RESUMO
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 (pâ¯=â¯0.021, 95% confidence interval: 1.249-16.017). Fibrosis progression was correlated with temporal changes in BDP (râ¯=â¯0.456, pâ¯=â¯0.001), but not with age (pâ¯=â¯0.283) or the interval between the biopsies (pâ¯=â¯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.
Assuntos
Atresia Biliar/complicações , Cirrose Hepática/patologia , Fígado/patologia , Atresia Biliar/diagnóstico , Biópsia , Progressão da Doença , Feminino , Seguimentos , Humanos , Lactente , Cirrose Hepática/etiologia , Masculino , Prognóstico , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the safety and efficacy of shortened 8-week regimen of ledipasvir/sofosbuvir (LED/SOF) combination therapy in treatment-naïve children without cirrhosis aged 4-10 years of age with chronic hepatitis C virus (HCV) infection. STUDY DESIGN: This observational single arm prospective study included 30 treatment-naïve children (20 males) with proved chronic HCV fulfilling inclusion criteria. Their body weights ranged from 17 to 26 kg. Four patients were excluded from the study. All the included children received a single oral dose of LED/SOF 45/200 mg for 8 weeks. Body weight, HCV-RNA, complete blood count, and liver function tests were monitored at 0, 2, 4, and 8 weeks and sustained virologic response was evaluated after 12 weeks after treatment (SVR12). The emergence of any side effects was also monitored. RESULTS: The most common risk factor (53.3%) was an parent or sibling with HCV infection. Twenty-nine patients (96.7%) were negative for HCV-RNA by week 2 of treatment and 1 patient became negative by week 4. The end of treatment response and SVR12 were 100%. Transaminases levels declined and returned to normal levels by week 2. Major side effects were fatigue in 90% (27/30) and headache in 76.7% (23/30). Side effects were minimal, tolerable, and did not interfere with daily activity or necessitate treatment discontinuation. CONCLUSIONS: A shortened 8-week regimen of LED/SOF (45/200 mg) is safe and effective with 100% SVR12 in treatment-naïve children with cirrhosis aged 4-10 years with chronic HCV infection genotype 4.
Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Criança , Pré-Escolar , Feminino , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/virologia , Humanos , Masculino , Estudos Prospectivos , Sofosbuvir , Fatores de Tempo , Resultado do Tratamento , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/efeitos adversosRESUMO
UNLABELLED: Background. T-cell populations regulate the balance of immune responses. The CD (Cluster of differentiation) 4+CD25+ regulatory T cells (Tregs) are crucial for maintaining negative control of various immune responses. There are different T-cell subpopulations with regulatory functions, as natural killer T cells, CD8+ and CD28. The forkhead box P3 (FOXP3) regulates Treg development and is required for its suppressive function. AIM: To evaluate the hepatic expression of the intrahepatic Tregs, Ig (immunoglobulin) G and IgM plasma cells in autoimmune hepatitis (AIH) and other chronic liver diseases (CLDs). MATERIAL AND METHODS: This study included 100 pediatric patients; 50 AIH and 50 CLDs other than AIH. All patients were subjected to routine investigations of CLDs plus immune-staining of liver tissue for FOXp3, IgG and IgM plasma cells, CD4 and CD8 T-cells. RESULTS: The FOXP3+ T cells in patients with AIH (6.3 ± 5) were significantly higher than that in the non-AIH (2.1 ± 2.6). FOXP3+ T cells were abundant in liver tissue with marked inflammatory cellular infiltrate. CD4+ and CD8+ infiltrating the liver tissue and IgG positive cells were significantly higher in AIH group, while the expression of IgM positive cells showed no significant difference. The IgG/IgM was significantly higher in the AIH treatment responders (3 ± 3) than non-responders (1.6 ± 0.5), while there was no significant difference regarding the intrahepatic expression of FOXP3+, CD4+, CD8+ cells, T-cells, IgG and IgM plasma cells. CONCLUSION: Intrahepatic Tregs were increased in number in patients with AIH in the initial presentation, and their presence is associated with increased activity and inflammation in liver biopsy.