Human parainfluenza virus type 3 (HPIV-3) can cause severe respiratory diseases, particularly in young children, the elderly and immunocompromised. There are no approved antiviral drugs against this virus. We report that the combination of ribavirin with either remdesivir or its parent nucleoside GS-441524 results in a pronounced antiviral effect against HPIV-3 in LLC-MK2 cells and in human airway epithelial cells grown at the air-liquid interface. In AG129 mice intranasally inoculated with HPIV-3, the combined treatment with ribavirin and GS-441524 decreased infectious viral lung titers by >2.5 log10 to undetectable levels in 4 out of 11 mice and by 1.6 log10 in the remaining 7 mice as compared with the vehicle. The lungs of all mice that received the combined treatment appeared histologically normal or virtually normal, whereas 8 of 11 vehicle-treated mice presented with bronchopneumonia. By contrast, ribavirin alone did not result in a reduction in infectious viral lung titers; GS-441524 alone reduced infectious viral lung titers by 1.2 log10. Moreover, several mice in the single-treatment groups exhibited severe lung pathology. These findings may warrant exploring this combination in patients with severe HPIV-3 infections and possibly also against infections with other viruses that are susceptible in vitro to these two drugs.

Egypt has the highest global prevalence of Hepatitis C Virus (HCV) infection, particularly of genotype 4. The development of a prophylactic vaccine remains crucial for HCV eradication, yet no such vaccine currently exists due to the vaccine development challenges. The ability of Virus-Like Particles (VLPs) to mimic the native virus and incorporate neutralizing and conformational epitopes, while effectively engaging both humoral and cellular immune responses, makes them a promising approach to addressing the challenges in HCV vaccine development.

Lentiviral-based vectors were constructed and employed to integrate the full-length sequence of Core, E1, E2, and P7 genes of HCV genotype 4 into the genome of Human Embryonic Kidney cells (HEK293T). Upon the expression, HCV structural proteins can oligomerize and self-assemble into VLPs mimicking the structure of HCV native virus. VLPs were purified and characterized for the development of a potential VLPs-based vaccine.

In this study, mammalian cells were successfully engineered to stably express HCV structural proteins and generate non-infectious VLPs for HCV genotype 4. The expression of HCV-integrated genes resulted in a successful production of HCV structural proteins, which oligomerized and self-assembled into two layers enveloped VLPs. Electron microscopy analysis of purified VLPs revealed spherical particles with an average diameter of 60-65 nm, closely resembling mature HCV virions. These results highlighted the potential of these VLPs as a vaccine candidate for HCV genotype 4.

HCV genotype 4 remains an underexplored target in vaccine development, despite its significant public health burden, especially in Egypt. The successful generation of VLPs for this genotype represents a promising avenue for further vaccine development. The established system provides a robust platform for the production and study of VLP-based vaccines targeting HCV genotype 4.

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. The development of prophylactic vaccine is essential for HCV global eradication. Despite over three decades of research, no effective vaccine for HCV has been developed, primarily due to the virus's genetic diversity, immune evasion mechanisms, and incomplete understanding of protective immunity. However, Virus-Like Particles (VLPs) offer a promising approach to overcoming these challenges. VLPs mimic the structure of native virus but without the infectious genome, making them safe and non-infectious vaccines candidates. The capability of VLPs to incorporate neutralizing and conformational epitopes, and engage humoral and cellular immune responses, positions them as a promising tool for overcoming challenges associated with the HCV vaccine development. This review examines the challenges and immunological considerations for HCV vaccine development and provides an overview of the VLPs-based vaccines development. It also discusses future directions and public health implications of HCV vaccine development.

Although E. coli is generally a well-opted platform for the overproduction of recombinant antigens as heterologous proteins, the optimization of expression conditions to maximize the yield of functional proteins remains empirical. Herein, we developed an optimized E. coli (BL21)-based system for the overproduction of soluble immunoreactive HCV core/envelope proteins that were utilized to establish a novel immunoassay for discrimination of active HCV infection.

The core/E1-E2 genes were amplified and expressed in E. coli BL21 (DE3) in the absence/presence of glycylglycine. The antigenic performance of soluble proteins was assessed against 63 HCV-seronegative (Ab-) sera that included normal and interferent sera (HBV and/or chronic renal failure), and 383 HCV-seropositive (Ab+) samples that included viremic (chronic/relapsers) and recovered patients' sera. The color intensity (OD450) and S/Co values were estimated.

The integration of 0.1-0.4M glycylglycine in the growth media significantly enhanced the solubility/yield of recombinant core and envelope proteins by ~ 225 and 242 fold, respectively. This was reflected in their immunoreactivity and antigenic performance in the developed immunoassay, where the soluble core/E1/E2 antigen mixture showed 100% accuracy in identifying HCV viremic sera with a viral RNA load as low as 3800 IU/mL, without cross-reactivity against normal/interferent HCV-Ab-sera. The ideal S/Co threshold predicting active viremia (> 2.75) showed an AUC value of 0.9362 (95% CI: 0.9132 to 0.9593), with 87.64, 91.23% sensitivity and specificity, and 94.14, 82.11% positive and negative predictive values, respectively. The different panels of samples assayed with our EIA showed a good concordance with the viral loads and also significant correlations with the golden standards of HCV diagnosis in viremic patients. The performance of the EIA was not affected by the immunocompromised conditions or HBV co-infection.

The applicability of the proposed platform would extend beyond the reported approach, where glycylglycine, low inducer concentration and post-induction temperature, combined with the moderately-strong constitutive promoter enables the stable production of soluble/active proteins, even those with reported toxicity. Also, the newly developed immunoassay provides a cost-effective point-of-care diagnostic tool for active HCV viremia that could be useful in resource-limited settings.

Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.

Despite the high sustained virologic response (SVR) rates of direct-acting antiviral (DAAs) therapy, a small number of patients does not eradicate the virus, and these patients represent a challenge. This study aims to compare the outcomes of three second-line regimens for DAAs-experienced patients with chronic hepatitis C (CHC). This prospective observational study was conducted at the Damanhur Viral Hepatitis Center from January 2017 to February 2020. We included patients with CHC who did not achieve SVR after the complete course of Sofosbuvir/Daclatasvir±Ribavirin (SOF/DAC±RBV). The primary endpoint was SVR-12 after re-treatment. This study included 360 patients (with a mean age of 51.53±11.38 years). Approximately 51.1% of the patients were males, and 65.5% had liver cirrhosis. All patients of group 1 (45 patients) received SOF/VEL/VOX over 12-weeks; SVR-12 was achieved in 44 patients (97.8%). Group 2 (28 patients) received SOF/DAC/RBV over 24-weeks; (one patient was lost during follow-ups and one patient discontinued treatment due to hepatic decompensation). SVR-12 was achieved in 25 patients (96.2%). Group 3 (287 patients) received SOF/Ombitasvir/Paritaprevir/Ritonavir/RBV) over 12-weeks. Eight patients were lost during follow-ups, and one patient discontinued treatment due to grade 4 adverse events. SVR-12 was achieved in 276 patients (99.3%). There was no difference between the groups regarding their age, gender distribution, baseline viral load or comorbidities. Adverse events (thrombocytopenia, anemia, hyperbilirubinaemia and prolonged INR) were significantly higher in group 3, while group 1 did not experience any. The three studied retreatment regimens can be used for DAAs treatment-experienced patients considering availability. The SOF/VEL/VOX combination had the least adverse events.

Simeprevir and sofosbuvir are direct-acting antiviral drugs approved for the treatment of chronic HCV infection. Reports demonstrate the similarities between HCV and SARS-CoV-2 in terms of structure and replication mechanism. Therefore, it is suggested that a combination of simeprevir and sofosbuvir may be considered for COVID-19 patients. To date, no spectrophotometric methods have been published for quantitative analysis of simeprevir and sofosbuvir in combination. In this work, two simple spectrophotometric methods allowed quantitative analysis of the studied drugs in the mixed form. The zero-order direct method allowed quantitative analysis of simeprevir at 333 nm, with sofosbuvir showing zero absorbance values. The dual wavelength method allowed quantitative analysis of sofosbuvir by measuring the difference in absorbance values at 259.40 and 276 nm, where the difference in absorbance values of simeprevir was zero. With the applied methods, the investigated drugs in the mixtures and tablets prepared in the laboratory were successfully analyzed quantitatively with acceptable results.

Efforts toward eradicating the Hepatitis C virus (HCV) have advanced rapidly, due to the development of direct-acting antivirals (DAAs), especially with the appearance of pan-genotypic combinations. Real-world studies, in particular, have verified the efficacy and safety of DAA combinations documented in registration trials. This review documents the results of using DAA combinations in real-life settings in everyday clinical practice in Egypt, the country with the highest prevalence of HCV. The significant number of treated patients in Egypt, which exceeded four million allowed tremendous data about the results of HCV management in real-life settings for different treatment regimens and disease conditions. DAA combinations have resulted in high sustained virologic response rates (SVR12) and few adverse reactions in real-life settings. SVR12 rates ranged from 90% to 100%, depending on the combination of drugs used, the HCV genotype, and the stage of liver disease. Most adverse reactions reported in real-world settings were mild and resulted in treatment discontinuation in only a minority of cases. Data from real-life studies covered most aspects of HCV management that were lacking after initial approval studies. More research is needed to tailor treatment and produce generic HCV combinations to overcome the residual limitations of the currently available DAAs.

Virus C infection is recently treated successfully with plenty of direct antiviral agents (DAAs). We aimed to evaluate the effect of disease stage and treatment outcome on the dynamics of liver functions during treatment of hepatitis C with DAAs.

We reported the liver function in 2354 subjects diagnosed as chronic hepatitis C before, during and after treatment with different DAAs regimens. Patients were classified into two groups according to treatment response with further subclassification according to the presence or absence of cirrhosis, and changes in liver functions were compared in each group and subgroup.

Totally 2213 (94%) achieved sustained virological response (SVR) to DAAs therapy with significant improvement in all liver biochemistry. Also, there was an improvement in the non-SVR group's liver enzymes in relapsers during and after treatment; however, there was no improvement in serum albumin. We noticed a slight increase in serum bilirubin at weeks 4 and 8 for both groups.

DAAs therapy is associated with improvement of the liver biochemical profile and improved outcome in the majority of chronic hepatitis C virus patients due to suppression of viral replication. However, the long-term impact of DAAs therapy needs to be further evaluated.

This study investigates different barriers preventing a cohort of Egyptian HIV/HCV coinfected patients from accessing HCV treatment, despite being available and free of charge, aiming to improve the long-term outcomes of coinfected patients and decreasing their liver-related morbidity and mortality.

This study included HIV patients who were referred to Kasr Alainy Viral Hepatitis Center to receive HCV treatment and who had to continue pretreatment assessment in order to receive direct acting antiviral agents free of charge. Patients who did not attend within 90 d were questioned via a telephone interview. Questions addressed sociodemographic status, HIV status and the main barriers to accessing healthcare.

Overall, 474 HIV/HCV coinfected patients were eligible for HCV treatment and 223 (47.1%) patients did not complete work-up for HCV treatment. Fear of community stigma concerning HIV/HCV was the most important barrier to compliance with treatment (73.3%), followed by lack of a supportive work environment and employment opportunities (51.5%), whereas 39.3% stopped follow-up due to the lack of integrated services in the healthcare facility.

Managing HCV in HCV/HIV coinfected patients still represents a major challenge, not only for healthcare providers, but also at a community level, to improve community awareness and manage the major obstacle facing those patients regarding community stigma.

The impact on male and female sexual dysfunction of treating hepatitis C virus (HCV) using direct-acting antiviral agents (DAAs) has not been sufficiently studied. The aim of this study was to assess the impact of HCV clearance with DAAs on sexual dysfunction (SD) in both sexes.

In chronic HCV patients who were eligible for DAAs, 100 sexually active men completed the Arabic version of the international index of erectile function questionnaire (IIEF-5), and the same number of sexually active women completed Female Sexual Function Index (FSFI), before, at the end of, and 3 months after, treatment for HCV.

The mean of the IIEF-5 scores for male patients was 16.29 ±.07 before treatment, 16.88 ± 3.63 3 months after treatment (p < .01), and was significantly higher, at 19.06 ± 3.31 6 months after treatment cessation (p < .01). In female patients, the mean total FSFI score at baseline was 19.22 ± 2.40 and after 3 months of treatment was 21.61 ± 3.45 (p < .01), with a significant increase (25.09 ± 4.52) after 6 months (p < .01). No difference in the improvement of sexual function was reported either after 3 months or at the end of treatment between males and females (p > .05).

Significant improvement in SD associated with HCV infection in both sexes was recorded following viral clearance using DAAs treatment.

Elimination of hepatitis C virus (HCV) may fail, leading to a non-response outcome because of inappropriate testing for viral RNA in peripheral blood mononuclear cells (PBMCs). Sequelae of HCV genotype 4 therapy with sofosbuvir and daclatasvir ± ribavirin were assessed in our study at the 12th week after end of treatment (EOT) by screening for viral genomic RNA in serum and PBMCs with correlation to hepatic parenchymal changes. We recruited 102 out of 2165 patients who had received sofosbuvir/daclatasvir, either alone (n = 1573) or together with ribavirin (n = 592). Subjects were classified into three groups based on testing by single-step reverse transcription PCR: group I, HCV negative in both serum and PBMCs (n = 25); group II, HCV positive in PBMCs only (n = 52); and group III, HCV positive in both serum and PBMCs (n = 25). Groups I and II (n = 77) were selected out of 2102 (every 27th subject), while group III (n = 25) were selected from every second or third serologic relapse (n = 63). The pre-sampling population (n = 2165) showed sustained virologic response (SVR) in 33.21%; serologic relapse in 2.91%; HCV RNA only in PBMCs (66.79%) compared to serologic relapses and potential cure (P < 0.0001); higher serologic (38 out of 63, P = 0.03210) and cellular (36 out of 52, P = 0.0002) relapses in dual therapy than in triple therapy. The post-sampling population (n = 102) showed more HCV relapses in dual (50 out of 60) than in triple (27 out of 42) therapy (P = 0.0351); increased HCV antisense RNA strand in relapses compared to positive-sense strands alone (P < 0.001); and significant SVR events in undetectable (15 out of 31) compared to early (10 out of 55, P = 0.0058) and cirrhotic liver tissue changes (0 out of 16, P = 0.0006). In summary, HCV treatment with sofosbuvir/daclatasvir is followed by higher rates of serologic and intracellular viral RNA relapse than treatment with sofosbuvir/daclatasvir plus ribavirin. Cellular and serum viral RNA relapses are accompanied by HCV-induced hepatic pathology. An increased SVR with no detectable liver tissue changes was observed after triple therapy due to elimination of HCV RNA from PBMCs.

Direct-acting antiviral (DAAs) therapy showed high safety and efficacy profile in patients with chronic hepatitis C (CHC) particularly those with previous or current psychiatric illness. The aim of this study was to evaluate the incidence and potential risk factors of depression and psychological distress following DAAs therapy in CHC euthymic Egyptian patients with no previous or current diagnosis of any psychiatric disorders.

This is a prospective study that included 126 patients diagnosed with chronic hepatitis C virus genotype-4. Patients were candidate for DAAs therapy and were recruited consecutively (convenient sample) from the viral hepatitis center, Department of Endemic medicine, Kasr Al-Ainy Hospitals, Cairo University. Symptom Checklist 90-R, Beck Depression Inventory (BDI) and Structured Clinical Interview for DSM-IV (SCID IV) were performed at baseline and at 12 weeks post-treatment with DAAs.

Forty-seven patients were included in the final analysis. Depression severity increased after treatment as BDI scores increased significantly than baseline scores (p= < 0.001). About one third of patients (32%) had moderate to severe depression. All Symptom Checklist-90 scores showed significant increase after treatment.

Dropout rate of patients for the 12 weeks post-treatment assessment was 33.8%.

Depression and psychological distress can occur with DAAs treatments. Close psychosocial assessment and patient monitoring are still needed.

The new anti-hepatitis C virus (HCV) molecules improve treatment regimens and outcomes, but there are drawbacks. New combinations should target the HCV infectious cycle and be effective against all HCV genotypes. We developed the novel formulation Catvira, composed of epigallocatechingallate (EGCG) + sofosbuvir + ribavirin. Here, we compared Catvira to sofosbuvir + ribavirin tablets in patients with CHC genotype 4 in a randomized open-label efficacy and safety study. Treatment-naïve and treatment-experienced patients (n = 80) were randomly assigned to receive a single daily fixed dose of Catvira or sofosbuvir + ribavirin for 12 or 24 weeks. Both Catvira and sofosbuvir + ribavirin yielded similar outcomes of viral load (p < 0.001). Patients receiving Catvira had a significantly more rapid rate of viral load decline with sustained virologic response (SVR12) achieved by 90% of patients receiving 12 weeks of treatment. Catvira did not impact hemoglobin levels while sofosbuvir + ribavirin showed significant decline in hemoglobin levels after 24 weeks (p < 0.05). In this clinical trial (ClinicalTrials.gov Identifier NCT02483156), we found that Catvira administered daily for 12 or 24 weeks is safe, effective, and well-tolerated in both naïve and treatment-experienced patients with HCV genotype 4.

Hepatitis C virus (HCV) is a disease with a significant global impact, affecting approximately 2%-2.5% of the world's population. New direct-acting antivirals (DAAs) have been introduced over the past few years with great success in viral eradication. The association of chronic HCV infection with a wide spectrum of cutaneous manifestations has been widely reported in the literature.

To assess the effect of treating HCV with DAAs on the extrahepatic cutaneous manifestations of HCV.

This prospective observational study included 1039 HCV positive Egyptian patients who were eligible to receive DAAs. A total of 30 patients were diagnosed with extrahepatic cutaneous manifestations and fulfilled the inclusion criteria of the study. Of these patients, 6 had classic lichen planus, 8 were diagnosed with psoriasis vulgaris and 16 had pruritus. All patients received DAAs from October 2018 to July 2019 in the form of a three-month course of sofosbuvir/daclatasvir combination. Patients with lichen planus or psoriasis were dermoscopically evaluated before treatment and 6 mo after treatment, while patients with hepatic pruritus were assessed using the 12-Item Pruritus Severity Scale over the same period.

All patients with psoriasis showed significant improvement in all psoriatic plaques, and all patients with hepatic pruritus scored 0 on the 12-Item Pruritus Severity Scale indicating total improvement of pruritus. In addition, four of six patients with lichen planus showed complete improvement.

Treatment of HCV with DAAs was significantly effective in improving virus-related extrahepatic cutaneous manifestations.

Chronic infection with Hepatitis C virus (HCV) is considered as a major cause for developing liver cirrhosis and hepatocellular carcinoma. A new era in HCV treatment is ongoing using Direct Acting Antiviral activity (DAA). The first approved DAA drug was Sofosbuvir which has a high tolerability and preferable pharmacokinetic profile. Another recently developed drug is Daclatasvir a first-in-class HCV NS5A replication complex inhibitor. Both drugs are administered orally once daily and have potent antiviral activity with wide genotypic coverage.

In the outpatient clinic, one hundred and fifty naïve difficult to treat chronic HCV patients were recruited from Tropical Medicine Department at Fayoum public hospital. A combination of Daclatasvir (60 mg) and Sofosbuvir (400 mg) (DCV/SOF) has been administered for those patients once daily with Ribavirin (1200 mg or 1000 mg based on patients' weight on two divided doses) over a period of 12 weeks. All patients have been followed up for clinical, laboratory assessment and HCV PCR to detect the efficacy and safety of the therapy.

Sustained Virologic Response rate (SVR12) was achieved in the vast majority of patients (90.67%). Cirrhotic patients showed lower SVR compared to non-cirrhotic patients (88.89% vs 90.91%, respectively). Around half of the patients (49.33%) developed adverse events (AEs) during treatment. The most common AEs were headache, fatigue and abdominal pain.

The available evidence seems to suggest that combination therapy of (DCV/SOF with RBV) in the treatment of chronic HCV genotype IV naïve difficult to treat patients either cirrhotic or non-cirrhotic is safe and effective. Monitoring for clinical and laboratory hepatic parameters was the basis for these findings.

The national committee for control of viral hepatitis (NCCVH) in Egypt, settled by the Ministry of health, treated over one million patients in around 60 centers with chronological changes in drug combinations. This research aims to study the health care facilities and services provided by NCCVH treatment centers in Egypt and explore hinders faced.

A cross-sectional operational research study. Multistage random sampling technique was applied for Egyptian governorates. From each stratum one governorate was chosen from which one center was randomly selected. Quality of recorded data for each center in the central server (Data-oriented parameter), newly designed score to assess the overall performance of the centers was retrieved from computer based recording system. A self-administered questionnaire was completed by the centers head.

This study included 24 treatment centers from urban, rural areas, Upper and Lower Egypt. The Upper centers showed the best completeness of follow-up records and the least compliance rates. None of the centers had 100% completeness of follow-up data. Proportion of SVR is minimally less than proportion of patient with known outcome in all treatment centers. A novel indicator standardizing the comparisons of performance of different facilities was introduced: Total number of physicians/total number of SVR patients with completed records. The highest response rate: Monfiya Governorate (Lower Egypt), Aswan (Upper Egypt), Completeness of follow-up records: Kalyoubia (Lower Egypt), Sohag governorate (Upper Egypt). The average administrative score was 64%.

Challenges of NCCVH program: overcrowdings, resistant sociocultural background among rural patients, limited accessibility for internal migrants and incompleteness of data entry are system lacking points. Strengths include, clear patient pathway, well-established database online application, well-trained physicians and treatment availability.

The introduction of direct acting antivirals (DAAs) has resulted in very high sustained virological response rates (SVR) in patients with chronic hepatitis-C (CHC). There are still a minority who fails to achieve SVR. This study aims to identify simple factors associated with nonresponse to DAAs using routine pretreatment workup.

A retrospective study included 10 655 CHC patients who were candidates for anti-viral therapy. Pretreatment demographics, laboratory results, ultrasonography and FIB-4were obtained.

At post-treatment week 4, 10 495 patients (98.5%) were responders and 160 (1.5%) were non-responders. About 50.6% of non-responders were males and 61.3% were cirrhotic. Non-responders had significantly higher baseline BMI, liver enzymes, AFP and a significantly lower albumin, platelet count by univariate analysis ((P < 0.001). Sex, previous treatment, BMI, liver cirrhosis, AST, Albumin and platelet counts were the independent predictors of non-response. At post-treatment week 12, HCV-PCR results were available only for 7259 patients and 210 (2.9%) were non-responders. 54.8% of non-responders were cirrhotic and 51.4% were males. Non-responders had significantly higher AST, AFP and INR and a significantly lower albumin level, platelet count by univariate analysis (P < 0.05). Sex, previous treatment, AST, Albumin, WBC and platelet counts were the independent predictors of non-response. SVR-4 among treatment naive patients was 98.6% while among treatment experienced was 96.8%. SVR-12 among treatment naive patients was 97.9% while among treatment experienced was 87.9%.Cirrhotics had SVR-4 rate 97.7% and SVR-12 rate 96.21%.

Routine pre-treatment work up for HCV G4 patients receiving DAAs can help in prediction of non-response.

Egypt succeeded in establishing a successful model of care for hepatitis C virus (HCV) management in the country with the highest worldwide disease prevalence. The Egyptian ministry of health announced an optimistic goal of near disease elimination. More steps are still required to achieve such a goal.

This review covers the efforts made in treatment and prevention of HCV by the Egyptian National Committee for the Control of Viral Hepatitis (NCCVH) with emphasis on the extensive screening program that was able to screen more than 57 million citizens, and future strategies implemented to ensure eradicating the virus from the country.

Despite the great efforts and the proven success in controlling the HCV epidemic in Egypt, some facets of the Egyptian program still need to be upgraded to reach the HCV elimination goal. A significant workload with follow up programs for those who were successfully treated, and treatment failure cases are existing. More enhancement for the currently performed prevention and control measure is missing. Also, we strongly recommend conducting a recent nationwide survey to document the actual infection rates of HCV after all these efforts.

This study aimed to assess the safety and efficacy of sofosbuvir (SOF)-based regimens in patients with moderate to severe renal impairment; a subject which has been questioned by many investigators with conflicting results.

This is a real-life multicentre retrospective cohort study on 4944 chronic Hepatitis C virus (HCV) patients with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m² ) who received SOF-based therapy in specialized treatment centres affiliated to the National Committee for the Control of Viral Hepatitis in Egypt. The efficacy and safety of SOF-based regimens was assessed.

Week 12 virological response rates were 97.5%, 96.7%, 85.7% and 80% in the total cohort, patients with eGFR <30 mL/min/1.73 m² , patients with associated hepatic decompensation and patients on dialysis respectively. Various treatment regimens did not statistically affect the response rates. Treatment experience, cirrhosis and diabetes were predictors of treatment failure on multivariate analysis. Serious adverse events occurred in 0.1% of cases. Forty patients (0.8%) discontinued treatment.

Sofosbuvir-based regimens are effective and safe for treating patients with chronic HCV and moderate to severe CKD, and in those with associated hepatic decompensation.

Nonstructural protein 5A (NS5A) is an important regimen for the treatment of chronic hepatitis C virus (HCV) genotype-4 infected patients. Retreatments for NS5A virologic failure are limited. The aim of this study is to provide real-life data regarding the effectiveness and safety of retreatment with different regimens after NS5A regimen virologic failure in GT4 patients.

A total of 524 HCV patients (mean age 48 ± 11 years, 71% males), with virologic failure to sofosbuvir+daclatasvir, n = 450 and sofosbuvir/ledipasvir, n = 74 were included in this study. Patients were retreated with sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin, n = 278 and sofosbuvir + simeprevir + daclatasvir + ribavirin, n = 246. Response was evaluated 12 weeks after the end of treatment (SVR12).

Overall, SVR12 was 95.2% [95% confidence interval (CI) 93.3%-97.1%]. In sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir + simeprevir + daclatasvir + ribavirin, SVR12s were 94.9% (95% CI 92.5%-97.4%) and 95.5% (95% CI 92.8%-98%), respectively. In liver cirrhosis patients, SVR12s were 96.4% (95% CI 90.7%-100%) and 98% (95% CI 94.9%-100%), respectively. Relapse in the sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin was n = 14 patients, and n = 11 patients in sofosbuvir + simeprevir + daclatasvir + ribavirin. Three patients developed hepatic encephalopathy, haematemesis, lower limb oedema, and one patient died in the SOF + OBV/PTV/RTV + RIB. In the sofosbuvir + simeprevir + daclatasvir + ribavirin, three patients developed hepatocellular carcinoma and one patient died. No treatment discontinuation due to anaemia.

Salvage treatment for NS5A-treatment failure is effective and well tolerated in genotype-4 patients, in both noncirrhotic and compensated cirrhotic groups.

Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal timing of DAA therapy remains unclear. Data on efficacy of DAA therapy in patients with HCC would inform this decision-making.

To evaluate response to DAA therapy among patients diagnosed with HCV infection and HCC.

Bibliographic databases and conference abstracts were searched. Meta-analysis was conducted to pool sustained virologic response (SVR) estimates.

Fifty-six studies with 5522 patients with HCV and HCC were included. Overall SVR was 88.3% (95% CI 86.1-90.4). Twenty-seven studies included patients with prior or present HCC (n = 3126) and patients without HCC (n = 49 138), in which SVR was 88.2% (95% CI 85.0-91.4) and 92.4% (95% CI 91.1-93.7) among patients with and without HCC, respectively (odds ratio: 0.54, 95% CI 0.43-0.68, P < .001). In the subgroup analyses, higher SVR was seen in patients who received curative HCC management (SVR 90.4%, 95% CI 88.3-92.4), or treated with sofosbuvir + NS5A inhibitor DAAs (SVR 96.9%, 95% CI 94.3-99.4), or in patients with HCV genotype 1 infection (SVR 92.0%, 95% CI 88.1-95.6).

Response to DAA therapy was lower in patients with HCC compared to those without HCC, regardless of cirrhosis status. Among HCC patients, there was an impact of proportion with curative HCC management on DAA therapy response.

The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC.

PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models.

We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66).

Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates.

There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.

The population of Asia exceeds 4.4 billion people. Chronic hepatitis C virus (HCV) infection in Asia is characterized by specific distribution of genotypes, lack of access to specific therapeutic agents, relatively high cost of treatment, and lack of experienced healthcare providers. Clear consensus on the diagnosis, management, and monitoring of HCV infection specific to the Asian region is a major unmet need. The consensus guidelines documents that have been published to date by major medical societies presume access to an array of direct acting antiviral agents and diagnostic tests that are not broadly applicable to resource limited settings, including Asia.

To address the lack of an Asia-specific set of HCV treatment guidelines, we assembled a panel of 15 HCV experts in the field of hepatology from India, Indonesia, Myanmar, Vietnam, Pakistan, Philippines, and Mongolia convened in April 2017 to review the updated literature and provide recommendations on the diagnosis and management of chronic HCV infection that reflects local conditions.

An evidence-based comprehensive compilation of the literature supported by the graded recommendations from the expert panel for the optimization of the diagnosis, pretreatment, on treatment, and posttreatment assessments, and management of chronic HCV infection has been presented in this article.

With the evolving treatment landscape and addition of several new direct-acting antiviral agents and combination regimens into the therapeutic armamentarium, the current article may serve as a guide to the clinicians in optimizing the diagnosis and treatment selection for the management of chronic HCV infection in resource-limited settings.

There is less data regarding the changes in body mass index (BMI) after treating hepatitis C virus (HCV) patients with new direct-acting antiviral agents (DAAs). This study aimed to assess the changes in BMI in chronic HCV patients treated with DAAs in Egypt and to explore other factors influencing this change.

The data of chronic HCV patients who received antiviral therapy with new DAAs in one of Egypt's specialized viral hepatitis treatment centers were retrospectively analyzed. In addition to the routine clinical and laboratory workup, changes in body weight during and after treatment were monitored and BMI was calculated. Viral load was measured at 12 weeks post-treatment to assess a sustained virological response. Patients with documented thyroid abnormalities, bariatric surgery, or ensuing special diets were excluded. BMI of >30 was taken as the cutoff for pa¬tients with obesity.

The study included 162 patients with a mean age of 48.56±11.49 years, of whom 61.1% were males, 16% were treatment-experienced, 12% were diabetic, and 29% were obese. Treatment duration was 12 weeks in 84% of patients and 24 weeks in 16% of patients. There was a significant increase in BMI post-treatment as compared to pretreatment measures (28.68±5.35 vs 28.18±4.55) (p=0.03). BMI changes were constant regardless of cirrhosis or previous treatment experience.

Treatment of chronic HCV with DAAs was associated with increased body mass index. Further studies are needed to explore if this effect is secondary to treatment with DAAs or is an improvement in the liver function and lifestyle of treated patients.

Recent studies have suggested a higher recurrence rate of hepatocellular carcinoma (HCC) in patients with a history of HCC and hepatitis C virus (HCV)-associated cirrhosis treated with direct-acting antiviral (DAA) agents.

We conducted a prospective analysis of 24 patients with HCV-associated cirrhosis and treated HCC who received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for 12 weeks. Prior therapies for HCC included resection (9/24 patients), radiofrequency ablation (RFA) (7/24) and trans-arterial chemoembolization (TACE) (8/24). All patients were eligible for treatment if they had no HCC recurrence 6 months after their last procedure. A control group was defined. All patients were followed every 6 months, with dynamic computed tomography and/or magnetic resonance imaging.

The sustained virological response rate per protocol was 21/24 (87.5%). The study group included 14 (59%) males, median age 64 years (51-77), 50% with associated non-alcoholic steatohepatitis and 24% with Child-Pugh A6 points. HCC recurrence rate/100 patient-years was lower in the DAA-HCC group versus control: 5.5 versus 24.6% patient-years for the resection+RFA group (p = 0.044), respectively, and 18.6 versus 72.7% patient-years for TACE group (p = 0.002). Survival without recurrence was higher in the resection+RFA group (45 compared to 18 months (p < 0.001)) and also in the TACE group (44 compared to 11.5 months (p = 0.002)).

DAA therapy significantly reduced the recurrence rate of HCC and improved survival without recurrence in patients with treated HCV-associated HCC.

A large Egyptian treatment program for HCV was launched in2014 after the introduction of direct-acting antiviral agents (DAAs). This program depended mainly on establishing specialized independent centres for HCV treatment. These centres represent the major strengths in the Egyptian model of care, as they provide integrated care for HCV patients and have enabled Egypt to treat more than one million patients in 3 years. The New Cairo Viral Hepatitis Treatment Center (NCVHTC) is an example of these specialized centres.

The Egyptian experience in the management of HCV was evaluated by analysing the data of real-life HCV management in the NCVHTC from 2014 to 2017. Results of different treatment regimens in addition to their strengths, limitations and areas for improvement are discussed in this report.

A total of 7042 HCV patients have been evaluated for treatment in the NCVHTC. Among them, 5517 patients received treatment by seven different DAA regimens with excellent results.

All regimens were highly effective at treating HCV in a real-life setting, apart from SOF/RBV, which was the least effective. A nationwide screening program and enhancing the follow-up of treated patients are the main missing pillars in the Egyptian model.

Worldwide, more than one million people die each year from hepatitis C virus (HCV) related diseases, and over 300 million people are chronically infected with hepatitis B or C. Egypt used to be on the top of the countries with heavy HCV burden. Some countries are making advances in elimination of HCV, yet multiple factors preventing progress; remain for the majority. These factors include lack of global funding sources for treatment, late diagnosis, poor data, and inadequate screening. Treatment of HCV in Egypt has become one of the top national priorities since 2007. Egypt started a national treatment program intending to provide cure for Egyptian HCV-infected patients. Mass HCV treatment program had started using Pegylated interferon and ribavirin between 2007 and 2014. Yet, with the development of highly-effective direct acting antivirals (DAAs) for HCV, elimination of viral hepatitis has become a real possibility. The Egyptian National Committee for the Control of Viral Hepatitis did its best to provide Egyptian HCV patients with DAAs. Egypt adopted a strategy that represents a model of care that could help other countries with high HCV prevalence rate in their battle against HCV. This review covers the effects of HCV management in Egyptian real life settings and the outcome of different treatment protocols. Also, it deals with the current and future strategies for HCV prevention and screening as well as the challenges facing HCV elimination and the prospect of future eradication of HCV.

The influence of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus on the risk of hepatocellular carcinoma (HCC) is conflicting.

We conducted a systematic review and meta-analysis to determine the incidence or recurrence of HCC associated with oral DAA therapy. We searched PubMed, Scopus, Embase from inception to August 2017 to identify observational studies reporting on HCC among patients treated with DAAs. Two independent reviewers extracted data and assessed the risk of bias. Data were pooled by random-effects model. The primary outcome was the proportion of participants with incidence or recurrence of HCC (PROSPERO number CRD42017057040).

After reviewing 2080 citations, we included 8 controlled studies and 36 uncontrolled studies. The pooled proportion for incident HCC was 1.5 % (95% CI 1.0% to 2.1%; I²=90.1%; n= 542/39 145) from 18 uncontrolled studies and 3.3% (95% CI 1.2% to 9%; I² =96%; n=109/6909) from 5 controlled studies, respectively. The pooled proportion for recurrent HCC was 16.7% (95% CI 10.2% to 26%; I²=84.8%; n=136/867) from 12 uncontrolled studies and 20.1% (95% CI 5.5% to 52.1%; I²=87.5%; n=36/225) from 3 controlled studies, respectively. There was no statistically significant effect on the risk of recurrent HCC (OR 0.50, 95%CI 0.16 to 1.59; I² =73.4%) in a meta-analysis of three studies.

Our findings show low proportion of incident HCC, but high proportion of recurrent HCC on treatment with DAAs. Continued active surveillance for HCC after treatment with DAAs remains prudent.

Interferon-free regimens are associated with high sustained virological response; however, associated adverse effects have yet to be fully reported.

To evaluate the adverse effects associated with the different direct-acting antiviral drug (DAA) regimens in Egyptian patients.

This multicenter retrospective study included all adverse effects during and after treatment with DAA regimens of 149 816 chronic hepatitis C treated Egyptian patients. Patients received sofosbuvir (SOF)/ribavirin (RBV) (n = 21 835), SOF/simeprevir (n = 24 215) SOF/daclatasvir (DCV) (n = 58 477), SOF/DCV/RBV (n = 45 188) and paritaprevir/ombitasvir/ritonavir/RBV (n = 101). The duration of treatment varied between 12 and 24 weeks. All changes in the treatment regimens, discontinuation, mortality, and serious side effects were reported.

Adverse effects developed in 2475 (1.7%) (mean age [54 ± 9], male gender [53%]) patients. Serious side effects developed in 68% of these patients, and SOF/RBV was the most common causing regimen (73%, P < 0.001). Anaemia and hyperbilirubinemia were the most common side effects (731/149816, 0.5% and 463/149816, 0.3%, respectively) and SOF/RBV (588/21835, 3% and 353/21835, 1.6%, respectively) showed the highest incidence in the treated patients. Hepatocellular carcinoma and mortality were reported in 0.02% and 0.06% of all treated patients, respectively. Patients with liver cirrhosis showed higher incidence of serious side effects (Log rank P = 0.045) and mortality (Log rank P = 0.025) than patients without liver cirrhosis. Male gender (P = 0.012), lower haemoglobin (P < 0.001), platelets (P < 0.001) and albumin (P = 0.001), higher bilirubin (P = 0.002) and cirrhosis (P < 0.001) were factors associated with serious side effects development.

Adverse effects associated with DAAs are few, anaemia being the most common. SOF/RBV regimen showed the highest rate of side effects while SOF/DCV showed the least.

Introduction: Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. Materials and methods: A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Results: Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Conclusions: Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV infection. A brief rational: Pregnant women with HCV infection are at risk of adverse obstetric outcome. Anti-D Ig therapy may be a risk factor for HCV infection. Hence, we conducted a cross sectional study with the objectives to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. We found that anti-HCV and HCV-RNA seroprevalence were significantly higher in women with anti-D Ig. In addition, women with anti-D Ig therapy were 3.6 times more at risk of positive HCV-RNA with genotype HCV-1b showed higher prevalence. Therefore, anti-D Ig therapy is a risk factor for acquiring HCV infection and we recommend screening for HCV for all recipients of anti-D Ig. In addition, the diagnosis of HCV infection, should be made with HCV antibodies and HCV-RNA detection.

The introduction of direct-acting antivirals for hepatitis C virus (HCV) in Egypt led to massive treatment uptake, with Egypt's national HCV treatment program becoming the largest in the world. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for patients with HCV, highlighting the difficulties and limitations of the program, as a guide for other countries of similarly limited resources.

Baseline data of 337,042 patients, treated between October 2014 to March 2016 in specialized viral hepatitis treatment centers, were grouped into three equal time intervals of six months each. Patients were treated with different combinations of direct-acting antivirals, with or without ribavirin and pegylated interferon. Baseline data, percentage of patients with known outcome, and sustained virological response at week 12 (SVR12) were analyzed for the three cohorts. The outcomes of 94,258 patients treated in the subsequent two months are also included.

For cohort-1, treatment was prioritized for patients with advanced fibrosis (F3-F4 fibrosis, liver stiffness ≥9.5 kPa, or Fibrosis-4 ≥3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The prioritization strategy in the initial phase caused delays in enrollment and massive backlogs. Cohort-1 patients were significantly older, and more had advanced fibrosis compared to subsequent cohorts. The percentage of patients with known SVR12 results were low initially, and increased with each cohort, as several methods to capture patient results were adopted. Sofosbuvir-ribavirin therapy for 24 weeks had the lowest SVR12 rate (82.7%); while other therapies were associated with SVR12 rates between 94% and 98%.

Prioritization based on fibrosis stage was not effective and enrollment increased greatly only after including all stages of fibrosis. The availability of generic drugs reduced costs, and helped massively increase uptake of the program. Post-treatment follow-up was initially very low, and although this has increased, further improvement is still needed.

We are presenting the largest national program for HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured efficiently in large scale real-life programs. This is a clear statement that global HCV eradication is foreseeable, providing a model for other countries with limited resources and prevalent HCV. Moreover, the availability of generic products has influenced the success of this program.

Around 70 to 100 million people are chronically infected with HCV worldwide. HCV antiviral drug development has revolutionised the treatment of HCV, with several direct-acting antiviral agents offering patients the chance of cure after only 8-12 weeks of treatment. Drug development was initially focussed on HCV genotype 1 (GT1) infection, since this was the most prevalent worldwide, although clinical trials included all genotypes prevalent in the US and Europe. Because the earliest in vitro assays utilised the GT1b and 2 replicons, the initial classes of direct-acting antivirals (protease inhibitors, non-nucleotide polymerase inhibitors) were GT1-specific, albeit they had an effect on other less prevalent genotypes. Epidemiological data has shown the regional importance of other HCV genotypes. More than 50% of all HCV infections around the globe are not with GT1. The prevalence of HCV genotype 4 (GT4), 5 (GT5), and 6 (GT6) is increasing in North America and Europe due to migration from the Middle East, Africa and South-East Asia. With the successful development of the multi and pan-genotypic non-structural protein 5A inhibitors, second generation protease inhibitors and nucleotide non-structural protein 5B inhibitors comes a unique opportunity to achieve global HCV elimination. The goal of this review is to summarise the available information pertaining to GT4, GT5 and GT6, with a specific focus on direct-acting antiviral agents.

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.

To assess the efficacy and safety of combined SOF-DCV in treating patients with HCV-G4 in a real-world setting.

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.

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.

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.

Ghrelin (GHRL) has important implications for liver disease. It has anti-inflammatory effects, regulates cell proliferation, modulates the fibrogenic response and protects liver tissue. Genetic variations in the GHRL gene may play a crucial role in the development of chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we examined the association of GHRL gene polymorphisms (rs26312 and rs27647), and its serum level to virologic responses to combined sofosbuvir and Simeprevir therapy for a course of 12 successive weeks in Egyptian chronic hepatitis C (CHC) patients.

Human genomic and clinical data were collected from 100 Egyptian participants in this study, 90 HCV patients who received sofosbuvir and Simeprevir and 10 non-HCV healthy subjects. Genotyping of GHRL rs26312 and rs27647, were determined with the TaqMan qRT-PCR allele detection assay. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA).

GHRL polymorphisms (rs26312 and rs27647) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. In addition, we found significant lower serum GHRL levels in CHC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26312 and rs27647 polymorphisms with GHRL levels in CHC patients. We conclude that GHRL SNPs (rs26312 and rs27647) do not affect response to combined sofosbuvir and Simeprevir treatment in chronic Egyptian HCV patients.