Kupffer Cell Hyaline Globules in Children With Autoimmune Hepatitis.

BACKGROUND: Hyaline globules (HGs) in the cytoplasm of Kupffer cells (KCs) have been appraised for being a typical feature of autoimmune hepatitis (AIH). This study aimed to determine how useful Kupffer cell hyaline globules (KCHGs) are in diagnosing AIH vs. other causes of pediatric chronic liver diseases (PCLDs). MATERIALS AND METHODS: This retrospective study recruited 124 children; 58 with AIH, 50 with chronic hepatitis C virus (HCV) infection, and 16 with Wilson's disease (WD). Two pathologists retrieved paraffin blocks of liver biopsies and prepared new cut sections for Periodic acid-Schiff-Diastase (PAS-D) stain. They independently examined liver biopsies before starting treatment. Two pediatricians reviewed medical records for demographic, clinical, laboratory, and serological findings. RESULTS: Females represented 48.6% of the studied children with a median age of 5.8 (4.9) years. Pathologists identified KCHGs in 67.24%, 12.5%, and 6.0% of AIH, WD, and HCV affected children respectively, P < 0.001. A significantly higher proportion of seropositive than seronegative AIH patients had KCHGs (77.5% vs. 50.0%), (P < 0.05). In multivariate analysis, KCHGs and prolonged prothrombin time were the only significant predictors that differentiate between AIH and the other studied PCLDs. The odds ratio of having AIH increased 68 times if KCHGs were seen. Among children with AIH, the presence of KCHGs was associated with higher median levels of direct bilirubin 2.2 (1.3) vs. 1.2 (2.2), and immunoglobulin G 3.2 (1.9) vs. 2.0 (1.7), (P < 0.05), but not to histopathological findings or hepatic fibrosis and activity. CONCLUSIONS: KCHGs are key indicators that can differentiate between AIH and other PCLDs, and between seropositive and seronegative AIH.

Temporal histopathological changes in biliary atresia: A perspective for rapid fibrosis progression.

INTRODUCTION AND OBJECTIVES: Biliary atresia (BA) is characterized by rapid progression of fibrosis with no definite causes. Histopathological findings have been extensively described, but very few studies have assessed temporal changes in BA. Understanding these short-term changes and their relationship with fibrosis progression could have an impact on ameliorating rapid fibrogenesis. We aimed to study the relationship between temporal histopathological changes and fibrosis progression in BA within a short time interval. PATIENTS AND METHODS: Forty-nine infants with BA who underwent Kasai portoenterostomy, a diagnostic liver biopsy, and an intraoperative liver biopsy were recruited. Histopathological characteristics of the two biopsies were examined. Temporal histopathological changes were assessed by comparing the two types of biopsies. Correlation of temporal changes in fibrosis with age, interval between biopsies, laboratory profiles, and temporal histopathological changes were studied. RESULTS: In the univariate analysis, bile ductular proliferation (BDP), portal infiltrate, giant cells, hepatocellular swelling, and fibrosis showed significant temporal changes within a short interval (5-31 days). BDP and fibrosis showed the most frequent increase in their grades (32/49 and 31/49 cases, respectively). In the multivariate analysis, BDP was the only independent pathological feature showing a significant temporal increase (p = 0.021, 95% confidence interval: 1.249-16.017). Fibrosis progression was correlated with temporal changes in BDP (r = 0.456, p = 0.001), but not with age (p = 0.283) or the interval between the biopsies (p = 0.309). CONCLUSIONS: Fibrosis in BA progresses rapidly and is significantly correlated with BDP. Assessment of targeting BDP as an adjuvant medical therapy is recommended.

Generic sofosbuvir/ledipasvir for the treatment of genotype 4 chronic hepatitis C in Egyptian children (9-12 years) and adolescents.

BACKGROUND/PURPOSE OF THE STUDY: Worldwide and national efforts are directed against eradication of HCV. The introduction of direct-acting antivirals (DAAs) has changed dramatically the outcome of HCV treatment. In spite of the Food and Drug Administration approval of the oral drugs sofosbuvir (SOF) and ledipasvir (LED) for the treatment of HCV in adolescents more than or equal to 12 years old, sufficient real-world experience is still lacking. The aim of this study was to assess the safety and efficacy of the generic SOF/LED fixed-dose combination 400/90 (400 mg SOF + 90 mg LED) for the treatment of adolescents and children (9-12 years) with chronic hepatitis C (CHC). METHODS: In this prospective observational study, 100 cases of genotype 4 CHC were recruited consecutively from those fulfilling the inclusion and exclusion criteria. All cases received the generic fixed-dose combination SOF/LED (400/90), one tablet daily for 12 weeks. All clinical, laboratory, and virologic characteristics were evaluated at base line, and week (W) 2, 4, 8, and 12 of therapy and W12 post-treatment (SVR12). RESULTS: Recruited children (9-12) and adolescents weighed 28-83 and 31-90 kg, respectively. Eighty cases were naïve and 20 cases were pegylated interferon/ribavirin treatment-experienced. Very rapid virologic response (vRVR) at W2 was 96%, while at W4 response rate was 100% and maintained till the end of treatment and at W12 post-treatment (SVR12). All reported side effects were mild and did not lead to treatment termination and disappeared at W12 post-treatment. CONCLUSION: The generic SOF/LED fixed-dose combination is safe and effective in children, 9-12 years, and adolescents with vRVR rate of 96%, 100% EOT response and SVR12.