Publications by authors named "Maissa El Raziky"

37 Publications

Hepatitis C virus infection and global kidney health: the consensus proceedings of the International Federation of Kidney Foundations.

Afr J Nephrol 2020 ;23(1):159-168

Nephrology Department, Cliniques universitaires Saint-Luc and Université catholique de Louvain, Brussels, Belgium.

Hepatitis C virus (HCV) infection is an important cause of major morbidities including chronic liver disease, liver cancer, and acute kidney injury (AKI) as well as chronic kidney disease (CKD). HCV can affect kidney health; among CKD and AKI patients with HCV infection, the clinical outcomes are worse. The prevalence of HCV infection is exceptionally high among dialysis and kidney transplant patients throughout the globe. It is estimated that 5% to 25% or more of dialysis dependent patients are affected by chronic HCV, based on the region of the world. Almost half of all deaths in CKD patients, including HCV-infected patients, are due to cardiovascular disease, and HCV infected patients have higher mortality. Given the importance and impact of the HCV epidemic on CKD and global kidney health, and the status of Egypt as the nation with highest prevalence of HCV infection in the world along with its leading initiatives to eradicate HCV, the International Federation of Kidney Foundations (IFKF) convened a consensus conference in Cairo in December 2017. This article reflects the opinions and recommendations of the contributing experts and reiterates that with the current availability of highly effective and well tolerated pharmacotherapy; CKD patients should be given priority for treatment of HCV, as an important step towards the elimination of viral hepatitis as a public health problem by 2030 according to World Health Organization and IFKF. Every country should have an action plan with the goal to improve kidney health and CKD patient outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751950PMC
January 2020

Retreatment of chronic hepatitis C virus genotype-4 patients after non-structural protein 5A inhibitors' failure: efficacy and safety of different regimens.

Eur J Gastroenterol Hepatol 2020 03;32(3):440-446

Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef.

Background: 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.

Patients And Methods: 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).

Results: 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.

Conclusion: Salvage treatment for NS5A-treatment failure is effective and well tolerated in genotype-4 patients, in both noncirrhotic and compensated cirrhotic groups.
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http://dx.doi.org/10.1097/MEG.0000000000001581DOI Listing
March 2020

High SVR rate following retreatment of non-sustained virological responders to sofosbuvir based anti-HCV therapies regardless of RAS testing: A real-life multicenter study.

Expert Rev Gastroenterol Hepatol 2019 Sep 23;13(9):907-914. Epub 2019 Jun 23.

Hepatology Department, National Liver Institute, Menoufiya University , Shebeen EL Kom , Egypt.

Evaluation of the efficacy and safety of sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV) in treating non-sustained virological responders (non-SVR12) to prior sofosbuvir-based therapy, in absence of RAS testing in mass treatment, and determination of the optimal timing to start re-treatment. Real-life prospective observational study included prior non-responders to 24-weeks SOF-RBV (n = 679, 67%) or 12-weeks SOF- RBV- PEG (n = 335, 33%). Patients were re-treated with daily SOF/DCV/RBV for 12 (n = 270) or 24 weeks (n = 744). The primary efficacy endpoint was SVR12. The primary safety endpoints were reported adverse events (AEs) from baseline to SVR12 time point. We included 1,014 patients [age 52 ± 9 years, 58.48% men]. Cirrhosis was documented in 46.98% and 27.5% of SOF-RBV and SOF-RBV-PEG non-responders respectively. Overall, SVR12 was 90.6% [92.2% for 12 weeks therapy and 90.05% for 24 weeks therapy]. Mild AEs occurred in 5.13% (n=52) and 3.1% (n=32) discontinued treatment including eight on-treatment mortalities. Higher baseline FIB-4 and shorter interval before starting retreatment (<6 months) were independent predictors of non-SVR12 on multivariate regression analysis. SOF/DCV/RBV is an effective and safe treatment option for non-responders to prior sofosbuvir-based therapy. Six months interval before retreatment is optimal for achieving favorable SVR.
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http://dx.doi.org/10.1080/17474124.2019.1629287DOI Listing
September 2019

Effect of Direct-Acting Agents on Fibrosis Regression in Chronic Hepatitis C Virus Patients' Treatment Compared with Interferon-Containing Regimens.

J Interferon Cytokine Res 2018 03 12;38(3):129-136. Epub 2018 Mar 12.

Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University , Cairo, Egypt .

Hepatitis C virus (HCV) treatment is aiming to cure and prevent the development, progression of fibrosis, and related complications. Interferon-based therapy was claimed to reduce or even reverse fibrosis. Although direct-acting agents have a better cure rate, we still lack the knowledge of their effect on fibrosis regression. We aim to assess fibrosis regression in direct-acting agents compared with interferon-based treatment regimens in the treatment of chronic HCV patients. The 204 chronic HCV patients were divided into 3 groups; group 1(N = 68) received Peg-IFN and ribavirin, group 2 (N = 69) received sofosbuvir and ribavirin, and group 3 (N = 67) received Peg-IFN, ribavirin, and sofosbuvir. Fibrosis assessment was performed by transient elastography (TE), APRI and FIB 4, in the pretreatment and at least 3 months after end of treatment. Of these, 66.2% of the patients did not show significant fibrosis changes, 6.4% fibrosis progressed, and 27.5% of fibrosis regressed (P < 0.0001) by TE. Similar results were detected in the different treatment regimens with no statistically significant difference between the regimens. Fibrosis regression was detected in 43.3% of cirrhotic patients who achieved sustained virological response (SVR) and only in 27.4% with significant fibrosis. Significant improvement of posttreatment aspartate transaminase, alanine transaminase, and alpha fetoprotein as well as APRI and FIB 4 scores were detected. Fibrosis regression (TE, APRI and FIB 4) was detected with direct-acting agents and interferon-based therapy. Treated patients with significant fibrosis will benefit of fibrosis regression irrespective to their treatment response, whereas fibrosis regression was associated with SVR in cirrhotic patients.
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http://dx.doi.org/10.1089/jir.2017.0137DOI Listing
March 2018

Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience.

J Hepatol 2018 04 6;68(4):691-698. Epub 2017 Dec 6.

Department of Hepatology, National Liver Institute, Menoufiya University, Menoufiya, Egypt.

Background And Aims: 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.

Methods: 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.

Results: 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%.

Conclusion: 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.

Lay Summary: 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.
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http://dx.doi.org/10.1016/j.jhep.2017.11.034DOI Listing
April 2018

High Dose of Silymarin in Patients with Decompensated Liver Disease: A Randomized Controlled Trial.

J Interferon Cytokine Res 2017 11;37(11):480-487

1 Endemic Gastroenterology and Hepatology, Faculty of Medicine, Cairo University , Cairo, Egypt .

Hepatitis C virus (HCV) is a major public health problem being the most common cause of chronic liver disease in Egypt. HCV-induced decompensated liver cirrhosis patients have a median survival of 2 years even with currently used new treatments. Silymarin is the most commonly used herbal product in chronic liver disease for its anti-inflammatory, antiviral, antioxidant, and antifibrotic effects. The aim of this study was to assess the effects of silymarin in high dose on the clinical and biochemical status of chronic HCV-associated decompensated liver cirrhosis. The study was conducted on 62 chronic HCV-decompensated cirrhotic patients. Patients were randomized according to treatment plans: group A, included 31 patients who received silymarin in dose of 1,050 mg/day, and group B, included 31 patients who received silymarin in dose of 420 mg/day. Patients were subjected to baseline history taking, laboratory evaluation, abdominal ultrasound, Child scoring, and quality-of-life (QoL) questionnaire. Follow-up was done every 2 weeks for 12 weeks. Silymarin in high dose had an effect on reducing alanine transaminase, aspartate aminotransferase levels (P ≤ 0.01), as well as improving albumin (P = 0.04), bilirubin (P = 0.02), and international normalized ratio (P = 0.03), thus resulted in improvement in Child score (P = 0.048), however, regular silymarin regimen (420 mg/day) failed to achieve the previous biochemical changes. High-dose regimen of silymarin also had a positive impact on improving QoL. No serious adverse events were reported. Silymarin in high dose is a good choice for improvement of liver biochemical profile and QoL in chronic HCV cirrhotic patients.
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http://dx.doi.org/10.1089/jir.2017.0051DOI Listing
November 2017

Association of vitamin D binding protein polymorphisms with response to therapy in Egyptian chronic hepatitis C patients.

J Infect Dev Ctries 2017 Oct 31;11(10):781-790. Epub 2017 Oct 31.

Cairo University, Cairo, Egypt.

Introduction: Vitamin D binding protein (VDBP) is a potential modulator of immune response and is associated with clinical progression of many diseases. Our aim was to assess influence of baseline 25-hydroxyvitamin D levels and VDBP single nucleotide polymorphisms (SNPs), rs4588 (C > A) and rs7041 (G > T), on baseline clinical parameters and response to interferon based therapy in chronic hepatitis C patients in Egypt.

Methodology: Genotyping was performed by RFLP (Restriction Fragment Length Polymorphism) in 112 treatment naïve hepatitis C patients and 50 healthy controls. Vitamin D levels were assessed by ELISA. HCV RNA quantification was performed by PCR to assess therapy outcome.

Results: Patients with VDBP WT+ diplotype (3 or 4 VDBP major alleles) had higher viral response rates at weeks 12, 48, and 72 (p = 0.046, 0.034 and 0.029, respectively) and lower base line viral load (p = 0.016). Multivariate logistic regression identified VDBP WT+ diplotype as an independent predictor of sustained viral response (SVR; p = 0.014, RR = 4.716, 95% CI = 1.371 - 16.609). Interestingly, WT- diplotype (less than 3 VDBP major alleles) was associated with significant liver fibrosis (p = 0.045).

Conclusions: VDBP WT+ diplotype is associated with lower baseline viral load and better therapy outcome in HCV treatment naïve patients. The rs4588 genotype is associated with SVR in the Egyptian population.
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http://dx.doi.org/10.3855/jidc.8830DOI Listing
October 2017

Effectiveness of ravidasvir plus sofosbuvir in interferon-naïve and treated patients with chronic hepatitis C genotype-4.

J Hepatol 2017 Sep 19. Epub 2017 Sep 19.

National Liver Institute, Menoufiya University, Shebeen EL Kom, Egypt. Electronic address:

Background & Aims: Although treatment of hepatitis C virus (HCV) and HCV-genotype-4 (GT4) has become very effective, it remains very expensive, and affordable options are needed, especially in limited resource countries. The aim of this study was to assess the efficacy and safety of the combination of ravidasvir (an NS5A inhibitor) and sofosbuvir to treat patients with chronic HCV-GT4 infection.

Methods: A total of 300 patients with HCV-GT4 infection were recruited in three groups: treatment-naïve patients with or without compensated Child-A cirrhosis (Group 1); interferon-experienced patients without cirrhosis (Group 2); and interferon-experienced patients with cirrhosis (Group 3). Groups 1 and 2 received ravidasvir 200 mg QD plus sofosbuvir 400 mg QD for 12 weeks and were randomized 1:1 to treatment with or without weight-based ribavirin. Group 3 patients received ravidasvir plus sofosbuvir with ribavirin and were randomized 1:1 to a treatment duration of 12 weeks or 16 weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12).

Results: A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated.

Conclusions: Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments.

Trial Registration Number: ClinicalTrials.gov Identifier: NCT02371408.

Lay Summary: This study evaluated efficacy and safety of the new oral hepatitis C drug ravidasvir in combination with the approved oral drug sofosbuvir in 298 patients infected with hepatitis C type 4. Our results showed that treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high response rate in patients with and without cirrhosis.
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http://dx.doi.org/10.1016/j.jhep.2017.09.006DOI Listing
September 2017

Impact of old Schistosomiasis infection on the use of transient elastography (Fibroscan) for staging of fibrosis in chronic HCV patients.

Acta Trop 2017 Dec 26;176:283-287. Epub 2017 Aug 26.

Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, 11562, Egypt.

Background And Aim: In tropical regions, Hepatitis C virus (HCV) - Schistosomiasis coinfection remains one of the health problems. With the new era of HCV treatment and the variety of methods of assessment of liver fibrosis so we aimed to evaluate the effectiveness of FibroScan for staging hepatic fibrosis in HCV-Schistosomiasis coinfected patients.

Methodology: Three groups of patients were enrolled. Group 1: chronic HCV with out antischistosomal antibody (122 patients), Group 2: chronic HCV with positive antischistosomal antibodies and without periportal tract thickening (122 patients), Group 3: chronic HCV with positive antischistosomal antibodies and ultrasonographic picture of periportal tract thickening (108 patients). Routine laboratory workup, serum Antischistosomal antibody, and Schistosomal antigen in serum were performed. Ultrasound guided liver biopsy with histopathological examination; abdominal ultrasound and fibroscan examination were done for all patients.

Results: The agreement between results of liver biopsy and results of fibroscan in the staging of fibrosis was the best in group 1 (55.7%), Although the agreement was higher among those with no periportal tract thickening (70.7%) and the disagreement was higher among those with positive schistosomal serology (66.5%), yet this relation was not statistically significant. Multivariate logistic regression analysis showed that disagreement is significantly associated with older age, higher BMI (≥30), and increase in anti Schistosomal antibody titer.

Conclusion: Fibroscan is a reliable, non-invasive tool for staging hepatic fibrosis among HCV-schistosomiasis co-infected patients with no effect of the induced periportal tract thickening on the readings. Only higher antischistosomal antibody titres may cause disagreement between liver biopsy and fibroscan.
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http://dx.doi.org/10.1016/j.actatropica.2017.08.019DOI Listing
December 2017

Circulating Hypermethylated RASSF1A as a Molecular Biomarker for Diagnosis of Hepatocellular Carcinoma

Asian Pac J Cancer Prev 2017 06 25;18(6):1637-1643. Epub 2017 Jun 25.

Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Email:

Background: Detection of circulating DNA can be applied for the diagnosis of many malignant neoplasms, including the hepatocellular carcinoma (HCC). The molecular pathogenesis of HCC is complex, involving different genetic and epigenetic alterations, chromosomal aberrations, gene mutations and altered molecular pathways. RASSF1A is a well-established tumor suppressor gene which suffers frequent inactivation due to promoter hypermethylation of CPG islands in multiple tumors including HCC, resulting in the reduction or loss of gene expression. Objective: To examine the role of circulating RASSF1A as a non-invasive diagnostic marker for HCC. Participant and Methods: A total of 45 HCC patients with a background of HCV infection, 40 cases of HCV infection without tumours and 40 apparently healthy controls were subjected to full history taking, clinical examination, routine laboratory investigations, assessment of serum AFP and detection of circulating hypermethylated RASSF1A gene by methylation-sensitive restriction enzyme digestion and real-time PCR. Results: The level of hypermethylated RASSF1A was significantly elevated in the HCC group as compared to the HCV and control groups (p=0.001 for both). Copy number in serum was associated with increased tumor size (p value <0.001). On the other hand, no significant correlation was observed between RASSF1A and AFP (p=0.5). Using ROC curve analysis, the best cut-off for circulating serum RASSF1A to differentiate the HCC group was 8 copies/μl. Conclusion: The presence of hypermethylated RASSF1A in serum may be a useful and informative biomarker for HCC diagnosis and might be introduced as a screening method for populations at risk of HCC development.
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http://dx.doi.org/10.22034/APJCP.2017.18.6.1637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373823PMC
June 2017

ITPA gene polymorphism (94C>A) effects on ribavirin-induced anemia during therapy in Egyptian patients with chronic hepatitis C.

J Med Virol 2017 10 29;89(10):1823-1829. Epub 2017 May 29.

Department of Clinical Pathology, Kasr Al Ainy, School of Medicine, Cairo University, Cairo, Egypt.

Inosine triphosphatase (ITPA) gene variants can protect against ribavirin (RBV)-induced anemia in patients treated for chronic hepatitis C. The aim of this study was to determine the relationship between genetic variants of ITPA polymorphism, anemia, RBV dose reduction, and treatment response in hepatitis C virus (HCV)-infected patients. This study was conducted on 97 Egyptian chronic HCV patients who were scheduled for pegylated-interferon (PEG-INF) /RBV therapy. ITPA genotypes rs1127354 were determined by Real Time PCR melting curve analysis. Effects of ITPA polymorphism on hemoglobin (Hb) levels, RBV dose reduction and treatment response were analyzed. The homozygous wild genotype (CC) was associated with Hb reduction at week 4 (P = 0.004). The minor allele protected against Hb reduction. No association with sustained virological response was observed (P = 0.492). Female gender; lower baseline Hb and higher baseline WBC were associated with week 4 anemia (P = 0.04; P = 0.023; 0.033, respectively). The ITPA gene polymorphism rs1127354 heterozygous genotype (CA) may influence Hb levels and protect against hemolytic anemia during RBV-containing regimens for HCV. However, such findings were not significantly related to treatment outcomes. Patients with wild ITPA genotype (CC) experienced a more Hb drop and RBV dose reductions more frequently.
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http://dx.doi.org/10.1002/jmv.24844DOI Listing
October 2017

Response to Real life Egyptian experience of efficacy / safety of Simeprevir\ Sofosbuvir in HCV genotype IV.

Liver Int 2017 05;37(5):766

Hepatology & Endemic Medicine Department, Cairo University, Cairo, Egypt.

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http://dx.doi.org/10.1111/liv.13319DOI Listing
May 2017

Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon.

J Gastroenterol Hepatol 2017 Sep;32(9):1624-1630

Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt.

Background And Aim: Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in non-invasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with Sofosbuvir-based treatment regimen.

Methods: This is a retrospective study including 337 chronic HCV Egyptian patients with genotype 4 mainly. They were treated with Sofosbuvir-based treatment regimen. Transient elastography values were recorded as well as FIB-4 and APRI were calculated at baseline and SVR12.

Results: There was a significant improvement of platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores at SVR12. Liver stiffness measurements were significantly lower in SVR12 (14.8 ± 10.7 vs 11.8 ± 8.8 kPa, P = 0.000). About 77% of responders and 81.1% of cirrhotic patients showed improvement in liver stiffness measurements at SVR12.Univariate and multivariate regression analysis showed that failure to achieve improvement in liver stiffness measurements were significantly associated with relapsers and low baseline liver stiffness measurement.

Conclusion: Sofosbuvir-based treatment resulted in a clinically significant improvement in parameters of liver fibrosis.
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http://dx.doi.org/10.1111/jgh.13758DOI Listing
September 2017

Regulatory and activated effector T cells in chronic hepatitis C virus: Relation to autoimmunity.

World J Hepatol 2016 Oct;8(30):1287-1294

Hanan Fouad, Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.

Aim: To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and , genes.

Methods: A prospective study was conducted on 120 subjects divided into 4 groups: Group I ( = 30) treatment naïve chronic HCV patients; Group II ( = 30) chronic HCV treated with Peg/Riba; Group III ( = 30) chronic HCV associated with non-organ specific autoantibody and Group IV ( = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction.

Results: Chronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group.

Conclusion: Elevated Tregs cells in chronic HCV patients dampen both CD4 and CD8 autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response.
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http://dx.doi.org/10.4254/wjh.v8.i30.1287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084058PMC
October 2016

Real life Egyptian experience of efficacy and safety of Simeprevir/Sofosbuvir therapy in 6211 chronic HCV genotype IV infected patients.

Liver Int 2017 04 4;37(4):534-541. Epub 2016 Nov 4.

Hepatology & Endemic Medicine Department, Cairo University, Cairo, Egypt.

Background & Aims: Major changes have emerged during the last few years in the therapy of chronic HCV. Several direct acting antiviral agents have been developed showing potent activity with higher rates of sustained virological response, even in difficult-to-treat patients. This study explores real life experience concerning efficacy, safety and possible predictors of response for the first cohort of Egyptian patients with chronic HCV genotype IV treated with Sofosbuvir/Simprevir combination therapy.

Methods: This real life study recruited the first (6211) chronic HCV genotype IV Egyptian patients, who received antiviral therapy in viral hepatitis specialized treatment centres affiliated to the National committee for control of viral hepatitis. All enrolled patients received 12 weeks course of daily combination of sofosbuvir (400 mg) and simeprevir (150 mg). Patients were closely monitored for treatment safety and efficacy.

Results: Overall sustained virological response 12 rate was 94.0% while the end of treatment response rate was 97.6%. sustained virological response 12 rates in easy and difficult-to-treat groups were 96% and 93% respectively. Univariate and multivariate logistic regression analysis revealed significant association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to liver cell failure adverse events or SAEs leading to treatment discontinuation occurred in 97 patients (1.6%).

Conclusion: Sofosbuvir/Simeprevir combination is an effective and well tolerated regimen for patients with chronic HCV genotype IV.
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http://dx.doi.org/10.1111/liv.13266DOI Listing
April 2017

Predictors of Virological Response in 3,235 Chronic HCV Egyptian Patients Treated with Peginterferon Alpha-2a Compared with Peginterferon Alpha-2b Using Statistical Methods and Data Mining Techniques.

J Interferon Cytokine Res 2016 05 9;36(5):338-46. Epub 2016 Feb 9.

1 Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University , Cairo, Egypt .

Despite the appearance of new oral antiviral drugs, pegylated interferon (PEG-IFN)/RBV may remain the standard of care therapy for some time, and several viral and host factors are reported to be correlated with therapeutic effects. This study aimed to reveal the independent variables associated with failure of sustained virological response (SVR) to PEG-IFN alpha-2a versus PEG-IFN alpha-2b in treatment of naive chronic hepatitis C virus (HCV) Egyptian patients using both statistical methods and data mining techniques. This retrospective cohort study included 3,235 chronic hepatitis C patients enrolled in a large Egyptian medical center: 1,728 patients had been treated with PEG-IFN alpha-2a plus ribavirin (RBV) and 1,507 patients with PEG-IFN alpha-2b plus RBV between 2007 and 2011. Both multivariate analysis and Reduced Error Pruning Tree (REPTree)-based model were used to reveal the independent variables associated with treatment response. In both treatment types, alpha-fetoprotein (AFP) >10 ng/mL and HCV viremia >600 × 10(3) IU/mL were the independent baseline variables associated with failure of SVR, while male gender, decreased hemoglobin, and thyroid-stimulating hormone were the independent variables associated with good response (P < 0.05). Using REPTree-based model showed that low AFP was the factor of initial split (best predictor) of response for either PEG-IFN alpha-2a or PEG-IFN alpha-2b (cutoff value 8.53, 4.89 ng/mL, AUROC = 0.68 and 0.61, P = 0.05). Serum AFP >10 ng/mL and viral load >600 × 10(3) IU/mL are variables associated with failure of response in both treatment types. REPTree-based model could be used to assess predictors of response.
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http://dx.doi.org/10.1089/jir.2015.0141DOI Listing
May 2016

Seroprevalence of HCV among Cairo University students in Egypt.

J Med Virol 2016 08 4;88(8):1384-7. Epub 2016 Feb 4.

Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Hepatitis C virus (HCV) is highly prevalent in Egypt. This work aimed at determining the seroprevalence of HCV among Cairo University students. The present study included 3,000 students from Cairo University, Egypt. Blood sample was obtained from each participant to be tested for HCV seromarker. HCV RNA detection by polymerase chain reaction (PCR) was carried out for those with positive anti-HCV. Overall prevalence rate of HCV antibody (anti-HCV) was 4.6%. It showed that the prevalence was relatively higher among females (86/1660; 5.2%) while males (51/1340; 3.8%) with no significant difference. PCR for HCV RNA was detected in 31.4% of the HCV antibody positive subjects (43/137). Which showed statistical significant difference between males (29/51) and females (14/86) at P = 0.001. Despite the prevalence rate reported in the present study was similar to anti-HCV prevalence among persons in the same age group, confirmed that HCV infection is detected among Cairo University students. J. Med. Virol. 88:1384-1387, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24469DOI Listing
August 2016

IP-10 Serum Level in Chronic Hepatitis C Virus Patients: Relation to Fibrosis and Response to Combined Interferon/Ribavirin Therapy.

J Interferon Cytokine Res 2015 Aug 14;35(8):649-53. Epub 2015 May 14.

1 Department of Endemic Hepatology and Gasteroenterology, Cairo University , Cairo, Egypt .

Despite the appearance of the direct acting antiviral drugs, pegylated interferon/ribavirin (PEG-IFN/RBV) still has a place in the standard of care (SOC) therapy for chronic HCV4. Studies were conducted to find an accurate prediction in response to SOC therapy. Pretreatment serum interferon-γ-inducible protein-10 (IP-10) is an independent predictive factor of sustained virological response (SVR) in HCV1-infected patients. To assess whether the pretreatment serum level of IP-10 influences hepatic fibrosis and PEG-IFN/RBV therapy response, a study was conducted on 88 chronic Hepatitis C virus (HCV) patients who received PEG-IFN/RBV. Patients were subjected to a pretreatment routine laboratory evaluation, liver biopsy, and serum IP-10 assessment. They were followed up for 6 months after cessation of therapy (week 72). Patients were classified into 3 groups according to their response; nonresponders, relapsers, or sustained virological responders. The relation of pretreatment IP-10 with fibrosis and response was assessed. The studied groups were matched regarding their demographic data. There was no statistically significant association between the pretreatment IP-10 level and fibrosis (P=0.86) and no relation to response was found at week 12, 24, 48, and 72 (P=0.58, 0.8, 0.47, and 0.43, respectively). Pretreatment IP-10 could not predict either fibrosis or response to PEG-IFN/RIB therapy in chronic HCV Egyptian patients.
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http://dx.doi.org/10.1089/jir.2014.0193DOI Listing
August 2015

Is rs8099917 polymorphism of IL-28B gene a good predictor of response to therapy of HCV than rs12979860? An Egyptian study.

Cell Biochem Biophys 2015 Jan;71(1):307-14

Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Giza, Egypt,

Hepatitis C virus (HCV) infection is the major etiology of chronic liver disease. Polymorphisms in the IL-28B gene region are important in predicting outcome following therapy for chronic hepatitis C virus infection. The aim of this study was to detect the relationship between IL-28B polymorphism and responses to therapy in patients infected with genotype 4. This study included one hundred chronic hepatitis C patients infected with genotype 4, received PEG-IFNα2b plus ribavirin for 24 weeks, as well as, 20 healthy subjects serving as control. Clinical and laboratory parameters, including genetic variation near the IL-28B gene (rs8099917 and rs12979860), were assessed. The results of this study showed significant difference between responders and non-responders as regard SNPs in the interleukin 28B gene at rs8099917 and rs12979860. In rs8099917, TT genotypes had more frequency in responders than GG genotypes. On the other hand, CC genotype in rs12979860 had more frequency in responders than TT genotype. By multiple regression analysis, rs8099917 (TT), total bilirubin, and prothrombin time were independent factors affecting the response to treatment. This results demonstrate that in HCV genotype 4-infected patients, rs12979860 (CC) and rs8099917 (TT) genotypes may identify patients who are likely to respond to treatment. IL-28B SNPs are good predictors of response to combination therapy of HCV.
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http://dx.doi.org/10.1007/s12013-014-0199-7DOI Listing
January 2015

Impact of vitamin D supplementation on sustained virological response in chronic hepatitis C genotype 4 patients treated by pegylated interferon/ribavirin.

J Interferon Cytokine Res 2015 Jan 25;35(1):49-54. Epub 2014 Jul 25.

1 Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University , Cairo, Egypt .

The current standard of care therapy (SOC) for chronic HCV is pegylated interferon/ribavirin (Peg-IFN/RBV). Many reports showed the possible role of vitamin D supplementation in augmenting the response to SOC. The aim of this study was to assess the role of vitamin D supplementation on the response to treatment in chronic HCV genotype 4 patients. One hundred and one chronic HCV patients were classified into two groups (Group 1): 51 patients received the SOC therapy consisting of Peg-interferon alfa-2b plus ribavirin, (Group 2): 50 patients received the SOC therapy+vitamin D3 (Cholecalciferol) in a dose of 15,000 IU/week during the treatment course. Vitamin D deficiency was found in 95% of patients. No correlation was found between vitamin D levels and stage of fibrosis in the whole population. Vitamin D supplementation had no positive impact on treatment outcome where sustained virological response (SVR) was achieved in 51.2% in group 2 and 71.4% in group 1 by per-protocol analysis and in 44% in group 2 and in 68.6% in group 1 by intention to treat analysis (P value 0.22 and 0.220 respectively). Despite its role in other genotypes, vitamin D supplementation has no significant impact on SVR in HCV Genotype 4 patient. No correlation was found between vitamin D levels and stage of liver fibrosis.
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http://dx.doi.org/10.1089/jir.2014.0060DOI Listing
January 2015

Clinical, biochemical and pathological profiles of 5464 Egyptian chronic hepatitis C-infected patients.

Hepatogastroenterology 2013 Oct;60(127):1731-5

Background/aims: In Egypt, hepatitis C virus (HC is highly endemic with at least 91% are genotype-4. However, HCV-specific burden data for Egypt are scarce. The study aims to identify clinical, biochemical and pathological features of chronic HCV population in Egypt.

Methodology: We analyzed retrospective data of 5,464 HCV-antibody and PCR positive patients attending pre-treatment assessment at one of the National Treatment Centers, Cairo, Egypt.

Results: Chronic HCV patients were males (81.4%) in their productive age, mean body mass index (BMI): 28 kg/m2. Laboratory profile demonstrated mean platelet count 214 x 10(3)/µ L with only 14% having thrombocytopenia, amino-transferases were mildly elevated: mean AST, ALT were 56 and 63 respectively,low viraemia: 50% had viral load <100 (x 10(3)) IU/mL,and median AFP level 3.3 ng/mL. Liver biopsy revealed ≤A2 in 92% of patients; 80% had ≤F2 and 7.3 % had F4 according to the METAVIR score. Meta regression demonstrated that advanced stages of fibrosis were significantly correlated with platelet count, AST/ALT ratio, AFP levels and BMI (p <0.001). However there was no correlation with viral load.

Conclusions: To our knowledge, this is the first study on nationwide scale that provided the demographic, biochemical,and histological characteristics for this number of chronic HCV patients presumably genotype-4.
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October 2013

Optimizing treatment for HCV genotype 4: PEG-IFN alfa 2a vs. PEG-IFN alfa 2b; the debate continues.

Liver Int 2014 Feb;34 Suppl 1:24-8

Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt; Tropical Medicine Department, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt.

Hepatitis C virus (HCV) remains one of the leading causes of morbidity and mortality worldwide. Combined therapy with pegylated interferon (PEG-IFN) and ribavirin is the current standard of care treatment for HCV genotype 4. Two types of PEG-IFN are commercially available. The limited number of trials that were conducted for HCV genotype 4 and the few head to head comparisons make it impossible to know which is the best option? In this article we review all available PEG-IFN trials performed worldwide for HCV genotype 4 since 2004. Unless another molecule is developed as a standalone for the treatment of HCV, PEG-IFN will continue to be a source of debate.
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http://dx.doi.org/10.1111/liv.12397DOI Listing
February 2014

Hepatic fibrosis and serum alpha-fetoprotein (AFP) as predictors of response to HCV treatment and factors associated with serum AFP normalisation after treatment.

Arab J Gastroenterol 2013 Sep 10;14(3):94-8. Epub 2013 Oct 10.

Endemic Medicine, Hepatogastroenterology Department, Cairo University, Cairo, Egypt. Electronic address:

Background And Study Aim: Elevated levels of alpha-fetoprotein (AFP) can be seen in patients with chronic hepatitis C (CHC) and liver cirrhosis without hepatocellular carcinoma and were negatively associated with treatment response. However, factors associated with its changes are not identified. We aimed in this study to verify a cut-off value for AFP as a predictor of response to standard of care (SOC) antiviral therapy in Egyptian chronic hepatitis C virus (HCV)-infected patients and identify factors associated with its changes post treatment.

Patients And Methods: A total of 175 chronic non-cirrhotic HCV-infected patients were evaluated for baseline serum AFP and liver biopsy were classified according to Ishak scoring system of hepatic fibrosis. All patients were scheduled to receive SOC antiviral therapy for 48weeks and had been followed up to week 72. Reassessment of AFP and repeated liver biopsy at week 72 were feasible only in 79 patients.

Results: High baseline AFP levels were observed in non-respondents (non-sustained virological respondents (non-SVRs)) (P<0.01); the AFP level decreased in all patients post treatment (P=0.01), especially in the SVRs (P<0.01). In multivariate analysis, hepatic fibrosis was a predictor of response to treatment (P=0.02), while body mass index (BMI) (25-30kgm(-2)), hepatic activity (A2), hepatic fibrosis stage (F2-F4) and fibrosis improvement were predictors of AFP difference (P=0.007, 0.01, 0.012, <0.001, 0.030, and 0.018), respectively. The diagnostic performance to predict the HCV treatment response was best by adding both AFP and hepatic fibrosis stage factors; the best cut-off value for AFP was 3.57ngdl(-1) with 50% sensitivity and 68% specificity with area under the curve (AUC) of 0.55 and for hepatic fibrosis stage was 3, with a sensitivity of 88%, a specificity of 30% with an AUC of 0.58.

Conclusion: In chronic HCV-infected patients, serum AFP below 3.57ngdl(-1) and hepatic fibrosis ⩽stage 3 are expected to have good response to treatment; BMI (25-30kgm(-1)), A2, fibrosis >2 and fibrosis improvement predict AFP change post treatment.
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http://dx.doi.org/10.1016/j.ajg.2013.08.005DOI Listing
September 2013

The Effect of Peginterferon Alpha-2a vs. Peginterferon Alpha-2b in Treatment of Naive Chronic HCV Genotype-4 Patients: A Single Centre Egyptian Study.

Hepat Mon 2013 May 28;13(5):e10069. Epub 2013 May 28.

Department of Endemic Medicine and Hepatology, Cairo University, Cairo, Egypt.

Background: Egypt has one of the highest (16-8%) prevalence rates of HCV infection in the world. Approximately 90% of Egyptian HCV isolates belong to a single subtype (4a), which responds less successfully to interferon therapy than other subtypes. Studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naive HCV-infected patients have shown conflicting results.

Objectives: Assessing the effects of Peginterferon alpha-2a versus Peginterferon alpha-2b on the sustained virological response in naive chronic HCV genotype-4 Egyptian patients.

Patients And Methods: This retrospective study cohort consists of 3718 chronic HCV patients admitted to a large, Egyptian medical center. 1985 patients had been treated with PEG-IFN alfa-2a plus RBV and 1733 patients with PEG-IFN alfa-2b plus RBV between years 2007-2011. Efficacy outcomes were sustained virologic response (SVR) and treatment discontinuation rates due to serious adverse effects.

Results: The ETR & SVR in patients treated with PEGIFN alfa-2a was 64.1% and 59.6% as compared to treatment with PEGIFN alfa-2b where these parameters were 58.2% and 53.9% respectively (P < 0.05). Treatment discontinuation rates, were similar in the two types of PEGIFN [0.66 (0.37-1.16); P = 0.15]. Significant dose reduction was evident with peginterferon alfa-2b (35.3%) than peginterferon alpha-2a (27.3 %) (P < 0.01). Patients with lower base line AFP and ALT were most likely to achieve SVR using INF alpha 2-a.

Conclusions: Peginterferon alpha-2a has a higher efficacy regarding ETR and SVR as compared to Peginterferon alfa-2b in treatment of naive chronic HCV genotype-4 patients.
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http://dx.doi.org/10.5812/hepatmon.10069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732660PMC
May 2013

Serum autoantibodies positivity prevalence in patients with chronic HCV and impact on pegylated interferon and ribavirin treatment response.

Liver Int 2013 Nov 14;33(10):1504-9. Epub 2013 Jun 14.

Endemic Medicine and Hepatology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background & Aims: Prevalence of serum autoantibodies in chronic hepatitis C (HCV) patients is higher than that in the general population. Interferon may induce autoimmune manifestations in patients treated with peg-interferon and ribavirin. Effect of autoantibody seropositivity and treatment response are limited and controversial. To detect the prevalence of serum autoantibodies in patients with chronic HCV and impact on histopathology and treatment response.

Methods: Retrospective study including 3673 Egyptian chronic HCV naïve patients enrolled in the Egyptian national programme for HCV treatment with pegylated interferon and ribavirin in the years 2007-2010. Antinuclear antibody (ANA) was determined by ELISA considered positive with a titre ≥ 1:40 by indirect immunofluorescence. ANA-positive patients pre treatment workup including serum aminotransferases, thyroid profile and liver biopsy, follow-up during treatment and sustained virological response (SVR) were assessed compared to ANA-negative patients.

Results: Serum ANA was positive in 1.6% of the studied patients. There were no statistically significant differences concerning the demographic, biochemical and histopathological data in ANA positive and negative patients. SVR was comparable between ANA-positive and ANA-negative patients (67.8% and 61.3% respectively). Follow-up treatment; ANA-positive patients' did not experience statistically significant haematological complications, flare-up of serum transaminases, thyroid dysfunction. No systemic autoimmune disorders developed during follow-up.

Conclusions: ANA positivity is not a factor in chronic HCV disease progression and does not affect the treatment response. Pegylated interferon and ribavirin therapy is safe and effective in autoantibodies-positive chronic HCV patients with no need for further follow-up or worry during the treatment in absence of systemic autoimmune disorders.
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http://dx.doi.org/10.1111/liv.12227DOI Listing
November 2013

Coinfection with hepatitis C virus and schistosomiasis: fibrosis and treatment response.

World J Gastroenterol 2013 May;19(17):2691-6

Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.

Aim: To assess whether schistosomiasis coinfection with chronic hepatitis C virus (HCV) influences hepatic fibrosis and pegylated-interferon/ribavirin (PEG-IFN/RIB) therapy response.

Methods: This study was designed as a retrospective analysis of 3596 chronic HCV patients enrolled in the Egyptian National Program for HCV treatment with PEG-IFN/RIB. All patients underwent liver biopsy and anti-schistosomal antibodies testing prior to HCV treatment. The serology results were used to categorize the patients into group A (positive schistosomal serology) or group B (negative schistosomal serology). Patients in group A were given oral antischistosomal treatment (praziquantel, single dose) at four weeks prior to PEG-IFN/RIB. All patients received a 48-wk course of PEG-IFN (PEG-IFNα2a or PEG-IFNα2b)/RIB therapy. Clinical and laboratory follow-up examinations were carried out for 24 wk after cessation of therapy (to week 72). Correlations of positive schistosomal serology with fibrosis and treatment response were assessed by multiple regression analysis.

Results: Schistosomal antibody was positive in 27.3% of patients (15.9% females and 84.1% males). The patients in group A were older (P = 0.008) and had a higher proportion of males (P = 0.002) than the patients in group B. There was no significant association between fibrosis stage and positive schistosomal serology (P = 0.703). Early virological response was achieved in significantly more patients in group B than in group A (89.4% vs 86.5%, P = 0.015). However, significantly more patients in group A experienced breakthrough at week 24 than patients in group B (36.3% vs 32.3%, P = 0.024). End of treatment response was achieved in more patients in group B than in group A (62.0% vs 59.1%) but the difference did not reach statistical significance (P = 0.108). Sustained virological response occurred in significantly more patients in group B than in group A (37.6% vs 27.7%, P = 0.000). Multivariate logistic regression analysis of patient data at treatment weeks 48 and 72 showed that positive schistosomal serology was associated with failure of response to treatment at week 48 (OR = 1.3, P = 0.02) and at week 72 (OR = 1.7, P < 0.01).

Conclusion: Positive schistosomal serology has no effect on fibrosis staging but is significantly associated with failure of response to HCV treatment despite antischistosomal therapy.
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http://dx.doi.org/10.3748/wjg.v19.i17.2691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645388PMC
May 2013

Human leukocyte antigen class II alleles (DQB1 and DRB1) as predictors for response to interferon therapy in HCV genotype 4.

Mediators Inflamm 2013 14;2013:392746. Epub 2013 Mar 14.

Departments of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66%) of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1*0313 allele and DRB1*04-DRB1*11, DQB1*0204-DQB1*0313, DQB1*0309-DQB1*0313, and DQB1*0313-DQB1*0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1*02, DQB1*06, DRB1*13, and DRB1*15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1*1301, DRB1*1361, and DRB1*1369 alleles and DRB1*1301-DRB1*1328, DRB1*1301-DRB1*1361, DRB1*1301-DRB1*1369, DRB1*1328-DRB1*1361, and DRB1*1328-DRB1*1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.
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http://dx.doi.org/10.1155/2013/392746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612450PMC
August 2013

Hepatitis C genotype 4 with normal transaminases: correlation with fibrosis and response to treatment, a cohort Egyptian study of 4277 patients.

Clin Res Hepatol Gastroenterol 2013 Nov 26;37(5):479-84. Epub 2013 Mar 26.

Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background And Objective: Chronic hepatitis C virus (HCV) patients with persistently normal transaminases represent a subgroup of patients with mild, slowly progressive disease, natural history, and optimal management of these patients needs to be investigated in Egypt. Our aim is to assess the severity of hepatic fibrosis and response to therapy in a cohort of Egyptian HCV patients with normal transaminases.

Patients And Methods: Retrospective demographics, laboratory, histological features and treatment outcome of patients included in the national program for the control of viral hepatitis in Egypt since 2007 were collected. Combined pegylated IFN/ribavirin therapy was given for patients with fibrosis stage ≥ F1 and elevated transaminases while those with normal transaminase; therapy was initiated only in patients with fibrosis stage ≥ F2.

Results: Normal ALT and AST were detected in 1308/4277 (30.6%) and 1662/4277 (38.9%) patients, respectively, while both enzymes were normal in 943 patients (22%). Multivariate regression analysis showed that lower AFP and higher platelets count (compared with elevated transaminases group) were significantly correlated with normal transaminases (P<0.01), however, HCV-RNA levels did not show such significance. The number of patients with HAI score ≥ A1 was significantly lower in normal than elevated transaminases (36.5% vs 40.9%, respectively, P<0.01) and patients with fibrosis ≥ F2 was significantly lower in normal than elevated transaminases (36.4%) and (43%), respectively (P<0.01). There was no significant correlation between baseline transaminases levels and response to treatment.

Conclusion: Normal transaminases are frequently encountered in chronic HCV Egyptian patients (22%). They show low AFP level, mild degree of activity and stage of fibrosis with no correlation with response to therapy.
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http://dx.doi.org/10.1016/j.clinre.2013.02.009DOI Listing
November 2013

Liver fibrosis staging through a stepwise analysis of non-invasive markers (FibroSteps) in patients with chronic hepatitis C infection.

Liver Int 2013 Aug 20;33(7):982-90. Epub 2013 Mar 20.

Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Non-invasive fibrosis markers can distinguish between liver fibrosis stages in lieu of liver biopsy or imaging elastography.

Aims: To develop a sensitive, non-invasive, freely-available algorithm that differentiates between individual liver fibrosis stages in chronic hepatitis C virus (HCV) patients.

Methods: Chronic HCV patients (n = 355) at Cairo University Hospital, Egypt, with liver biopsy to determine fibrosis stage (METAVIR), were tested for preselected fibrosis markers. A novel multistage stepwise fibrosis classification algorithm (FibroSteps) was developed using random forest analysis for biomarker selection, and logistic regression for modelling. FibroSteps predicted fibrosis stage using four steps: Step 1 distinguished no(F0)/mild fibrosis(F1) vs. moderate(F2)/severe fibrosis(F3)/cirrhosis(F4); Step 2a distinguished F0 vs. F1; Step 2b distinguished F2 vs. F3/F4; and Step 3 distinguished F3 vs. F4. FibroSteps was developed using a randomly-selected training set (n = 234) and evaluated using the remaining patients (n = 118) as a validation set.

Results: Hyaluronic Acid, TGF-β1, α2-macroglobulin, MMP-2, Apolipoprotein-A1, Urea, MMP-1, alpha-fetoprotein, haptoglobin, RBCs, haemoglobin and TIMP-1 were selected into the models, which had areas under the receiver operating curve (AUC) of 0.973, 0.923 (Step 1); 0.943, 0.872 (Step 2a); 0.916, 0.883 (Step 2b) and 0.944, 0.946 (Step 3), in the training and validation sets respectively. The final classification had accuracies of 94.9% (95% CI: 91.3-97.4%) and 89.8% (95% CI: 82.9-94.6%) for the training and validation sets respectively.

Conclusions: FibroSteps, a freely available, non-invasive liver fibrosis classification, is accurate and can assist clinicians in making prognostic and therapeutic decisions. The statistical code for FibroSteps using R software is provided in the supplementary materials.
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http://dx.doi.org/10.1111/liv.12139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793639PMC
August 2013

Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4.

Cell Biochem Funct 2013 Oct 11;31(7):620-5. Epub 2013 Feb 11.

Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.

This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon-based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa-2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real-time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide -155, -443 and -1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at -443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide -443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment.
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http://dx.doi.org/10.1002/cbf.2954DOI Listing
October 2013
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