Nanda Kerkar

Antibody‐mediated rejection (AMR) is an important but infrequent cause of pediatric liver allograft injury. There is a lack of standardized guidance, and treatment approaches vary across institutions. A writing group from the Society of Pediatric Liver Transplantation conducted a comprehensive review of the published literature and collected institutional guidance documents from pediatric transplant centers across the United States to synthesize current diagnostic and management approaches to AMR in pediatric liver transplant recipients. AMR is diagnosed by the presence of characteristic histologic injury, C4d deposition, circulating donor‐specific antibody (DSA), and exclusion of alternative causes of graft dysfunction, including T cell–mediated rejection. Management strategies focus on reducing circulating DSA through therapeutic plasma exchange and suppressing ongoing immune activation with corticosteroids and intravenous immunoglobulin. In severe or refractory cases, targeted therapies such as rituximab, bortezomib, and eculizumab may be considered. A stepwise diagnostic and management algorithm is presented. This resource outlines a practical approach to the diagnosis and management of AMR in pediatric liver transplantation, serving as a reference for busy clinicians who may encounter this serious but underrecognized cause of graft dysfunction and loss.

Background: The Society of Pediatric Liver Transplantation (SPLIT) has undergone tremendous growth with > 45 sites contributing data focusing on improving outcomes in pediatric liver transplantation (LT). We report and compare outcomes from the SPLIT Registry. Methods: Patients < 18 years with first‐time LT only enrolled into the SPLIT Registry between 2011 and 2023 were included. Data was stratified into eras from the last published registry update (era 1: 2011–2018, era 2: 2018–2023). Results: Three thousand five hundred four participants from 47 centers were included (era 1: n = 2159; era 2: n = 1345). Age distribution differed with more children < 1 year. of age at LT in era 2 (era 1: 29% vs. era 2: 33%, p = 0.01). Indications for LT were similar, with biliary atresia (38.8%) and metabolic disease (16.0%) being most common. Exception point use was higher in era 2 (era 1: 45% vs. era 2: 56%, p < 0.001). No difference in graft type (deceased: 81% era 1 vs. 78% era 2, p = 0.78), patient survival at 90 days (era 1: 98.7% vs. era 2: 98.3%), 1 year (era 1: 97.2 vs. era 2: 96.8%), or 3 years (era 1: 95.3% vs. era 2: 95.2%) was noted. Rate of hepatic artery thrombosis was lower in era 2 (era 1: 7% vs. era 2: 5%, p = 0.02). Conclusions: Trends in pediatric LT within SPLIT note similar LT indications and graft type, higher utilization of exception points, and lower HAT rates despite transplanting more children < 10 kg. This data underscores the evolution of pediatric LT toward higher survivability and overall patient outcomes.

Editorial: The association between HLA genes and autoimmune liver diseases

Autoimmune liver disease (AILD) spans a spectrum of chronic disorders affecting the liver parenchyma and biliary system. Three main categories of AILD are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). This review condenses the presentation and discussions of the Single Topic Conference (STC) on AILD that was held in Ottawa, Ontario, in November 2019. We cover generalities regarding disease presentation and clinical diagnosis; mechanistic themes; treatment paradigms; clinical trials, including approaches and challenges to new therapies; and looking beyond traditional disease boundaries. Although these diseases are considered autoimmune, the etiology and role of environmental triggers are poorly understood. AILDs are progressive and chronic conditions that affect survival and quality of life. Advances have been made in PBC treatment because second-line treatments are now available (obeticholic acid, bezafibrate); however, a significant proportion still present suboptimal response. AIH treatment has remained unchanged for several decades, and data suggest that fewer than 50% of patients achieve a complete response and as many as 80% develop treatment-related side effects. B-cell depletion therapy to treat AIH is in an early stage of development and has shown promising results. An effective treatment for PSC is urgently needed. Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.

The AASLD has recently issued updated guidelines for the diagnosis and management of autoimmune hepatitis (AIH). Following the Institute of Medicine format for creating practice guidelines, a committee of experts selected the important clinical issues to address, conducted systematic reviews of the literature, and rated the quality of the evidence to determine the final recommendations. Below is a synopsis of the recommendations that are most relevant to liver transplantation (LT).