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.

Sofosbuvir-based treatment regimens: real life results of 14 409 chronic HCV genotype 4 patients in Egypt.

BACKGROUND: Chronic hepatitis C virus infection is one of the most important health problems in Egypt. The Ministry of Health's National Treatment Programme introduced sofosbuvir-based therapy in October 2014. AIM: To assess the clinical effectiveness and predictors of response to SOF-based treatment regimens, either dual therapy, with SOF/ribavirin (RBV) for 6 months or triple therapy with SOF/peg-IFN-alfa-2a/RBV for 3 months, in a cohort of patients treated in National Treatment Programme affiliated centres in Egypt. METHODS: Between October 2014 and end of 2014, patients who were eligible for treatment were classified according to their eligibility for interferon therapy: Group 1 (interferon eligible) were treated with triple therapy for 12 weeks and Group 2 (interferon ineligible) were treated with dual therapy for 24 weeks. Difficult to treat patients included those with F3-F4 on Metavir score, Fib-4 >3.25, albumin ≤3.5, total Bilirubin >1.2 mg/dL, INR >1.2 and platelet count <150 000 mm3 . RESULTS: Twelve weeks post-treatment data were available on 14 409 patients; 8742 in group 1 and 5667 in group 2. In group 1, the sustained virological response at week 12 (SVR12) was 94% and in group 2 the SVR12 was 78.7%. Multivariate logistic regression analysis in which treatment failure is the dependent variable was done. Male gender, being a difficult to treat patient and previous interferon therapy were significant predictors of nonresponse in both treatment groups. CONCLUSION: Results of sofosbuvir-based therapies in Egypt achieved similar rates of SVR12 as seen in phase III efficacy studies.

Transcriptional response of MxA, PKR and SOCS3 to interferon-based therapy in HCV genotype 4-infected patients and contribution of p53 to host antiviral response.

AIMS: To investigate the myxovirus-resistance protein A (MxA) and double-stranded RNA-activated protein kinase (PKR) genetic response to interferon (IFN) therapy in hepatitis C virus (HCV) genotype 4-infected patients. Moreover, we studied the association between suppressor of cytokine signaling 3 (SOCS3) gene expression and therapy resistance in genotype 4. Finally, we investigated the novel link between p53 and IFN-stimulated genes (ISGs) in humans. METHODS: Gene expression analyses were performed in peripheral blood using TaqMan real-time PCR. Virologic response was assessed with a branched-DNA assay. Genotyping was confirmed. RESULTS: Early virologic responders (EVRs, n = 23) but not non-EVRs (n = 7) showed strong upregulation of PKR at week 12 of therapy compared to baseline. Both EVRs and non-EVRs showed MxA upregulation at week 12 compared to baseline. Baseline SOCS3 expression did not distinguish EVRs from non-EVRs in genotype 4. An association was found between p53 and MxA and PKR gene expression. CONCLUSION: Measurement of MxA and PKR transcriptional induction during treatment may distinguish EVRs from non-EVRs in genotype 4. SOCS3 gene does not seem to be implicated in therapy resistance in genotype 4. An association between p53 and ISGs expression was shown for the first time in HCV-infected patients, further supporting the contribution of p53 to host antiviral response.

Outcome of living donor liver transplantation for Egyptian patients with hepatitis C (genotype 4)-related cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) recurrence after living donor liver transplantation (LDLT) represents a challenging issue due to universal viral recurrence and invasion into the graft, although the incidence of histological recurrence, risk factors, and survival rates are still controversial. PATIENTS AND METHODS: Recurrence of HCV was studied in 38 of 53 adult patients who underwent LDLT. RESULTS: Recipient and graft survivals were 86.6% at the end of the follow-up which was comparable to literature reports for deceased donor liver transplantation (DDLT). Clinical HCV recurrence was observed in 10/38 patients (26.3%). Four patients developed mild fibrosis with a mean fibrosis score of 0.6 and mean grade of histological activity index (HAI) of 7.1. None of the recipients developed allograft cirrhosis during the mean follow-up period of 16 +/- 8.18 months (range, 4-35 months). Estimated and actual graft volumes were negatively correlated with the incidence and early clinical HCV recurrence. None of the other risk factors were significantly correlated with clinical HCV recurrence: gender, donor and recipient ages, pretransplantation Child-Pugh or model for end-stage liver disease (MELD) scores, pre- and postoperative viremia, immunosuppressive drugs, pulse steroid therapy, and preoperative anti-HBc status. CONCLUSIONS: Postoperative patient and graft survival rates for HCV (genotype 4)-related cirrhosis were more or less comparable to DDLT reported in the literature. Clinical HCV recurrence after LDLT in our study was low. Small graft volume was a significant risk factor for HCV recurrence. A longer follow-up and a larger number of patients are required to clarify these issues.

Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs.

In this study, we evaluated the effect of low level occupational exposure of nurses in a medical oncology unit in Cairo, Egypt, to anticancer drugs. Twenty nurses who constantly handled these drugs and 20 controls, matched according to age and sex, were examined. Metaphase chromosomes were studied. Percentages of metaphases with chromosomal aberrations were significantly higher (P < 0.001) in the exposed group (6.1 +/- 2.7) versus the controls (2.6 +/- 1.6). The detected chromosomal aberrations were in the form of chromatid gaps, chromatid breaks and acentric fragments. Micronucleated peripheral blood lymphocytes were also analyzed in cytochalasin B treated binucleated lymphocytes. There was significant increase in cells with micronuclei (P < 0.001) in nurses (10.05 +/- 4.71) in comparison to the matched control (5.42 +/- 2.22) (P < 0.001). Nurses exposed to the cytotoxic drugs for > or = 48 months showed a slightly higher frequency of cells with chromosomal aberrations as well as micronucleated cells than those exposed for < 48 months, but these differences were not statistically significant (P > 0.05).