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Ogura T, Shiraishi C. Efficacy of Prednisone Avoidance in Patients With Liver Transplant Using the U.S. Food and Drug Administration Adverse Event Reporting System. Cureus 2024; 16:e60193. [PMID: 38868240 PMCID: PMC11168242 DOI: 10.7759/cureus.60193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/11/2024] [Indexed: 06/14/2024] Open
Abstract
Background Immunosuppressants are administered in various combinations to prevent immune-induced transplant rejection in patients with liver transplant, as each immunosuppressant acts on different cellular sites. However, the use of multiple immunosuppressants also increases the risk for adverse events. Therefore, it is desirable to reduce the types of immunosuppressants administered without increasing the incidence of transplant rejection. The effectiveness of prednisone avoidance has been suggested, although this was not based on statistical significance in many instances. To definitively establish the effectiveness of prednisone avoidance, a statistically significant difference from a prednisone-use group should be demonstrated. Additionally, the effectiveness of prednisone avoidance might vary depending on the combination of other immunosuppressants administered. It has therefore been considered necessary to investigate, for various immunosuppressant combinations, the administration patterns in which prednisone avoidance is effective. Objectives This study aimed to investigate the effectiveness of prednisone avoidance in patients with liver transplant and discuss the results based on statistically significant differences. Methods Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) were obtained. In studying immunosuppressant combinations, it was essential to control for confounding. Thus, the immunosuppressant combinations, excluding prednisone, were kept the same in the two groups being compared (prednisone-use and prednisone-avoidance groups). The large sample from FAERS allowed for those various immunosuppressant combinations to be compared. Comparisons of transplant rejection in the prednisone-use and prednisone-avoidance groups used the reporting odds ratio (ROR) and the adjusted ROR (aROR), which controlled for differences in patient background. Results With the prednisone-use groups being set as the reference, ROR and aROR were calculated for the prednisone-avoidance groups. Various immunosuppressant combinations were evaluated, and in four patterns - (1) the combination of prednisone and tacrolimus, (2) the combination of prednisone, cyclosporine, and tacrolimus, (3) the combination of prednisone, tacrolimus, and basiliximab, and (4) the combination of prednisone and everolimus) - both the ROR and the aROR for transplant rejection in the prednisone-avoidance group were significantly <1.000. Conclusions This study identified effective immunosuppressant combinations for prednisone avoidance that were not associated with increased transplant rejection. The evidence supporting the effectiveness of prednisone avoidance is strengthened when combined with results from previous studies.
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Affiliation(s)
- Toru Ogura
- Clinical Research Support Center, Mie University Hospital, Tsu, JPN
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Toro J, Gaitán J, Medina T, Reyes S. Guillain-Barré syndrome following primary cytomegalovirus infection in a patient with liver transplantation. BMJ Case Rep 2024; 17:e255739. [PMID: 38176755 PMCID: PMC10773336 DOI: 10.1136/bcr-2023-255739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2024] Open
Abstract
We present the case of a man in his 60s with a 5-month medical history of deceased donor liver transplantation, who developed Guillain-Barré syndrome (GBS) secondary to a primary cytomegalovirus (CMV) infection. This was confirmed by molecular tests and serology antibodies that ruled out other frequent aetiologies. Therapy with intravenous immunoglobulin and valganciclovir was started and the patient gradually improved over the weeks. GBS is the most common aetiology of paralysis worldwide, and it is an autoimmune-mediated neuropathy that is frequently caused by a preceding infection. Few cases of GBS have been reported in the context of liver transplant recipients, and those related to CMV infection are extremely rare. This case highlights the importance of considering GBS as a possible differential diagnosis in patients with solid organ transplantation, and it contributes to the knowledge of other infrequent aetiologies of this condition.
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Affiliation(s)
- Jaime Toro
- Neurology, Universidad El Bosque, Bogota, Colombia
- Neurology, Fundacion Santa Fe de Bogota, Bogota, Colombia
| | - Jairo Gaitán
- Neurology, Fundacion Santa Fe de Bogota, Bogota, Colombia
- Neurology, Universidad de los Andes, Bogota, Colombia
| | - Thomas Medina
- Neurology, Universidad El Bosque, Bogota, Colombia
- Neurology, Fundacion Santa Fe de Bogota, Bogota, Colombia
| | - Saúl Reyes
- Neurology, Fundacion Santa Fe de Bogota, Bogota, Colombia
- Neurology, Universidad de los Andes, Bogota, Colombia
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Chen CH, Low YY, Liu YH, Lin HH, Ho MW, Hsueh PR. Rapid detection of gastrointestinal pathogens using a multiplex polymerase chain reaction gastrointestinal panel and its role in antimicrobial stewardship. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:1273-1283. [PMID: 37926631 DOI: 10.1016/j.jmii.2023.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 10/07/2023] [Accepted: 10/10/2023] [Indexed: 11/07/2023]
Abstract
OBJECTIVES The FilmArray gastrointestinal panel (FAGIP) is widely used to detect infectious diarrhoea due to its outstanding sensitivity compared to conventional methods, but there is geographic variation, such as in the distribution of pathogens, among populations. METHODS This was a retrospective study that analysed patients with acute diarrhoea who underwent FAGIP tests from all age groups during 2022. We compared positive rates of FAGIP between paediatric (n = 245) and adult patients (n = 242) of different origins. The targeted therapy rate and antimicrobial agent use rate were also analysed. RESULTS Among the 487 stool samples evaluated, the overall, community-origin (CO), and nosocomial (NC) positivity rates of paediatric patients were significantly higher than those of adults (73.9 % vs. 43.0 %, p = 0.000; 76.2 % vs. 51.7 %, p = 0.000; 50.0 % vs. 19.7 %, p = 0.000). Salmonella was the most frequently detected pathogen (35.9 %) in children, while the predominant pathogen in adult patients was toxin A/B-genic Clostridioides difficile (13.2 %). There was a significantly lower antimicrobial agent use rate after FAGIP results were available (79.1 % vs. 64.5 %, p = 0.000) and a higher rate of targeted therapy towards C. difficile infection in adults than in children (84.4 % vs. 69.0 %, p = 0.011). CONCLUSION Paediatric diarrhoea patients showed higher positivity rates than adult patients. Application of FAGIP for acute diarrhoea might lower unnecessary antimicrobial use.
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Affiliation(s)
- Chih-Hao Chen
- Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Yan-Yi Low
- Division of Pediatric Infectious Diseases, China Medical University Children's Hospital, China Medical University, Taichung, Taiwan
| | - Yu-Hsuan Liu
- Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsiu-Hsien Lin
- Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Mao-Wang Ho
- Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan
| | - Po-Ren Hsueh
- Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan; Department of Laboratory Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan; PhD Program for Aging, School of Medicine, China Medical University, Taichung, Taiwan.
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Zhang P, Mao R, Zhang C, Qiu Y, Chen M. Gastrointestinal injury induced by immunomodulators: A review article. Therap Adv Gastroenterol 2023; 16:17562848231158549. [PMID: 37113189 PMCID: PMC10126616 DOI: 10.1177/17562848231158549] [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: 06/29/2022] [Accepted: 02/02/2023] [Indexed: 04/29/2023] Open
Abstract
An increasing number of immunomodulators, either anti-inflammatory or immunity-enhancing, have brought about a revolutionary effect in the management of a variety of autoimmune disorders and malignancies. However, their ability to cause gastrointestinal (GI) injury and induce GI symptoms has been increasingly and unexpectedly recognized. GI injury associated with immunomodulators may demonstrate various histologic and endoscopic patterns. Optimal diagnosis and treatment require a multidisciplinary approach. This review aims to provide an overview of the literature on its pathogenesis, the clinical, endoscopic, and histologic features, and suggested approaches to manage these newly recognized immunomodulator-induced GI adverse effects (AEs). We also reviewed current biomarkers predictive of GI toxicity and potential risk factors to identify susceptible patients. In addition, these immune-mediated AEs were compared with inflammatory bowel disease, a well-documented form of inflammation-driven GI injury. We hope this review will raise awareness and vigilance among clinicians of these entities to increase early diagnosis and rapid referral to specialist care.
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Affiliation(s)
- Pingxin Zhang
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
| | - Ren Mao
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
| | - Chuhan Zhang
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
| | | | - Minhu Chen
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
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Ching CK, Nobel YR, Pereira MR, Verna EC. The role of gastrointestinal pathogen PCR testing in liver transplant recipients hospitalized with diarrhea. Transpl Infect Dis 2022; 24:e13873. [PMID: 35748886 DOI: 10.1111/tid.13873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 04/22/2022] [Accepted: 05/16/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Diarrhea is a common symptom among liver transplant (LT) recipients and can result in significant morbidity. The utility of PCR-based multiplex gastrointestinal (GI) pathogen panels in this population is unknown. METHODS We assessed incidence, predictors, and outcomes of GI PCR positivity among inpatients who underwent stool pathogen testing with the FilmArray multiplex GI PCR panel at our institution within 1 year following LT from April 2015 to December 2019. RESULTS 112 patients were identified. 14 (12.5%) had a positive PCR for any pathogen. Escherichia coli (n = 9) and Norovirus (n = 5) were the most common pathogens detected. Recipients with a positive PCR were significantly further from LT (median 74.5 vs 15.5 days, p < 0.01) and tested earlier during hospitalization (median 1.0 vs 9.0 days, p < 0.01). C. difficile was positive in 20.0% of patients with a positive PCR and 11.4% with a negative PCR. CMV viremia was observed in 11.6% of patients, all in the negative PCR group. Following a positive PCR, patients were more likely to have a change in antimicrobial regimen (71.4% vs 28.6%, p = 0.02), a shorter length of stay (median 7.5 vs. 17.5 days, p < 0.01), and a trend toward lower rates of readmission and colonoscopy within 30 days. CONCLUSIONS In hospitalized LT recipients with diarrhea, GI PCR pathogen identification was associated with the use of targeted antimicrobial therapy and a shorter length of stay. GI PCR testing should be considered early during admission and later in the post-LT period. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Charlotte K Ching
- Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
| | - Yael R Nobel
- Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, New York, USA
| | - Marcus R Pereira
- Division of Infectious Diseases, Columbia University Irving Medical Center, New York, New York, USA
| | - Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, New York, USA
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Smedman TM, Guren TK, Tveit KM, Thomsen M, Andersen MH, Line PD, Dueland S. Health-Related Quality of Life in Colorectal Cancer Patients Treated With Liver Transplantation Compared to Chemotherapy. Transpl Int 2022; 35:10404. [PMID: 35707633 PMCID: PMC9189292 DOI: 10.3389/ti.2022.10404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 05/12/2022] [Indexed: 11/13/2022]
Abstract
Liver transplantation (LT) for patients with non-resectable colorectal liver metastases (CRLM) offers improved survival and has gained increased interest internationally the last years. The aim of this study was to describe the health-related quality of life (HRQoL) in patients with non-resectable CRLM receiving LT and how baseline HRQoL factors affect overall survival (OS). HRQoL data in the SECA (SEcondary CAncer) LT cohort was compared to data obtained from colorectal cancer patients starting first-line chemotherapy for metastatic disease in a clinical trial and data from a Norwegian normal population. HRQoL data from the QLQ-C30 questionnaire used in the SECA LT study and the NORDIC- VII study were reported. The relationship between patient-reported symptom burden at baseline and OS was investigated. In the SECA study longitudinal HRQoL assessment was used to describe the time until definitive deterioration as well as mean values at different time points. Patients in the SECA and NORDIC-VII studies reported similar baseline HRQoL. The median time until definitive deterioration in the transplanted patients was estimated to 36 months. In the SECA study appetite loss and pain at baseline had negative impact on OS (25.3 versus 71.7 months, p = 0.002 and 39.7 versus 71.7 months, p = 0.038, respectively). Despite a relapse in most of the LT patients the Global Health Score (GHS) remained good. Pain, and especially appetite loss at time of transplantation is associated with poor outcome after LT.
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Affiliation(s)
- Tor Magnus Smedman
- Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- *Correspondence: Tor Magnus Smedman,
| | | | | | | | | | - Pål-Dag Line
- Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Makharia G, Mohta S, Sridharan S, Gopalakrishnan R, Prasad N, Bansal S. Diarrhea in solid organ transplant recipients in the South Asian Region - Expert group opinion for diagnosis and management. INDIAN JOURNAL OF TRANSPLANTATION 2022; 16:23. [DOI: 10.4103/ijot.ijot_79_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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Hamdeh S, Micic D, Hanauer S. Review article: drug-induced small bowel injury. Aliment Pharmacol Ther 2021; 54:1370-1388. [PMID: 34668591 DOI: 10.1111/apt.16642] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/05/2021] [Accepted: 09/29/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Drug-induced gastrointestinal injury has been increasingly reported, but its exact incidence is not known. The small and large intestines represent the most affected sites of injury, accounting for 20%-40% of all gastrointestinal side effects. AIM To provide an updated literature review detailing medications linked to the development of small bowel injury. METHODS We conducted a literature search on PubMed from its inception to May 1, 2021. We included English-language original studies, meta-analyses, systematic reviews, review articles and case reports. RESULTS Drug-induced enteropathy can range from asymptomatic histological changes resulting in a subtle, self-limited disease to a chronic inflammatory condition mimicking inflammatory bowel disease, or bowel perforation. Endoscopy can demonstrate erythema, mucosal friability, oedema, erosions, ulcers or strictures in severe cases. Histology may include mucosal erosions and ulcerations, focal active enteritis, villous atrophy, epithelial apoptosis or necrotising enteritis. A well-established association has been found with the use of nonsteroidal anti-inflammatory drugs, immunosuppressants, chemotherapeutic agents, antibiotics, immunotherapies, etanercept and olmesartan. Possible associations have been reported with other biologic agents, medications used for glycemic control, antihypertensives, cholinesterase inhibitors, potassium and iron supplements, with conflicting data regarding contraceptives/hormonal therapy and isotretinoin. CONCLUSION Physicians should be aware of the manifestations of drug-induced enteropathy as early recognition can lead to prompt discontinuation of the offending therapy and, therefore, a reduced risk of future complications.
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Affiliation(s)
- Shadi Hamdeh
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Motility, University of Kansas, Lawrence, KS, USA
| | - Dejan Micic
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL, USA
| | - Stephen Hanauer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Phrommas J, Tanpowpong P, Getsuwan S, Lertudomphonwanit C, Chantarogh S, Anurathapan U, Treepongkaruna S. Diarrhea in pediatric recipients of solid organ or bone marrow transplants. Medicine (Baltimore) 2021; 100:e27625. [PMID: 34713851 PMCID: PMC8556011 DOI: 10.1097/md.0000000000027625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 10/14/2021] [Indexed: 01/05/2023] Open
Abstract
Diarrhea is common in adults after solid organ transplantation (SOT) and bone marrow transplantation (BMT), but data in children are limited. Therefore, we aimed to determine the incidence and etiology of pediatric early-onset diarrhea in post SOT and BMT.We reviewed children aged 6 months to 18 years who underwent liver transplantation, kidney transplantation or BMT between January 2015 and December 2019 with duration of diarrhea > 72 hours within the first 6 months after transplantation. Clinical data and diarrheal course were collected. Regression analyses were performed to define factors associated with the interested outcomes.Among 252 transplanted patients, 168 patients (66.6%) had 289 documented episodes of diarrhea. A diagnosis of 68.2% of post-transplant diarrhea remained 'indefinite'. Enteric infection in SOT and gastrointestinal acute graft-versus-host disease (GI-aGVHD) in BMT were the commonly identified etiologies. Among 182 episodes among BMT children, skin rash was more pronounced when compared the ones with diarrhea > 7 days vs ≤ 7 days (odds ratio [OR] 13.9; 95% CI 1.8, 107.6). Males were more likely to develop GI-aGVHD as compared to females (OR 8.9). We found that GI-aGVHD was more common in the ones with skin rash and the presence of white blood cells in stool examination (OR 8.4 and 3.1, respectively). Deaths occurred in 7.7%.Two-thirds of post-transplant children experienced at least one episode of early-onset diarrhea, of which the etiology mainly remains undefined. Various clinical factors of prolonged/chronic diarrhea and GI-aGVHD may help clinicians when managing these children.
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Mantle Cell Lymphoma Presenting as Diarrhea in a Liver Transplant Recipient. ACG Case Rep J 2021; 8:e00635. [PMID: 34307713 PMCID: PMC8297721 DOI: 10.14309/crj.0000000000000635] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 03/30/2021] [Indexed: 01/20/2023] Open
Abstract
We present a 63-year-old man with a medical history of hepatocellular carcinoma who underwent orthotopic liver transplant 10 years prior on long-term immunosuppressive therapy. The patient presented to the clinic with diarrhea, and the workup revealed mantle cell lymphoma. Mantle cell lymphoma is an extremely rare finding in transplanted livers. It is essential to include mantle cell lymphoma, along with a broad differential, during the workup of diarrhea in post-transplant patients.
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Disease Course and Treatment Response of Eosinophilic Gastrointestinal Diseases in Children With Liver Transplantation: Long-Term Follow-Up. Am J Gastroenterol 2021; 116:188-197. [PMID: 33065587 DOI: 10.14309/ajg.0000000000000934] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 08/24/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION To describe the clinical and laboratory profile, natural course, treatment outcome, and risk factors of posttransplant esophageal and nonesophageal eosinophilic gastrointestinal disorders (EGIDs). METHODS All children (aged <18 years) who underwent liver transplantation, between 2011 and 2019, in a single transplant center with a follow-up period of 1 year or more posttransplant and with a history of posttransplant endoscopic evaluation were included in this study. RESULTS During the study period, 89 children met the inclusion criteria. Patients were followed for a median of 8.0 years. A total of 39 (44%) patients were diagnosed with EGID after transplantation. Of these, 29 (33%) had eosinophilic esophagitis (EoE), and 10 (11%) had eosinophilic gastritis, gastroenteritis or enterocolitis. In comparison with the non-EGID group, patients with EGID were younger at transplant (P ≤ 0.0001), transplanted more frequently due to biliary atresia (P ≤ 0.0001), and had higher rates of pretransplant allergy (P = 0.019). In the posttransplant period, they had higher rates of mammalian Target of Rapamycin inhibitor use (P = 0.006), Epstein-Barr virus viremia (P = 0.03), post-transplant lymphoproliferative disease (P = 0.005), and allergen sensitization (P ≤ 0.0001). In regression analysis, young age at transplant, age at diagnosis, pretransplant atopic dermatitis, and post-transplant lymphoproliferative disease were associated with an increased risk of EGID or EoE. Laboratory abnormalities such as anemia (P = 0.007), thrombocytosis (P = 0.012), and hypoalbuminemia (P = 0.031) were more commonly observed in the eosinophilic gastritis, gastroenteritis or enterocolitis group than in the EoE group. Following treatment, most patients had symptomatic resolution at 3 months and histologic resolution at 6 months postdiagnosis. Among the patients who had 5 years of follow-up, none recurred. DISCUSSION EGID is a common posttransplant diagnosis, which seems to affect patients who are transplanted earlier and who have pretransplant atopy. Posttransplant EGID is responsive to treatment, but as histologic remission occurs after symptomatic resolution, the decision to perform control endoscopy should be delayed.
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Neuberger M, Sommerer C, Böhnisch S, Metzendorf N, Mehrabi A, Stremmel W, Gotthardt D, Zeier M, Weiss KH, Rupp C. Effect of mycophenolic acid on inosine monophosphate dehydrogenase (IMPDH) activity in liver transplant patients. Clin Res Hepatol Gastroenterol 2020; 44:543-550. [PMID: 31924555 DOI: 10.1016/j.clinre.2019.12.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 12/02/2019] [Accepted: 12/03/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Due to the development of immunosuppressants, the focus in transplanted patients has shifted from short-term to long-term survival as well as a better adjustment of these drugs in order to prevent over- and under-immunosuppression. Mycophenolic acid (MPA) is a noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) and approved for prophylaxis of acute rejection after kidney, heart, and liver transplantation, where it has become a part of the standard therapy. Targeting inosine monophosphate IMPDH activity as a surrogate pharmacodynamic marker of MPA-induced immunosuppression may allow a more accurate assessment of efficacy and aid in limiting toxicity in liver transplanted patients. AIM Assess IMPDH-inhibition in liver transplant recipients and its impact on biliary/infectious complications, acute cellular rejection (ACR) and liver dependent survival. METHODS This observational cohort study comprises 117 liver transplanted patients that were treated with mycophenolate mofetil (MMF) for at least 3 months. Blood samples (BS) were collected and MPA serum level and IMPDH activity were measured before (t(0)), 30minutes (t(30)) and 2h after (t(120)) MMF morning dose administration. Regarding MPA, we assessed the area under the curve (AUC). Patients were prospectively followed up for one year and assessed for infectious and biliary complications, episodes of ACR and liver dependent survival. RESULTS The MPA levels showed a broad interindividual variability at t(0) (2.0±1.8ng/ml), t(30) (12.7±9.0ng/ml) and t(120) (7.5±4.3ng/ml). Corresponding IMPDH activity was at t(o) (23.2±9.5 nmol/h/mg), at t(30) (16.3±8.8 nmol/h/mg) and t(120) (18.2±8.7 nmol/h/mg). With regard to MPA level we found no correlation with infectious or biliary complications within the follow-up period. Patients with baseline IMPDH(a) below the median had significant more viral infections (6 (10.2%) vs. 17 (29.3%); P=0.009) with especially more cytomegalovirus (CMV) infections (1 (3.4%) vs. 6 (21.4%); P=0.03)). Furthermore, patients with baseline IMPDH(a) above the median developed more often non-anastomotic biliary strictures (8 (13.6%) vs. 1 (1.7%), P=0.03). We found the group reaching the combined clinical endpoint of death and re-transplantation showing significantly lower MPA baseline values (t(0) 0.9±0.7 vs. 2.1±1.8μg/ml Mann-Whitney-U: P=0.02). We calculated a simplified MPA(AUC) with the MPA level at baseline, 30 and 120minutes after MPA administration. Whereas we found no differences with regard to baseline characteristics at entry into the study patients with MPA (AUC) below the median experienced significantly more often the combined clinical endpoint (12.1% (7/58) vs. 0.0% (0/57); P=0.002) and had a reduced actuarial re-transplantation-free survival (1.0 year vs. 0.58 years; Log-rank: P=0.007) during the prospective one-year follow-up period. In univariate and multivariate analysis including gender, age, BMI, ACR, MPA (AUC) and IMPDH(a) only BMI, MPA (AUC) and IMPDH(a) were independently associated with reduced actuarial re-transplantation-free survival. CONCLUSION MPA-levels and IMPDH-activity in liver transplanted patients allows individual risk assessment. Patients with higher IMPDH inhibition acquire more often viral infections. Insufficient IMPDH inhibition is associated with development of non-anastomotic bile duct strictures and reduced re-transplantation-free survival.
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Affiliation(s)
- M Neuberger
- University Hospital Heidelberg, Internal Medicine IV, 69120 Heidelberg, Germany
| | - C Sommerer
- University Hospital Heidelberg, Division of Nephrology, 69120 Heidelberg, Germany
| | - S Böhnisch
- University Hospital Heidelberg, Division of Nephrology, 69120 Heidelberg, Germany
| | - N Metzendorf
- University Hospital Heidelberg, Division of Nephrology, 69120 Heidelberg, Germany
| | - A Mehrabi
- University of Heidelberg, Department of General, Visceral, and Transplantation Surgery, 69120 Heidelberg, Germany
| | - W Stremmel
- University Hospital Heidelberg, Internal Medicine IV, 69120 Heidelberg, Germany
| | - D Gotthardt
- University Hospital Heidelberg, Internal Medicine IV, 69120 Heidelberg, Germany
| | - M Zeier
- University Hospital Heidelberg, Division of Nephrology, 69120 Heidelberg, Germany
| | - K H Weiss
- University Hospital Heidelberg, Internal Medicine IV, 69120 Heidelberg, Germany
| | - C Rupp
- University Hospital Heidelberg, Internal Medicine IV, 69120 Heidelberg, Germany.
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Abstract
PURPOSE OF REVIEW Long-term survival is now the rule rather than the exception for infants and children who undergo liver transplantation for end-stage liver disease, metabolic liver conditions and a variety of other indications. Pediatricians and primary care providers play vital roles in the care and management of this patient population. The purpose of this review is to highlight key aspects important to the care of the pediatric liver transplant recipient. RECENT FINDINGS Significant advances in immunosuppressive therapies and surgical techniques have contributed to improved graft and patient survival rates, shifting the focus beyond immediate survival to strategies to minimize comorbidities related to long-term immunosuppression during growing years, attend to patient and parent-reported outcomes and enhance quality of life. A multidisciplinary approach allows for monitoring and surveillance of both routine (growth, nutritional rehabilitation, cognitive development, mental and psychosocial health, contraception and daily activities) and transplant-related (adverse effects of immunosuppression, susceptible infections, extra-hepatic systems, transition from childhood to adolescence to adulthood) themes. SUMMARY Effective communication between the primary care physician and the transplant team is imperative for optimizing best outcomes. The primary care provider should be aware of the multifacet nature of posttransplant management, which includes medication regimens, common complications and infections.
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Impacts and Challenges of Advanced Diagnostic Assays for Transplant Infectious Diseases. PRINCIPLES AND PRACTICE OF TRANSPLANT INFECTIOUS DISEASES 2019. [PMCID: PMC7121269 DOI: 10.1007/978-1-4939-9034-4_47] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The advanced technologies described in this chapter should allow for full inventories to be made of bacterial genes, their time- and place-dependent expression, and the resulting proteins as well as their outcome metabolites. The evolution of these molecular technologies will continue, not only in the microbial pathogens but also in the context of host-pathogen interactions targeting human genomics and transcriptomics. Their performance characteristics and limitations must be clearly understood by both laboratory personnel and clinicians to ensure proper utilization and interpretation.
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15
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Cystoisospora belli Gallbladder Infection in a Liver Transplant Donor. Case Rep Infect Dis 2018; 2018:3170238. [PMID: 30057834 PMCID: PMC6051245 DOI: 10.1155/2018/3170238] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 05/14/2018] [Accepted: 06/13/2018] [Indexed: 11/17/2022] Open
Abstract
Introduction Cystoisospora belli (previously Isospora belli) is a parasitic protozoan of the human gastrointestinal system. It rarely causes symptoms in immunocompetent hosts but can cause severe diarrhea in immunocompromised patients, with a rate of recurrence and risk of dissemination. Gallbladder infections are however rare. The treatment of choice for symptomatic patients is a 7–10-day course of trimethoprim-sulfamethoxazole. Case In this case, we report on an incidental finding of Cystoisospora belli organisms in the donor gallbladder following a transplant cholecystectomy. There was no report of symptoms in the donor. The recipient was treated with a course of trimethoprim-sulfamethoxazole, without evidence of cystoisosporiasis. Given the risk of recurrence in immunocompromised hosts, the patient will continue to be monitored for reactivation in the future. Conclusion Despite advances in transplant protocols and screening, disease transmission from the donor to recipient still occurs in about 0.2% of all organ transplants. With the increased use of organs from drug overdose victims and other high-risk donors, practitioners (including pathologists, hepatologists, and surgeons) must maintain a high index of suspicion for such potentially harmful organisms.
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The gastroenterologist's guide to management of the post-liver transplant patient. Am J Gastroenterol 2018; 113:819-828. [PMID: 29748558 DOI: 10.1038/s41395-018-0049-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 02/11/2018] [Indexed: 12/11/2022]
Abstract
The management of the post-liver transplant patient is complex and involves a large interdisciplinary team. After referral to a transplant center, evaluation and listing, and eventual transplantation, the patient is cared for closely by the transplant center. Once deemed ready for discharge, the patient returns to the primary care provider for ongoing management of the various issues that increase in incidence post transplant such as osteoporosis, cardiovascular, and renal diseases, as well as metabolic syndrome. The role of the gastroenterologist is not well defined, but certainly, he or she may be called upon for the initial evaluation and ongoing management of gastrointestinal as well as hepatobiliary issues. This includes but is not limited to the investigation of abnormal liver tests, non-specific gastrointestinal complaints such as nausea, vomiting, or diarrhea, biliary complications, and even recurrent hepatic disease. Having familiarity with post-transplant immunosuppressive agents, drug interactions, and potential infectious and malignancy-related complications of transplant is essential, as the primary gastroenterologist may be expected in some situations to field the initial work-up, if patient access to the transplant center is limited. The aim of this review is to summarize the gastroenterologist's role in the management of the post-liver transplant patient.
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Silva ROS, de Oliveira Júnior CA, Blanc DS, Pereira ST, de Araujo MCR, Vasconcelos A, Lobato FCF. Clostridioides difficile infection in dogs with chronic-recurring diarrhea responsive to dietary changes. Anaerobe 2018; 51:50-53. [PMID: 29621604 PMCID: PMC7111076 DOI: 10.1016/j.anaerobe.2018.03.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 03/13/2018] [Accepted: 03/26/2018] [Indexed: 01/26/2023]
Abstract
Five dogs with chronic-recurring diarrhea were positive for Clostridioides difficile infection (CDI), but were unresponsive to treatment with metronidazole. One of these animals was subjected to a colonoscopy, which revealed eosinophilic infiltration of the colon. All five animals completely recovered after dietary changes. The present work suggests that CDI might occur in dogs with other intestinal alterations. In addition, this report suggests that dysbiosis should be considered in animals that have chronic-recurring diarrhea and test positive for C. difficile.
C. difficile infection (CDI) in dogs are still largely unknown. Five dogs with chronic-recurring diarrhea were positive for CDI. All animals completely recovered after dietary changes. Dysbiosis should be considered in dogs with chronic-recurring diarrhea and CDI.
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Affiliation(s)
- Rodrigo Otávio Silveira Silva
- Veterinary School, Universidade Federal de Minas Gerais (UFMG), Antônio Carlos Avenue, 6627, Belo Horizonte, MG, 31.270-901, Brazil.
| | | | - Dominique S Blanc
- Service of Hospital Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland
| | | | | | - Artur Vasconcelos
- Veterinary School, Universidade Federal de Minas Gerais (UFMG), Antônio Carlos Avenue, 6627, Belo Horizonte, MG, 31.270-901, Brazil
| | - Francisco Carlos Faria Lobato
- Veterinary School, Universidade Federal de Minas Gerais (UFMG), Antônio Carlos Avenue, 6627, Belo Horizonte, MG, 31.270-901, Brazil
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Abe K, Shiba H, Furukawa K, Sakamoto T, Ishida Y, Yanaga K. Repeated Clostridium difficile infection after living donor liver transplantation. Clin J Gastroenterol 2018; 11:309-311. [DOI: 10.1007/s12328-018-0840-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 02/19/2018] [Indexed: 12/19/2022]
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19
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Liu K, Strasser SI, Koorey DJ, Leong RW, Solomon M, McCaughan GW. Interactions between primary sclerosing cholangitis and inflammatory bowel disease: implications in the adult liver transplant setting. Expert Rev Gastroenterol Hepatol 2017. [PMID: 28627935 DOI: 10.1080/17474124.2017.1343666] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which is associated with inflammatory bowel disease (IBD) in most cases. As there is currently no medical therapy which alters the natural history of PSC, liver transplantation may be required. Areas covered: We searched for articles in PubMed and critically reviewed current literature on the interrelationship between PSC and IBD with a specific focus on considerations for patients in the liver transplant setting. Expert commentary: PSC is an uncommon disease which limits available studies to be either retrospective or contain relatively small numbers of patients. Based on observations from these studies, the behavior and complications of PSC and IBD impact on each other both before and after a liver transplant. Both these autoimmune conditions and their associated cancer risk also influence patient selection for transplantation and may be impacted by immunosuppression use post-transplant. Hence, a complex interplay exists between PSC, IBD and liver transplantation which requires clarification with ongoing research.
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Affiliation(s)
- Ken Liu
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,c Liver Injury and Cancer Program, Centenary Institute , The University of Sydney , Sydney , NSW , Australia
| | - Simone I Strasser
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - David J Koorey
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - Rupert W Leong
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,d Gastroenterology and Liver Services , Concord Hospital , Sydney , NSW , Australia
| | - Michael Solomon
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,e Department of Colorectal Surgery , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - Geoffrey W McCaughan
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,c Liver Injury and Cancer Program, Centenary Institute , The University of Sydney , Sydney , NSW , Australia
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20
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Cesaretti M, Dioguardi Burgio M, Zarzavadjian Le Bian A. Abdominal emergencies after liver transplantation: Presentation and surgical management. Clin Transplant 2017; 31. [PMID: 28871618 DOI: 10.1111/ctr.13102] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2017] [Indexed: 12/18/2022]
Affiliation(s)
- Manuela Cesaretti
- HPB surgery and Liver Transplantation department; Hôpital Beaujon; Clichy; Assistance Publique - Hôpitaux de Paris; Paris Diderot University; Paris France
- Istituto Italiano di Tecnologia; Genova Italy
| | - Marco Dioguardi Burgio
- Diagnostic and Interventional Radiology; Hôpital Beaujon; Clichy; Assistance Publique - Hôpitaux de Paris; Paris Diderot University; Paris France
| | - Alban Zarzavadjian Le Bian
- Service de Chirurgie Digestive; Centre Hospitalier Simone Veil; Eaubonne France
- Laboratoire d'Ethique Médicale et de Médecine Légale; Université Paris Descartes; Paris France
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21
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Sikanderkhel S, Choudhry MW, Valentine V, Al-Dossari G, Khalife WI. Diarrhea-An uncommon presentation of tertiary adrenal insufficiency following heart transplantation. J Card Surg 2017; 32:522-525. [PMID: 28670701 DOI: 10.1111/jocs.13175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Diarrhea following organ transplantation is usually associated with infection and immunosuppression therapy. We describe two patients with diarrhea following orthotopic heart transplantation due to tertiary adrenal insufficiency.
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Affiliation(s)
- Saad Sikanderkhel
- Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - M Waqas Choudhry
- Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Vincent Valentine
- Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama, Birmingham, Alabama
| | - Ghannam Al-Dossari
- Department of Cardiothoracic Surgery, University of Texas Medical Branch, Galveston, Texas
| | - Wissam I Khalife
- Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
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22
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Bonatti HJR, Sadik KW, Krebs ED, Sifri CD, Pruett TL, Sawyer RG. Clostridium difficile-Associated Colitis Post-Transplant Is Not Associated with Elevation of Tacrolimus Concentrations. Surg Infect (Larchmt) 2017. [PMID: 28650734 DOI: 10.1089/sur.2016.180] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Diarrhea is a common condition after solid organ transplant (SOT); Clostridium difficile-associated colitis (CDAC) is one of the most common infections after SOT. We documented previously that some types of enteritis are associated with an elevation of tacrolimus (TAC) trough concentrations by interfering with the drug's complex metabolism. PATIENTS AND METHODS Tacrolimus concentrations of 25 SOT recipients including 12 renal and 13 liver recipients before, during, and after CDAC were analyzed retrospectively. RESULTS Median age of the 25 patients was 54 y (range, 36-71), there were 15 males and 10 females. Clostridium difficile-associated colitis developed at a median of 55 d (range 2-4551) post-SOT. Median TAC concentrations prior to the outbreak of CDAC were 6.9 ng/mL (range, <1.5-17.2), 5.6 ng/mL (range, <1.5-13.2) during diarrhea, and 7.4 ng/mL (range, <1.5-24.3) after resolution of diarrhea (p > 0.05, NS). Treatment of CDAC consisted of metronidazole for 14 d in all cases. All patients recovered from CDAC but seven patients had CDAC relapse. CONCLUSIONS In contrast to other types of infectious diarrhea such as rotavirus enteritis and cryptosporidiosis, CDAC is not associated with an increase in TAC concentrations. This is because C. difficile causes primarily colitis as opposed to other organisms, which are associated with enteritis.
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Affiliation(s)
- Hugo J R Bonatti
- 1 Department of Surgery, University of Virginia Health System , Charlottesville, Virginia.,3 University of Maryland , Shore Regional Health, Easton, Maryland
| | - Karim W Sadik
- 1 Department of Surgery, University of Virginia Health System , Charlottesville, Virginia.,4 Guthrie, Plastic Surgery , Sayre, Pennsylvania
| | - Elizabeth D Krebs
- 1 Department of Surgery, University of Virginia Health System , Charlottesville, Virginia
| | - Costi D Sifri
- 2 Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System , Charlottesville, Virginia
| | - Timothy L Pruett
- 1 Department of Surgery, University of Virginia Health System , Charlottesville, Virginia.,5 Division of Transplantation, University of Minnesota , Minneapolis, Minnesota
| | - Robert G Sawyer
- 1 Department of Surgery, University of Virginia Health System , Charlottesville, Virginia
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Graft Versus Host Disease After Liver Transplantation in Adults: A Case series, Review of Literature, and an Approach to Management. Transplantation 2017; 100:2661-2670. [PMID: 27495762 DOI: 10.1097/tp.0000000000001406] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Graft-versus-host-disease (GVHD) after liver transplantation (LT) is a deadly complication with very limited data on risk factors, diagnosis and management. We report a case series and a comprehensive review of the literature. METHODS Data were systematically extracted from reports of GVHD after LT, and from the United Network for Organ Sharing database. Group comparisons were performed. RESULTS One hundred fifty-six adult patients with GVHD after LT have been reported. Median time to GVHD onset was 28 days. Clinical features were skin rash (92%), pancytopenia (78%), and diarrhea (65%). Six-month mortality with GVHD after LT was 73%. Sepsis was the most common cause of death (60%). Enterobacter bacteremia, invasive aspergillosis, and disseminated Candida infections were frequently reported. Recipient age over 50 years is a risk factor for GVHD after LT. Hepatocellular carcinoma was overrepresented, whereas chronic hepatitis C was underrepresented, in reported United States GVHD cases relative to all United Network for Organ Sharing database LT cases. Mortality rate with treatment of GVHD after LT was 84% with high-dose steroids alone, 75% to 100% with regimens using dose increases of calcineurin inhibitors, and 55% with IL-2 antagonists. Mortality was 25% in small case series using the CD2-blocker alefacept or TNF-α antagonists. CONCLUSIONS Age older than 50 years and hepatocellular carcinoma appear to be risk factors for GVHD. Hepatitis C may be protective. High-dose steroids and calcineurin inhibitors are ineffective in the treatment of GVHD after LT. CD2-blockers and TNF-α antagonists appear promising. We propose a diagnostic algorithm to assist clinicians in managing adults with GVHD after LT.
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Filipec Kanizaj T, Mijic M. Inflammatory bowel disease in liver transplanted patients. World J Gastroenterol 2017; 23:3214-3227. [PMID: 28566881 PMCID: PMC5434427 DOI: 10.3748/wjg.v23.i18.3214] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 04/13/2017] [Accepted: 04/21/2017] [Indexed: 02/06/2023] Open
Abstract
Most common hepatobiliary manifestation of inflammatory bowel disease (IBD) are primary sclerosing cholangitis (PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation (LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Anti-tumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.
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Trinh SA, Echenique IA, Penugonda S, Angarone MP. Optimal strategies for the diagnosis of community-onset diarrhea in solid organ transplant recipients: Less is more. Transpl Infect Dis 2017; 19. [PMID: 28170133 DOI: 10.1111/tid.12673] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 10/01/2016] [Accepted: 11/06/2016] [Indexed: 01/05/2023]
Abstract
BACKGROUND Diarrhea, a common complication after solid organ transplant (SOT), is associated with allograft failure and death. No evidence-based guidelines exist for the evaluation of diarrhea in SOT recipients. We performed a cost analysis to derive a testing algorithm for the diagnosis of community-onset diarrhea that minimizes costs without compromising diagnostic yields. DESIGN A cost analysis was performed on a retrospective cohort of 422 SOT admissions for community-onset diarrhea over an 18-month period. A stepwise testing model was applied on a population level to assess test costs relative to diagnostic yields. RESULTS Over an 18-month period, 1564 diagnostic tests were performed and 127 (8.1%) returned positive. Diagnostic testing accounted for $95 625 of hospital costs. The tests with the lowest cost per decrease in the false-omission rate (FOR) were stool Clostridium difficile polymerase chain reaction (PCR) ($156), serum cytomegalovirus quantitative PCR ($1529), stool norovirus (NV) PCR ($4673), and stool culture ($6804). A time-to-event analysis found no significant difference in the length of hospital stay between patients with and without NV testing (P=.520). CONCLUSIONS A stepwise testing strategy can reduce costs without compromising diagnostic yields. In the first-stage testing, we recommend assessment for C. difficile, cytomegalovirus, and food-borne bacterial pathogens. For persistent diarrheal episodes, second-stage evaluation should include stool NV PCR, Giardia/Cryptosporidium enzyme immunoassay, stool ova and parasite, reductions in immunosuppressive therapy, and possibly endoscopy. Although NV testing had a relatively low cost per FOR, we recommend NV testing during second-stage evaluation, as an NV diagnosis may not lead to changes in clinical management or further reductions in length of hospital stay.
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Affiliation(s)
- Sonya A Trinh
- Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Ignacio A Echenique
- Department of Infectious Diseases, Cleveland Clinic Florida, Weston, FL, USA
| | - Sudhir Penugonda
- Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Michael P Angarone
- Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Lee CY, Chen YH, Lu PL. Reactivated cytomegalovirus proctitis in an immunocompetent patient presenting as nosocomial diarrhea: a case report and literature review. BMC Infect Dis 2017; 17:113. [PMID: 28143418 PMCID: PMC5286859 DOI: 10.1186/s12879-017-2218-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 01/24/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Reactivated cytomegalovirus (CMV) infection has been known to cause significant morbidity and mortality in immunocompromised patients. However, CMV disease rarely develops in immunocompetent patients, and reported cases often present with a mild, self-limiting course, without severe life-threatening sequelae. While the colon is the most common gastrointestinal site affected by CMV disease in immunocompetent patients, rectal involvement is rarely reported. CMV proctitis can present in two distinct forms, primary and reactivated. However, reactivated CMV proctitis is rarely reported as a causative etiology of nosocomial diarrhea, except in transplant patients. Herein we present a case of reactivated CMV proctitis in an immunocompetent patient, presenting as nosocomial diarrhea. Previously reported cases of reactivated CMV proctitis in immunocompetent patients are also reviewed. CASE PRESENTATION A 79-year-old female was admitted because of metabolic encephalopathy caused by dehydration and hypernatremia. The patient's consciousness level returned rapidly after fluid supplementation. However, she subsequently presented with abdominal pain and diarrhea on day 8 of admission. Abdominal contrast-enhanced computed tomography on day 10 of admission demonstrated inflammation around the rectum, suggesting proctitis. Colonoscopy on day 16 of admission showed a giant ulcer at the rectum. Pathology of rectal biopsy confirmed CMV infection. The patient recovered without sequelae after 38 days of valganciclovir treatment. Follow-up colonoscopy revealed a healed ulcer over the rectum. Ten cases in the literature, plus our case, with reactivated CMV proctitis in immunocompetent patients were reviewed. We found that most patients were elderly (mean, 72 years) with a high prevalence of diabetes mellitus (54.5%). Cardinal manifestations are often non-specific (diarrhea, hematochezia, tenesmus), and eight (72.7%) developed CMV proctitis following a preceding acute, life-threatening disease, rather than as an initial presentation on admission. These manifestations frequently develop during hospitalization, and are thus often regarded as nosocomial diarrhea. CONCLUSIONS Clinicians should be aware of the possibility of nosocomial onset of reactivated CMV proctitis in patients hospitalized due to a preceding critical illness, although the benefits of antiviral therapy remain unclear.
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Affiliation(s)
- Chun-Yuan Lee
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yen-Hsu Chen
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Sepsis Research Center, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Graduate Institute of Medicine, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsin Chu, Taiwan
| | - Po-Liang Lu
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. .,School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. .,Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
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Ghosh N, Malik FA, Daver RG, Vanichanan J, Okhuysen PC. Viral associated diarrhea in immunocompromised and cancer patients at a large comprehensive cancer center: a 10-year retrospective study. Infect Dis (Lond) 2016; 49:113-119. [PMID: 27620005 DOI: 10.1080/23744235.2016.1224384] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
BACKGROUND Viral associated diarrhea (VAD) due to Norovirus (NV), Rotavirus (RV) and Adenovirus (AV) is common in immunocompromised and cancer patients. We sought to determine if the clinical characteristics, morbidity and seasonality of infection differed according to the type of enteric virus identified. METHODS Cases of NV, RV and AV were identified in stool specimens submitted to the clinical microbiology laboratory between November 2005 and February 2015. Clinical characteristics of patients, potential risk factors and outcomes were compared. RESULTS A total of 97 VAD cases were identified: NV (n = 49), RV (n = 34) and AV (n = 14). The majority of cases were in patients with leukemia and lymphoma. NV (59%), RV (74%) and AV (78%) were identified in hematopoietic stem cell transplant (HSCT) recipients; and in patients with graft versus host disease (GVHD): NV (34%), RV (46%) and AV (57%). Nine cases of NV were genotyped; all were due to genotype II. Nine of 49 (18%) cases of NV, 7 of 34 (20%) cases of RV and 2 of 14 (14%) cases of AV were considered to be health care acquired (HCA). In multivariate analysis, immunosuppression (OR 2.8 95% CI 1.26-6.60, p = .01) and neutropenia (OR 4.8 95% CI 1.27-18.5, p = .01) were identified as risk factors for NV diarrhea compared to RV and AV. CONCLUSIONS In our study, agents responsible for VAD occurred year round but predominated in the winter time; caused prolonged illness and were frequently health care associated. Presentations were atypical in many cases without upper gastrointestinal symptoms such as nausea and vomiting.
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Affiliation(s)
- Natasha Ghosh
- a Department of Infectious Diseases , Infection Control and Employee Health University of Texas MD Anderson Cancer Center , Houston , TX , USA.,b University of Texas School of Public Health , Houston , TX , USA
| | - Farida A Malik
- a Department of Infectious Diseases , Infection Control and Employee Health University of Texas MD Anderson Cancer Center , Houston , TX , USA.,c McGovern Medical School , Houston , TX , USA
| | - Roshni G Daver
- a Department of Infectious Diseases , Infection Control and Employee Health University of Texas MD Anderson Cancer Center , Houston , TX , USA.,c McGovern Medical School , Houston , TX , USA
| | - Jakapat Vanichanan
- a Department of Infectious Diseases , Infection Control and Employee Health University of Texas MD Anderson Cancer Center , Houston , TX , USA.,c McGovern Medical School , Houston , TX , USA
| | - Pablo C Okhuysen
- a Department of Infectious Diseases , Infection Control and Employee Health University of Texas MD Anderson Cancer Center , Houston , TX , USA.,b University of Texas School of Public Health , Houston , TX , USA.,c McGovern Medical School , Houston , TX , USA
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Mahjub R, Allahyar R, Rafiee-Tehrani M, Dorkoosh FA. Preparation and characterization of nanoparticles composed of methylated N-(4-N,N-dimethyl aminobenzyl) chitosan for oral delivery of cyclosporine A. EUROPEAN JOURNAL OF NANOMEDICINE 2016. [DOI: 10.1515/ejnm-2015-0034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AbstractCyclosporine is considered a highly lypophilic compound meaning low bioavailability through oral administration. In this study, cyclosporine was entrapped in a novel aromatic, quaternized derivative of chitosan (i.e. methylated N-(4-N,N-dimethyl aminobenzyl) chitosan) in order to improve solubility and bioavailability. Methylated N-(4,N,N-dimethyl aminobenzyl) chitosan was synthesized by the Schiff base reaction method. Polymeric nanoparticles containing cyclosporine was prepared and the physico-chemical properties of prepared nanoparticles were determined. The nanoparticles were studied morphologically using transmission electron microscopy (TEM). Finally, the release of cyclosporine from nanoparticles was studied in vitro using simulated intestinal fluid adjusted to pH of 6.8. For the preparation of nanoparticles, different formulations were studied and it was found that proper nanoparticles were prepared in equal concentration (1 mg/mL) of polymer and sodium tri-poly phosphate (TPP). The size, zeta potential, PdI, EE% and LE% of the prepared nanoparticles were reported as 173±36 nm, 23.1±4.18 mV, 0.243±0.05, 97.1±4.38% and 3.2±0.21%, respectively. The TEM images of nanoparticles revealed spherical to sub-spherical nanoparticles with no sign of agglomeration. This study suggests that preparations of nanoparticles composed of methylated N-(4,N,N-dimethyl aminobenzyl) chitosan can be a good candidate for improving the oral bioavailability of cyclosporine.
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Gairard-Dory AC, Dégot T, Hirschi S, Schuller A, Leclercq A, Renaud-Picard B, Gourieux B, Kessler R. Clinical usefulness of oral immunoglobulins in lung transplant recipients with norovirus gastroenteritis: a case series. Transplant Proc 2015; 46:3603-5. [PMID: 25498097 DOI: 10.1016/j.transproceed.2014.09.095] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Revised: 08/23/2014] [Accepted: 09/17/2014] [Indexed: 10/24/2022]
Abstract
Viral gastroenteritis causing diarrhea is a common complication observed in lung transplant recipients. Differently from the mild and typically self-limited disease seen in immunocompetent subjects, immunocompromised patients frequently have a more severe course. Norovirus and rotavirus are among the leading causes of severe gastroenteritis in transplant recipients. Specific treatment is unavailable, although good supportive treatment can significantly reduce morbidity. Previous studies have suggested that oral immunoglobulins may be used for the treatment of acute viral gastroenteritis after solid-organ transplantation. Herein, we conducted a retrospective chart review of 12 lung transplant recipients with norovirus-induced gastroenteritis who were treated with oral immunoglobulins for 2 days. Eleven patients were successfully treated, whereas 1 subject was only mildly improved. Four patients had at least 1 recurrence. No significant adverse effects were observed. We conclude that oral immunoglobulins may be clinically useful for lung transplant recipients with norovirus-induced gastroenteritis.
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Affiliation(s)
- A-C Gairard-Dory
- Department of Pharmacy, Strasbourg University Hospital, Strasbourg, France
| | - T Dégot
- Department of Pneumology, Strasbourg University Hospital, Strasbourg, France
| | - S Hirschi
- Department of Pneumology, Strasbourg University Hospital, Strasbourg, France
| | - A Schuller
- Department of Pneumology, Strasbourg University Hospital, Strasbourg, France
| | - A Leclercq
- Department of Pneumology, Strasbourg University Hospital, Strasbourg, France
| | - B Renaud-Picard
- Department of Pneumology, Strasbourg University Hospital, Strasbourg, France
| | - B Gourieux
- Department of Pharmacy, Strasbourg University Hospital, Strasbourg, France
| | - R Kessler
- Department of Pneumology, Strasbourg University Hospital, Strasbourg, France.
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Ye X, Van JN, Munoz FM, Revell PA, Kozinetz CA, Krance RA, Atmar RL, Estes MK, Koo HL. Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients. Am J Transplant 2015; 15:1874-81. [PMID: 25788003 PMCID: PMC4780324 DOI: 10.1111/ajt.13227] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Revised: 01/05/2015] [Accepted: 01/14/2015] [Indexed: 01/25/2023]
Abstract
Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1-324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.
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Affiliation(s)
- Xunyan Ye
- Department of Medicine, Baylor College of Medicine, Houston, TX
| | - John N. Van
- Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Flor M. Munoz
- Department of Pediatrics, Baylor College of Medicine, Houston, TX,Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX,Texas Children’s Hospital, Houston, TX
| | - Paula A. Revell
- Department of Pediatrics, Baylor College of Medicine, Houston, TX,Department of Pathology, Baylor College of Medicine, Houston, TX,Texas Children’s Hospital, Houston, TX
| | - Claudia A Kozinetz
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN
| | - Robert A. Krance
- Department of Pediatrics, Baylor College of Medicine, Houston, TX,Texas Children’s Hospital, Houston, TX
| | - Robert L. Atmar
- Department of Medicine, Baylor College of Medicine, Houston, TX,Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX
| | - Mary K. Estes
- Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX
| | - Hoonmo L. Koo
- Department of Medicine, Baylor College of Medicine, Houston, TX,Texas Children’s Hospital, Houston, TX
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Yang J, Zhao X, Patel A, Potru R, Azizi-Ghannad S, Dolinger M, Cao J, Bartholomew C, Mazurkiewicz J, Conti D, Jones D, Huang Y, Zhu XC. Rapamycin Inhibition of mTOR Reduces Levels of the Na+/H+ Exchanger 3 in Intestines of Mice and Humans, Leading to Diarrhea. Gastroenterology 2015; 149:151-62. [PMID: 25836987 PMCID: PMC4849539 DOI: 10.1053/j.gastro.2015.03.046] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Revised: 03/11/2015] [Accepted: 03/25/2015] [Indexed: 01/04/2023]
Abstract
BACKGROUND & AIMS The immunosuppressant rapamycin frequently causes noninfectious diarrhea in organ transplant recipients. We investigated the mechanisms of this process. METHODS We performed a retrospective analysis of renal transplant recipients treated with rapamycin from 2003 through 2010 at Albany Medical College, collecting data on serum levels of rapamycin. Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsy specimens from patients who did and did not receive rapamycin (controls), in ileum tissues from rats or mice given rapamycin, and in mice with intestine-specific disruption of mammalian target of rapamycin (Mtor) (mTOR(f/f):Villin-cre mice) or Atg7 (Atg7(flox/flox); Villin-Cre). Exchange activity and intestinal water absorption were measured using a pH-sensitive dye and small intestine perfusion, respectively. RESULTS Episodes of noninfectious diarrhea occurred in organ recipients after increases in serum levels of rapamycin. The expression of NHE3 was reduced in the ileal brush border of patients with diarrhea. In rats and mice, continuous administration of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed in mice with intestinal deletion of ATG7, indicating that autophagy is required for the reduction. Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). The intestines of mice with intestine-specific deletion of mTOR were dilated and contained large amounts of liquid stools; they also had reduced levels of total NHE3 and NHERF1 compared with control mice. We observed a significant reduction in Na(+)/H(+) exchange activity in ileum tissues from these mice. CONCLUSIONS Rapamycin inhibition of mTOR reduces levels of NHE3 and Na(+)/H(+) exchange activity in intestinal tissues of patients and rodents. This process appears to require the autophagic activity mediated by ATG7. Loss of mTOR regulation of NHE3 could mediate the development of diarrhea in patients undergoing rapamycin therapy.
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Affiliation(s)
- Jun Yang
- Department of Medicine, Division of Gastroenterology and Hepatology, Albany Medical College, Albany, New York; Center of Cardiovascular Sciences, Albany Medical College, Albany, New York
| | - Xiaofeng Zhao
- Department of Medicine, Division of Gastroenterology and Hepatology, Albany Medical College, Albany, New York; Center of Cardiovascular Sciences, Albany Medical College, Albany, New York
| | - Archana Patel
- Department of Medicine, Division of Gastroenterology and Hepatology, Albany Medical College, Albany, New York
| | - Rachana Potru
- Department of Medicine, Division of Gastroenterology and Hepatology, Albany Medical College, Albany, New York
| | - Sadra Azizi-Ghannad
- Department of Medicine, Division of Gastroenterology and Hepatology, Albany Medical College, Albany, New York
| | - Michael Dolinger
- Department of Medicine, Division of Gastroenterology and Hepatology, Albany Medical College, Albany, New York
| | - James Cao
- Center of Cardiovascular Sciences, Albany Medical College, Albany, New York
| | - Catherine Bartholomew
- Department of Medicine, Division of Gastroenterology and Hepatology, Albany Medical College, Albany, New York
| | - Joseph Mazurkiewicz
- Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York
| | - David Conti
- Department of Transplant Surgery, Albany Medical College, Albany, New York
| | - David Jones
- Department of Pathology, Albany Medical College, Albany, New York
| | - Yunfei Huang
- Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York
| | - Xinjun Cindy Zhu
- Department of Medicine, Division of Gastroenterology and Hepatology, Albany Medical College, Albany, New York; Center of Cardiovascular Sciences, Albany Medical College, Albany, New York.
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Mukai S, Onoe T, Tashiro H, Ohdan H. Small bowel obstruction due to an unconjugated ursodeoxycholic acid enterolith following living donor liver transplantation: Report of a case. Hepatol Res 2015; 45:818-22. [PMID: 25091893 DOI: 10.1111/hepr.12401] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Revised: 07/29/2014] [Accepted: 07/30/2014] [Indexed: 02/08/2023]
Abstract
We report an unusual case of small bowel obstruction due to an ursodeoxycholic acid (UDCA) enterolith that occurred 7 years after liver transplantation. A 70-year-old man had undergone multiple operations, including a living donor liver transplantation (LDLT) and hepaticojejunostomy. Four years after the LDLT, cholestasis developed, for which oral UDCA was administrated. Seven years after the LDLT, he was admitted to our hospital because of pneumonia; intestinal obstruction occurred following its resolution. A radiographic contrast study and computed tomographic scan indicated a movable mass as the cause of the ileus, suggesting a giant stone. We were unable to observe or remove the stone by double balloon enteroscopy owing to the presence of severe adhesion; thus, we surgically removed the mass. The patient's postoperative course was uneventful. He was discharged 20 days after the operation. An infrared spectrophotometric analysis revealed that the stone was a true enterolith, primarily composed of unconjugated UDCA. An ileus caused by a true enterolith is a rare clinical complication of LDLT. Nevertheless, it must be considered in the differential diagnosis of intestinal obstructions in liver transplant recipients with Roux-en-Y hepaticojejunostomies and/or bowel stasis.
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Affiliation(s)
- Shoichiro Mukai
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takashi Onoe
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Institute for Clinical Research, National Hospital Organization Kure Medical Center/Chugoku Cancer Center, Kure, Japan
| | - Hirotaka Tashiro
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Curtin BF, Rachakonda VP, Von Rosenvinge EC. Unusually late-onset mycophenolate mofetil-related colitis. Am J Health Syst Pharm 2015; 71:1858-61. [PMID: 25320135 DOI: 10.2146/ajhp140085] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Serious gastrointestinal complications arising 13 years after the initiation of posttransplant immunosuppressant therapy with mycophenolate mofetil are reported. SUMMARY Over a three-month period, a male heart transplant recipient who had taken oral mycophenolate mofetil (2 g daily) for 13 years as part of an immunosuppressant maintenance regimen developed diarrhea and weight loss leading to renal failure and metabolic acidosis. There was no evidence of opportunistic infection, and immunostaining for cytomegalovirus yielded negative results. Colonoscopy revealed areas of congested, erythematous, and nodular mucosa. Histological examination of mucosal biopsy specimens revealed pathological abnormalities typical of those seen in cases of mycophenolate mofetil-associated colitis. On discontinuation of mycophenolate mofetil use, the patient's diarrhea resolved and his renal function improved. Colitis, diarrhea, and other gastrointestinal complications are commonly reported in patients receiving mycophenolate mofetil, an immunosuppressant widely used to prevent rejection of solid organ or bone marrow transplants; however, the onset of such symptoms after more than a decade of continuous use of the drug has not been previously reported. This case suggests that mycophenolate mofetil toxicity should be considered in the evaluation of late-onset posttransplant diarrhea regardless of the duration of therapy. CONCLUSION A 33-year-old man maintained on mycophenolate mofetil for 13 years after heart transplantation developed diarrhea, weight loss, and acute kidney injury over a three-month period. Colonoscopy and biopsy revealed pathological changes consistent with mycophenolate mofetil toxicity, and the patient's symptoms resolved after the drug was discontinued.
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Affiliation(s)
- Bryan F Curtin
- Bryan F. Curtin, M.D., is Resident in Internal Medicine, Department of Internal Medicine; and Vikrant P. Rachakonda, M.D., Ph.D., is Fellow in Gastroenterology/Hepatology, Department of Internal Medicine, University of Maryland Medical Center, Baltimore. Erik C. von Rosenvinge, M.D., is Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine and Department of Veterans Affairs Maryland Health Care System, Baltimore.
| | - Vikrant P Rachakonda
- Bryan F. Curtin, M.D., is Resident in Internal Medicine, Department of Internal Medicine; and Vikrant P. Rachakonda, M.D., Ph.D., is Fellow in Gastroenterology/Hepatology, Department of Internal Medicine, University of Maryland Medical Center, Baltimore. Erik C. von Rosenvinge, M.D., is Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine and Department of Veterans Affairs Maryland Health Care System, Baltimore
| | - Erik C Von Rosenvinge
- Bryan F. Curtin, M.D., is Resident in Internal Medicine, Department of Internal Medicine; and Vikrant P. Rachakonda, M.D., Ph.D., is Fellow in Gastroenterology/Hepatology, Department of Internal Medicine, University of Maryland Medical Center, Baltimore. Erik C. von Rosenvinge, M.D., is Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine and Department of Veterans Affairs Maryland Health Care System, Baltimore
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Handreck A, Mall EM, Elger DA, Gey L, Gernert M. Different preparations, doses, and treatment regimens of cyclosporine A cause adverse effects but no robust changes in seizure thresholds in rats. Epilepsy Res 2015; 112:1-17. [DOI: 10.1016/j.eplepsyres.2015.02.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Revised: 11/27/2014] [Accepted: 02/04/2015] [Indexed: 10/24/2022]
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Wixner J, Sundström T, Karling P, Anan I, Suhr OB. Outcome of gastric emptying and gastrointestinal symptoms after liver transplantation for hereditary transthyretin amyloidosis. BMC Gastroenterol 2015; 15:51. [PMID: 25908211 PMCID: PMC4415350 DOI: 10.1186/s12876-015-0284-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 04/17/2015] [Indexed: 01/03/2023] Open
Abstract
Background Hereditary transthyretin amyloid (ATTR) amyloidosis is a rare but fatal autosomal dominant condition that is present all over the world. A liver transplantation has been shown to halt the progress of the disease in selected patients and is currently considered to be the standard treatment. Gastrointestinal manifestations are common in hereditary ATTR amyloidosis and are important for the patients’ morbidity and mortality. The aim of this study was to evaluate the long-term outcome of gastric emptying, gastrointestinal symptoms and nutritional status after liver transplantation for the disease. Methods Swedish patients with hereditary ATTR amyloidosis transplanted between 1990 and 2012 were included. A standardized method for measuring gastric emptying with a Tc99m-labelled meal followed by scintigraphy was utilized. Validated questionnaires were used to assess gastrointestinal symptoms and the modified body mass index (mBMI), in which BMI is multiplied by s-albumin, was used to evaluate nutritional status. Non-parametrical statistical tests were used. Results Gastric emptying rates and nutritional statuses were evaluated approximately eight months before and two and five years after liver transplantation, whereas gastrointestinal symptoms were assessed in median nine months before and two and nine years after transplantation. No significant change was found in gastric emptying (median half-time 137 vs. 132 vs. 125 min, p = 0.52) or nutritional status (median mBMI 975 vs. 991 vs. 973, p = 0.75) after transplantation. Gastrointestinal symptom scores, however, had increased significantly over time (median score 7 vs. 10 vs. 13, p < 0.01). Conclusions Gastric emptying and nutritional status were maintained after liver transplantation for hereditary ATTR amyloidosis, although gastrointestinal symptom scores had increased over time. Electronic supplementary material The online version of this article (doi:10.1186/s12876-015-0284-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jonas Wixner
- Departments of Public Health and Clinical Medicine, Umeå University, S-90187, Umeå, Sweden.
| | | | - Pontus Karling
- Departments of Public Health and Clinical Medicine, Umeå University, S-90187, Umeå, Sweden.
| | - Intissar Anan
- Departments of Public Health and Clinical Medicine, Umeå University, S-90187, Umeå, Sweden.
| | - Ole B Suhr
- Departments of Public Health and Clinical Medicine, Umeå University, S-90187, Umeå, Sweden.
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Cotter MB, AbuShanab A, Merriman R, McCormick A, Sheahan K. Coeliac-like duodenal pathology in orthotopic liver transplant patients on mycophenolic acid therapy. Histopathology 2015; 66:500-7. [PMID: 25195696 DOI: 10.1111/his.12541] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Accepted: 08/29/2014] [Indexed: 12/20/2022]
Abstract
AIMS Diarrhoea following orthotopic liver transplantation (OLT) is a significant clinical problem associated with mycophenolic acid (MPA). The histological injury pattern associated with MPA in the large bowel is well documented in the literature; however, that in the duodenum is less extensively documented. The aim of this study was to investigate the histological spectrum of duodenal injury specifically in symptomatic OLT patients on MPA, and to compare this with the spectrum in patients with coeliac disease and in normal controls. METHODS AND RESULTS We reviewed our pathology database for all duodenal biopsies from patients on the OLT list over a period of 19 years. Medical records, anti-tissue transglutaminase IgA serology and histology were reviewed. Of the 667 patients who underwent endoscopy, 127 had duodenal biopsies (152 biopsies). Of these, 87.5% were normal. Sixteen showed abnormal histology, and seven (43.8%) of these were on MPA at the time of biopsy. Significant features included coeliac-like changes (shortened villi and increased intraepithelial lymphocyte counts), and novel findings included increased endocrine cell counts, apoptotic counts and lamina propria eosinophil counts in comparison with normal duodenal biopsies. CONCLUSIONS Pathologists should be aware of the features of MPA-associated duodenal injury, including coeliac-like changes and increased apoptotic counts. In those with abnormal histology, discontinuation or a reduction in the dose of MPA should be discussed.
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Affiliation(s)
- Maura B Cotter
- Department of Histopathology, Centre for Colorectal Disease, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
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Haiqing W, Jiayin Y, Jian Y, Lunan Y. Intractable and dramatic diarrhea in liver transplantation recipient with vasoactive intestinal peptide-producing tumor after split liver transplantation: a case report. Transplant Proc 2015; 47:171-3. [PMID: 25596962 DOI: 10.1016/j.transproceed.2014.07.078] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Revised: 06/23/2014] [Accepted: 07/15/2014] [Indexed: 02/05/2023]
Abstract
Diarrhea after liver transplantation is a common complication. Vasoactive intestinal peptide-producing tumor (VIPoma) is a rare cause of watery diarrhea; 80% of such tumors occur in the pancreas, but it is rare in liver. Hypersecretion of vasoactive intestinal polypeptide can stimulate intestinal water and electrolyte secretion, and patients with VIPoma present with watery diarrhea, hypokalemia, and dehydration. Here we report on a 50-year-old man who presented with a 7-month history of watery diarrhea. He had undergone an orthotopic split-liver transplantation for hepatocellular carcinoma in November 2011. Two months after the liver transplantation, he presented with watery diarrhea, dehydration, and hypokalemia. Antibiotics, immunosuppressive drugs modification, antidiarrheal agents, antispasmodics, adsorbents, and fasting were alternately used to control the diarrhea, but his symptoms remained unchanged. A chromogranin examination, a marker of pancreatic neuroendocrine neoplasm, was positive in the third month of the diarrhea history and VIPoma was considered. Treatment with somatostatin immediately controlled the diarrhea, but the primary lesion could not be identified even after corresponding examinations were completed. In the ninth month of diarrhea, a 1 × 1-cm lesion was detected in the right liver by ultrasonography. Radiofrequency ablation was performed, and the diarrhea stopped. Seventeen months later, the chromogranin level decreased to normal and the patient was asymptomatic. Neither the recipient sharing the other liver portion nor the donor presented with any symptoms, so we wondered how the tumor occurred. It is possible that a small VIPoma lesion existed in the liver donor before the transplantation, and that the immunosuppressive drugs induced tumor development.
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Affiliation(s)
- W Haiqing
- Department of Liver Transplantation Center, West China Hospital of Sichuan University, Sichuan Province, China
| | - Y Jiayin
- Department of Liver Transplantation Center, West China Hospital of Sichuan University, Sichuan Province, China
| | - Y Jian
- Department of Liver Transplantation Center, West China Hospital of Sichuan University, Sichuan Province, China
| | - Y Lunan
- Department of Liver Transplantation Center, West China Hospital of Sichuan University, Sichuan Province, China.
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Bhadauria D, Goel A, Kaul A, Sharma RK, Gupta A, Ruhela V, Gupta A, Vardhan H, Prasad N. Cryptosporidium infection after renal transplantation in an endemic area. Transpl Infect Dis 2015; 17:48-55. [PMID: 25620388 DOI: 10.1111/tid.12336] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Revised: 08/21/2014] [Accepted: 10/26/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND Cryptosporidium is one of the common causes of infective diarrhea in post-transplant patients in endemic areas. However, data are limited on Cryptosporidium infection in recipients of solid organ transplantation. The aim of this study was to determine the incidence, disease manifestation, management, and outcome of Cryptosporidium infection in living-donor renal transplant recipients (RTR). METHODS We performed a detailed retrospective review of the data on all RTR who had diarrheal illness requiring evaluation and hospitalization, and Cryptosporidium infection. RESULTS During the study period, 119/1235 (8.98%) RTR developed diarrhea, and Cryptosporidium was found in 34/119 (28.5%). Nine of 680 (1.3%) patients were on a cyclosporine (CSA)-based regimen, and 25/643 (3.8%) patients were on a tacrolimus (Tac)-based regimen. The relative risk of developing Cryptosporidium infection was lower on the CSA-based regimen, compared with the Tac-based regimen (odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.17-0.72, P = 0.003). Twelve of the 34 patients had acute graft dysfunction, mainly caused by combined Tac toxicity and dehydration. Mean serum creatinine and trough Tac level were 2.04 ± 0.65 mg/dL and 8.24 ± 1.19 ng/dL, respectively. Nitazoxanide alone was used in 13 patients, and nitazoxanide in combination with fluoroquinolone in 21 patients, with duration of treatment ranging from 16 to 60 days. Tac was changed to CSA in 8/11 patients. The clearance of cysts and response to nitazoxanide alone were significantly lower, compared with combination therapy (61.53% vs. 95.23%, P = 0.01, 38.46 vs. 85.71%, P = 0.004, respectively). The OR for cyst clearance and response was also significantly lower with nitazoxanide alone, in comparison with combination therapy (OR: 0.65, 95% CI: 0.34-0.92, P = 0.01, OR: 0.45, 95% CI: 0.21-0.81, respectively). Four (16%) of 24 patients with response had relapse. CONCLUSION Patients with Tac and mycophenolate mofetil combination therapy had a significantly high risk of Cryptosporidium infection. Cryptosporidial infection may require prolonged nitazoxanide therapy, either alone or in combination, with or without reduction in immunosuppression.
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Affiliation(s)
- D Bhadauria
- Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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Abstract
The assessment of gastrointestinal (GI) specimens from transplant patients is complicated by the wide range of potentially rare pathologies that may be found in this clinical setting. Acute GI graft-versus-host disease (GvHD) is characterized by epithelial cell apoptosis, although there is increasing recognition that acute and/or chronic inflammation may also be present. By contrast, thus far there are no histological features known to be specific to chronic GI GvHD. Mycophenolate mofetil colitis may mimic both GvHD and inflammatory bowel disease, whereas both cytomegalovirus (CMV) and adenovirus infections can cause gland apoptosis. Post-transplant lymphoproliferative disorder should be considered if a Crohn's-like histological picture is seen, and granulomas in biopsies from umbilical cord blood recipients should raise a suspicion of cord colitis syndrome. Finally, the GI tract may be involved directly or indirectly by the disease that originally required haematopoietic stem cell or liver transplantation.
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40
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Mittal C, Hassan S, Arshad S, Jeepalyam S, Bruni S, Miceli M, Jacobsen G, Abouljoud M, Bajjoka I, Ramesh M, Alangaden G. Clostridium difficile infection in liver transplant recipients: a retrospective study of rates, risk factors and outcomes. Am J Transplant 2014; 14:1901-7. [PMID: 24902610 DOI: 10.1111/ajt.12798] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Revised: 04/23/2014] [Accepted: 04/23/2014] [Indexed: 01/25/2023]
Abstract
Clostridium difficile infection (CDI) occurs in 3-7% of liver transplant recipients (LTR). However, few data exist on the recent epidemiology, predictors and outcomes of CDI in LTR. A cohort study was performed including LTR from 2000 to 2010 at a tertiary care hospital in Detroit. CDI was defined as diarrhea with a stool C. difficile positive test. Data analyzed included demographics, comorbidities, length of stay (LOS), severity of CDI, rates of recurrence (<12 weeks), relapse (<4 weeks) and overall mortality. Predictors of CDI were calculated using Cox proportional hazard model; 970 LTR were followed for years. Overall prevalence of CDI was 18.9%. Incidence of CDI within 1 year of transplant was 12.4%. Severe CDI occurred in 29.1%. CDI recurrence and relapse rates were 16.9% and 9.7%, respectively. Independent predictors of CDI were year of transplant (hazard ratio [HR] 1.137, 95% confidence interval [CI] 1.06-1.22; p < 0.001), white race (105/162 whites, HR 1.47, 95% CI 1.03-2.1; p = 0.035), Model for End-Stage Liver Disease score (HR 1.03, 95% CI 1.01-1.045, p = 0.003) and LOS (HR 1.01, 95% CI 1.005-1.02, p < 0.001). Significant mortality was observed among LTR with CDI compared to those without CDI (p = 0.003). We concluded that CDI is common among LTR and is associated with higher mortality.
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Affiliation(s)
- C Mittal
- Division of Infectious Diseases, Henry Ford Health System, Detroit, MI
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Bonatti HJR, Metzger R, Swenson BR, Pawlowski S, Krell RW, Pruett TL, Brayman KL, Sifri CD, Sawyer RG. Solid organ recipients are at increased risk for recurrent Clostridium difficile colitis. Eur Surg 2014; 46:160-164. [DOI: 10.1007/s10353-014-0279-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Ihara S, Yamaji Y, Kinoshita H, Yamada A, Hirata Y, Hasegawa K, Sugawara Y, Kokudo N, Koike K. First case report of de novo ulcerative colitis developing after orthotopic liver transplantation successfully treated by granulocyte and monocyte apheresis. Transplant Proc 2014; 46:2414-7. [PMID: 25015850 DOI: 10.1016/j.transproceed.2014.02.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 01/24/2014] [Accepted: 02/27/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Immunosuppressants such as tacrolimus and cyclosporine are prescribed long-term after orthotopic liver transplantation (OLT) to prevent allograft rejection. Although these immunosuppressants are known to effectively control ulcerative colitis (UC), some post-OLT patients develop exacerbation of preexisting UC or de novo UC. Although aminosalicylates and corticosteroid courses are usually effective to treat such UC, several patients have developed uncontrollable disease and required colectomies. CASE REPORT We have reported a patient who developed de novo UC after OLT to treat liver cirrhosis and hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. Existence of the HBV infection made us avoid to increase the corticosteroid dose or to use other immunosuppressants such as azathioprine or infliximab. CONCLUSIONS In this patient, granulocyte and monocyte apheresis was highly effective in terms of inducing remission of de novo UC. No adverse event was noted.
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Affiliation(s)
- S Ihara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Y Yamaji
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - H Kinoshita
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - A Yamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Y Hirata
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - K Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Y Sugawara
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - N Kokudo
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - K Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Kim SI. Bacterial infection after liver transplantation. World J Gastroenterol 2014; 20:6211-6220. [PMID: 24876741 PMCID: PMC4033458 DOI: 10.3748/wjg.v20.i20.6211] [Citation(s) in RCA: 119] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 12/23/2013] [Accepted: 02/20/2014] [Indexed: 02/07/2023] Open
Abstract
Infectious complications are major causes of morbidity and mortality after liver transplantation, despite recent advances in the transplant field. Bacteria, fungi, viruses and parasites can cause infection before and after transplantation. Among them, bacterial infections are predominant during the first two months post-transplantation and affect patient and graft survival. They might cause surgical site infections, including deep intra-abdominal infections, bacteremia, pneumonia, catheter-related infections and urinary tract infections. The risk factors for bacterial infections differ between the periods after transplant, and between centers. Recently, the emergence of multi-drug resistant bacteria is great concern in liver transplant (LT) patients. The instructive data about effects of infections with extended-spectrum beta lactamase producing bacteria, carbapenem-resistant gram-negative bacteria, and glycopeptide-resistant gram-positive bacteria were reported on a center-by-center basis. To prevent post-transplant bacterial infections, proper strategies need to be established based upon center-specific data and evidence from well-controlled studies. This article reviewed the recent epidemiological data, risk factors for each type of infections and important clinical issues in bacterial infection after LT.
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Pant C, Deshpande A, Larson A, O'Connor J, Rolston DDK, Sferra TJ. Diarrhea in solid-organ transplant recipients: a review of the evidence. Curr Med Res Opin 2013; 29:1315-28. [PMID: 23777312 DOI: 10.1185/03007995.2013.816278] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To provide a comprehensive review of the literature as it relates to diarrhea in solid organ transplant (SOT) recipients. In this article, we review the epidemiology, pathogenesis, clinical manifestations, diagnosis and management of diarrhea in SOT recipients and discuss recent advances and challenges. METHODS Two investigators conducted independent literature searches using PubMed, Web of Science, and Scopus until January 1st, 2013. All databases were searched using a combination of the terms diarrhea, solid organ transplant, SOT, transplant associated diarrhea, and transplant recipients. Articles that discussed diarrhea in SOT recipients were reviewed and relevant cross-references also read and evaluated for inclusion. Selection bias could be a possible limitation of the approach used in selecting or finding articles for this article. FINDINGS Post-transplant diarrhea is a common and distressing occurrence in patients, which can have significant deleterious effects on the clinical course and well-being of the organ recipient. A majority of cases are due to infectious and drug-related etiologies. However, various other etiologies including inflammatory bowel disease must be considered in the differential diagnosis. A step-wise, informed approach to post-transplant diarrhea will help the clinician achieve the best diagnostic yield. The use of diagnostic endoscopy should be preceded by exclusion of an infectious or drug-related cause of diarrhea. Empiric management with antidiarrheal agents, probiotics, and lactose-free diets may have a role in managing patients for whom no cause can be determined even after an extensive investigation. CONCLUSIONS Physicians should be familiar with the common etiologies that result in post-transplant diarrhea. A directed approach to diagnosis and treatment will not only help to resolve the diarrhea but also prevent potentially life-threatening consequences including loss of the graft as well. Prospective studies are required to determine the etiology of post-transplant diarrhea in different clinical and geographic settings.
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Affiliation(s)
- Chaitanya Pant
- University of Oklahoma Health Sciences Center , Oklahoma City, OK , USA
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Liapis G, Boletis J, Skalioti C, Bamias G, Tsimaratou K, Patsouris E, Delladetsima I. Histological spectrum of mycophenolate mofetil-related colitis: association with apoptosis. Histopathology 2013; 63:649-58. [PMID: 24025088 DOI: 10.1111/his.12222] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 07/01/2013] [Indexed: 12/26/2022]
Abstract
AIMS The main purpose of this study was to define diagnostic histological characteristics of mycophenolate mofetil (MMF)-related colitis in association with crypt epithelial cell turnover. METHODS AND RESULTS The examined material included 43 colonic biopsies from renal transplant recipients with MMF administration and persistent diarrhoea. Thirty-three cases showed MMF-related colitis, while 10 showed no significant changes. The histological findings were scored and correlated with the apoptotic index (AI) and with the proliferation rate (PR) of the crypt epithelium examined by TUNEL assay and Ki-67 immunoexpression. Ten cases of Crohn disease and 10 of ulcerative colitis were used as comparative groups. Crypt distortion and loss as well as increased apoptosis constituted the main features, their degree and combination leading either to an inflammatory bowel disease (IBD)-like (82%) or to a graft-versus-host disease-like pattern (18%). A high AI was associated more frequently with moderate and severe crypt distortion, while the values were significantly higher compared with the control groups (P < 0.01). High PR was noted in 18 of 29 (62.1%) of the cases. CONCLUSIONS The diagnostic hallmark of MMF-related colitis is an IBD-like histological pattern in association with increased epithelial apoptosis, while apoptotic cell death seems to be a potential pathogenetic factor of mucosa injury.
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Affiliation(s)
- George Liapis
- 1st Department of Pathology Medical School, National and Kapodistrian University of Athens, Athens, Greece
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46
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Singh S, Loftus EV, Talwalkar JA. Inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Am J Gastroenterol 2013; 108:1417-25. [PMID: 23896954 DOI: 10.1038/ajg.2013.163] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 04/23/2013] [Indexed: 02/07/2023]
Abstract
The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complex, with several IBD-, PSC-, and transplant-related factors interplaying with each other. Approximately one-third of patients with known IBD improve, and one-third paradoxically worsen, after LT for PSC. Active IBD, discontinuation of 5-aminosalicylates (5-ASA) at time of LT and tacrolimus-based immunosuppression may be associated with an unfavorable course of IBD after LT. Approximately 14-30% patients with PSC may develop de novo IBD 10 years after LT. LT confers a high risk of pouchitis after ileal pouch-anal anastomosis, although it may not be higher than baseline rates for PSC patients. The risk of colorectal cancer continues to be high after LT for PSC, and is higher in this cohort of patients with PSC-IBD, compared with patients undergoing LT for other indications. IBD does not adversely affect patient survival after LT, although the risk of recurrent PSC in the allograft may be higher in patients with IBD and an intact colon at time of LT. Standard therapy with 5-ASA and/or azathioprine may be appropriate for treatment of active IBD after LT and maintenance of remission. Anti-tumor necrosis factor-α agents are effective, but should be used with caution because of high risk of adverse events. The management of IBD after LT requires close coordination between transplant hepatologists and IBD experts.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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47
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Ison MG. Diagnosis of gastrointestinal cytomegalovirus infections: an imperfect science. Clin Infect Dis 2013; 57:1560-1. [PMID: 23956171 DOI: 10.1093/cid/cit524] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Blank G, Li J, Kratt T, Handgretinger R, Königsrainer A, Nadalin S. Treatment of liver transplant graft-versus-host disease with antibodies against tumor necrosis factor-α. EXP CLIN TRANSPLANT 2013; 11:68-71. [PMID: 23387543 DOI: 10.6002/ect.2012.0083] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Acute graft-versus-host disease is uncommon after liver transplant. We recently treated a 60-year-old man with liver transplant for hepatocellular carcinoma. After the primary liver transplant graft did not function, revision liver transplant resulted in excellent function. Subsequently, the patient developed watery diarrhea, systemic inflammatory response syndrome, a skin rash on his limbs and trunk, and palmar erythema. Skin biopsy suggested viral exanthems consistent with cytomegalovirus. Despite treatment for cytomegalovirus, intestinal symptoms worsened. Analysis of peripheral blood with fluorescence-activated cell sorting showed a high proportion of T lymphocytes, with 5% to 10% T cells specific to the second donor, suggestive of graft-versus-host disease. Within 48 hours after beginning therapy with antibodies against tumor necrosis factor-α (infliximab), the skin rash disappeared and endoscopy showed slight improvement of the mucosal regeneration. However, despite antifungal prophylaxis with caspofungin, the patient developed angioinvasive pulmonary aspergillosis and multiple organ failure, and he died. In conclusion, typical clinical symptoms of graft-versus-host disease after liver transplant may include skin rash and gastrointestinal symptoms, and diagnosis may be confirmed by histologic examination and testing for blood chimerism. A consensus for the treatment of graft-versus-host disease still is lacking, but tumor necrosis factor-α is an encouraging target for therapy to decrease the symptoms of graft-versus-host disease and enable mucosal regeneration.
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Affiliation(s)
- Gregor Blank
- Department of General, Visceral and Transplant Surgery, University Hospital, Tübingen, Germany.
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49
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De Bruyne R, Dullaers M, Van Biervliet S, Vande Velde S, Raes A, Gevaert P, Van Winckel M. Post-transplant food allergy in children is associated with liver and not with renal transplantation: a monocentric comparative study. Eur J Pediatr 2013; 172:1069-75. [PMID: 23609525 DOI: 10.1007/s00431-013-2002-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Accepted: 03/27/2013] [Indexed: 11/26/2022]
Abstract
UNLABELLED Food allergy is increasingly reported after paediatric liver transplantation. The underlying physiopathological mechanism remains incompletely understood. Therefore, we aimed to determine the incidence, clinical presentation, possible risk factors, and prognosis of post-transplant food allergy in children currently followed after liver and renal transplantation. The study population consists of 49 liver and 21 renal transplant patients transplanted between the age of 22 months and 15 years. Data were collected retrospectively from medical records and via a doctor's questionnaire taken from the parents in a monocentric setting. Post-transplant food allergy has developed in 13 liver transplant patients and in none of the renal transplant recipients. Within the liver transplant group, median age at liver transplantation is significantly lower in the food-allergic (10 months) versus non-food-allergic group (3.3 years; p = 0.002). The use of tacrolimus as primary maintenance immunosuppression is associated with food allergy (p = 0.032) and mean donor age is significantly lower in the food-allergic group (p = 0.009). Compared to the renal transplant group, median age at transplantation is significantly lower in the liver patients (p < 0.001). No significant differences are found in primary immunosuppressive regimens between renal and liver transplant patients. CONCLUSION Post-transplant food allergy is an important clinical problem in children after liver transplantation which does not affect renal transplant patients despite similar immunosuppressive regimens. Within the group of liver transplant recipients, tacrolimus use, young age at time of transplant and younger donor age were associated with the development of food allergy.
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Affiliation(s)
- Ruth De Bruyne
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Princess Elisabeth Children's Hospital, Ghent University Hospital, Belgium De Pintelaan 185, 9000 Ghent, Belgium.
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Abstract
Diarrhea is a common symptom after solid organ transplantation or hematopoietic stem cell transplantation, with a reported prevalence up to 72%. One of the uncommon causes for diarrhea in the posttransplant setting is development of de novo inflammatory bowel disease (IBD). The incidence of posttransplantation de novo IBD was shown to be higher than that in the general population (206 versus 20 per 100,000 cases annually). The frequency seems to be much higher following orthotopic liver transplantation than the transplantation of other solid organs. De novo IBD has also been described in the setting of bone marrow transplantation though not as commonly as after SOT. While IBD is considered an immune-mediated disorder and responds favorably to immunosuppressive, de novo IBD or IBD-like conditions can occur in the posttransplant period despite antirejection immunosuppressive therapy. Damage or pathogen-associated molecular pattern molecules and their associated ongoing inflammation within the transplanted organ and the recipients' intestine have been implicated as possible etiologies. Various viral, bacterial, and protozoal infections can mimic IBD in postorgan transplantation. Common IBD mimickers in the postbone marrow transplant setting are graft-versus-host disease, infectious enteritis/colitis, and less commonly "cord colitis" that is described in detail below. In this article, we discuss the epidemiology, clinical features, and outcomes of de novo IBD after transplantation and highlight their differences in presentation, diagnosis, and management.
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