{
  "abstract": "The role of donor specific antibodies (DSA) in allograft injury is poorly understood in liver transplants (LTx). 1 DSA have potential associations with ductopenia, biliary strictures and accelerated fibrosis.2 3 A retrospective analysis was performed to understand the prevalence of DSA in LTx children attending protocol liver biopsy (LB) and correlate the association of DSAs with histopathological and biochemical findings.Demographic details of LTx children undergoing simultaneous protocol LB and DSA testing from Jan 20- Dec 23 were included 115 children (age -15 months to 18 years, median – 11 years, 63 male and 52 female) had DSA testing performed around the time of liver biopsy. 41/115 patients (36%) had positive DSAs.37/41 children (90.2%) had DSA against HLA class II, HLA-DQ being the most prevalent (70.3%). 35 patients (73%) had mean fluorescence intensity (MFI) levels > 10,000 (5 patients had acute cellular rejection and 2 had chronic antibody mediated rejection).Children with negative DSA had statistically significant normal liver biopsy (p 0.016) compared to DSA positive group (table 1). Acute cellular rejection (ACR) was seen in both DSA positive and DSA negative children with no statistical significance (p 0.098). Children with Positive DSA were more likely to have moderate -severe fibrosis (n=7, p 0.04). Their prior protocol biopsies showed no significant changes (n=4) or mild fibrosis (n=3) with negative DSA.Three patients with chronic antibody mediated rejection (AMR) had de novo DSA against HLA-DQ and/or -DQA and their protocol biopsy post liver transplant was > 5 years.4 All of their previous protocol biopsy showed ACR with negative DSA. These patients were on dual or triple immunosuppression at the time of biopsy with normal liver biochemistry.There was no significant difference in liver function test and immunosuppression (single vs dual/triple and tacrolimus levels) between DSA positive and negative groups. There was no correlation of ACR or graft fibrosis with MFI titres and hence have to be used in conjunction with liver histopathology.ACR was seen in post LTx children with DSA positive as well as DSA negative children, thus confirming uncertainty about the role of DSA in contributing to ACR. There should be a high index of suspicion in children who change status from DSA negative to DSA positive for detection of children evolving into AMR. The presence of DSA with high MFI titres on its own without a liver biopsy do not give any further information about the graft function or abnormalitiesDSA in combination with protocol biopsies may help in understanding the underlying pathogenetic mechanisms contributing towards graft fibrosis, which may further improve long term outcome in liver transplantation.Abstract OC7 Table 1Findings on protocol liver biopsy Histopathology DSA negative (n=74) DSA positive (n=41) p value No significant changes 22 (29.7%) 3 (7.3%) 0.016 Acute cellular rejection 9 (12.1%) 9 (22%) 0.098 Acute antibody mediated rejection 0 0 Chronic antibody mediated rejection 0 3 (7.3%) 0.018 Mild fibrosis 37 (50%) 18 (43.9%) 0.57 Moderate to severe fibrosis 4 (5.4%) 7 (17%) 0.042 Cirrhosis 0 0 References Schotters FL, Beime J, et al. Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation. World J Hepatol. 2021 Jun 27;13(6):673–685. doi: 10.4254/wjh.v13.i6.673. PMID: 34239702; PMCID: PMC8239487.O’Leary JG, Demetris AJ, et al. The role of donor-specific HLA alloantibodies in liver transplantation. Am J Transplant. 2014;14:779–787. doi: 10.1111/ajt.12667.Cuadrado A, San Segundo D, et al. Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation. World J Gastroenterol. 2015 Oct 21;21(39):11016–26. doi: 10.3748/wjg.v21.i39.11016. PMID: 26494958; PMCID: PMC4607901.Demetris AJ, Bellamy C, et al. 2016 comprehensive update of the Banff working group on liver allograft pathology: introduction of antibody-mediated rejection. Am J Transplant. 2016 Oct;16(10):2816–2835. doi: 10.1111/ajt.13909. Epub 2016 Jul 14. PMID: 27273869.",
  "authors": [
    {
      "affiliations": [
        "Birmingham Children’s Hospital"
      ],
      "name": "Bharanikumar Ravikumar"
    },
    {
      "affiliations": [
        "Birmingham Children’s Hospital"
      ],
      "name": "Girish Gupte"
    },
    {
      "affiliations": [
        "Histocompatibility & Immunogenetics, NHS Blood and Transplant"
      ],
      "name": "Luke Foster"
    },
    {
      "affiliations": [
        "Birmingham Children’s Hospital"
      ],
      "name": "Chayarani Kelgeri"
    },
    {
      "affiliations": [
        "Birmingham Children’s Hospital"
      ],
      "name": "Jane Hartley"
    },
    {
      "affiliations": [
        "Birmingham Children’s Hospital"
      ],
      "name": "Joseph Valamparampil"
    },
    {
      "affiliations": [
        "Birmingham Children’s Hospital"
      ],
      "name": "Lauren Johansen"
    },
    {
      "affiliations": [
        "Birmingham Children’s Hospital"
      ],
      "name": "Khalid Sharif"
    }
  ],
  "title": "OC7 The prevalence and clinical significance of donor specific antibodies in paediatric liver transplantation",
  "uid": "33a502e9-fe06-57c0-880a-fb124f387211"
}