A two decade long study of disease progression of de novo and recurrent autoimmune hepatitis in the pediatric population.

Recurrent autoimmune hepatitis (rAIH) occurs in patients who undergo liver transplantation (LT) for AIH and de novo AIH (dAIH) is seen in patients who are transplanted for etiologies other than AIH. Whether these are distinct diseases with a similar phenotype remains understudied. The aim of this study was to identify clinical and immunologic factors affecting outcome in patients with dAIH and rAIH. A retrospective review of 387 LT patients from 1997 to 2014 was carried out, and they were followed until 2018. Patients with rAIH or dAIH were identified based on the pre-transplant diagnosis of AIH (or not) and characteristic histology. Liver biopsies were stained with H&E, B-cell marker CD20, and plasma cell marker CD138. Out of 387 patients, 31 were transplanted for AIH, and 8/31 developed rAIH. Of the remaining 356 patients, eight developed dAIH. Compared to the dAIH group, rAIH occurred in older patients, had an earlier onset in the allograft, and had higher IgG and serum ALT levels. It was most commonly seen in African American (AA) patients (87%). rAIH patients had significantly higher CD20 and CD138 positivity in liver biopsies. In addition, they had increased rejection episodes prior to the onset of recurrence, increased graft loss, and mortality. rAIH is a more aggressive disease, and has a preponderance of B cells and plasma cells in the liver tissue as compared to dAIH. The concurrent association with increased graft loss and patient mortality in rAIH warrants further investigations into B cell-targeted therapies.

Influence of Fat on Differential Receptor Interacting Serine/Threonine Protein Kinase 1 Activity Leading to Apoptotic Cell Death in Murine Liver Ischemia Reperfusion Injury Through Caspase 8.

Current understanding is that receptor interacting serine/threonine protein kinase 1 (RIPK1) can lead to two distinct forms of cell death: RIPK3-mediated necroptosis or caspase 8 (Casp8)-mediated apoptosis. Here, we report that RIPK1 signaling is indispensable for protection from hepatocellular injury in a steatotic liver undergoing ischemia reperfusion injury (IRI) but not in the lean liver. In lean liver IRI, RIPK1-mediated cell death is operational, leading to protection in RIP1 kinase-dead knock-in (RIPK1K45A) mice and necrostatin-1s (Nec1s)-treated lean wild-type (WT) mice. However, when fed a high-fat diet (HFD), RIPK1K45A-treated and Nec1s-treated WT mice undergoing IRI demonstrate exacerbated hepatocellular injury along with decreased RIPK1 ubiquitylation. Furthermore, we demonstrate that HFD-fed RIPK3-/-/Casp8-/- mice show protection from IRI, but HFD-fed RIPK3-/-/Casp8-/+ mice do not. We also show that blockade of RIPK1 leads to increased Casp8 activity and decreases mitochondrial viability. Conclusion: Although more studies are required, we provide important proof of concept for RIPK1 inhibition leading to distinctive outcomes in lean and steatotic liver undergoing IRI. Considering the rising incidence of nonalcoholic fatty liver disease (NAFLD) in the general population, it will be imperative to address this critical difference when treating patients with RIPK1 inhibitors. This study also presents a new target for drug therapy to prevent hepatocellular injury in NAFLD.

Racial disparities in presentation and outcomes of paediatric autoimmune hepatitis.

BACKGROUND & AIMS: Most studies on autoimmune hepatitis (AIH) in children are in predominantly Caucasian cohorts. Paediatric AIH in African Americans (AA) is understudied, with a dearth of clinical predictors of outcome, often leading to serious complications and even mortality. The aim of the study was to define disease presentation, progression, response to therapy and outcomes in paediatric AIH in a well-defined, large, single centre, demographically diverse population. METHODS: We conducted a review of patients with AIH who were followed at this tertiary liver transplant centre. Clinical and laboratory covariates were assessed with regard to disease presentation, progression and outcomes in AA vs Non-AA children. RESULTS: African Americans patients constituted 42% of this cohort. At 1-year follow-up, AA children were receiving significantly higher doses of steroids compared to non-AA. More AA presented with end-stage liver disease (ESLD) with high immunoglobulin G and GGT:platelet ratio. After adjusting for other risk factor variables like gender, age at presentation and ESLD, AA children were at 4.5 times higher risk for significant outcome liver transplant/death within the first 12 months of presentation. Post-transplant, recurrent AIH was seen in 50% of AA vs 8% in non-AA. CONCLUSIONS: African American patients with AIH are more likely to present with ESLD and have an increased early risk for transplantation with high likelihood of disease recurrence post-transplantation. Studies are needed to delineate factors such as inherent biology, genetics and access to care. Early referral and tailored immunosuppressive regimens are required for AA patients with AIH.

Education, enjoyment, and empowerment: Outcomes of an adolescent transplant camp (I own it).

Peer group camping experiences have a positive influence on adolescents with chronic illnesses, but the data in solid organ transplant recipients are lacking. The aim of this study was to evaluate the outcomes of adolescent transplant attendees of an educational camp. A weekend camp, "I own it" was organized which provided educational training regarding career and health choices, money matters, and managing medications following which a knowledge assessment was performed. The ACLSA questionnaire was also administered. To test the adolescents' medication knowledge, they were asked to provide written documentation of their medications, which was compared with their medical records. In the ACLSA questionnaire, 32% reported deficiency in work/study, 46% in housing/money management, and 3% in the remaining categories. A significant improvement in knowledge was noted in areas of career choices, money matters, and managing medications, but not in healthy choices. In the medication recall, 75% did not know their medication list, and 92% could not recall dosages or frequencies. In conclusion, adolescents showed quantitative improvements in certain areas while identifying deficiencies in others, areas which were targeted in future initiatives. Prospective longitudinal studies addressing the impact of camps on post-transplant outcomes should be conducted to better alter the course post-transplant.

Approach to a Child with Colitis.

In this review, the authors discuss the etiology, pathogenesis, and clinical presentations of colitis in children, and provide current recommendations for the approach to a child with colitis. In addition, they discuss in detail one of the important and emerging causes of chronic colitis in children; inflammatory bowel disease (IBD). Diagnostic and management approaches to colitis in children vary considerably based on several factors, including if the colitis is acute in onset or chronic, the age of the child, and the geographical region of the affected child. Broader classification or differential diagnosis of colitis falls under infectious, inflammatory, allergic, and less commonly, immune-mediated and ischemic colitis. Recent epidemiologic reports have elucidated a shift in our understanding of ethnicities and geographic regions affected by IBD. The incidence and prevalence of IBD has been steadily increasing in developing countries, including South-East Asia/India. Also, the risk of developing IBD among the second-generation South-Asians immigrants has greatly increased, with rates approaching those in the Western country to which they immigrated. Current research is focusing on genetic, environmental, and dietary factors to understand the increased incidence of IBD in developing countries and immigrants from developing nations.