Pediatric consensus of autoimmune hepatitis.

Purpose: Introduction: Autoimmune hepatitis (AIH) is a progressive inflammatory disorder that is characterized by increased serum IgG level, circulating autoantibodies, and chronic destruction of the architecture of the liver. AIH is a rare entity in the pediatric population and has wide clinical spectrum ranging from asymptomatic presentation to an acute liver disease. We present a case of AIH type 1 in a young girl who presented with GI bleed. Case: A 13-year-old African American female with no significant past medical history admitted to pediatric ward with one-week history of melena and RUQ abdominal pain. Physical examination showed scleral icterus and mild RUQ abdominal tenderness. Laboratory investigations showed anemia (Hb 8.3 gm/dl) and deranged liver function tests (AST 450 U/L, ALT 194 U/L, ALP 243 U/L, total bilirubin 4.3 mg/dl, PT 20.2 sec, INR 1.85 and PTT 42 sec). Liver ultrasound with Doppler was unremarkable. CT abdomen and pelvis with contrast showed splenomegaly with mesenteric and retroperitoneal lymphadenopathy. Further testing for infectious etiologies including hepatitis panel, HIV, syphilis, TB, Histoplasma, Coxsackie virus, EBV, HSV, and CMV were all negative. EGD and colonoscopy showed mild gastritis (antrum) and some ulceration in the rectosigmoid colon. Serum IgG was elevated (4990 mg/dl). Only serum anti-smooth muscle antibodies (SMA) was positive (>1:80), where as serum antinuclear antibody (ANA), anti-Liver kidney microsomal antibody, and anti-mitochondrial antibodies were all negative. Liver biopsy revealed chronic hepatitis grade 3-4, stage 2. Patient was diagnosed with ANA negative type 1 AIH based on American Association for the study of liver diseases (AASLD) AIH guidelines and International autoimmune hepatitis group (IAHG) scoring system. The patient responded well to oral prednisone 60 mg/day and was discharged home on weaning dose of steroids. Discussion: Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory condition of the liver. AIH is more common in women than men. Diagnosis is based on combination of biochemical, autoimmune, and histological parameters. AIH is categorized into type 1 and 2 based on their auto antibody profiles. Immunosuppression with corticosteroids is the main stay of treatment. Azathioprine and 6-mercaptopurine are other drugs used for AIH treatment. The presentation of our patient was consistent with AIH and responded well to oral steroids. AIH presenting as a GI bleed is consistent with the coagulopathy that comes from hepatic dysfunction although this particular presentation is rare. Pediatricians need to consider AIH in their differential diagnosis when a patient presents with GI bleeding with elevated liver enzymes.

BackgroundChildhood obesity is a major public health concern. The causes of obesity within the paediatric population are multifaced, contributing to its complex management approach. Most children do not meet the...

Family occurrence of autoimmune hepatitis: A Danish nationwide registry-based cohort study

Reply to “Further considerations in autoimmune hepatitis”

THU-192 - Pregnancy and birth outcomes in a Danish nationwide cohort of women with autoimmune hepatitis and matched population controls

Autoimmune hepatitis: review of histologic features included in the simplified criteria proposed by the international autoimmune hepatitis group and proposal for new histologic criteria

Many patients with autoimmune hepatitis are women of fertile age. Some concerns of these patients are related to pregnancy. To conduct a nationwide study on risk of miscarriage, birth rate, and birth outcomes in women with autoimmune hepatitis. From Danish healthcare registries, 1994-2015, we identified 179 births in 103 women with autoimmune hepatitis, 70 of which were first-time singleton births, and 1623 births in 1051 age-matched women (population controls), 662 of which were first-time singleton births. We calculated the risk of miscarriage and the birth rate after autoimmune hepatitis diagnosis in women with autoimmune hepatitis and controls. We used logistic regression to compare the odds of adverse birth outcomes (preterm birth, small for gestational age, congenital malformations and stillbirth) between women with autoimmune hepatitis and controls, adjusting for maternal age and smoking habits. The risk of miscarriage was similar in women with autoimmune hepatitis and controls: risk ratio 1.17 (95% confidence interval 0.81-1.68). The first-time birth rate, including singleton and multiple births, per 1000 person-years in women with autoimmune hepatitis was 37 (95% confidence interval 29-46), in controls 32 (95% confidence interval 30-35). Age at first-births was similar in women with autoimmune hepatitis and controls. Women with autoimmune hepatitis had an increased risk of preterm birth (adjusted odds ratio 3.19, 95% confidence interval 1.53-6.64) and small for gestational age babies (adjusted odds ratio = 3.20, 95% confidence interval 0.33-31.29), but not of congenital malformations (adjusted odds ratio = 1.27, 95% confidence interval 0.48-3.34) or stillbirth. Birth outcomes did not differ in autoimmune hepatitis patients on or off immunosuppression, and with or without cirrhosis. In Danish women with autoimmune hepatitis, fertility was unaffected. They had an increased risk of preterm birth and small for gestational age children, but not of congenital malformations or stillbirth.

Another case of autoimmune hepatitis after SARS-CoV-2 vaccination – still casualty?

P-81 ALTERNATIVE THERAPIES FOR DIFFICULT-TO-TREAT AUTOIMMUNE HEPATITIS: AN EXPERIENCE OF THREE BRAZILIAN REFERRAL CENTERS

Quo vadis autoimmune hepatitis? - Summary of the 5th international autoimmune hepatitis group research workshop 2024

Antibodies against soluble liver antigen/liver-pancreas (SLA/LP) have been associated with severe autoimmune hepatitis (AIH) and poor outcome, but most of these reports have focused on adult patients. The aim of this study was to assess the prevalence and clinical significance of anti-SLA/LP antibodies in a pediatric population with AIH. We developed a quantitative enzyme-linked immuno-assay (ELISA), a Western blot (WB) and an immunoprecipitation assay (IPA) based on recombinant cDNA from activated Jurkat cells. The specificity of these tests was validated by testing 200 serum samples from healthy subjects, and from patients with liver and non-liver diseases. Anti-SLA/LP antibodies were found in patients with type 1 and type 2 AIH. The prevalence of these antibodies in patients with type 1 AIH was: 42% when tested by ELISA, 15% by WB and 50% by IPA. In patients with type 2 AIH, the prevalence rates were 42% by ELISA, 18% by WB and 44% by IPA. The mean titer values for anti-SLA/LP antibodies was significantly higher in type 2 AIH (1:1,300 - 339) than in type 1 AIH (1:600 - 71; p < 0.0001) and closely associated with higher titers of anti-liver kidney microsome type 1 (LKM1) and anti-liver cytosol type 1 (LC1) antibodies in sera. The presence of anti-SLA/LP showed a significant female preponderance in type 1 and 2 AIH patients (p = 0.0003 and p = 0.003, respectively), and was significantly correlated with a lower age at diagnosis (p = 0.05) in type 1 AIH patients. In conclusion, anti-SLA/LP antibodies in pediatric patients are associated with both type 1 and 2 AIH.

Giant cell hepatitis (GCH) is a rare entity in adults that is characterized by large multinucleated hepatocyte formation and parenchymal inflammation. We present a case of acute liver failure in a 33-year-old woman secondary to autoimmune hepatitis (AIH). A liver biopsy revealed submassive hepatocyte necrosis consistent with GCH. We conducted a literature review of 187 reported cases of post-infantile GCH in adults. AIH was the most commonly reported cause of GCH, but GCH was associated with a wide spectrum of etiologies, including infections, rheumatological diseases, hematological diseases, malignancies, and medications. The severity of disease can range from mild hepatitis to fulminant hepatic failure. The mortality rate among the cases in the literature was 18.82%. GCH is managed by treating the underlying cause, and ribavirin has been proposed as a treatment option for idiopathic GCH. A small number of patients progress to requiring orthotopic liver transplant, but recurrence is possible post-transplant.

Comparison of simplified score with the revised original score for the diagnosis of autoimmune hepatitis: A new or a complementary diagnostic score?

Background: Autoimmune hepatitis (AIH) is a hepatocyte injury characterized by a dis-regulated immune system, inflammation of the liver with interface hepatitis, serum antibodies and elevated gamma-globulins. Currently, it exists 2 mainly types on autoimmune hepatitis, based on the presentation of their autoantibodies: type 1 and 2. Type 1 is the one of interest in this review. Autoimmune hepatitis type 1 is an indolent inflammatory disease mediated by abnormal autoimmune reaction, commonly seeing in women (4:1), with no preference of age, however typically present in 4th and 6th decade’s individuals, and a good response to immunosuppressive therapy. Autoimmune hepatitis is known to present not specific symptoms which can go from inexistent to fulminant or exacerbate presentation. The incidence of autoimmune hepatitis in western country is 1/5000 - 1/10,000. Although the detection rate of AIH increasing, especially in China, autoimmune hepatitis diagnosis and treatment remain challenging. Most AIH case do not present pathognomonic biomarkers, however the diagnostic has to considerate other features, which had been codified into validated diagnosis scoring systems. Regarding the treatment, based on prior literature autoimmune hepatitis is mostly sensitive to prednisone or azathioprine, however the use of other immunosuppressive agent or event their combination had offer distinct advantages. Autoimmune hepatitis presents a great life threatening disorder especially because of the delay in the early stage on the disease, the not specific presentations, and the large overlap syndrome associate with it. A deep knowledge in its identification, specific diagnostic criteria, and its therapeutic strategy is much needed. Conclusion: Autoimmune hepatitis is a systemic disease that is difficult to recognize because of its variable clinical presentation and histological features that are not strictly specific. Several new autoantibodies as well as recently simplified diagnostic criteria may allow the primary care physician to progress in the diagnostic process. This is all the more important as undiagnosed and therefore untreated autoimmune hepatitis has a poor prognosis and immunosuppressive treatment leads to remission in a large majority of cases.

Introduction: Immune mediated liver diseases entail a broad category which are associated with increased morbidity and mortality amongst the paediatric population. Programmed Death 1 (PD1) is an inhibitory receptor mainly expressed by T cells, and when activated shed into plasma as soluble PD1(sPD1). The AIM of this study was to evaluate sPD1 levels in plasma of paediatric patients with Autoimmune Hepatitis (AIH), Primary Sclerosing Cholangitis (PSC), AIH and PSC overlap, Inflammatory Bowel Disease (IBD) alone, and concurrent PSC/IBD and AIH/IBD in order to identify a biomarker to response or predict relapse verses remission.Methods: Plasma samples were collected from 41 paediatric patients. AIH patients were further categorized into active, incomplete responders and responders, based on response to standard therapy. sPD1 levels were measured and compared between PSC, PSC/AIH, IBD alone, PSC/IBD and AIH/IBD patients and between active AIH, incomplete responders and responders. Flow cytometry was performed to further analyze CD45RA+, CD3CD4, CD8, CCR7, CXCR3, CD38 and PD1.Results: In the AIH group, those with active disease demonstrated a significantly higher sPD1 levels in comparison to responders (*p > .001). However, the incomplete responders didn’t show a reduction in sPD1 in comparison to active AIH and patients with IBD alone. Interestingly, patients with PSC showed significantly lower level of sPD1 compared to active AIH (*p < .002), whereas, patients with PSC in conjunction with AIH (*p < .006) or IBD (*p < .02) demonstrated a significant increase in sPD1. In addition, we have observed increased levels of circulating CD4 and CD8 bound PD1 in active AIH but not in PSC or responders suggesting T cells activation. CD4+ PD1 double positive cells demonstrated increased expression of CXCR3. Thus, suggesting the activation of PD1 + T cells is mediating through CXCR3 in Autoimmune hepatitis.Conclusions: Our study demonstrates that sPD1 levels correlate with active disease state of AIH and IBD. sPD1 levels did not correlate with PSC. However, PSC in conjunction with AIH or IBD showed higher levels of sPD1. This suggests that T cell activation plays a critical role in active AIH and IBD but not in PSC. Soluble PDI levels could be used as a clinical biomarker to assess response in patients with AIH and for prospectively monitoring PSC patients for development of IBD or AIH.