Steroid-resistant Acute Rejection Research Articles

Living-related partial liver transplantation in unresectable liver metastatic colorectal cancer. A case report

Aim. The purpose of the article is to study the outcome of using living-related partial liver transplantation in the treatment of unresectable liver metastatic colorectal cancer. Case report. A woman, born in 1989, applied to the Medical Center Universal Clinic “Oberig” with a diagnosis of stage IV sigmoid colon cancer pT4N2M1 with synchronous liver metastases after sigmoidectomy and adjuvant chemotherapy. The patient underwent surgical intervention to the extent of right-sided hemihepatectomy with total caudate lobectomy, enucleation of metastases from the left liver lobe, cholecystectomy, extended lymphadenectomy, followed by systemic antitumor therapy. Six months later, according to laboratory and instrumental examinations, the progression of the disease was revealed in the form of new metastases development in the left liver lobe. After a thorough examination, a decision was made to treat the patient by living-related partial liver transplantation. On February 16, 2021, the patient underwent orthotopic transplantation of the left liver lobe from a living-related donor. The patient was discharged on the 31st postoperative day in a satisfactory condition. According to a control MRI after discharge, no signs of disease progression were detected. In the post-transplantation period, the patient developed an acute steroid-resistant rejection requiring antiplatelet immunoglobulin prescription. Three months after discharge, the patient was diagnosed with a high stricture of the bilio-biliary anastomosis, so resections of liver segment IV, hepaticocholedochus, and bihepaticojejunostomy on a defunctionalized Roux loop of the small intestine were performed. In the post-transplantation period, no signs of disease progression were detected, and no special antitumor treatment was used. Conclusions. Liver transplantation is an effective and radical method of treatment for patients with unresectable liver metastatic colorectal cancer.

Treatment of steroid-resistant acute rejection after living donor liver transplantation

Treatment of steroid-resistant acute rejection after living donor liver transplantation

Clinical Outcomes of Everolimus With Reduced-Dose Tacrolimus vs Mycophenolate Mofetil With Standard-Dose Tacrolimus in De Novo ABO-Incompatible Kidney Transplant Recipients: 1-Year Follow-up

One of the major barriers for long-term renal graft survival is considered to be calcineurin inhibitor nephrotoxicity, contributing to chronic graft dysfunction. Thus, recent immunosuppressive strategies are focused on regimens that can reduce or avoid exposure to calcineurin inhibitors. Herein, we carried out a small-scale pilot study to assess whether everolimus (EVR) with reduced-dose tacrolimus (Tac) is an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant compared with mycophenolate mofetil (MMF) with standard-dose Tac. This retrospective single-center cohort study included patients who underwent ABO-incompatible kidney transplant at our institution between January 2016 and December 2019. Those whose immunosuppressive regimen was changed by reasons other than rejection during the 1-year follow-up period were excluded. A total of 24 patients were enrolled in this study: 10 patients who received an EVR with reduced-dose Tac regimen and 14 patients who received an MMF with standard-dose Tac regimen. Tac trough levels in the EVR group were significantly lower than those in the MMF group (P < .001). No patients died or lost their grafts during the follow-up period. There were no significant differences in renal function, proteinuria, and prevalence of hyperlipidemia between the 2 groups at 1 year after transplant. There were no significant differences in the incidence of rejection (acute cellular rejection, steroid-resistant acute cellular rejection, acute antibody-mediated rejection) and infection (cytomegalovirus viremia, cytomegalovirus disease, BK viremia, BK virus nephropathy) between the 2 groups. Comparable with MMF with standard-dose Tac, EVR with reduced-dose Tac might be an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant.

Surgical Complications After Deceased Donor Renal Transplant.

Deceased donor renal transplant is an accepted treatment for patients with end-stage renal disease. We retrospectively analyzed urological and surgical complications and outcomes in our series. Since 2016, we have performed 263 renal transplants at the Gazi University Transplantation Center, Ankara, and 92 of these were from deceased donors. We retrospectively analyzed outcomes of these 92 deceased donor transplants from our database records. There were 45 female and 47 male recipients, and 20 were pediatric recipients. Mean recipient and donor ages were 36 ± 14 and 38 ± 18 years old, respectively. Immunosuppression therapy consisted of steroids, mycophenolate, and calcineurin inhibitors. Induction therapy was 20 mg basiliximab (Simulect) on day 0 and day 4. Antithymocyte globulin (2 mg∕kg) was used in steroid-resistant acute rejection cases. There were 13 surgical complications (14.1%) after 92 consecutive deceased donor renal transplants, and 4 of these were classified as miscellaneous surgical complications. Four of 9 cases were early, and the rest were classified as late complications. Postoperative early complications were bleeding (n = 2), urine leak (n = 1), and renal artery thrombosis (n = 1). Lymphoceles (n = 4) and urine leak (n = 1) occurred as late complications. Postoperative median follow-up was 78 months, during which 11 grafts (12%) were lost and 7 patients (7.6%) died from sepsis (n = 4), myocardial infarction, aortic dissection, and fungal pneumonia. No patients died from any surgical complications. The 1-year, 5-year, and 10-year survival rates of patients were 98%, 94%, and 94% and for grafts were 97%, 94%, and 88%, respectively. Despite the limited number of deceased donor organs, improvements of surgical techniques at our center have facilitated success with deceased donor renal transplant at rates similar to other successful centers in the world.

Treatment of steroid-resistant acute rejection after living donor liver transplantation

Treatment of steroid-resistant acute rejection after living donor liver transplantation

2235 Nivolumab-Induced Severe Allograft Rejection in Recurrent Post-Transplant Hepatocellular Carcinoma

INTRODUCTION: Hepatocellular carcinoma (HCC) is an established indication for liver transplantation (LT), but recurrent HCC post LT presents a unique therapeutic challenge. Nivolumab is an immune checkpoint inhibitor (ICPI) approved for treatment of HCC, but data on its safety following LT is limited. We present a case of Nivolumab-induced severe, steroid-resistant acute cellular rejection (ACR) in a patient with recurrent HCC post LT, treated successfully with thymoglobulin and plasmapheresis. CASE DESCRIPTION/METHODS: A 64-year-old male was noted to have evidence of locally advanced recurrent HCC on surveillance imaging two years post-LT. Systemic therapy using Sorafenib had to be discontinued due to severe proteinuria. Given limited therapeutic options and evidence of progressive disease, a decision was made to initiate Nivolumab. A week later, liver tests were elevated and continued to worsen significantly (peak values 3 weeks post infusion: ALT 424 U/L, AST 215 U/L, ALP 1074 IU/L, Br 16 mg/dL). Further infusions were discontinued. Liver biopsy revealed features of ACR with moderate portal inflammation, patchy bile duct injury and endotheliitis. Since ACR was resistant to high dose steroids, thymoglobulin was administered with some improvement. However, given persistent liver test elevation, we proceeded with plasmapheresis and after 5 sessions, marked improvement was noted and repeat biopsy showed resolution of ACR (Figure 1). DISCUSSION: Nivolumab, a monoclonal antibody that targets programmed cell death protein 1, was FDA approved in 2017 for the treatment of HCC in patients previously treated with Sorafenib. However, there is limited experience with its use in solid organ transplant recipients. The immunological mechanism of nivolumab induced ACR is unclear and there is no consensus on management. As with our patient, none of the reported cases responded to high-dose steroid therapy. Use of thymoglobulin and plasmapheresis has not been reported in this setting previously. Even though plasmapheresis would likely not impact nivolumab-induced T cell–mediated immune rejection, given its long half- life, we hypothesized that plasmapheresis could help by removing the medication from the circulation. Severe ACR with ICPI therapy could result in allograft failure, with limited therapeutic options. Factors that contribute to ACR and whether this may be impacted by length of time after LT remain unclear. There is a critical need for safe and effective systemic options for treatment of recurrent HCC post-LT.

Safety and Efficacy of Reduced Prolonged-release Tacrolimus Exposure in De Novo Kidney Transplantation: A Randomized, Open-label, Pilot Study in Asia-OPTIMIZE Study.

A multicenter, randomized, open-label, parallel group, pilot, 52-week study in Asian countries that assessed the renal function, efficacy, and safety of reduced-exposure versus standard-exposure prolonged-release tacrolimus (PR-T) in adult kidney transplant recipients (KTRs). Posttransplantation, KTRs received PR-T from weeks 0 to 4 (initial dose, 0.2-0.3 mg/kg; target trough level, 6-10 ng/mL). At week 4, KTRs were randomized (1:1) to receive reduced-exposure PR-T (target 4-6 ng/mL, weeks 4-12; 3-5 ng/mL, weeks 12-52) or standard-exposure PR-T (target: 6-10 ng/mL, weeks 4-52). Primary end point: estimated glomerular filtration rate (eGFR) over 52 weeks. Secondary end points (week 52) included creatinine clearance, serum creatinine, graft/patient survival, biopsy-confirmed acute rejection (AR), composite of graft loss/patient death/biopsy-confirmed AR, and steroid-resistant AR. Treatment-emergent adverse events were recorded. Sixty-six KTRs received PR-T (reduced-exposure, n = 32; standard-exposure, n = 34) and were analyzed. After per-protocol dose adjustment, mean ± standard deviation tacrolimus trough level was lower with reduced- versus standard-exposure PR-T (week 52, 4.5 ± 1.1 ng/mL vs 8.0 ± 2.2 ng/mL). In the reduced- versus standard-exposure group, eGFR was similar at weeks 8 to 52 (overall least-square mean difference, -2.82; 95% confidence interval, -7.91 to 2.27; P = 0.272). At week 52, there was no significant difference in creatinine clearance (P = 0.375) or serum creatinine (P = 0.547) between groups. All grafts/patients survived, no steroid-resistant AR was reported, and 4 and 3 patients had AR in reduced- and standard-exposure groups, respectively. Drug-related treatment-emergent adverse events were reported in 34.4% and 38.2% of patients, respectively. Reducing exposure to PR-T resulted in a clinically acceptable short-term safety profile and was generally as effective as standard tacrolimus exposure for Asian patients.

Treatment of steroid-resistant acute rejection after living donor liver transplantation

Introduction: Liver transplantation (LT) is the definitive treatment for the end-stage liver disease. Acute rejection used to be a common complication up to 70% of recipients within the first year. Steroid pulse therapy is useful treatment for this complication but is not a preferred treatment for steroid-resistant acute rejection (SRAR). We report the successful treatment of patient diagnosed with steroid-resistant acute rejection. Method: The patient, a 42-year-old male, who diagnosed chronic hepatitis b related liver cirrhosis, underwent living donor liver transplantation in 28th December 2015. This patient was given 20mg basiliximab as induction therapy on days 0 and 4 post-transplantation. The maintenance immunosuppressive regimens for this patient included a double regimen (tacrolimus and steroid). At 20 months after transplantation, he was admitted to our hospital presenting with the elevated serum levels of the liver enzymes and total bilirubin. We performed liver biopsy, after vascular or biliary complications were excluded by computed tomography. A liver biopsy showed acute cellular rejection. Steroid pulse therapy was not effective. Result: We was suspicious of steroid-resistant acute rejection, so liver biopsy was repeated to obtain exact diagnosis. Second liver biopsy also confirmed acute cellular rejection. He received 1.5mg/kg/day antithymocyte globulin for 5 days. He received antihistamine and antipyretic before antithymocyte globulin infusion to reduce or prevent adverse effects of antithymocyste globulin. Patient was stopped tacrolimus and 5mg/kg/day ganciclovir, ceftazidime prophylaxis was given during antithymocyte globulin therapy. After antithymocyte globulin treatment, His liver enzymes and total bilirubin were decreased. He was discharge 34 days later, and almost normalized his liver enzymes and total bilirubin. Conclusion: We have shown that antithymocyte globulin is safe and effective for treatment of steroid-resistant acute rejection, preventing from graft loss of chronic rejection.

Immunosuppressive therapy in liver transplantation: strategies for personalization approaches

Immunosuppressive therapy in organ transplantation is tentatively moving from a phase of empirical administration towards individualized therapy. This process is highly dependent on the development of monitoring methods to detect individual immune states. Anti-donor alloreactivity, which depends on the number and phenotype of alloreactive precursors in the recipient, could be used to monitor the immune state for individualizing immunosuppressive therapy. For this purpose, we have applied the mixed lymphocyte reaction assay, an assay in which CFSE-labeled PBMCs from recipients are cultured with allogeneic lymphocytes from donors as stimuli, to clinical liver transplantation (LT). This method allows for the separate quantification of the proliferation of CD4 and CD8 responder T cells in response to allo-stimulation by using multiparameter FCM. In addition to the cellular ex vivo assay, analyses by molecular genetics such as the single nucleotide polymorphism (SNP) testing would lead to an improvement in risk prediction, early detection and prevention of various complications after organ transplantation. We have recently demonstrated that Fc-gamma receptor SNPs are predisposing factors for bloodstream infections and can predict mortality after living donor LT. We have also investigated the impact of SNPs in the FOXP3 gene, a master regulator gene of regulatory T cells, on rejection severity in liver transplant recipients. We found that FOXP3 SNP rs3761548 A/C could be a predisposing factor for steroid-resistant acute rejection after liver transplantation. In this talk, I would like to introduce how we practice individualizing immunosuppressive therapy by making use of cellular immunology and molecular genetics in LT.

Myelopathy due to Human T-cell Leukemia Virus Type-1 from the Donor after ABO-incompatible Liver Transplantation

We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.

Urinary C-X-C Motif Chemokines 13 is a Noninvasive Biomarker of Antibody-Mediated Renal Allograft Rejection

Background Since acute rejection remains one of the major complications which necessitate periodic surveillance, noninvasive diagnostic/prognostic methods are preferred by renal transplant recipients. Here we explored whether urinary C-X-C motif chemokines 13(CXCL13) could be apotential candidate to reflect ongoing immune processes within the renal graft. Methods We investigated urinary CXCL13 levels by a cross-sectional analysisof 146 renal allograft recipients and 40 healthy controls. Besides, a subset of patients (n = 57) were followed-up for kinetic monitoring of immune status. Results Urinary CXCL13/Cr was lower in normal transplants compared to those withacute tubular necrosis (ATN, P = 0.001), chronic allograft nephropathy (CAN, P = 0.01) andacute rejection (AR, P < 0.0001), which yielded a good diagnosis performance of urinary CXCL13 for AR (AUC = 0.818, P< 0.0001). Interestingly, urinary CXCL13 furtherdistinguished acute antibody mediated rejection (ABMR)from acute cellular rejection, with an AUC of 0.856. Besides,patients with steroid-resistant acute rejection had distinctly greater urinary CXCL13/Cr levels than patients with reversible acute rejection, P =0.001. Follow-up data revealed that urinary CXCL13/Cr varied in line with the occurrence of ABMR. Furthermore, elevated levels of urinary CXCL13/Cr within the first monthwas predictive of graft function at 3, 6 months, P=0.044 and 0.4. Conclusion This study demonstrated that monitoring of urinary CXCL13/Cr might be a valuable noninvasive approach for the detection of AR, especially ABMR. Additionally, high urinary CXCL13/Cr levels related to the poor response to steroid treatment and predicted a compromised graft function after AR. Key Words:C-X-C motif chemokines 13; kidney transplantation; rejection; urine Key Laboratory of Multiple Organ Transplantation, Ministry ofHealth.

Renal Blood Flow Measurements by Magnetic Resonance Imaging using Arterial Spin Labelling as a Novel Non-Invasive Biomarker in Paediatric Renal Transplant Recipients

Introduction To investigate our hypothesis that non-invasive cortical renal blood flow (cRBF) measurements using functional magnetic resonance imaging (MRI) arterial spin labelling (ASL) are sensitive biomarkers of early damage of the transplanted kidney in paediatric renal transplant recipients (pRTR). Methods Prospective study of pRTR undergoing MRI imaging using 1.5T Siemens Avanto system with multi-TI pulsed ASL acquisition performed at 10-20 days, 2 and 12 months with a FAIR labelling scheme and multi-shot 3D grase imaging module with background suppression. Results 14 pRTR (50% (7) male) aged 9.2-17.1 (median 13.2) years of whom 64% (9) had ESKD due to congenital anomalies of the kidneys and urinary tract underwent MRI ASL after transplantation (86% (12) living-related) with eGFR of 41.0-92.0 (median 60.9) mls/min/1.73m2 at follow-up of 3.5-5.4 (median 4.5) years. 46% (6) were pre-emptive transplants with 7% (1) re-transplanted. Patients had 0-5 (median 1) post-transplant UTI with 50% (7) EBV viraemia and underwent 1-7 (median 2) percutaneous renal transplant biopsies with evidence of steroid-resistant acute rejection episode due to non-adherence and borderline rejection in 7% (1) and 14% (2) pRTR respectively. Baseline MRI ASL at median 10 days showed cRBF of 86-268 (median 198) mls/100g/min with changes at subsequent and latest MRI performed at median 70 and 344 days respectively of -70 to +121 (median 52) and -56 to +147 (median 36) mls/100g/min respectively.Discussion Renal blood flow maximises in the first month after renal transplantation with subsequent reduction in first year in pRTR. There are multiple causes of renal allograft dysfunction in pRTR and associated risks in performing surveillance percutaneous renal transplant biopsies. MRI ASL is a useful and novel non-invasive biomarker of renal allograft function in pRTR.

WITHDRAWN: Mesenchymal stem cells for treatment of steroid-resistant acute rejection after liver transplantation

WITHDRAWN: Mesenchymal stem cells for treatment of steroid-resistant acute rejection after liver transplantation

Mesenchymal stem cells for treatment of steroid-resistant acute rejection after liver transplantation

A patient with steroid-resistant acute rejection 50 days after ABO-compatible orthotopic liver transplantation (LT) received regular infusion of allogeneic mesenchymal stem cells (MSCs) after three sessions of steroid pulse therapy which failed to control the pathogenetic condition as shown by biopsy. Liver function improved gradually after intravenous injection of MSCs once weekly for 10 weeks (as confirmed by biopsy) and remained stable under administration of conventional immunosuppressive agents. There was no evidence of neoplasms 5 years after treatment. MSCs infusion appears to successfully reverse resistance to immunosuppressive agents and may be a useful treatment for post-liver transplant steroid-resistant rejection.

Significant association between FOXP3 gene polymorphism and steroid-resistant acute rejection in living donor liver transplantation.

Previous studies have found that preferential accumulation of regulatory T (Treg) cells in liver allografts during acute cellular rejection (ACR) is associated with less severe rejection, suggesting a role of Treg cells in preventing excessive progress of ACR. We investigated the impact of single nucleotide polymorphisms (SNPs) in the Forkhead box P3 (FOXP3) gene, a master regulator gene of Treg cells, on ACR severity in liver transplant (LT) recipients. In total, 102 living donor LT patients were enrolled in this study and categorized into no rejection (n = 86), steroid‐sensitive acute rejection (SSAR; n = 11), and steroid‐resistant acute rejection (SRAR; n = 5). FOXP3 SNPs –3499 A/G (rs3761547), –3279 A/C (rs3761548), and –924 A/G (rs2232365) were genotyped using the polymerase chain reaction restriction fragment length polymorphism technique. T‐cell responses to allostimulation were evaluated by the mixed lymphocyte reaction assay. We found no statistical association between the FOXP3 SNP genotype frequencies and ACR incidence. However, significantly higher incidence of SRAR was observed in LT patients with the FOXP3 rs3761548 A/C+A/A genotype than in those with the C/C genotype (A/C+A/A versus C/C; no rejection, SSAR, SRAR, 85.71%, 0%, 14.29% versus 83.58%, 16.42%, 0%, respectively; P = 0.0005). The mixed lymphocyte reaction assay performed at the time of ACR diagnosis showed higher anti‐donor CD4+ T‐cell responses in patients carrying rs3761548 A/C+A/A than in those with the C/C genotype (P = 0.019). No significant association was observed between the incidence of SRAR and either rs3761547A/G or rs2232365 A/G. Infectious complications and overall survival were not related to FOXP3 SNPs. Conclusion: Our findings indicate that FOXP3 SNP rs3761548 A/C might be a predisposing factor for SRAR after liver transplantation. (Hepatology Communications 2017;1:406–420)

Efficacy of rabbit anti-thymocyte globulin for steroid-resistant acute rejection after liver transplantation.

Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child–Turcotte–Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients’ median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver transplant recipients. However, the occurrence of HCV reactivation and CMV infection in LT patients should be monitored after rATG treatment in these patients.

Anti-CD28 Antibody and Belatacept Exert Differential Effects on Mechanisms of Renal Allograft Rejection.

Belatacept is a biologic that targets CD80/86 and prevents its interaction with CD28 and its alternative ligand, cytotoxic T lymphocyte antigen 4 (CTLA-4). Clinical experience in kidney transplantation has revealed a high incidence of rejection with belatacept, especially with intensive regimens, suggesting that blocking CTLA-4 is deleterious. We performed a head to head assessment of FR104 (n=5), a selective pegylated Fab' antibody fragment antagonist of CD28 that does not block the CTLA-4 pathway, and belatacept (n=5) in kidney allotransplantation in baboons. The biologics were supplemented with an initial 1-month treatment with low-dose tacrolimus. In cases of acute rejection, animals also received steroids. In the belatacept group, four of five recipients developed severe, steroid-resistant acute cellular rejection, whereas FR104-treated animals did not. Assessment of regulatory T cell-specific demethylated region methylation status in 1-month biopsy samples revealed a nonsignificant trend for higher regulatory T cell frequencies in FR104-treated animals. Transcriptional analysis did not reveal significant differences in Th17 cytokines but did reveal higher levels of IL-21, the main cytokine secreted by CD4 T follicular helper (Tfh) cells, in belatacept-treated animals. In vitro, FR104 controlled the proliferative response of human preexisting Tfh cells more efficiently than belatacept. In mice, selective CD28 blockade also controlled Tfh memory cell responses to KLH stimulation more efficiently than CD80/86 blockade. Our data reveal that selective CD28 blockade and belatacept exert different effects on mechanisms of renal allograft rejection, particularly at the level of Tfh cell stimulation.

Strategies in clinical diagnosis and treatment of steroid-resistant acute rejection after orthotopic liver transplantation

To explore the diagnostic evidence and treatment strategies for steroid-resistant acute rejection (SRAR) after orthotopic liver transplantation. A retrospective analysis was performed among 1038 patients undergoing orthotopic liver transplantation in our hospital from January 2004 to December 2013. A total of 169 acute rejection (AR) episodes occurred in 153 patients. Sixteen of the patients were diagnosed with SRAR because of no response to large-dose steroid pulse therapy. The diagnosis and treatment of the 16 patients were analyzed retrospectively. Comparison of data was made by χ2 test or t test, and a P value of <0.05 was considered to be significant. The incidence of AR after liver transplantation was 14.74% (153/1038) in all the patients. The incidence of SRAR was 9.47% (16/169) in patients with AR. In the 16 patients with SRAR, 3 were treated with anti-CD3 monoclonal antibody (OKT3), 9 were treated with monoclonal antibody against IL-2 receptor, and 4 received antithymocyte globulin (ATG) therapy. After treatment, SRAR was reversed in 12 of the 16 patients and caused death of the other 4 patients, yielding a reversal rate of 75% and a mortality rate of 25%. SRAR after liver transplantation has a low incidence rate but poor prognosis. The diagnosis of SRAR is mainly based on the clinical manifestation, laboratory test, liver biopsy, and poor response or rejection to methyl prednisolone pulse therapy. ATG and OKT3 achieve substantial outcomes in most of the patients in the treatment of SRAR. Particularly, compared with OKT3, ATG achieves a higher reversal rate and fewer adverse reactions, which is expected to become the first-line treatment of SRAR.

Hepatobiliary Quiz (Answers)—15 (2015)

Hepatobiliary Quiz (Answers)—15 (2015)

Initial Experience of Dual Maintenance Immunosuppression With Steroid Withdrawal in Vascular Composite Tissue Allotransplantation

Current immunosuppression in VCA is largely based on the experience in solid organ transplantation. It remains unclear if steroids can be reduced safely in VCA recipients. We report on five VCA recipients who were weaned off maintenance steroids after a median of 2 months (mean: 4.8 months, range 2-12 months). Patients were kept subsequently on a low dose, dual maintenance consisting of tacrolimus and mycophenolate mofetil/mycophenloic acid with a mean follow-up of 43.6 months (median = 40 months, range 34-64 months). Early and late acute rejections responded well to temporarily augmented maintenance, topical immunosuppression, and/or steroid bolus treatment. One late steroid-resistant acute rejection required treatment with thymoglobulin. All patients have been gradually weaned off steroids subsequent to the treatment of acute rejections. Low levels of tacrolimus (<5 ng/mL) appeared as a risk for acute rejections. Although further experience and a cautious approach are warranted, dual-steroid free maintenance immunosuppression appears feasible in a series of five VCA recipients.