pervez S, Hassan S, Kayani N. How our practice of histopathology, especially tumour pathology has changed in the last two decades: reflections from a major referral center in Pakistan. Asian Pac J Cancer Prev 2014; 15:3829-49. [PMID: 24935563 DOI: 10.7314/apjcp.2014.15.9.3829] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Continued advances in the field of histo-pathology (and cyto-pathology) over the past two decades have resulted in dramatic changes in the manner in which these disciplines are now practiced. This is especially true in the setting of a large university hospital where the role of pathologists as clinicians (diagnosticians), undergraduate and postgraduate educators, and researchers has evolved considerably. The world around us has changed significantly during this period bringing about a considerable change in our lifestyles and the way we live. This is the world of the internet and the world-wide web, the world of Google and Wikipedia, of Youtube and Facebook where anyone can obtain any information one desires at the push of a button. The practice of histo (and cyto) pathology has also evolved in line with these changes. For those practicing this discipline in a poor, developing country these changes have been breathtaking. This is an attempt to document these changes as experienced by histo (and cyto) pathologists practicing in the biggest center for Histopathology in Pakistan, a developing country in South Asia with a large (180 million) and ever growing population. The Section of Histopathology, Department of Pathology and Microbiology at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan's largest city has since its inception in the mid-1980s transformed the way histopathology is practiced in Pakistan by incorporating modern methods and rescuing histopathology in Pakistan from the primitive and outdated groove in which it was stuck for decades. It set histopathology in Pakistan firmly on the path of modernity and change which are essential for better patient management and care through accurate and complete diagnosis and more recently prognostic and predictive information as well.
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Affiliation(s)
- Zubair Ahmad
- Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan E-mail :
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