{
  "abstract": "Progressive familial intrahepatic cholestasis (PFIC) is a heterogenous group of inherited autosomal recessive disorders which is known to cause chronic cholestatic liver disease, often requiring liver transplant (LT). 1 Homozygous and bi-allelic compound heterozygous mutations TJP2 protein results in TJP2 deficiency which is also known as PFIC4.2 TJP2 deficiency causes disruption of tight junctions leading to progressive chronic liver disease. Extrahepatic manifestations of TJP2 deficiency includes subdural haematomas and chronic respiratory disease. There is little evidence on the outcomes of liver transplantation in TJP2 deficiency.The objective of this study was to describe the clinicopathological features and posttransplant course of six LT recipients with TJP2 genetic mutation (PFIC 4). Data was retrospectively collected from electronic case records of children (1–18 years) with TJP2 deficiency, who underwent LT between March 2008 and December 2013.We identified 6 patients with genetically confirmed TJP2 deficiency. 4/6 patients presented with neonatal jaundice. One patient presented at 5 years of age with focal seizures and deranged Liver function tests. One patient presented with pruritus. The median (IQR) bilirubin on presentation was 108.5 (83–131.2). 3/6 patients had severe pruritus for which one patient required external biliary diversion. 4/6 patients had undergone liver transplant and the remaining 2 patients had milder phenotype and have been transitioned to adult services. All the transplanted patients were homozygous for pathogenic mutations. The median age at transplantation was 11.5 years. The outcomes of LT are listed in table 1. One patient was transferred to another centre for LT and hence no long-term data was available. All three patients under our care recovered uneventfully after LT. One patient had to undergo a re-transplant in 2017 due to recurrent cholangitis and unfortunately died of multi-organ dysfunction due to sepsis at 19 years of age.Abstract OC57 Table 1Pre-transplant profile and post liver-transplant course Variable Patient 1 Patient 2 Patient 3 Sex F M F Genetic mutation TJP2: c.1099C>T; p. (Arg367Ter) homozygous c.813delC homozygous c.813delC Type of mutation Stop gain change pathogenic frameshift pathogenic frameshift Pruritus Yes Yes Yes Explant histopathology Cholestatic Giant Cell Hepatitis Cirrhosis CirrhosisEarly Hepatocellular carcinoma Age at LT (years) 1 10 14 Indication for LT End stage liver disease End stage liver disease End stage liver disease Follow up in months post LT 120 98 56 Post operative complications Hypertension, Chylous ascites Small bowel obstruction due to adhesions,Recurrent cholangitis Splenic artery embolization for steal phenomenon,Hepatic vein anastomotic stricture Graft Rejection Yes Yes Yes Retransplant No Yes No TJP2 deficiency is a rare cause of molecular cholestasis which can result in progressive endstage liver disease needing liver transplant. The severity of liver disease correlates with the type of change caused by the mutation. No functional protein leads to very severe disease requiring LT early in their life. LT experience in TJP2 deficiency is not widely reported and this case series adds to the evidence.References Bull LN, Thompson RJ. Progressive familial intrahepatic cholestasis. Clin Liver Dis. 2018 Nov;22(4):657–669. doi: 10.1016/j.cld.2018.06.003. Epub 2018 Aug 3. PMID: 30266155.Lal BB, Alam S, Sibal A, Kumar K, Hosaagrahara Ramakrishna S, Shah V, Dheivamani N, Bavdekar A, Nagral A, Wadhwa N, Maria A, Shah A, Shah I, Nalwalla Z, Snehavardhan P, Srikanth KP, Gupta S, Sivaramakrishnan VM, Waikar Y, Suchismita A, Ashritha A, Sood V, Khanna R. Indian PFIC registry. Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency-related cholestasis. Hepatology 2024 Sep 1;80(3):511–526. doi: 10.1097/HEP.0000000000000828. Epub 2024 Mar 6. PMID: 38447037.",
  "authors": [
    {
      "affiliations": [
        "Leeds Teaching Hospital NHS Trust"
      ],
      "name": "Shilpa Dugar"
    },
    {
      "affiliations": [
        "Leeds Teaching Hospital NHS Trust"
      ],
      "name": "Palaniswamy Karthikeyan"
    },
    {
      "affiliations": [
        "Leeds Teaching Hospital NHS Trust"
      ],
      "name": "Marumbo Mtegha"
    },
    {
      "affiliations": [
        "Leeds Teaching Hospital NHS Trust"
      ],
      "name": "Kavita Jayaprakash"
    },
    {
      "affiliations": [
        "Leeds Teaching Hospital NHS Trust"
      ],
      "name": "Sanjay Rajwal"
    }
  ],
  "title": "OC57 Paediatric liver transplantation in tight junction protein 2 (TJP 2) deficiency",
  "uid": "b7c82756-942b-5c9d-85d9-55cb5af53314"
}