Features and outcome of autoimmune hepatitis type 2 presenting with isolated positivity for anti-liver cytosol antibody

Autoimmune hepatitis (AIH) type 2 is identified by the presence in the serum of anti-liver/kidney microsome type 1 autoantibody. Anti-liver cytosol autoantibody has been reported in children with autoimmune liver disorders mostly in association with anti-liver/kidney microsome reactivity. However, its role as a sole marker of AIH type 2 is debated. We describe here a series of 18 children and adolescents (15 girls, 3 boys) with AIH with serum anti-liver cytosol type 1 (aLC1) as the only autoimmune marker. A retrospective review was conducted from 3 pediatric hepatology units of all children with an autoimmune liver disease associated with aLC1 as found by immunofluorescence and/or immunodiffusion or immunoblotting. Age at first symptoms ranged from 11 months to 14 years; 12 children presented with acute hepatitis, 1 with progressive jaundice, and 5 were asymptomatic. Anti-liver/kidney microsome, antimitochondria, and anti-actin autoantibodies were not detected. Signs of cirrhosis were present in 11 children. Immunosuppressive treatment was effective in all except 2 children who had subfulminant hepatic failure and who required liver transplantation. Sixteen patients (14 with their native liver) currently are alive; 14 patients still are on immunosuppressive therapy after 1 to 22 years. According to the international scoring system for the diagnosis of AIH, 16 patients corresponded to a definite diagnosis and 2 corresponded to a probable diagnosis. In conclusion, the presence of aLC1 in children with acute or chronic liver disease of unknown origin strongly supports a diagnosis of AIH and is an indication for early immunosuppressive therapy

Intérêt de l'élastométrie impulsionnelle dans l'évaluation non invasive du stade de fibrose hépatique chez l'enfant. [Value of transient elastography in noninvasive assessment in children's hepatic fibrosis].

International audienceAIM: Transient elastography (FibroScan) is a novel, noninvasive, rapid bedside method to assess liver fibrosis by measuring liver stiffness. This study aimed to determine the feasibility and reliability of liver stiffness measurement in children with liver diseases. PATIENTS AND METHODS: Liver stiffness measurements were carried out on 72 children, from 4 to 18 years of age, with potential hepatic fibrosis disease. The clinical, biological, ultrasonographic, and endoscopic parameters were noted to identify children with portal hypertension syndrome. The APRI (ASAT-to-platelet ratio index) test was calculated according to the standard formula. An APRI test score higher than 1.5 indicates significant hepatic fibrosis. METAVIR scoring from 14 liver biopsies was compared to the liver stiffness using the Kappa statistic. RESULTS: Twenty-eight patients had viral hepatitis, 20 cystic fibrosis, 16 chronic liver cholestasis, 5 autoimmune hepatitis, and 3 patients had liver fibrosis with uncertain etiology. FibroScan measurements were available in all children. There was good agreement between FibroScan and pathological studies (weighted kappa=0.814). Only 9 children had portal hypertension syndrome with an average measurement of liver stiffness significantly higher than children without portal hypertension (26.5kPa vs 6.4kPa; p<0.01). The APRI test for 6 out of 9 patients scored higher than 1.5. CONCLUSION: These results indicate that liver stiffness measurement is feasible in children and seems to be related to liver fibrosis. Larger prospective studies are needed to validate this FibroScan method

Endoscopy

BACKGROUND: Esophagogastroduodenoscopy (EGD) is the standard method for diagnosis of esophageal and gastric varices in children. In this prospective study we evaluated the use of PillCam esophageal capsule endoscopy (ECE) in pediatric patients. METHODS: Patients aged 7 to 18 years presenting with portal hypertension and/or cirrhosis underwent ECE (PillCam ESO 2, Given Imaging Ltd.) followed by EGD. RESULTS: 102 patients were screened, 81 (52 boys; mean age 13.96 +/- 0.25 years) were included and 21 were excluded (16 for "candy test" failure). Esophageal varices were identified by EGD in 62 patients (77 %) and by ECE in 57 patients (70 %) using the de Franchis classification (DFC). The sensitivity of ECE for esophageal varices was 92 % and the specificity was 100 % using DFC. Based upon 57/81 patients with small, medium, and large varices on both ECE and EGD, using DFC, the sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were 55 %, 92 %, 89 %, and 63 %, respectively, giving a total overall accuracy of 72 %. To improve sensitivity and specificity in classification of esophageal varices, we propose using a modified score. This score detected esophageal varices with 100 % sensitivity, 93 % specificity, 94 % PPV, and 100 % NPV, giving a total overall accuracy of 97 %. All patients preferred ECE over EGD. No capsule retention was recorded. CONCLUSIONS: ECE is a well-tolerated and safe procedure in children. Using the modified score, the sensitivity of ECE is currently sufficient to detect esophageal varices and replace EGD in infants with suspicion of esophageal varices or when EGD is refused

Liver Int

BACKGROUND & AIMS: To identify prognostic factors for liver disease in children with alpha-1 antitrypsin deficiency, irrespective of phenotype, using the DEFI-ALPHA cohort. METHODS: Retrospective, then prospective from 2010, multicentre study including children known to have alpha-1 antitrypsin blood concentration below 0.8 g/L, born in France since 1989. Clinical and biological data were collected. Liver disease was classified as "severe" (portal hypertension, liver failure, liver transplantation or death); "moderate" (persistent abnormal liver biology without portal hypertension); and "mild/none" (normal or almost normal liver biology and native liver). Prognostic factors for severe liver disease were evaluated using a Cox semiparametric model. RESULTS: In January 2017, 153 patients from 19 centres had been included; genotypes were PIZZ in 81.9%, PISZ in 8.1%, other in 10.0%. Mean +/- SD follow-up was 4.7 +/- 2.1 years. Half of patients had moderate liver disease. Twenty-eight children (18.3%) had severe liver disease (mean age 2.5 years, range: 0-11.6): diagnosis of alpha-1 antitrypsin deficiency was made before two months of age in 65.4%, genotypes were PIZZ in 25 (89.3%), PISZ in 2, PIMlike Z in 1, 15 children underwent liver transplantation, 1 child died at 3 years of age. Neonatal cholestasis was significantly associated with severe liver disease (P = 0.007). CONCLUSION: Alpha-1 antitrypsin-deficient patients presenting with neonatal cholestasis were likely to develop severe liver disease. Some patients with non-homozygous ZZ genotype can develop severe liver disease, such as PISZ and M variants, when associated with predisposing factors. Further genetic studies will help to identify other factors involved in the development of liver complications

Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management

Autoimmune hepatitis (AIH), primary biliary cirrhosis, and primary sclerosing cholangitis are the three major autoimmune diseases affecting the liver, and of these three, AIH is the most typical autoimmune disease being characterized by a T-cell-rich infiltrate, raised circulating γ-globulins, autoantibodies, HLA associations, and links with other autoimmune diseases. It is the only one, of the three diseases, that responds well to immunosuppressive therapy. AIH is caused by dysregulation of immunoregulatory networks and the consequent emergence of autoreactive T cells that orchestrate a progressive destruction of hepatocytes leading untreated to liver failure. T cells play a major role in the immunopathogenesis, and both CD4+ and CD8+ T cells are involved together with effector responses mediated by NK cells, γδ T cells, and macrophages. A number of triggering factors have been proposed including viruses, xenobiotics, and drugs, but none have been conclusively shown to be involved in pathogenesis