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.

National treatment programme of hepatitis C in Egypt: Hepatitis C virus model of care.

Hepatitis C virus (HCV) infection is a major health problem in Egypt as the nation bears the highest prevalence rate worldwide. This necessitated establishing a novel model of care (MOC) to contain the epidemic, deliver patient care and ensure global treatment access. In this review, we describe the process of development of the Egyptian model and future strategies for sustainability. Although the magnitude of the HCV problem was known for many years, the HCV MOC only came into being in 2006 with the establishment of the National Committee for Control of Viral Hepatitis (NCCVH) to set up and implement a national control strategy for the disease and other causes of viral hepatitis. The strategy outlines best practices for patient care delivery by applying a set of service principles through identified clinical streams and patient flow continuums. The Egyptian national viral hepatitis treatment programme is considered one of the most successful and effective public health programmes. To date, more than one million patients were evaluated and more than 850 000 received treatment under the umbrella of the programme since 2006. The NCCVH has been successful in establishing a strong infrastructure for controlling viral hepatitis in Egypt. It established a nationwide network of digitally connected viral hepatitis-specialized treatment centres covering the country map to enhance treatment access. Practice guidelines suiting local circumstances were issued and regularly updated and are applied in all affiliated centres. This review illustrates the model and the successful Egyptian experience. It sets an exemplar for states, organizations and policy-makers setting up programmes for care and management of people with hepatitis C.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Effect of infection control strategy on knowledge, attitude and practice towards hepatitis B transmission and prevention in vulnerable populations.

BACKGROUND: Health care workers (HCWs) and hematological patients needing blood/ blood product transfusion are particularly vulnerable to blood born infections (BBI) including viral hepatitis. OBJECTIVE: To evaluate knowledge, attitude and practice (KAP) of these target groups regarding viral hepatitis B (HBV) transmission and its change with implementing infection control policy and procedures. METHODS: An anonymous questionnaire with closed questions was used to evaluate KAP including vaccination status in 2 target groups, in Children Hospital, Ain Shams University, Cairo, Egypt: 184 nurses and 210 children and adolescents with blood diseases. One year after instituting infection control as a part of hospital procedures, the same questionnaire was reused to evaluate KAP towards HBV. RESULTS: Baseline knowledge regarding HBV transmission, sequelae and preventive measures, was poor in both groups. Among nurses, only 62% wore gloves on withdrawing or giving blood to patients, 43.5% routinely washed hands between patients and 37.5% reported exposure after sharp injury. Only 38% of patients and 40% of nurses received HBV vaccination. Targeted infection control policy and procedures significantly improved KAP regarding HBV in both groups. Vaccination coverage significantly increased and reached 88.7% for nurses and 72% for patients. CONCLUSIONS: Hospital based infection control units with established policy and procedures against BBI significantly improved KAP towards HBV including a significant increase in vaccination intake.

IL-1, IL-4 production and IgE levels in acute and chronic fasciolosis before and after triclabendazole treatment.

IL-1 generation by mononuclear phagocytes, IL-4 production by Th2 lymphocytes and IgE levels in serum were measured in eight patients with acute fasciolosis and seven patients in the chronic stage of the disease before and after triclabendazole treatment. Results were compared with those of a control group of ten individuals. The monocytes and lymphocytes from patients with acute and chronic fasciolosis produced significantly lower levels of IL-1 and IL-4 respectively, particularly in the chronic phase of the disease, as compared to the control. A significant increase in IgE level in both acute and chronic fasciolosis was observed. The level was significantly higher in acute as compared to chronic cases. After treatment with triclabendazole IL-1, IL-4 and IgE levels moved towards the control indicating obvious improvement in the immunological responses of the patients.

Diagnostic significance of Schistosoma mansoni proteins Sm31 and Sm32 in human schistosomiasis in an endemic area in Egypt.

We performed a series of ELISAs to evaluate the diagnostic significance of two Schistosoma mansoni proteins, Sm31 (cysteine proteinase, cathepsin B) and Sm32 (asparaginyl endopeptidase). Our study populations were chosen from two villages in an endemic area close to Alexandria. Using fusion proteins MS2-Sm31 and MS2-Sm32 as antigens, 70% and 78.9%, respectively, of patient sera from 134 parasitologically confirmed cases reacted positively. The percentage of seropositivity increased to 84.5% when parasite-derived proteins Sm31 and Sm32 were used. The serum levels of antibodies to these two proteins in recombinant or native forms do not correlate with intensity of infection and hence are detected even when egg counts are low, which makes proteins Sm31 and Sm32 useful antigens in the identification of S. mansoni infected cases, particularly in endemic areas in Egypt.

Effect of triclabendazole on the tegument of Schistosoma mansoni: a scanning electron microscopic study.

The in vitro effect of Triclabendazole on the tegument of Schistosma mansoni was studied by means of scanning microscopy. Two different concentrations of drug were used (15 micrograms/ml and 75 micrograms/ml) and the worms examined after different exposure times (1 hr, 3 hrs, 24 hrs). It was found that, exposure of S. mansoni to Triclabendazole resulted in quick reactions: (1) The tegument was immediately destroyed after exposure in several places leading to the formation of defects in the surface of the worms. (2) The parasites contracted and became immobilized within one hour showing that the uptake of the drug was very rapid. (3) Triclabendazole caused 100% mortality after 24 hrs in the two concentrations. The ultrastructural changes were proportional to the concentration of drug and time elapsed.

High prevalence of islet cell antibody and defective insulin release in children with schistosomiasis.

The importance of islet cell antibodies (ICA) as a predictor of insulin dependent diabetes mellitus (IDDM) has been emphasized by several investigators since 1974. The ICA was also detected in patients with various immune-mediated diseases such as auto-immune thyroiditis. Schistosomiasis is a wide-spread helminthic disease which affects more than 200 million patients all over the world. Immunological abnormalities and pancreatic affection are features of the disease. We studied the prevalence of ICA in 40 children with schistosomiasis (20 males and 20 females), 14 children with IDDM, and 30 of the non-diabetic siblings of patients with IDDM, and evaluated the oral glucose tolerance and early release of insulin after an i.v. load of glucose in children with schistosomiasis, diabetics' siblings, and 10 normal age-matched controls. The age of onset of IDDM and duration of the disease were 6.5 +/- 2.3 and 4.1 +/- 1.2, respectively, and the age of onset and duration of schistosomiasis were 8.3 +/- 2.7 and 2.5 +/- 1.5 years, respectively. Sex, consanguinity, history of previous virus diseases (mumps, measles and rubella), and sex maturity rating did not differ among the three study groups; however, children with schistosomiasis were significantly older. The prevalence of ICA was 50 per cent in children with IDDM, 13 per cent in the diabetics' siblings, and 25 per cent of children with schistosomiasis. Glucose tolerance was normal in children with schistosomiasis and diabetics' siblings. Early release of insulin after i.v. glucose load was significantly lower in children with schistosomiasis compared to the other two groups. In conclusion, the high prevalence of ICA and the decreased early release of insulin in response to an i.v. glucose load in children with schistosomiasis suggest that auto-immune aggression against the islet cells contributes in the pathogenesis of pancreatic disease in these patients, and might increase the risk for developing glucose intolerance and diabetes.

Epidemiological studies on human scabies in Cairo.

Nowadays, human scabies is more or less a public health problem in Egypt, particularly among school children. The results of this epidemiological studies among one hundred scabietic patients showed that (a) Scabies is widespread among children and youth particularly students (b) The sex and the site distribution are attributed to the risk factor of exposure to infestation (c) Scabies is a disease determined by Sociodemographic and Hygienic customs of the population with high familial incidence among the patients. The whole results were discussed on the light of the work done in Egypt and similar countries.

Prevalence of hepatitis C viral antibody in transfused and nontransfused Egyptian children.

Hepatitis C (HCV) virus is recognized as the major cause of what was previously referred to as parenterally acquired (blood-mediated) non-A, non-B hepatitis. A study involving 252 transfused and nontransfused Egyptian children was conducted from November 1990 through February 1991 to determine the prevalence of HCV and the role of blood and blood and blood product transfusions in the spread of the virus. Serum specimens were assayed by a second generation enzyme immunoassay and were considered reactive only after supplemental testing using the second generation recombinant immunoblot assay. Prevalence among 84 young study subjects with hematologic disorders was 55% (46 of 84), while no HCV antibodies were detected among the two nonhematologic pediatric populations studied: 84 hospital admissions and 84 acutely ill but otherwise healthy outpatients (seeking treatment for symptoms associated with a new condition less than three weeks old in the absence of any chronic health problem). Ninety-two percent (77 of 84) of the hematology-related cases had medical histories of multiple transfusions. Positive antibody responses (46) were significantly associated with increased duration of illness (P < 0.001) and the volume and number of transfusions (P < 0.01) when compared with negative ones (38). However, prior hospitalization and/or surgery were not related to HCV antibody status. The high prevalence of HCV antibody among multiply transfused infants and children suggests that blood and blood product supplies should be regularly screened for HCV antibody.