A Single Centre Experience of Effective Desensitization Strategy for Children with High Anti-HLA Donor-Specific Antibodies Undergoing Haploidentical Hematopoietic Stem Cell Transplantation.

To assess the incidence of anti-HLA donor-specific antibodies and the effectiveness of desensitization strategy in children who underwent haploidentical HSCT at our hospital. A retrospective review, management and outcomes of children with positive anti-HLA DSA who underwent haploidentical HSCT at our hospital from 2020 to 2022. Three patients with Thalassemia major were treated with 2 cycles of pretransplant immune suppression (PTIS) comprising Fludarabine and Dexamethasone in addition to desensitization. Five out of the 26 children who underwent haploidentical HSCT had positive anti-HLA DSA. Post desensitization, three out of the 5 children engrafted with sustained full donor chimerism, 1 patient developed primary graft rejection, while 1 patient died. It is feasible to desensitize children with high anti-HLA donor specific antibodies undergoing haploidentical HSCT to improve outcomes.

Emergency ABO-incompatible living donor liver transplantation in Wilson disease-induced acute liver failure.

We report the clinical outcome of an emergency ABO incompatible-liver transplantation (LT) for an 8-year-old child with Wilson's disease-induced acute liver failure. The pretransplant anti-A antibody titer was 1:64, and hence he underwent three cycles of conventional plasma exchange as pretransplant liver supportive treatment for deranged coagulopathy and liver function followed by one cycle of immunoadsorption (IA) prior to LT. The posttransplant immunosuppression consisted of rituximab, tacrolimus, mycophenolate mofetil, and corticosteroid. The patient had anti-A isoagglutinin rebound with elevated aminotransferases levels from postoperative day 7 for which he was restarted on IA plasmapheresis, but antibody titers did not decrease. Hence, he was switched to conventional plasmapheresis (CP) with which anti-A antibody titers decreased. The total dose of rituximab (150 milligrams/square meter of body surface area) was given in two divided doses of 75 mg at D-1 and D + 8 which was much less than the dose conventionally advocated (375 milligrams/square meter of body surface area). He is clinically well with good graft function without rejection after 1 year of follow-up. This case illustrates that IA and CP in conjunction with adequate immunosuppression is a viable approach in emergency ABO-incompatible-LT in Wilson disease-induced acute liver failure.

Living Donor Liver transplantation in an alloimmunised patient: Immunological challenges and Management in Indian Settings.

Liver transplantation (LT) is often associated with hematological abnormalities with immune or non-immune etiologies and require timely diagnosis and interventions. We report a case of a patient suffering from non-alcoholic steato-hepatitis (NASH) related end stage liver disease (ESLD) with multiple red cell antibodies who underwent LT surgery. In postoperative phase, she developed immune hemolysis as well as acute antibody mediated rejection (AMR) which was managed with therapeutic plasma exchange and IVIG. The case highlights the need to develop an algorithm for red cell and HLA antibody screening in high-risk patients for timely detection and management.

Versatility of Anabolic Androgenic Steroid-Induced Hepatotoxicity.

The modified derivatives of testosterone, termed as androgenic steroids are indicated in the management of hypogonadism, visceral obesity and metabolic disorders. Anabolic androgenic steroids (AASs) however are surreptitiously used by athletes and body builders for cosmetic purpose owing to their anabolic effects on muscle mass and strength. The unsurveilled use of AASs subjects these users to various side effects involving multiple systems such as the endocrine, genitourinary, hepatobiliary, central nervous, musculoskeletal and psychosocial system. The liver is a hormone-sensitive organ owing to abundance of androgen receptors and is vulnerable to a wide array of hepatotoxicity ranging from asymptomatic liver enzyme elevation to life-threatening subacute liver failure. The type of drug-induced liver injury (DILI) due to AASs can be hepatocellular injury, cholestasis, fatty liver disease, chronic vascular injury and neoplastic disease. Herein, we report three cases of AAS-related DILI associated with AAS abuse.

ABO-Incompatible Living Donor Liver Transplant From a Blood Type A2 Donor to a Type B Recipient: A Note of Caution.

Standardization of immunomodulation protocols has enabled ABO-incompatible liver transplants with outcomes similar to those of ABO-compatible liver transplants. Patients with the A2 blood group are unique because they have a diminished expression of the A antigen. Despite rare immune complications, this phenomenon of diminished expression has led to treatment of type A2 donors according to the regimen for type O blood group donors in ABO-incompatible liver transplants. Additionally, the requirement for pretransplant recipient immunomodulation is consi dered minimal when considering these donors. The transplant of a type A2 donor kidney to a type B recipient is well recognized; however, for liver donation the A2-to-B transplant is rare. Here, we present a case of 48-year-old male patient with blood group type B who underwent ABO-incompatible liver transplant of a right lobe liver graft from a type A2 donor. Postoperatively, despite adequate immunosuppression and initiation of thera - peutic plasma exchange, the patient developed severe and refractory antibody-mediated rejection that ultimately abated with a splenectomy. This report highlights the low but tangible risk of antibody-mediated rejection in ABO-incompatible liver transp lants from type A2 donors and emphasizes the importance of serial monitoring of anti-A isohemag glutinin titers and posttransplant splenectomy to ensure that liver grafts with antibody-mediated rejection can be rescued.

Therapeutic Plasma Exchange for Management of Early Allograft Dysfunction After Living Donor Liver Transplant: An Unmatched Cohort Study.

OBJECTIVES: Therapeutic plasma exchange has been reported to be useful in the management of acute liver failure and acute-on-chronic liver failure. This retrospective study evaluated therapeutic plasma exchange as an adjunct to standard supportive care for early allograft dysfunction after living donor liver transplant. MATERIALS AND METHODS: All consecutive adult living donor liver transplants performed from January 2015 to February 2019 were included. Patients treated without or with therapeutic plasma exchange for early allograft dysfunction (Olthoff criteria) were compared. RESULTS: There were 465 adult transplant recipients, and 67 (14.4%) had early allograft dysfunction, of which 43 (64%) had therapeutic plasma exchange and 24 (36%) did not. Fourteen patients were excluded, as they had both preoperative and immediate postoperative therapeutic plasma exchange (5 patients with acute liver failure and 9 with acute-on-chronic liver failure). The therapeutic plasma exchange group (n = 29) had more preoperative acute kidney injury (55.2% vs 25.0%; P = .009), lower graft-recipient weight ratio (0.96 vs 1.09; P = .043), and slightly higher final portal pressure (11 vs 10 mg/dL; P = .027). Therapeutic plasma exchange was started at a median of postoperative day 9, with median serum bilirubin of 13.6 mg/dL and a median of 3 sessions per patient. There was no 90-day mortality in the group without therapeutic plasma exchange; however, in the therapeutic plasma exchange group, 13 patients (45%) died (P < .001). Patients who received therapeutic plasma exchange had more septic complications (62.1% vs 12.5%; P < .001) and needed more postoperative renal replacement therapy (51.7% vs 8.3%; P < .001). CONCLUSIONS: This is the first study to compare patients treated with or without therapeutic plasma exchange for early allograft dysfunction in the living donor liver transplant setting. Within the limitations of this retrospective study, we were unable to confirm whether therapeutic plasma exchange could increase early mortality.

Liver Transplantation Society of India Guidelines for the Management of Acute Liver Injury Secondary to Yellow Phosphorus-Containing Rodenticide Poisoning Using the Modified Delphi Technique of Consensus Development.

BACKGROUND: Acute liver failure caused by the ingestion of yellow phosphorus-containing rodenticide has been increasing in incidence over the last decade and is a common indication for emergency liver transplantation in Southern and Western India and other countries. Clear guidelines for its management are necessary, given its unpredictable course, potential for rapid deterioration and variation in clinical practice. METHODS: A modified Delphi approach was used for developing consensus guidelines under the aegis of the Liver Transplantation Society of India. A detailed review of the published literature was performed. Recommendations for three areas of clinical practice, assessment and initial management, intensive care unit (ICU) management and liver transplantation, were developed. RESULTS: The expert panel consisted of 16 clinicians, 3 nonclinical specialists and 5 senior advisory members from 11 centres. Thirty-one recommendations with regard to criteria for hospital admission and discharge, role of medical therapies, ICU management, evidence for extracorporeal therapies such as renal replacement therapy and therapeutic plasma exchange, early predictors of need for liver transplantation and perioperative care were developed based on published evidence and combined clinical experience. CONCLUSION: Development of these guidelines should help standardise care for patients with yellow phosphorus poisoning and identify areas for collaborative research.

Pediatric metabolic liver diseases: Evolving role of liver transplantation.

Metabolic liver diseases (MLD) are the second most common indication for liver transplantation (LT) in children. This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation. LT is also performed in metabolic disorders for end-stage liver disease, its sequelae including hepatocellular cancer. It is also performed for preventing metabolic crisis', arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia. Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis, cholestasis, inflammation, variable amount of fibrosis, and cirrhosis. The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT. A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters. Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver. The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.

Patient blood management in a patient with multiple red cell antibodies (anti-C, anti-e, and anti-K) undergoing liver transplant in South India: A team approach.

End-stage liver disease (ESLD) patients undergoing liver transplant (LT) surgery are often multiply alloimmunized and pose significant challenges to the transfusion services in terms of red cell cross-match incompatibility, unpredictable blood requirements, and often lead to significant delays in availing compatible red cell units. We report a case of a 64-year-old female from Bahrain, a known case of hepatitis C-related ESLD referred for LT surgery. She had a history of multiple uneventful transfusions in the preceding year. Her blood group was A-positive, direct antiglobulin test, and cold antibodies were negative. Indirect antiglobulin test was positive, and antibody identification confirmed the presence of anti-C, anti-e, and anti-K. Her red cell phenotype was R2R2 and Kell negative (C-c+E+e-K-). The patient was started on erythropoietin. Requests for R2R2 and Kell negative units were sent to various blood banks across the country. After >800 A/O group units phenotyping and a waiting period of 6 weeks, two compatible R2R2 phenotypes and Kell negative could be arranged in-house and three units were received from Gurgaon, North India. Intraoperative management included blood preservation techniques including cell salvage, antifibrinolytic drug, and monitoring using thromboelastography. The estimated blood loss was 350 ml with pre- and postoperative Hb 10.4 gm% and 9.2 gm%, respectively. She received intraoperatively two units of single-donor platelet and four units of fresh frozen plasma and postoperatively one unit of leukocyte-depleted-packed red cells and doing well at 12-month follow-up. This case highlights the importance of advance immunohematology for timely detection of alloimmunization and providing antigen-negative compatible units, proper communication between the transfusion specialists, and the clinical team for proper patient blood management as well as the need for central rare donor registry program to avoid delays in providing compatible blood in such inevitable cases.

Incidence and Analysis of 7 Years Adverse Transfusion Reaction: A Retrospective Analysis.

Safe blood transfusion is the primary need of all the health care delivery system. Though with the advances of transfusion medicine, the incidences of transfusion risk is gradually reduced, but the adverse transfusion reaction (ATR) of non hemolytic type still prevails. The purpose of this study was to estimate the incidence and pattern of transfusion-related adverse events at our centre. The present retrospective observational study was conducted in the Department of Transfusion Medicine from April 2011 to April 2018, at a multi-organ transplant centre in South India. All the Adverse transfusion reactions were investigated in detail in the blood bank for the clerical errors, immunohematology workup and classified according to their nature with imputability assessment. A total of 140 ATR were reported out of 100,569 blood components distributed during the study period. After the analysis and workup of the reported reactions, majority of the reactions were observed in males (71%, n = 99). Most common symptom presented was Itching/Rashes in 43.6% (n = 61) ATR. Allergic reactions (51.4%, n = 72), were the most commonly encountered ATR followed by FNHTR (25.7%, n = 36). FFP transfusions (0.2%) contributed to the majority of the reactions followed by Red cell transfusion (0.15%). ATR were observed maximum in Hepato-biliary disease and liver transplantation patients (62%) followed by oncology patients (15%). The overall incidence of ATR in our study is 0.14% which is comparatively low compared to other studies due to well established hemovigilance systems. Adoption of more equipped methods & sensitive technology in various areas of blood banking will help to bring down the unwanted adverse transfusion reactions.

Role of therapeutic plasma exchange in acute liver failure due to yellow phosphorus poisoning.

BACKGROUND: Therapeutic plasma exchange (TPE) has been utilized in various liver disorders. There is limited data on the efficacy of TPE in patients with acute liver failure (ALF). METHODS: Study group consisted of patients who underwent TPE for ALF due to yellow phosphorous poisoning (YPP) between 2015 and 2019. Demographic data and biochemical parameters were recorded before and after TPE. Overall survival and transplant-free survival (based on King's College Hospital Criteria [KCHC]) were analyzed. RESULTS: Forty-three patients underwent TPE for ALF due to YPP. Most of them were young males. Overall survival was 34 (79.06%). In our study population, 20 patients fulfilled KCHC (Group A) and 23 did not fulfill KCHC (Group B). Both the groups showed significant improvement in alanine aminotransferase, aspartate aminotransferase, and international normalized ratio (INR) after TPE (p < 0.05). In Group B, there was significant improvement in ammonia after TPE (p < 0.05) and all 23 patients (100%) survived after TPE. In Group A, 4 underwent liver transplantation (LT), 7 survived without LT, and the remaining 9 died without LT. Mean survival after completing TPE was 41.2 ± 44.5 days in Group A and 90 days in Group B. This difference was statistically significant (p = 0.001). There was statistically significant difference in post-TPE values of INR (p = 0.012) and ammonia (p = 0.011) between non-survivors and survivors. Adverse events such as hypotension (11.62%) and minor allergic reaction (4.65%) were managed conservatively. CONCLUSION: TPE is an effective procedure in ALF due to YPP, not fulfilling KCHC for LT. In KCHC fulfilled group, though it shows LT-free survival benefit, there is requirement of prospective, large volume, multi-center study to assess its efficacy.

A rare Bombay (Oh) phenotype to 'A' blood group - Live donor liver transplant.

Bombay (Oh) phenotype is the rarest blood group in India characterized by the absence of A, B, and H antigens and the presence of anti-H antibodies besides anti-A and anti-B. There is no literature predicting the safety of Oh blood group organ donation to non-Oh blood group recipient. We present the first reported case of successful live donor liver transplantation from an Oh-positive liver donor to an A-positive blood group recipient with hepatitis B virus-related chronic liver disease. The case highlights the need for proper immunohematological workup, national registry of rare group blood donors and need of protocol for perioperative monitoring and blood management in ABO-incompatible organ transplants involving Oh group donor or recipient.

Detection of antibodies to co-trimoxazole (preservative drug) interfering with routine red cell antibody screening.

Drug-dependent antibodies can rarely cause interference in pretransfusion antibody screening. The diluents for commercial reagent red blood cells contain different antibiotics, such as chloramphenicol, neomycin sulfate, and gentamycin as a preservative. The presence of antibodies to a given drug in patient may lead to positive results when performing antibody identification. We present a rare case of detection of anti-co-trimoxazole antibody during routine antibody screening in a female patient undergoing neurosurgery. These antibodies mimicked as antibody against high-frequency red cell antigens reacting in both saline phase as well as antiglobulin phase. Anti-co-trimoxazole antibody was confirmed by repeating antibody screen using reagent red cells of different manufacturers with and without co-trimoxazole drug as preservative as well as using washed red cell panels. There were no associated clinical or laboratory evidence of hemolysis.

von Willebrand Factor: A Tool to Predict Severity and Prognosis in Liver Disease.

Von Willebrand factor (vWF) is an adhesive and multimeric glycoprotein that has a central role in primary hemostasis. v W F levels correlate with thrombosis risk and inversely with bleeding risk within the apparently healthy population. Recently, numerous publications in Indian and western literature have focussed to its role in liver diseases like acute liver failure, chronic liver disease, non cirrhotic portal hypertension and tropical infections eg. dengue. The present review encapsulates the recent advances in this aspect.