Association of the polymorphism of the Toll-like receptor (TLR)-3 and TLR-9 genes with hepatitis C virus-specific cell-mediated immunity outcomes among Egyptian health-care workers.

Variations in the immune response could explain resistance to hepatitis C virus (HCV) infection. Toll-like receptor gene (TLR)-3 is an innate detector of dsRNA viruses, and the TLR-9 gene recognizes bacterial and viral unmethylated cytosine-phosphate-guanosine (CpG) motifs. We previously reported that the TLR-3.rs3775290 CC genotype was associated with HCV chronicity and that the TLR-9 gene played no major role in this infection. This study identified the role of TLR-3.rs3775290 (c.1377C/T), TLR-9.rs5743836 (-1237T→C) and TLR-9.rs352140 (G2848A) gene polymorphisms in predicting the outcome of HCV-specific cell-mediated immunity (CMI) among Egyptian health-care workers (HCWs). We enrolled 265 HCWs in this study and divided them into four groups. Group 1: 140 seronegative-aviraemic HCWs; group 2: 20 seronegative-viraemic HCWs; group 3: 35 subjects with spontaneously resolved HCV infection; and group 4: 70 chronic HCV HCWs (patients). All subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for the TLR-3.rs3775290, TLR-9.rs5743836 and TLR-9.rs352140 single nucleotide polymorphisms (SNPs). We also quantified HCV-specific CMI in the four groups using an interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay in response to nine HCV genotype 4a, overlapping 15mer peptide pools covering the whole viral genome. No statistically significant difference was found between CMI-responding subjects with different HCV states and TLR-3.rs3775290 or TLR-9.rs352140 genotypes. However, there was a significant relationship between the outcome of the HCV-specific CMI and the TLR-9.rs5743836 genotype among the responding subjects (P = 0·005) and the chronic HCV patients (P = 0·044). In conclusion, TLR-9.rs5743836 SNP, but not TLR-3.rs3775290 or TLR-9.rs352140 genotypes, could predict the outcome of HCV-specific CMI responses among Egyptians infected with genotype-4.

Does transcutaneous electrical nerve stimulation have an antipruritic effect in lichen planus? A randomized clinical trial.

BACKGROUND: Lichen planus (LP) is a moderately prevalent inflammatory disorder that affects the skin and the oral mucosa, leading to a characteristic appearance and causing severe itching. AIM: To assess the potency of transcutaneous electrical nerve stimulation (TENS) as an antipruritic line of treatment in patients with LP. METHODS: We enrolled 30 patients with LP who had a history of recurrent relapses of confined pruritus forcing them to scratch or rub the affected area intensively. Patients were treated with TENS three times per week for 4 weeks. Severity of itching was estimated by visual analogue scale (VAS) and Dermatology Life Quality Index (DLQI). RESULTS: There was a statistically significant decline in mean VAS score at weeks 2 and 4 of treatment compared with baseline (P < 0.05, with 74% of participants having an improvement of > 50%. Significant improvement in itching intensity also resulted in better quality of life, as there was also a significant reduction in median DLQI at weeks 2 and 4 of therapy compared with baseline (P < 0.05), with 65% of patients having an improvement of > 50% in median DLQI score. CONCLUSION: TENS may be an alternative safe treatment for LP-induced itching.

Estimating HCV disease burden-volume 4 (editorial).

Hepatitis C virus (HCV) is a major global public health issue, with an estimated 71 million people living with HCV infection and a rising burden of cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality. The advent of interferon-free, direct acting antiviral-based (DAA) therapies, with short duration (8-12 weeks), high efficacy, excellent tolerability and ease of delivery (once daily oral dosing), is one of the major advances in clinical medicine in recent decades, and provides the opportunity to address this growing global HCV burden. In May 2014, January 2015 and December 2015, three supplements were published in the Journal of Viral Hepatitis presenting data from 47 countries on the historical epidemiology of HCV, the current HCV-related morbidity and mortality and potential strategies to manage the HCV disease burden in the future. The countries included in those manuscripts were from multiple regions including North and South America, Europe, Asia, the Middle East, Africa and Oceania. In this supplement, data from an additional 17 countries are presented, following a similar pattern as in the previous manuscripts. These countries represent a mixture of high-, middle- and low-income countries that hail from five geographical regions: Africa, Asia, Europe, Middle East and South America. Expert advisory panels were convened in each country to identify the best data sources to use and to review the assumptions and outputs from the model. In the countries considered in the current analyses, there is a wide variance in the availability of robust data.

Simeprevir plus sofosbuvir for eight or 12 weeks in treatment-naïve and treatment-experienced hepatitis C virus genotype 4 patients with or without cirrhosis.

The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4-infected patients with METAVIR F0-F4 fibrosis. Sixty-three patients (33 treatment-naïve and 30 peg-interferon/ribavirin (Peg-IFN/RBV)-experienced) enrolled in a partly randomized, open-label, multicentre, phase IIa study. Patients with F0-F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82-97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg-IFN/RBV null responders. The most commonly reported treatment-emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4-infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight- and 12-week regimens.

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.

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.

Ravidasvir hydrochloride for genotype 1 hepatitis C treatment.

Effective oral combination regimens have been approved for treatment of hepatitis C virus (HCV) infection and demonstrated high cure rates in different HCV genotypes. These direct-acting agents target a variety of HCV proteins, including HCV-NS5A (nonstructural protein 5A). Ravidasvir hydrochloride, a potent pan-genotypic HCV-NS5A inhibitor approved in Egypt for treatment of HCV genotype 4 (G4), demonstrated impressive efficacy, safety profiles and a high barrier to resistance in multiple clinical trials when used as a key component in combination with other direct-acting agents in treating patients with HCV-G1.

Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real-world results from 18 378 patients in Egypt.

BACKGROUND: Treatment of chronic hepatitis C using combination of sofosbuvir (SOF) and daclatasvir (DCV) was used in several clinical trials and multicentre studies, which were somewhat limited to genotypes 1-3. The national program in Egypt is using SOF-DCV combination for large scale treatment. AIM: To assess the efficacy and safety of combined SOF-DCV in treating patients with HCV-G4 in a real-world setting. METHODS: Data and outcome of chronic HCV patients who were treated for 12 weeks with generic medications: DCV 60 mg plus SOF 400 mg ± ribavirin (RBV) within the national hepatitis C treatment program in Egypt are presented. Treatment-naïve patients without cirrhosis were treated without RBV, and those who had cirrhosis or were treatment-experienced (interferon experienced or SOF experienced) received RBV. Efficacy and safety were assessed, and baseline factors associated with sustained virological response at post-treatment week 12 (SVR12) were explored. RESULTS: During the first 2 months of the programme, 18 378 patients with HCV-G4 started treatment with SOF-DCV with or without RBV. Overall, 95.1% achieved SVR12 (95.4% among patients treated without RBV and 94.7% for patients treated with RBV, P = .32). Treatment was prematurely discontinued in only 1.5% of patients. The most common events leading to discontinuation were patient withdrawal (n = 76) and pregnancy (n = 5). Five deaths occurred within this group. CONCLUSIONS: Real-world experience of generic SOF-DCV in patients with chronic HCV-G4 proved to be safe and associated with a high SVR12 rate, in patients with different stages of fibrosis.

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.

Economic burden of hepatitis C in Egypt: the future impact of highly effective therapies.

BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in Egypt is the highest in the world, yet the total economic burden has not been quantified. Improved understanding of costs and the impact of treatment strategies will provide for better allocation of resources to reduce HCV disease and economic burden. AIM: A modelling approach was used to quantify the current HCV-infected population, future disease progression and associated costs in Egypt. METHODS: Direct healthcare costs were calculated from a nationally representative hospital and a disability adjusted life year (DALY) template was used with monetary value assigned to lost life years. Three scenarios were considered: (i) Historical treatment scenario: 50% SVR; 65,000 treated annually, (ii) Current treatment scenario: 90% sustained virologic response (SVR); 65,000 treated annually, (iii) Increased treatment scenario: 90% SVR; 325,000 treated annually by 2018. RESULTS: Cumulative DALYs (2015-2030) under Scenario 1 were estimated at 7.88 million and cumulative costs estimated at $89.07 billion. Annual DALYs increased 16% during 2015-2030 while annual costs more than doubled. Scenario 2 reduced cumulative DALYs and costs by 7% and 4%, respectively. Under Scenario 3, total costs declined 73% to $1047 million during 2015-2030. As compared to Scenario 1, cumulative DALYs and costs decreased 37% and 35%, respectively. CONCLUSIONS: This is the first estimate of the total economic burden of HCV in Egypt. Extraordinary measures are necessary to substantially reduce HCV disease and cost burden. With newer therapies, strategies to reduce disease burden are feasible and cost-effective.

Analysis of long-term endoscopic surveillance during follow-up after variceal sclerotherapy from a 13-year experience.

PURPOSE: To evaluate the course of patients with bleeding esophageal varices treated with endoscopic sclerotherapy after obliterating varices and to determine the cost benefits of long-term endoscopic surveillance from a retrospective analysis of a 13-year experience. LOCATION: University-affiliated teaching hospital and county facility. METHODS: Patients whose varices were obliterated by endoscopic sclerotherapy were considered for the study if they had a minimum of 12 months of follow-up. Sclerotherapy was initially performed weekly, increasing intervals to eventual yearly treatments. Varices were reobliterated if they reformed. Variables assessed were rebleeding, mortality, employment status, and cost based on allowable and reimbursed Medicare rates. RESULTS: Of 324 patients who achieved variceal obliteration, analysis included 104 eligible patients who were followed up for > 12 months (41 +/- 28). Varices reformed in 73 patients (71%), mostly in the first year after obliteration or reobliteration. Abstinent alcoholic patients were least likely to reform varices. Nineteen patients (18%) had 23 rebleeding episodes, and in 10 patients (10%) portalsystemic shunt was placed. Survival was 84% and bleeding-related mortality was 6%. Significantly more patients were employed while on the program compared with entry. The yearly cost of treating variceal reformers ($2,117) was significantly higher than variceal nonreformers ($1,735), but the overall cost of maintaining a patient on a chronic sclerotherapy program was relatively small. CONCLUSIONS: The low rebleeding, low mortality, and relatively low cost in patients managed long term by chronic sclerotherapy underscores the benefits of this treatment program.

Experience with interferon in chronic hepatitis B in Egypt.

Forty patients with compensated chronic active hepatitis B and elevated aminotransferases who were HBsAg and HBeAg positive were randomised to a treatment group receiving recombinant interferon alpha-2b (rIFN alpha-2b) or no treatment as a control group. The treated patients were divided into 2 groups, group I (n = 12) received IFN in a dose of 5 MU/m2 thrice weekly by subcutaneous injection for 16 weeks, and group II (n = 8) received the same dose daily for the same duration. Patients were followed up for 12 months after therapy ended. Initiation of IFN therapy was associated with an increase in aminotransferases, reaching a peak at 4-6 weeks in most patients, associated with clearance of HBeAg. At end of follow-up, 81% of the treated patients had cleared HBeAg vs 33% of the control group (p less than 0.01). Changes in other HBV markers were more frequent in the treated patients, though insignificantly. The type of response to therapy was significantly related to the duration of illness, being shortest in those who cleared HBsAg. A complete response to therapy with loss of HBsAg was associated with marked reduction in biochemical and histological activity. A partial response with clearance of HBeAg was associated with moderate improvement in biochemical parameters and ongoing activity in liver histology; whereas persistence of HBeAg was associated with elevated aminotransferases and histological deterioration in most cases. The rise in aminotransferases during seroconversion was associated with hepatic decompensation and death on 3 occasions: one during spontaneous seroconversion, and the other 2 during IFN therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin (IL)-4, IL-10, IL-18 and IFN-gamma cytokines pattern in patients with combined hepatitis C virus and Schistosoma mansoni infections.

Schistosoma mansoni infection is characterized by a strong T-helper type 2 (Th2) cell-associated immune response, but in the case of viral infection, it is associated with interferon-gamma (IFN-gamma) increase and induction of Th1 immune response. Few data are available about the immune response of cases infected with combined hepatitis C virus (HCV) and schistosomiasis. Thus, the investigation of the cytokine pattern in patients coinfected with both HCV and Schistosoma mansoni was our rationale. This study included four patient groups: Group 1 included 20 patients infected with chronic HCV, Group 2 included 15 patients infected with schistosomiasis alone, Group 3 included 20 patients with chronic HCV and schistosomiasis and Group 4 included 15 healthy control individuals with matched age and sex. Serum levels of IFN-gamma, interleukin (IL)-4, IL-10 and IL-18 were measured in all groups by enzyme-linked immunosorbent assay. The results showed that the patients infected with HCV had significantly higher serum levels of IFN-gamma and IL-18 compared with the controls and with the patients with schistosomiasis and coinfection (P < 0.001). On the other hand, serum levels of IL-4 and IL-10 were significantly higher in patients with schistosomiasis and coinfection compared with the control group (P < 0.001 and 0.0001, respectively) and with the HCV patients (P < 0.05 and P < 0.001, respectively). A significant increase in serum levels of IL-4 and IL-10 was also found in HCV patients compared with the control (P < 0.05). Schistosomiasis appears to induce a Th2 cytokine profile, with increase in serum levels of IL-4 and IL-10, even in the presence of HCV coinfection. In conclusion, schistosomiasis may downregulate the stimulatory effect of HCV on Th1 cytokines and this may lead to the chronicity of HCV infection in coinfected patients.

Interferon in chronic active hepatitis B. Preliminary results.

Twenty patients with documented chronic active hepatitis B were randomized in equal numbers to either an alpha-2b interferon treatment group or a control group with no treatment. Patients in the first group received 5 IU interferon three times weekly by subcutaneous injection for 16 weeks. All 20 patients were HBeAg positive at the beginning. All 10 patients in the interferon-treated group lost their initial e antigen while only 2 patients in the control group turned HBeAg negative. Six patients in the treated group acquired HBe antibodies in comparison with two patients only in the untreated group. Other markers of suppression of viral replication as well as a 24-month follow-up are ongoing at the moment for final assessment of the value of interferon therapy in chronic active hepatitis B.

Biliary complications of Fasciola hepatica: the role of endoscopic retrograde cholangiography in management.

The parasite Fasciola hepatica resides in the biliary tree but rarely causes significant clinical sequelae. In this report, we review our experience with four patients in whom F. hepatica infection resulted in biliary complications, especially severe biliary colic and jaundice. The diagnosis was achieved with endoscopic retrograde cholangiography which demonstrated the worms in the extrahepatic bile ducts. Endoscopic sphincterotomy was performed uneventfully in all patients allowing balloon extraction of the parasites and resolution of their symptoms.

High prevalence of hepatitis C in Egyptian patients with chronic liver disease.

The highest prevalence rates of hepatitis C virus infection in the world have been recently reported among Egyptian blood donors and frequent recipients of transfusions and other blood products. This is the first report, however, demonstrating hepatitis C as the most frequent association with chronic liver disease in Egypt. Of 1023 patients referred to the Liver Institute in Menoufia governorate for evaluation of chronic liver disease, 752 (73.5%) had antibodies to hepatitis C compared with 168 (16.4%) with hepatitis B surface antigen. Hepatitis C antibody was more common in patients with active schistosomiasis and patients without hepatitis B surface antigenaemia. Of 100 patients having liver biopsies, histological findings consistent with chronic viral hepatitis or its complications were found in 89 and antibody to hepatitis C was present in 75 (84.3%) of these patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma. These data pointing to the importance of hepatitis C as a cause of chronic liver disease in Egypt emphasise the necessity of studies delineating its routes of transmission in this country.