A pilot single arm observational study of sofosbuvir/ledipasvir (200 + 45 mg) in 6- to 12- year old children.

BACKGROUND: No available data on the use of sofosbuvir/ledipasvir combination in treatment of hepatitis C virus (HCV) infection in children 6- to 12- year old. AIM: To assess the safety and efficacy of sofosbuvir plus ledipasvir in children 6- to 12- year old with chronic HCV genotype 4 infection. METHODS: This is a pilot prospective single arm observational open-label multicentre study. A total of 20 consecutive eligible chronic HCV infected children, aged from 6- to 12- years were included in this study and treated with a fixed sofosbuvir/ledipasvir combination in half the adult dose (200/45 mg) once daily for 12 weeks. Laboratory tests including virological markers were measured at baseline, 2, 4, 8 and 12 weeks (end of treatment [EOT]), and 12 weeks after end of treatment for sustained virological response 12 (SVR12). RESULTS: The intention-to-treat (ITT) SVR12 rate was 19/20 (95%; 95% CI: 76.4%-99.1%). SVR12 was not assessed in one patient who was lost to follow-up after showing viral negativity at the EOT12. All the remaining 19 patients (100%, 95% CI: 83.18%-100%) who completed the full protocol and follow-up visits achieved SVR12 with normal liver, haematological, and renal function tests and no side effects or fatalities. CONCLUSIONS: This pilot study demonstrated that the fixed dose sofosbuvir/ledipasvir combination could be safe and effective treatment in children 6- to 12- years with chronic hepatitis C genotype 4 infection. Our pilot results might encourage larger and multicentre studies in this age group.

The effectiveness and safety of ledipasvir plus sofosbuvir in adolescents with chronic hepatitis C virus genotype 4 infection: a real-world experience.

BACKGROUND: The combination of ledipasvir plus sofosbuvir was recently approved for treatment of adolescent (12-17 years) HCV genotype 1, 4, 5 & 6 patients. However, few clinical trials have been performed in genotype 1 patients. AIM: To investigate the effectiveness and safety of ledipasvir plus sofosbuvir in chronic HCV adolescent patients with genotype 4 in the real world. METHODS: This prospective multicentre (six centres) open-label study included 144 adolescent chronic HCV patients with genotype 4 (mean age 14 ± 2, 69% males). All patients received a combination tablet containing 400 mg sofosbuvir and 90 mg ledipasvir once daily for 12 weeks. Laboratory and virological markers were evaluated at baseline, week 4, week 8 and week 12 (EOT), and 12 weeks after end of treatment (SVR12). RESULTS: SVR12 was observed in 142/144 patients (99%). The relapsers occurred in previous naïve patients (n = 2/128, 2%), while the experienced patients showed 100% SVR12. SVR12 was 98% in F0/F1 patients in comparison to 100% in F2 patients (P = 0.552). No serious side effects were observed, nor was treatment discontinuation or death. Headache was the most common side effect in all patients (20%). In experienced patients, pruritus (31%, P = 0.007), diarrhoea (44%, P < 0.001) and skin rash (19%, P = 0.002) were higher than in naïve patients. CONCLUSIONS: A ledipasvir plus sofosbuvir regimen is well tolerated and effective, and can be used safely in treating adolescent patients with chronic hepatitis C genotype 4.

Treatment of hepatitis B and C in children.

Chronic viral hepatitis B and C infections are highly prevalent and create a substantial burden to healthcare systems globally. These two chronic infections are the cause of significant global morbidity and mortality with approximately 1 million annual deaths attributable to them and their sequelae. Children are vulnerable to both infections. The availability of new drugs and new therapeutic strategies are increasing the complexity and individualizing the management of children with viral hepatitis. Therefore, it is extremely important to educate and advise pediatricians concerning the new lines of treatment. More than 350 million persons worldwide are infected with HBV. Although its incidence has dramatically declined since the implementation of universal immunization programs in many countries, scores of children are still being infected each year. Despite its benign course, chronic hepatitis B (CHB) during childhood and adolescence, 3-5% and 0.01-0.03% of chronic carriers develop cirrhosis or hepatocellular carcinoma (HCC), respectively, before adulthood. Treatment of CHB in childhood has been hampered by the long delay in licensing new drugs for pediatric use. Safe and effective antiviral therapies are available in adults, but few are labeled for use in children, and an accurate selection of whom to treat and the identification of the right timing for treatment are needed to optimize response and reduce the risk of antiviral resistance. Although several guidelines on the management of adult patients with CHB have been published by major international societies, the clinical approach to infected children is still evolving, and is mostly based on the expert opinions. Standard interferon (IFN)-α is still the treatment of choice for most children with HBV infection. Licensing of highly-effective nucleoside/nucleotide analogues (NA) for older children and adolescents has opened new possibilities of treatment. However, the risk of emergence of drug resistant strains is a public health problem and a major long-term issue for young patients. Before starting a child on NAs, the risks of treatment should be carefully weighed against the possible benefits. As the management of special patient populations is problematic and not evidence-based, their referral to highly specialized centers is strongly recommended. The World Health Organization estimates that over 250 million people worldwide are chronically infected with HCV. In countries where adults have a high prevalence of HCV infection, an increased prevalence in children can also be expected. In Egypt, for example, approximately 1-2% of children are infected. The child infected with HCV must be over 2 years old in order to be treated by a licensed drug. The standard of care therapy is pegylated IFN-α plus ribavirin with success rates as similar in adults. The first-wave, first-generation oral direct acting anti-virals (DAAs) telaprevir and boceprevir were licensed by the FDA for use in HCV genotype 1 infection in adults in 2011. Telaprevir and boceprevir must be coadministered with pegylated IFN-α and ribavirin. Sofosbuvir, the second-wave DAA has been approved in adults in January 2014 and other DAAs are on the way of approval soon in adults. Some DAAs are being tested for children and the results are eagerly awaited.

Adolescent growth: genes, hormones and the peer group. Proceedings of the 20th Aschauer Soiree, held at Glücksburg castle, Germany, 15th to 17th November 2013.

The association between poverty, malnutrition, illness and poor socioeconomic conditions on the one side, and poor growth and short adult stature on the other side, is well recognized. Yet, the simple assumption by implication that poor growth and short stature result from poor living conditions, should be questioned. Recent evidence on the impact of the social network on adolescent growth and adult height further challenges the traditional concept of growth being a mirror of health. Twenty-nine scientists met at Glücksburg castle, Northern Germany, November 15th - 17th 2013, to discuss genetic, endocrine, mathematical and psychological aspects and related issues, of child and adolescent growth and final height.

Diversity in auxology: between theory and practice. Proceedings of the 18th Aschauer Soiree, 13th November 2010.

Auxology has developed from mere describing child and adolescent growth into a vivid and interdisciplinary research area encompassing human biologists, physicians, social scientists, economists and biostatisticians. The meeting illustrated the diversity in auxology, with the various social, medical, biological and biostatistical aspects in studies on child growth and development.

Colorectal polyps: a frequently-missed cause of rectal bleeding in Egyptian children.

OBJECTIVES: Colorectal polyps are important causes of rectal bleeding but they have been infrequently reported in Egyptian children. The prevalence and characteristics of colorectal polyps in a consecutive cohort of Egyptian children with rectal bleeding are presented. METHODS: A total of 174 children aged 2-12 years [mean (SD) 6.4 (3.7)] with fresh rectal bleeding were enrolled prospectively. Rectal examination, laboratory investigations and fibre-optic colonoscopy were performed in all patients. RESULTS: The source of bleeding was diagnosed as colorectal polyps in 100 patients (57.4%) and was owing to other causes in 74. The interval between onset of symptoms and presentation ranged from 2 to 48 months [mean (SD) 18.3 (16)]. In patients with other causes, rectal bleeding was attributed to intestinal amoebiasis (42), diarrhoea/dysentery (18), severe constipation (2) and intestinal schistosomiasis (2). Polyps were solitary in 56 children (56%) and ranged from 2 to 5 in 34 (34%) and >5 in 10 (10%). Polyps were confined to the rectum in 68 children, were rectosigmoid in 20, in the descending colon in 8, and splenic flexure in 4. Polyps were juvenile in 84 children (84%), inflammatory in 10 (10%) and hyperplastic, schistosomal or adenomatous in 2 each (6%). Colonoscopic polypectomy was successful and arrested the bleeding in all cases. CONCLUSION: In Egyptian children, colorectal polyps are relatively common and an easily treatable cause of fresh rectal bleeding. They should be high on the list of differential diagnoses.

Anti-HCV prevalence among diabetic and non-diabetic Egyptian children.

Our aim was to determine the prevalence of the HCV infection among children with type 1 DM as compared to a group of non-diabetic children attending the general outpatient clinics of the same hospital and investigate the possible risk factors. The study was carried out on 692 children with type 1 DM attending the Pediatric Diabetes Unit at Cairo University Pediatric Hospital, Egypt, and 1042 non-diabetic children attending the general outpatient clinics of the same hospital. They were screened for HCV antibodies using third generation ELISA. Anti-HCV antibody prevalence in diabetic children below 9 years of age was comparable to that of non diabetic children (2.5% vs. 1.4%; p=0.25). Diabetic children had higher exposure to medical care (p=0.04); all diabetics were exposed to daily insulin injections and daily blood glucose monitoring. Non-diabetics had higher exposure to razors used by others (p=0.05) and higher rate of traditional hair cutting (p=0.05). To conclude, the prevalence of anti-HCV in diabetic children below 9 years of age was comparable to non diabetic children of the same age group. Application of standard precautions for infection control could successfully limit spread of HCV infection in our Pediatric Diabetes Unit, in a country with high HCV load as Egypt.

Human fascioliasis: clinical features and diagnostic difficulties in Egyptian children.

Human fascioliasis (HF) has been reported in children worldwide and occasionally from Egypt. In the past 7 years we diagnosed 16 children aged 3.5-11 years (mean age: 6.5 years), 13 of them were boys, as HF. They were referred to Cairo University, Paediatric Hospital (CUPH), with pyrexia of undetermined origin (PUO) and abdominal pain. Diagnosis was based on high peripheral blood eosinophilia (14-82 per cent) in all patients along with Fasciola hepatica egg detection on direct stool smear in three or stool concentration in four, antibody detection by indirect haemagglutination test (IHAT) in seven egg-negative patients and ultrasonographic detection of hepatic and/or biliary lesions of HF in two egg-negative patients. Percutaneous liver biopsy confirmed the diagnosis of an eosinophilic abscess (parasitic granuloma) in 12 of 13 patients. Therefore, HF does occur in Egyptian children and its diagnosis needs a high index of suspicion supported by stool microscopy, serology, imaging procedures, and probably liver biopsy.

Primary sclerosing cholangitis in childhood.

Thirteen children (8 female) with primary sclerosing cholangitis are described, in whom the diagnosis was confirmed by the presence of characteristic changes on endoscopic retrograde cholangiopancreatography. Nine had clinical features of chronic inflammatory bowel disease 1 mo to 5 yr before the onset of primary sclerosing cholangitis (6 patients) or appearing simultaneously with primary sclerosing cholangitis (3 patients). In 4 patients clinical evidence of chronic inflammatory bowel disease was absent but 1 of the 4 was found to have microscopic colitis in colonoscopic biopsy specimens. Biopsies were not performed in the remaining 3 patients. High immunoglobulin G concentrations and positive antinuclear or smooth muscle antibodies were present in all patients except 1 who had been given immunosuppressants. In 7 patients treated with immunosuppressants and followed up for 9 mo to 10 yr there was modest symptomatic improvement. This improvement was accompanied by a fall in transaminase levels in 6 of the patients and histologic improvement in 3 of 4 patients who had undergone biopsy. Greater use of endoscopic retrograde cholangiopancreatography in the last 6 yr led to the identification of 10 of these 13 cases, suggesting a higher incidence of primary sclerosing cholangitis in childhood than would appear from the literature.