From intestinal failure to transplantation: Review on the current need for transplant indications under multidisciplinary transplant programs worldwide.

INTRODUCTION: Intestinal failure, defined as the loss of gastrointestinal function to the point where nutrition cannot be maintained by enteral intake alone, presents numerous challenges in children, not least the timing of consideration of intestine transplantation. OBJECTIVES: To describe the evolution of care of infants and children with intestinal failure including parenteral nutrition, intestine transplantation, and contemporary intestinal failure care. METHODS: The review is based on the authors' experience supported by an in-depth review of the published literature. RESULTS: The history of parenteral nutrition, including out-patient (home) administration, and intestine transplantation are reviewed along with the complications of intestinal failure that may become indications for consideration of intestine transplantation. Current management strategies for children with intestinal failure are discussed along with changes in need for intestine transplantation, recognizing the difficulty in generalizing recommendations due to the high level of heterogeneity of intestinal pathology and residual bowel anatomy and function. DISCUSSION: Advances in the medical and surgical care of children with intestinal failure have resulted in improved transplant-free survival and a significant fall in demand for transplantation. Despite these improvements a number of children continue to fail rehabilitative care and require intestine transplantation as life-saving therapy or when the burden on ongoing parenteral nutrition becomes too great to bear.

Pathophysiology of Ascites: The importance of the intestine. A surgical contribution to the understanding of a medical problem.

The understanding of the mechanisms for the development of ascites has evolved over the years, involving the liver, peritoneum, heart, and kidneys as key responsible for its formation. In this article, we review the pathophysiology of ascites formation, introducing the role of the intestine as a major responsible for ascites production through "a game changer" case.

Endoscopic Surveillance of the Intestinal Allograft: Recommendations From the Intestinal Rehabilitation and Transplant Association Working Group.

Intestinal transplant (ITx) rejection lacks a reliable noninvasive biomarker and rejection surveillance relies on serial endoscopies and mucosal biopsies followed by histologic assessment. Endoscopic biopsies are also essential for identifying other ITx-related complications such as infectious, allergic, and inflammatory graft enteritis as well as post-transplant lymphoproliferative disease or graft versus host disease. In spite of its central role in ITx, published guidelines on endoscopy and biopsy are lacking and significant variability between centers in terms of timing and technical performance exists. Therefore, an international expert group convened and discussed several aspects related to the surveillance endoscopy after ITx with the aim to summarize and standardize its practice. This article summarizes these considerations on endoscopic ITx monitoring and highlights practices of surveillance and for-cause endoscopy, biopsy techniques, pathologic evaluation, potential risks and complications, outsourcing, and less-invasive monitoring techniques.

Recomendaciones de expertos acerca del uso de teduglutide en pacientes pediátricos con sindrome de intestino corto / Expert recommendations on the use of teduglutide in pediatric patients with short bowel syndrome

Resumen El síndrome de intestino corto es una entidad de baja incidencia en los pacientes pediátricos, pero se asocia con elevadas tasas de morbimortalidad. El abordaje de estos pacientes por un equipo interdisciplinario de expertos enfocados en la rehabilitación intestinal mejora los resultados a corto y a largo plazo. Entre los recursos disponibles para el tratamiento se incluye el teduglutide, un análogo del péptido similar al glucagón tipo 2 (GLP-2) elaborado mediante técnicas recombinantes. Por medio de la aplicación del método Delphi, a partir de la evidencia disponible y de la experiencia de los autores, se proponen recomendaciones para el uso de teduglutide, dirigidas a los profesionales de la salud que tratan a los pacientes pediátricos con síndrome de intestino corto, así como a las autoridades sanitarias.

Abstract Short bowel syndrome is a low-incidence disorder among pediatric patients, but it is associated with high morbidity and mortality rates. Management of these patients by an interdisciplinary team of experts focused on intestinal rehabilitation improves short- and long-term outcomes. Available resources for treatment include teduglutide, a glucagon-like peptide type 2 (GLP-2) analog made by recombinant techniques. Considering the available evi dence and the authors' experience, Delphi-based recommendations for the use of teduglutide are suggested for healthcare professionals who treat pediatric patients with short bowel syndrome, as well as for health authorities.

[Expert recommendations on the use of teduglutide in pediatric patients with short bowel syndrome]. / Recomendaciones de expertos acerca del uso de teduglutide en pacientes pediátricos con síndrome de intestino corto.

Short bowel syndrome is a low-incidence disorder among pediatric patients, but it is associated with high morbidity and mortality rates. Management of these patients by an interdisciplinary team of experts focused on intestinal rehabilitation improves short- and long-term outcomes. Available resources for treatment include teduglutide, a glucagon-like peptide type 2 (GLP-2) analog made by recombinant techniques. Considering the available evidence and the authors' experience, Delphi-based recommendations for the use of teduglutide are suggested for healthcare professionals who treat pediatric patients with short bowel syndrome, as well as for health authorities.

El síndrome de intestino corto es una entidad de baja incidencia en los pacientes pediátricos, pero se asocia con elevadas tasas de morbimortalidad. El abordaje de estos pacientes por un equipo interdisciplinario de expertos enfocados en la rehabilitación intestinal mejora los resultados a corto y a largo plazo. Entre los recursos disponibles para el tratamiento se incluye el teduglutide, un análogo del péptido similar al glucagón tipo 2 (GLP-2) elaborado mediante técnicas recombinantes. Por medio de la aplicación del método Delphi, a partir de la evidencia disponible y de la experiencia de los autores, se proponen recomendaciones para el uso de teduglutide, dirigidas a los profesionales de la salud que tratan a los pacientes pediátricos con síndrome de intestino corto, así como a las autoridades sanitarias.

Autologous gastrointestinal reconstruction surgery for short bowel syndrome: the cornerstone for intestinal rehabilitation.

PURPOSE OF REVIEW: Intestinal failure (IF) evolved from being the last recognized organ failure, to become one of the most progressive fields in terms of therapeutic alternatives and results. Short bowel syndrome (SBS) is the main cause of IF in adults and children. The use of surgery allowed patients with unfavorable anatomy type and length to be wean off parenteral nutrition. We aim to evaluate its current impact on intestinal rehabilitation. RECENT FINDINGS: Autologous gastro-intestinal reconstructive surgery (AGIRS), including bowel lengthening contributes by converting patient's anatomy to a more favorable one, improving quality of life, and modifying the natural history of the disease, allowing to recover intestinal autonomy in approximately 70% of the adults and 50% of the children's with SBS-IF. The current use of postsurgical medical rehabilitation strategies including the use of enterohormones complement the path to sufficiency, increasing the chances of success in both age group of patients. SUMMARY: The development of AGIRS has changed the outcome of SBS-IF patients, becoming the main surgical procedure prescribed in multidisciplinary units, allowing to enhance the number of patients achieving intestinal autonomy throughout rehabilitation, leaving transplantation as the last surgical alternative.

Induction Versus Maintenance Immunosuppression After Intestinal Transplant: Determining Which Treatment Most Impacts Long-Term Patient And Graft Survival.

OBJECTIVES: Immunosuppressive strategies for intestinal transplant have changed over time. However, specific intestinal transplant-oriented protocols and reports on long-term maintenance regimens are scarce. Our objective was to evaluate the impact of 2 different initial immunosuppressive protocols based on thymoglobulin (group A) and basiliximab (anti-interleukin 2 antibody) (group B) and of changes to maintenance immunosuppression over long-term follow-up in intestinal transplant recipients. MATERIALS AND METHODS: We performed a retrospective analysis of a prospectively established protocol for intestinal transplant immunosuppression, conducted between May 2006 and December 2020. We analyzed 51 intestinal transplant recipients, with 6 patients excluded because of early death or graft loss. Acute cellular rejection frequency and grade, number of acute cellular rejection episodes, time to the first acute cellular rejection episode, response to treatment, number of patients who progressed to chronic allograft rejection, kidney function, infections, incidence of posttransplant lymphoproliferative disorder and graft-versus-host disease, and patient and graft survival were analyzed. RESULTS: In the study groups, there were 87 acute cellular rejection episodes in 45 patients (33 in group A and 54 in group B). We found degree of acute cellular rejection to be mild in 45 patients, moderate in 18, and severe in 24 (not significant between groups). Our comparison of induction therapy (thymoglobulin [group A] vs interleukin 2 antibody [group B]) did not show any statistical difference during clinical followup. Long-term review showed that all patients were on tacrolimus. Five-year patient and graft survival rates were 62% and 45% for group A and 54% and 46% for group B, respectively (not significant). CONCLUSIONS: Long-term patient and graft outcomes reflected the use of an individualized follow-up with adjustments and changes in immunosuppressive medications according to the patient's clinical course and complications rather than based on the induction immunosuppressive protocol used.

Non-conventional vascular accesses for the management of superior vena cava syndrome in patients with Intestinal Failure. Case series and systematic review.

BACKGROUND: Type III Intestinal Failure (IF) is a devastating clinical condition.characterized by the inability of the gut to absorb necessary macronutrients, and/or water and electrolytes, requiring Parenteral Nutrition (PN) as chronic therapy. Long-term PN may lead to life-threatening complications; the loss of central venous access (LCVA) is the most frequent and challenging. To date, few studies in the literature have reported the relevance of Non-conventional Vascular Accesses (NCVA) in the management IF as part of the comprehensive multidisciplinary care. METHODS: A retrospective analysis of a database collected from January 2006 to December 2019 was performed using SPSS v25.0 for statistical analysis, followed by a systematic review, using the PRISMA.methodology RESULTS: From January 2006 to December 2019, 184 NCVA were placed in 71 patients with LCVA as IF-related complication; 173 were placed in 61 patients by interventional radiology (IR) and 11 NCVA were placed in 10 patients by the surgical team during the intestinal transplant (ITx) operation. From the 173 IR procedures 166 (95.9%) were successful with 3 ± 2.7 procedures/patient; average catheter permanence rate was 738.68 ± 997 days; complications related to the procedures occurred in 18/173 (10.4%), including two deaths. On the other hand, among the 11 NCVA implanted by the surgical team, 7 (64%) were successful and were safely withdrawn 30 days after ITx when were no longer needed; 2 (18%) catheters malfunctioned during the first week and could not be further used, and 1 was accidently removed; average catheter permanence rate was 26 ± 4 days. There was one complication (9%) requiring laparotomy; there was no mortality associated the procedure in this group. A systematic review was conducted to evaluate the success and safety of NCVA as part of the treatment of HPN-related complications; from 337,542 papers, 14 studies were included. A total of 28 HPN-patients with LCVA received NCVA; 34 procedures were successfully performed, while procedure-related complications were reported in 11.7%, as well as one death. CONCLUSIONS: The data analyzed show that NCVAs may be successfully placed by expert teams, allowing to sustain long-term PN, as well as increasing the Intestinal Transplantation applicability for candidates in the extreme need of vascular access.

[Clinical guidelines for the managment of intestinal failure secondary to pediatric short bowel syndrome]. / Guía clínica para el manejo de la falla intestinal secundaria a síndrome de intestino corto en pediatría.

Intestinal failure secondary to short bowel syndrome in pediatrics, is a rare condition with high morbimortality. A follow up multidisciplinary team is necessary to minimize complications and optimize the intestinal rehabilitation. There are no gold standard guidelines for the management of this group of complex patients. The development of clinical guidelines may contribute for an adequate management of patients with intestinal failure and short bowel syndrome. This Clinical Guideline for the Management was developed by 16 experts based on modified Delphi methodology. The meetings were held at the Argentinian Association of Enteral and Parenteral Nutrition (Asociación Argentina de Nutrición Enteral y Parenteral); the topics analyzed were definitions, epidemiology, enteral and parenteral nutrition, pharmacological and surgical treatments, and criteria for referring patients to intestinal rehabilitation centers. The document is aimed to provide basic scientific knowledge for medical institutions, health providers, healthcare providers, patients and families.

La falla intestinal secundaria a síndrome de intestino corto en pediatría es una entidad poco frecuente, de alta morbimortalidad. Requiere de un equipo interdisciplinario para su abordaje, lo cual ha demostrado que disminuye la morbimortalidad y aumenta la posibilidad de que los pacientes logren la autonomía intestinal. Existe una falta de evidencia científica en diferentes abordajes de la patología. Consideramos necesario el desarrollo de esta Guía para el Manejo Clínico construida sobre la base de la metodología Delphi modificada, en la Asociación Argentina de Nutrición Enteral y Parenteral, por 16 expertos que se reunieron para discutir y consensuar los principales aspectos de tratamiento clínico. Se analizaron 4 aspectos: definiciones y epidemiología; nutrición enteral, nutrición parenteral; tratamientos farmacológicos y quirúrgicos, y criterios de derivación a centros de alta complejidad. Sin duda este documento será de utilidad para los pacientes, los profesionales y las instituciones, así como para los diferentes financiadores del sistema de salud.

Guía clínica para el manejo de la falla intestinal secundaria a síndrome de intestino corto en pediatría / Clinical guidelines for the managment of intestinal failure secondary to pediatric short bowel syndrome

La falla intestinal secundaria a síndrome de intestino corto en pediatría es una entidad poco frecuente, de alta morbimortalidad. Requiere de un equipo interdisciplinario para su abordaje, lo cual ha demostrado que disminuye la morbimortalidad y aumenta la posibilidad de que los pacientes logren la autonomía intestinal. Existe una falta de evidencia científica en diferentes abordajes de la patología. Consideramos necesario el desarrollo de esta Guía para el Manejo Clínico construida sobre la base de la metodología Delphi modificada, en la Asociación Argentina de Nutrición Enteral y Parenteral, por 16 expertos que se reunieron para discutir y consensuar los principales aspectos de tratamiento clínico. Se analizaron 4 aspectos: definiciones y epidemiología; nutrición enteral, nutrición parenteral; tratamientos farmacológicos y quirúrgicos,y criterios de derivación a centros de alta complejidad. Sin duda este documento será de utilidad para los pacientes, los profesionales y las instituciones, así como para los diferentes financiadores del sistema de salud.

Intestinal failure secondary to short bowel syndrome in pediatrics, is a rare condition with high morbimortality. A follow up multidisciplinary team is necessary to minimize complications and optimize the intestinal rehabilitation. There are no gold standard guidelines for the management of this group of complex patients. The development of clinical guidelines may contribute for an adequate management of patients with intestinal failure and short bowel syndrome. This Clinical Guideline for the Management was developed by 16 experts based on modified Delphi methodology. The meetings were held at the Argentinian Association of Enteral and Parenteral Nutrition (Asociación Argentina de Nutrición Enteral y Parenteral); the topics analyzed were definitions, epidemiology, enteral and parenteral nutrition, pharmacological and surgical treatments, and criteria for referring patients to intestinal rehabilitation centers. The document is aimed to provide basic scientific knowledge for medical institutions, health providers, healthcare providers, patients and families.

Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis.

Acute cellular rejection (ACR) remains as one of the main causes of graft loss and death in intestinal transplant (ITx) patients. ACR promotes intestinal injury, disruption of the mucosal barrier, bacterial translocation, and organ dysfunction. As epithelial regeneration is critical in reversing these consequences, the functional axis between the innate lymphoid cell subpopulation 3 (ILC3) and interleukin 22 plays an essential role in that process. Natural-cytotoxic-receptor-positive (NCR+) ILC3 cells have been demonstrated to induce intestinal-stem-cell proliferation along with an IL-22-dependent expansion of that population in several intestinal pathologies, though thus far not after ITx. Therefore, we intended to determine the impact of chronic immunosuppression and ACR on ILC3 cells and interleukin-22 (IL-22) production in the lamina propria after that intervention. MATERIALS AND METHODS: We compared biopsies from healthy volunteers with biopsies from ITx recipients without or with mild-to-moderate ACR, using flow cytometry and the quantitative-PCR. RESULTS: NCR+ ILC3 cells were found to be unaffected by immunosuppression at different time points posttransplant when patients did not experience ACR, but were diminished upon the occurrence of ACR independently of the post-ITx time. Moreover, IL-22-expression levels were notably reduced in ACR. CONCLUSION: The NCR+-ILC3/IL-22 axis is impaired during ACR contributing to a delay in or lack of a complete and efficient epithelial regeneration. Thus, our findings reveal that IL-22 analogues could potentially be used as a new complementary therapeutic approach, in conjunction with immunosuppressant drugs, in order to promote mucosal regeneration upon ACR.

Changing Etiologies and Prognostic Factors in Pediatric Acute Liver Failure.

After the implementation of universal hepatitis A virus vaccination in Argentina, the outcome of pediatric acute liver failure (PALF) remains unknown. We aimed to identify variables associated with the risk of liver transplantation (LT) or death and to determine the causes and short-term outcomes of PALF in Argentina. We retrospectively included 135 patients with PALF listed for LT between 2007 and 2016. Patients with autoimmune hepatitis (AIH), Wilson's disease (WD), or inborn errors of metabolism (IEM) were classified as PALF-chronic liver disease (CLD), and others were classified as "pure" PALF. A logistic regression model was developed to identify factors independently associated with death or need of LT and risk stratification. The most common etiologies were indeterminate (52%), AIH (23%), WD (6%), and IEM (6%). Overall, transplant-free survival was 35%, whereas 50% of the patients underwent LT and 15% died on the waiting list. The 3-month risk of LT or death was significantly higher among patients with pure PALF compared with PALF-CLD (76.5% versus 42.5%; relative risk, 1.8 [1.3-2.5]; P < 0.001), and 3 risk factors were independently associated with worse outcome: international normalized ratio (INR) ≥3.5 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3-7.2]), bilirubin ≥17 mg/dL (OR, 4.4; 95% CI, 1.9-10.3]), and pure PALF (OR, 3.8; 95% CI, 1.6-8.9). Patients were identified by the number of risk factors: Patients with 0, 1, or ≥2 risk factors presented a 3-month risk of worse outcome of 17.6%, 36.6%, and 82%, respectively. In conclusion, although lacking external validation, this simple risk-staging model might help stratify patients with different transplant-free survival rates and may contribute to establishing the optimal timing for LT.

Results of Surgical and Medical Rehabilitation for Adult Patients With Type III Intestinal Failure in a Comprehensive Unit Today: Building a New Model to Predict Parenteral Nutrition Independency.

BACKGROUND: Short-bowel syndrome remains the primary cause of intestinal failure (IF) in adult patients. We aim to report the long-term results of medical and surgical rehabilitation in a cohort of patients with type III IF (III-IF) and develop a formula to predict parenteral nutrition (PN) independency. METHODS: We used a retrospective analysis of a prospective database for III-IF patients undergoing autologous gastrointestinal reconstruction surgery (AGIRS) from March 2006 to August 2018. Analyzed variables included demographic data, postsurgical intestinal length (PSIL), postsurgical anatomy, teduglutide (TED) treatment, and PN volume reduction. Univariate analysis, Cox regression, logistic regression forward stepwise models, and receiver operating characteristic (ROC) curve were done using SPSS v20. RESULTS: AGIRS was performed in 88 patients. The most frequent anatomy at first visit was type 1. Prevailing anatomy after surgery was type 3. Eight patients started TED; 6 achieved freedom from PN. At a mean follow-up time of 1606.1 ± 1190.25 days, freedom from PN survival was achieved in 83%. Variables identified at the logistic regression analysis led to a novel formula to predict intestinal rehabilitation, including PSIL, presence of ileocecal valve, and use of TED as part of postsurgical treatment. CONCLUSIONS: AGIRS in this group of patients enabled intestinal length increase and also intestinal anatomy conversion into a more favorable type for intestinal rehabilitation. TED treatment was useful to discontinue PN in patients with classical negative anatomical predictors. The novel predicting formula has an ROC area under the curve = 0.82. Further studies are necessary to validate this formula.

Pediatric living donor liver transplant in a recipient with biliary atresia and portal vein duplication-How did we manage it?

Portal vein malformations might occur during the embryonic period, as a consequence of abnormal remodeling of vitelline veins during embryonic life. Patients suffering from biliary atresia are particularly prone to have vascular malformations; although being the most frequent indication for liver transplantation in the pediatric age, portal vein duplication has not been so far associated with biliary atresia, and to the best of our knowledge, there is no-written evidence describing how to manage it when it is first diagnosed while performing a pediatric liver transplant. Therefore, we present a recent case from our group, describing the intraoperative diagnosis of a double portal system in a patient with biliary atresia and failed Kasai. We aim to describe its surgical management, understanding that it is a real challenge to find them unexpectedly during the surgical procedure in the setting of cirrhosis and portal hypertension, particularly in small patients; therefore, by reporting this case, we aim to make readers aware about the chance of finding it, and how to managed it, to include this approach as part of the surgical armamentarium.

Unusual spontaneous porto-systemic shunt: The importance of diagnosing non-anatomical porto-systemic shunts to improve portal flow in pediatric living-related liver transplantation. Case report.

Collateral circulation secondary to liver cirrhosis may cause the development of large PSSs that may steal flow from the main portal circulation. It is important to identify these shunts prior to, or during the transplant surgery because they might cause an insufficient portal flow to the implanted graft. There are few reports of "steal flow syndrome" cases in pediatrics, even in biliary atresia patients that may have portal hypoplasia as an associated malformation. We present a 12-month-old female who received an uneventful LDLT from her mother, and the GRWR was 4.8. During the early post-operative period, she became hemodynamically unstable, developed ascites, and altered LFT. The post-operative ultrasound identified reversed portal flow, finding a non-anatomical PSS. A 3D CT scan confirmed the presence of a mesocaval shunt through the territory of the right gonadal vein, draining into the right iliac vein, with no portal inflow into the liver. The patient was re-operated, and the shunt was ligated. An intraoperative Doppler ultrasound showed adequate portal inflow after the procedure; the patient evolved satisfactorily and was discharged home on day number 49. The aim was to report a case of post-operative steal syndrome in a pediatric recipient due to a mesocaval shunt not diagnosed during the pretransplant evaluation.

Utility of Aminotransferase/Platelet Ratio Index to Predict Liver Fibrosis in Intestinal Failure-Associated Liver Disease in Pediatric Patients.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) is a frequent indication for intestinal transplantation. Liver biopsy (LBX) is the gold standard test for its diagnosis. Identifying noninvasive markers of fibrosis progression would be of considerable clinical use. Aspartate aminotransferase/platelet ratio index (APRI) has a good correlation in adult patients with chronic liver disease; few studies have been performed in children with IFALD. AIM: To evaluate APRI in a cohort of children with IFALD. MATERIALS AND METHODS: Retrospective analysis of a prospective database of patients <18 years with severe intestinal failure and at least 1 LBX, registered in our unit from March 2006 to December 2014. RESULTS: Forty-nine LBX were done on 36 patients: 20 were male, and 31 had short gut. Fibrosis was found in 71% of LBX. Biopsies were grouped according to the fibrosis stage (METAVIR [M]): (1) group 1 (G1) LBX with M 0, 1, 2 (n = 33) and (2) group 2 (G2) LBX with M 3, 4 (n = 16). The median APRI score was 0.92 (interquartile range [IQR] 0.63-1.50) for G1 and 2.50 (IQR 1.81-5.82) for G2 ( P = .001) The c statistic of the receiving operating characteristic curve was 0.79 (95% CI 0.64-0.94; P < .001). The analyses allowed identifying a cutoff value for APRI of 1.6 as the point with the best sensitivity (81%) and specificity (76%) to predict advanced fibrosis. CONCLUSIONS: APRI in this cohort of patients shows that a score >1.6 correlates with advanced fibrosis.

Avances en Gastroenterología Trasplante intestinal desde la clínica a la investigación traslacional: contribuciones de una unidad integral de insuficiencia intestinal, rehabilitación y trasplante. Seguimiento biomédico del proceso de trasplante intestinal y su correlación con los distintos eventos fisiopatológicos que atraviesa el paciente.

One of the greatest achievements in gastroenterology and surgery of the last 50 years has been the capability to transplant different abdominal organs of the digestive system separately or as a whole. The complexity of the intestinal transplantation demands a multidisciplinary team engaged in the management of patients with intestinal failure responsible for defining the need for nutritional support, rehabilitation, or intestinal transplantation. This team should include a basic research area to provide answers to unresolved clinical problems. The aim of this work is to update the current status of intestinal transplantation, and to show the progress and results of our center; emphasizing our achievements in the clinical area, and the contributions of the translational research and mucosal immunology studies as part of the integral unit of intestinal failure, rehabilitation and transplantation. The data reported here demonstrate that the intestinal transplantation has been established as a therapeutic option in our country and Latin America, with long term results that have ranked our service at the level of the best centers in the world positioning us as referent in the specialty.

Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers.

BACKGROUND AND AIMS: Acute cellular rejection (ACR) and infections are leading causes of graft loss and death in intestinal transplant patients. Our aim was to evaluate the impact of maintenance immunosuppressive therapies on the expression of pro-inflammatory mediators in small bowel at ACR diagnosis. MATERIALS AND METHODS: We analyzed expression levels of Th1-associated genes, IFNG, CXCL10, and CXCL11 by qPCR in 46 selected graft biopsies unequivocally assigned to mild ACR (n = 14) or normal histopathology and clinical condition (n = 32) from 15 patients receiving two different immunosuppressive (IS) schemes. Double treatment: corticosteroids and tacrolimus (n = 17) and triple treatment: sirolimus or mycophenolate mofetil in addition to the basal therapy (n = 29). RESULTS: IFNG, CXCL10, and CXCL11 were induced during rejection (p < 0.05; p < 0.005, and p < 0.05, respectively). However, when rejection and control groups were classified according to immunosuppressive treatment, in the rejection group, significant differences of IFNG, CXCL10, and CXCL11 expression (p < 0.001; p < 0.005, and 0.01, respectively) were detected, whereas no differences were observed in the control group. CONCLUSION: Gene expression of Th1 response mediators is higher during ACR. Triple IS group showed significantly lower expression of pro-inflammatory Th1 mediators during mild ACR indicating that use of these markers to monitor rejection can be affected by the IS treatment used.