Safety and Efficacy of 8 Weeks Ledipasvir/Sofosbuvir for Chronic Hepatitis C Genotype 4 in Children Aged 4-10 Years.

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.

Hepatic immunohistochemistry of bile transporters in progressive familial intrahepatic cholestasis.

UNLABELLED:  Background. Diagnosis of progressive familial intrahepatic cholestasis (PFIC) is a challenging matter that involves the summation of clinical, laboratory, radiological, and liver histological parameters; in addition to specific investigations to exclude other causes of neonatal cholestasis. The aim of this study was to evaluate liver tissue immunohistochemistry of bile salt export pump (BSEP) and multidrug resistance 3 (MDR3) proteins in differentiating PFIC from other causes of neonatal cholestasis, particularly, when genotyping is unavailable. MATERIAL AND METHODS: The study included 25 patients diagnosed phenotypically as PFIC including 2 with PFIC1, 17 with PFIC2 and 6 with PFIC3. A second group of 25 cholestatic newborns with confirmed etiologies other than PFIC, termed as non-PFIC, included as controls. Liver biopsies from all patients were obtained and immunostained for BSEP and MDR3. RESULTS: Negative immunoreaction of BSEP and MDR3 was found in the majority of PFIC group (76 and 64% respectively). Nonetheless, the negative immunoreaction was demonstrated in a considerable number of the non-PFIC group. BSEP immunoreaction was negative in the majority (82.4%) of PFIC2 but in none of the two patients with PFIC1. In addition, negative MDR3 immunoreaction was more frequently associated with PFIC3 compared to non-PFIC group. CONCLUSION: MDR3 and BSEP immunostaining would be a helpful tool in supporting the phenotypic diagnosis of PFIC subtypes and in differentiating PFIC from other causes of neonatal cholestasis.