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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). 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). Recruited children (9–12) and adolescents weighed 28–83 and 31–90 kg, respectively. Eighty cases were naive 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. 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.

Biliary atresia (BA) is a rare disease characterized by ascending obstruction of bile ducts that exclusively affects newborn infants. The etiology of the disease is not known. BA is considered to be a phenotype resulting from several pathogenic processes leading to obstruction of the biliary tree. It usually presents shortly after birth, characterized by persistent jaundice, hepatosplenomegaly, clay-colored stool, and dark urine. It affects both the extra-hepatic biliary ducts (EHBDs) and the intra-hepatic biliary system (IHBDs), but the former is more severely affected. Diagnosis of BA is a great challenge and must be achieved as early as possible to delay progression to cirrhosis. Laboratory tests reveal direct hyperbilirubinemia and, variable levels of transaminases, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP), which overlap significantly with other causes of neonatal cholestasis. The intraoperative cholangiogram is considered the gold standard for the diagnosis of BA and is performed routinely in many institutions. BA can be divided into correctable and non-correctable types; the former accounts for (10–15%) of cases, in which the proximal common hepatic duct is patent, allowing primary anastomosis of the EHBDs to the bowel. All patients are subjected to identical surgical and medical treatments; consisting of Kasai portoenterostomy (KPE), which entails removal of the atretic extra-hepatic tissue and a Roux-en-Y jejunal loop anastomosed to the hepatic hilum. Kasai portoenterstomy is considered a transition to liver transplantation, as the pathology may be still ongoing. BA is the most frequent indication for liver transplantation in infants, which is the only treatment that can definitively arrest the natural disease course. In conclusion: BA is a serious liver disease that needs to be further studied, and awareness of BA should be increased among the public and health care workers to prevent the complications of this disease.

BackgroundNeonatal physiological jaundice is a common benign condition that rarely extends behind the second week of life; however, it may interfere with the diagnosis of a pathological condition termed neonatal cholestasis (NC). The latter is a critical, uncommon problem characterized by conjugated hyperbilirubinaemia. This review aims to highlight the differences between physiological and pathological jaundice, identify different causes of NC, and provide a recent approach to diagnosis and management of this serious condition.Main textNC affects 1/2500 live births, resulting in life-threatening complications due to associated hepatobiliary or metabolic abnormalities. NC is rarely benign and indicates the presence of severe underlying disease. If jaundice extends more than 14 days in full-term infants or 21 days in preterm infants, the serum bilirubin level fractionated into conjugated (direct) and unconjugated (indirect) bilirubin should be measured. A stepwise diagnostic approach starts with obtaining a complete history, and a physical examination which are valuable for the rapid diagnosis of the underlying disease. The most frequently diagnosed causes of NC are biliary atresia (BA) and idiopathic neonatal hepatitis (INH). The early diagnosis of NC ensures more accurate management and better prognosis. Despite the unavailability of any specific treatments for some causes of NC, the patient can benefit from nutritional management and early medical intervention. Future research should attempt to shed light on methods of screening for NC, especially for causes that can be effectively treated either through proper nutritional support, appropriate chemotherapeutic management, or timely surgical intervention.ConclusionFurther attention should be paid for diagnosis and treatment of NC as it may be misdiagnosed as physiological jaundice; this may delay the proper management of the underlying diseases and aggravates its complications.

The standard-of-care treatment for biliary atresia (BA) is surgical restoration of bile flow by Kasai portoenterostomy. We aimed to study serum interleukin- (IL-) 12p40, a natural antagonist for the proinflammatory IL-12p70, and its relation to surgical outcomes of BA. The study included 75 infants with neonatal cholestasis: BA group (n=25), non-BA cholestasis group (n=30), and neglected BA group (n=20), in addition to thirty healthy neonates serving as controls. IL-12p40 was measured by ELISA in all individuals and a second assessment was performed 3 months postoperatively in the BA group. The surgical outcomes were classified as successful (bilirubin ≤ 2 mg/dl) or failed (bilirubin > 2 mg/dl). IL-12p40 was higher in BA compared to that in the non-BA and control groups (P values were 0.036 and

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important.Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls.Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p<0.0001,p=0.071, andp=0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p<0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders,p<0.0001andp=0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p=0.044).Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.