Egyptian Hepatitis C Virus Patients Research Articles

Incidence of Hepatocellular Carcinoma in Hepatitis C Patients Treated with Direct-Acting Antivirals and Its Relation to Hepatic Fibrosis Stage

Abstract Introduction Significant advances in understanding of the molecular virology, life cycle, and pathogenesis of Hepatitis C Virus (HCV) led to the Direct-Acting Anti-viral (DAA) era of HCV therapy in 2011 (Hezode et al.,2015). It can be expected that rates of HCV-associated hepatocellular carcinoma (HCC) will decrease significantly after the widespread adoption of DAAs, However Hepatitis C patients with cirrhosis who were treated with direct-acting antivirals had increased likelihood of developing HCC (Tayyab et al., 2020) (Kozbial et al., 2016). HCC was also associated with greater liver stiffness according to transient elastography and lower platelet counts (Conti et al., 2016). The aim of this study is to investigate incidence of HCC in Egyptian HCV patients in whom other predominant HCV genotypes are prevalent and different treatment protocols followed. Methods This was a retrospective study including 400 chronic HCV patients who were following up their medical condition at Kobri El-Koba Military Hospital hepatology outpatient clinic from January 2018 to September 2019. Patients were divided into two main equal groups regarding either received HCV direct acting antivirals or not. Incidence of HCC after 18 months of follow up were compared between two groups. Its relation to hepatic fibrosis stage was calculated in both groups. Results DAA receiving group had significantly lower incidence of HCC than non DAA receiving group (control group). Eleven patients in DAA receiving group developed HCC (5.5%) compared to twenty-two patients in control group (11%) with P- value 0.04. Although there was no significant difference between two groups regarding pre-treatment prevalence of ascites, splenomegaly, or esophageal varices, DAA receiving group had statistically significant advanced hepatic fibrosis when compared to control group. Before starting treatment, DAA Receiving group shows (4.5% F0, 14% F1, 7% F2, 11.5% F3 and 63% F4) versus (20.5% F0, 14% F1, 18.5% F2, 6.5% F3 and 40.5% F4) in control group with highly significant P value 0.00. Conclusion Incidence of HCC decreased significantly after DAA in chronic HCV patients. Decreased incidence occurred despite advanced hepatic fibrosis in this group of patients.

Effect of Direct Acting Antivirals (DAAs) on Myeloid-Derived Suppressor Cells Population in Egyptian Chronic Hepatitis C Virus Patients: A Potential Immunomodulatory Role of DAAs.

Chronic hepatitis C is a major health concern with high morbidity and mortality rates. The introduction of direct acting antivirals (DAAs) as a first-line treatment for hepatitis C virus (HCV) has significantly enhanced HCV eradication. However, DAA therapy is facing rising concerns regarding long-term safety, viral resistance, and reinfection. HCV is associated with different immune alteration mechanisms that can evade immunity and establish persistent infection. One of these suggested mechanisms is the accumulation of myeloid-derived suppressor cells (MDSCs), which is known to accumulate in chronic inflammatory conditions. Moreover, the role of DAA in restoring immunity after successful viral eradication is still unclear and needs further investigations. Thus, we aimed to investigate the role of MDSCs in chronic HCV Egyptian patients and its response to DAA in treated compared with untreated patients. Fifty untreated chronic hepatitis C (CHC) patients, 50 DAA-treated CHC patients, and 30 healthy individuals were recruited. We used flow cytometer analysis to measure MDSCs frequency and enzyme-linked immunosorbent assay analysis to evaluate the serum level of interferon (IFN)-γ. We found a significant elevation in MDSC% among the untreated group (34.5 ± 12.4%) compared with the DAA-treated group (18.3 ± 6.7%), while the control group had a mean of (3.8 ± 1.6%). IFN-γ concentration was higher in treated patients compared with untreated. We also found a significant negative correlation (rs -0.662) (p < 0.001) between MDSC% and IFN-γ concentration among treated HCV patients. Our results revealed important evidence of MDSCs accumulation in CHC patients and partial retrieval of the immune system regulatory function after DAA therapy.

Programmed death-ligand 1 (PD-L1) polymorphisms as predictive biomarkers for the development of liver cirrhosis and hepatocellular carcinoma in HCV Egyptian patients

BackgroundConsidering the immune evasion role of programmed death-ligand 1 (PD-L1) in cancer development, its genomic variations might be closely associated with disease development and cancer risks. Accordingly, this study was performed to investigate how the PD-L1 gene polymorphisms affect the susceptibility to hepatitis C virus (HCV)-induced liver cirrhosis and cancer development in the Egyptian population. MethodologyTwo single nucleotide polymorphisms of the PD-L1 gene; rs2297136 (A > G) and rs4143815 (C > G), were studied in 50 HCV, 51 liver cirrhosis, and 52 hepatocellular carcinoma (HCC) patients as well as 50 healthy subjects using real-time PCR. ResultsThe frequencies of PD-L1 rs2297136 AA and rs4143815 GG genotypes were significantly higher in the liver cirrhosis than the control and HCV groups. The rs4143815 CG and GG genotypes were linked to a higher risk of developing HCC and were positively associated with the clinicopathological features of HCC. ConclusionsThe PD-L1 rs2297136 AA and rs4143815 GG genotypes increase the susceptibility to liver cirrhosis. The rs4143815 CG and GG genotypes are positively associated with HCC risk and its clinicopathological characteristics. Therefore, HCV patients carrying the PD-L1 rs4143815 G-allele should be followed up on a regular basis to allow for early HCC management.

Assessment of Renal Function in Egyptian HCV Patients Treated with Combination Therapy of Sofosbuvir and Daclatasvir

BACKGROUND: According to the most recent Egyptian demographic health census, the estimated Hepatitis C virus (HCV) prevalence in the 15–59 age range was 14.7%. Globally, the incidence of renal impairment in HCV-positive individuals is 40% higher than in HCV-negative patients. HCV-induced renal impairment can range from mild-to-severe, and it frequently complicates the treatment outcome of HCV infection. AIM: This study aimed to explore the changes in renal function in Egyptian HCV patients treated with a combination of Sofosbuvir (SOF) and Daclatasvir (DCV). METHODOLOGY: Six hundred and eleven chronic HCV patients treated with SOF-DCV were enrolled. Patients were classified into three groups according to their baseline renal function: unimpaired group (estimated glomerular filtration rate [eGFR] ≥ 90 ml/min/1.73 m2), mildly impaired group (eGFR of ≥60–89 ml/min/1.73 m2), and moderately impaired group (eGFR of ≥30–59 ml/min/1.73 m2). Every month during treatment and at 24 weeks after treatment (sustained virological response 24), the eGFR level was evaluated. RESULTS: Our findings indicated that the eGFR level was significantly increased (p &lt; 0.001) in all groups during the treatment but subsequent decline (p &lt; 0.001) in all groups was documented after 6 months of treatment. Multivariate analysis identified baseline renal impairment (&lt;90 ml/min/1.73 m2, p &lt; 0.001) and baseline anemia (p &lt; 0.001) as independent risk factors for renal function deterioration at the end of treatment. CONCLUSION: Clinical physicians should closely monitor renal function in patients treated with SOF-DCV. Furthermore, anemia therapy prior to SOF-DCV treatment should be recommended.

The Effect of HCV Eradication after Direct-Acting Antiviral Agents on Hepatic Steatosis: A Prospective Observational Study

Eradication of hepatitis C virus (HCV) by direct-acting-antiviral- agents (DAAs) was followed by fibrosis regression, but little is available about hepatic steatosis changes after DAAs. The aim of this work was to assess the prevalence of hepatic steatosis among HCV Egyptian patients and the long term changes occuring after viral eradication. This prospective cohort study included 150 HCV patients with significant fibrosis. They were examined by Transient elastography to evaluate liver stiffness measurement (LSM) and hepatic steatosis before treatment, at SVR12 and 1 year after the end of therapy. LSM showed a significant positive correlation to pretreatment of hepatic steatosis. LSM significantly decreased and hepatic steatosis significantly increased both at SVR12 and one year after DAAs. Patients with steatosis showed significantly higher median LSM and controlled attenuation parameter (CAP) values at: baseline, SVR12, and one year after therapy. Also, the pretreatment steatosis and body mass index (BMI) had a significant negative correlation with fibrosis regression one year after therapy in all studied groups. Hepatic steatosis is common in HCV Egyptian patients and increases after HCV eradication with DAAs. BMI and CAP values are negatively correlated to hepatic fibrosis regression and positively correlated to steatosis progression one year after DAAs. So, HCV patients with hepatic steatosis may need close follow up for atherosclerotic and HCC risk after DAAs, especially if they are overweight.

Assessment of Hepatic Steatosis Before and After Treatment In Egyptian HCV Patients Treated With DAAs Using Non Invasive Parameters

Abstract Background Hepatitis C virus (HCV) is a major health problem worldwide. More than one million people die each year from hepatitis C virus (HCV) related diseases. Aim of the Work to evaluate the effect of direct acting antiviral drugs on hepatic steatosis in naïve HCV chronically infected Egyptian patients after reaching SVR12. Patients and Methods study was carried out on 100 treatment naive patients with chronic infection of HCV attending the out-patient clinic. The patients were diagnosed having HCV by detecting HCV antibodies by ELISA &amp; PCR for HCV RNA at The Gastro-enterolgy and Hepatology Department, Ain Shams University and Kobry El Koba Military Hospital between August 2017 till February 2019. Results The mean TG, mean s. cholesterol and APRI Score decreased significantly showing a high statistical significant difference between baseline and SVR12. The mean HDL and LDL significantly increased showing a high statistical significant difference between baseline and SVR12. NAFLD Score increased from baseline to SVR12 showing a statistical significant difference in NAFLD Score between baseline and SVR12. Fibroscan median mean decreased showing a highly statistical difference in Fibroscan Median between baseline and SVR12. Out of 100 patients, cirrhosis regressed to F3 in 33 patients, F2 in 3 patients and didn’t regress to F1 in any patient, while the majority (43 patients) remained as F4 at SVR12. Conclusion APRI Score mean and Fibroscan median mean were significantly decreased, while NAFLD Score was increased among the studied groups from baseline and SVR12.

Safety and Efficacy of Sofosbuvir Based Regimens in Treating Chronic ‎Hepatitis C Virus in Egyptian Patients: Real World Study: Single Center ‎Experience

Backgroundand study aims:Hepatitis C virus (HCV) is the main leading cause of liver disease in ‎Egypt. A new era of HCV treatment has been started with the evolution ‎of direct acting antiviral agents. Sofosbuvir (SOF)-based therapy was ‎introduced by the Egyptian ministry of health in 2014 in an attempt to ‎decrease disease burden. We aimed to evaluate efficacy and safety of ‎Sofosbuvir-based regimens in HCV Egyptian patients with compensated ‎liver disease‎. Patients and Method:‎This study was conducted in National Liver Institute, Menoufia‎University, Egypt. Seven hundred patients out of seven hundred fifty-‎eight chronic HCV patients with compensated liver disease who met the ‎inclusion criteria were included. According to treatment regimen patients ‎were divided to 4 groups; group 1 received Sofosbuvir (SOF), ‎Pegylated interferon (PEG-IFN) plus ribavirin (RBV), group 2 received ‎SOF plus RBV, group 3 received SOF and Simeprevir± RBV, group 4 ‎received SOF and Daclatasvir ±RBV‎.‎ Results:The overall SVR was 90.9%, 81.5%, 95% and 98% in groups 1, 2, 3, ‎and 4 respectively. SVR in patients with liver cirrhosis was 90.56, ‎‎79.16, 95 and 96% in the 4 groups respectively. In treatment ‎experienced patients, SVR was 86.8% in group 1, 78.3% in group 2, ‎‎100% in group 3 and 86.7% in group 4‎‎‎‎. Conclusion: Sofosbuvir plus daclatasvir with or without ribavirin is the safest ‎andmost effective SOF-based regimen in treatment of HCV Egyptian ‎patients with compensated liver disease‎‎‎‎.

The association of Fat Mass and Obesity-Associated (FTO) gene polymorphism (rs9939609) with metabolic disturbances and response to sofosbuvir, ribavirin and interferon triple therapy in patients with viral hepatitis C

ObjectivesChronic hepatitis C virus (HCV) infection is a major health problem in Egypt. The Fat mass and obesity associated (FTO) gene has metabolic regulatory roles. HCV affects the signaling cascade of insulin. This study aimed to assess the relation of FTO rs9939609 polymorphisms with treatment outcomes and metabolic disturbance in HCV Egyptian patients. Subjects and methodsThe study included 200 HCV genotype 4 patients treated with triple therapy (sofosbuvir, ribavirin and interferon) for 12 weeks. The principal efficiency endpoint was sustained viral response at 12 weeks (HCV RNA < 12 IU/mL) and FTO rs9939609 gene was analyzed by real-time PCR. Fasting serum insulin and alpha-feto protein (AFP) and were measured by ELISA. ResultsPatients response to HCV triple therapy was 93%. Stepwise logistic regression showed that the chance of non-response increases by 7.9% with every unit increase of the AFP value (OR = 1.079, 95% CI = 1.036; 1.124, P < 0.001). There was no correlation between the FTO variant and treatment outcome. There was a significant increase in HOMA-IR in non-responders compared with responder patients. ConclusionFTO rs9939609 variant is not associated with treatment outcome of HCV patients on triple therapy. However, insulin resistance and AFP levels were associated with achievement of successful virological response.

Hepatitis C core antigen: a simple predictive marker for treatment response to the new direct-acting antiviral drugs in chronic HCV Egyptian patients

BackgroundSuccessful eradication of hepatitis C virus (HCV) has great impact on the prognosis of HCV-related complications and the associated mortality. The development of the new direct-acting antiviral drugs (DAAs) has revolutionized the treatment of HCV infection. HCV core antigen (HCVcAg) is a recently developed marker that displayed a good correlation with HCV RNA assays. Our main objectives were to correlate between serum levels of HCVcAg and HCV RNA loads in chronic HCV patients as well as to explore the potential value of HCVcAg assay in predicting treatment response to the new DAAs. The study enrolled a total of 280 chronic HCV-infected patients scheduled to start the new regimen for treatment of chronic HCV by all-oral, interferon-free DAAs. According to the viral load, the studied individuals were arranged into three groups corresponding to mild, moderate, and sever viremia. Serum level of HCVcAg was determined by ELISA technique and HCV RNA viral loads were quantified using the real-time PCR system. The assays were performed three times for all participants: prior to initiation of treatment, at the end of treatment (week 12), and 3 months post-treatment cessation (week 24).ResultsA statistically significant difference between HCV RNA and HCVcAg baseline levels among different viremia groups was detected (P < 0.001). There was a significant positive correlation between HCV RNA and HCVcAg baseline values among all the studied cases (P < 0.05) with a correlation coefficient of 0.752, 0.976, and 1.00 respectively for mild, moderate, and severe viremia groups. 92.9% (260/280) of the studied patients achieved sustained virologic response, 3.6% (10/280) were non-responders, and 3.6% (10/280) had recurrent viremia/relapse as regards RT-PCR results.ConclusionHCVcAg is a promising alternative to HCV RNA assay. The ELISAs for HCVcAg proved excellent correlations with HCV RNA levels. Moreover, HCVcAg can be introduced as a simple and highly specific tool for monitoring the new DAA regimens particularly in low-resource settings.

Chemokine receptor CXCR6 gene polymorphism and treatment response of chronic hepatitis C virus in Egyptian patients.

Aim of the studyDespite achieving a high cure rate of chronic hepatitis C nowadays, treatment failure remains a major concern and host genetic polymorphism could have a possible relation. The aim was to evaluate the role of chemokine receptor CXCR6 gene polymorphism in treatment response to direct acting antivirals (DAAs) in chronic hepatitis C virus (HCV) patients.Material and methodsWe investigated the chemokine receptor CXCR6 gene single nucleotide polymorphism rs2234358 in three groups. Responder and non-responder groups (each comprising 50 naïve patients) and a control group of 50 apparently healthy individuals were studied.ResultsGenotype distribution revealed a significant difference (p = 0.037) between non-responders and the other 2 groups. Both control and responder groups showed allelic frequencies of 20% having the wild allele G and 80% having the variant allele T, while in the non-responder group 39% had G and 61% had the T alleles. Genotype GG was associated with significant increased risk of not responding to treatment by 4.25 times as compared with TT genotype (p = 0.019) and the G allele was associated with highly significant risk of not responding to treatment by 2.56 times compared with the T allele (p = 0.003).ConclusionsCXCR6 gene (rs2234358) polymorphism could have a potential role in the virological treatment response with a protective effect of the T allele. This could explain the higher treatment success rate of Egyptian HCV patients.

Modulation of Memory B Cell Phenotypes and Toll-Like Receptor-7 in Chronic Hepatitis C Virus Infection During Direct-Acting Antiviral Interferon-Free Therapy: Correlation with Interleukin-7.

Hepatitis C virus (HCV) infection is a major worldwide problem with the highest incidence rates in Egypt. It affects B cells that serve as reservoirs for persistent HCV, resulting in phenotypic B cell alterations. Interleukin-7 (IL-7) is a cytokine with antiviral activity, important for B cell physiology. In addition, B cell-intrinsic toll-like receptor-7 (TLR7) signaling is required for optimal B cell responses during chronic viral infection, and the deficiency of TLR7 in B cells is sufficient to significantly impact antibody responses. Based on their known immunomodulatory effects, we hypothesized that direct-acting antiviral interferon-free therapy may affect TLR7 expression and the exhausted peripheral B cell compartment with the possibility of their restoration in patients who achieved a sustained virological response and their correlation to IL-7 level. This prospective study was accomplished on 80 Egyptian HCV patients and 75 controls. Frequencies of peripheral B cell subsets, TLR7 gene expression, TLR7 protein, and serum IL-7 levels were investigated by flow cytometry, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. B cell subpopulations were exhausted and partially restored among HCV patients after receiving treatment, but not recovered with regard to activated mature or resting memory B cells. Almost all responders to direct antiviral drugs showed upregulation of TLR7 gene expression and correlated with the frequency of memory B cell, but not with IL-7. Moreover, IL-7 was not significantly different between groups although correlated with immature transitional B cells. Results may indicate the interplay between TLR7 and B cells during remission or progression of HCV. Thus, TLR7 could be used as a promising biomarker for assessment of antiviral treatment efficacy among chronically infected HCV patients, and that targeting TLR7 may be used as a potential prophylactic and/or therapeutic agent during chronic HCV as well as immune-potentiation of memory B cells.

Impact of interleukin IL-6 rs-1474347 and IL-10 rs-1800896 genetic polymorphisms on the susceptibility of HCV-infected Egyptian patients to hepatocellular carcinoma.

Hepatitis C virus (HCV) is considered leading cause of cirrhosis and hepatocellular carcinoma (HCC). We aimed to examine the association of IL-6 and IL-10 single-nucleotide polymorphisms with the progression of chronic HCV (CHC) infection to cirrhosis and HCC. For comparative purposes, four groups were enrolled; chronic HCV group (CHC, n= 22), HCV-related liver cirrhosis group (HCV-LC, n= 22), HCV-related HCC group (HCV-HCC, n= 54), and an apparently healthy control group (controls, n= 48). HCC diagnosis and staging were in concordance to Barcelona Clinic Liver Cancer (BCLC) staging system. IL-6 rs-1474347 and IL-10 rs-1800896 genotyping was performed by allelic (VIC- and FAM-labeled) discrimination method using assay-on-demand TaqMan real-time PCR assays. For IL-6 rs1474347, the AA genotype was more frequent in CHC, HCV-LC, and HCV-HCC compared to controls. Also, the IL-6 rs1474347 AC genotype was favorable for the progression of HCV chronic infection to cirrhosis and HCC. On the other hand, the IL-10 rs1800896 TT genotype was found to be prominent in the HCC group. Additionally, the IL-10 rs180096 TT genotype was favorable for the progression of chronic HCV infection to cirrhosis and HCC. Furthermore, higher levels of AFP were observed in HCC patients with IL-6 rs1474347 AA genotype and HCC patients with IL-10 rs1800896 CC and TT genotypes. Screening for IL-6 rs 1474347 AC genotype and IL-10 rs180096 TT genotype as well as the determination of AFP level showed to be good markers for examining the susceptibility of HCV Egyptian patients to develop cirrhosis and HCC.

XRCC1 Gene Polymorphism Increases the Risk of Hepatocellular Carcinoma in Egyptian Population.

Section TitleSeveral major risk factors for hepatocellular carcinoma (HCC) have been identified, including chronic infection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Nevertheless, only a fraction of infected patients develops HCC during their lifetime suggesting that genetic factors might modulate HCC development. X-ray repair cross complementing group1 (XRCC1) participates in the repair pathways of DNA. Aim:to investigate the association between XRCC1 gene polymorphism and HCC in Egyptian chronic hepatitis C patients. Methods:This study was assessed on 40 patients with HCC secondary to chronic HCV infection who were compared to 20 cirrhotic HCV patients and 40- age and gender- matched healthy control group. After collection of relevant clinical data and basic laboratory tests, c.1517G>C SNP of XRCC1 gene polymorphism was performed by (PCR-RFLP) technique. Results:A statistically higher frequency of XRCC1 (CC, GC) genotypes and increased (C) allele frequency in patients with HCC was found in comparison to cirrhotic HCV patients as well as control group. In addition, patients with the XRCC1 (CC, GC) genotypes had significantly higher number and larger size of tumor foci and significantly higher Child Pugh grades. Multivariate analysis showed that the presence of c.1517G>C SNP of XRCC1 gene is an independent risk for the development of HCC in chronic HCV patients with 3.7 fold increased risk of HCC development. In conclusion: XRCC1 gene polymorphism could be associated with increased risk of HCC development in chronic HCV Egyptian patients.

Serum microRNA let-7a-1/let-7d/let-7f and miRNA 143/145 Gene Expression Profiles as Potential Biomarkers in HCV Induced Hepatocellular Carcinoma.

Background:Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Which make liver cirrhosis and hepatocellular carcinoma (HCC) major health concerns in Egypt. Circulating microRNAs (miRNAs) have been investigated as biomarkers for malignancies. We investigated miRNA gene expression of Lethal-7 (let-7) cluster: let7-a-1, let-7d-1, let-7f-1 and miRNA (miR)143/145 cluster in sera of HCC patients and chronic HCV patients. Methods:The study included 40 post HCV-Hepatocellular carcinoma patients, 40 chronic HCV patients divided into 2 subgroups, 20 cirrhotic patients and 20 non-cirrhotic patients, and 40 apparently healthy subjects as a control group. Gene expression analysis for studied miRNAs was done using quantitative SYBR Green reverse-transcription Real-Time polymerase chain reaction (PCR). Results:We found that Let-7a-1 gene expression was significantly downregulated in the serum of HCV-HCC patients than in HCV non HCC cirrhotic group and was significantly upregulated in the serum of liver cirrhosis patients than HCV non-cirrhotic group. miR-143 and miR-145 expressions were significantly downregulated in the serum of HCC patients than in control group and miR-143 was significantly downregulated in the serum of non-cirrhotic HCV patients than in control group. Conclusion:The downregulation of serum let-7-a1, miR-143, and miR-145 gene expression may exhibit significant influence on the development of HCC in chronic HCV Egyptian patients and can be used as biomarkers for HCC diagnosis.

Fibroscan and FIB-4 Assessment Versus Lymphocyte / Monocyte Ratio as Predictors of Post-Hepatectomy Liver Failure in HCV Egyptian Patients with Hepatocellular Carcinoma

Background: Post-hepatectomy liver failure (PHLF) is the most leading cause of mortality in patients diagnosed with hepatocellular carcinoma (HCC) and undergoing resection of the affected part of the liver. Objectives: This research aimed to determine the value of the lymphocyte to monocyte ratio (LMR), fibrosis score 4 (FIB-4) and liver stiffness measurements (LSM) using Fibroscan as pre-operative predictors of PHLF in Egyptian patients with post- hepatitis C virus (HCV) liver cirrhosis and HCC. Methods: In this prospective cohort study definition of PHLF was done according to the “50-50 criteria”. Multivariate analysis was done to identify PHLF independent predictors. The predictive accuracy of the pre-operative LMR, FIB-4 and LSM with Fibroscan were evaluated by receiver operating characteristic (ROC) curve. Results: Enrollment of fifty Egyptian patients was done. 14 patients (28%) experienced PHLF. The presence of oesophageal varices, serum AST, serum albumin, LMR, FIB-4 score, and LSM (P<0.05) were independent pre-operative predictors for PHLF. According to ROC curve analysis, LMR yielded the best accuracy for predicting PHLF at cutoff <3.33 [AUC = 0.940; sensitivity = 93.65%; specificity = 94.44%; positive predictive value = 86.67%; negative predictive value = 97.14%]. FIB-4 score and LSM had lower AUC (0.886 and 0.875) respectively. Conclusion: The pre-operative LMR has a higher predictive ability for PHLF in patients with HCV-related HCC undergoing hepatectomy compared with FIB-4 score and LSM using Fibroscan.

Tolerance and Effectiveness of Oral Direct Acting Antivirals in Treatment of HCV Egyptian patients with Decompensated Liver Cirrhosis

Background: Medical treatment of decompensated cirrhosis due to hepatitis C virus (HCV) remains a clinical challenge even in the era of direct-acting antiviral drugs (DAAs). We evaluated the efficacy and safety of DAAs in the management of HCV-related decompensated cirrhosis. Objective: The current study aimed to evaluate the efficacy and safety of DAAs in managing HCV patients with decompensated cirrhosis and the impact of achieving sustained virological response on improving the quality of life, short term survival and if viral eradication would step down CTP score. Patients and Methods: The study included a treatment group I (n = 25) composed of HCV patients with decompensated cirrhosis Child B and group II (n = 22) with decompensated cirrhosis Child C. both groups received DAAs (sofosbuvir 400 mg, daclatasvir 60 mg) plus ribavirin as tolerated for 3 months and follow-up was done for 6 months. Results: In both treated groups, there were improvements in platelet count, albumin, Child-Torcout-Pugh (CTP) (p = 0.001) and a significant reduction in the frequency of hepatic encephalopathy (HE). Also, there was improvement in quality of life of both treated groups. Conclusion: Treatment of HCV with decompensated cirrhosis with DAAS had improved CTP score, quality of life and survival.

Lack of association between 4 key TNF-alpha promoter polymorphisms and hepatitis C virus infection in a population of Egyptian patients

Introduction: With 170 million chronic hepatitis C virus (HCV) cases worldwide, HCV is considered a major life-threatening pathogen. HCV is a crucial causative of liver cirrhosis and hepatocellular carcinoma. Tumor necrosis factor-alpha (TNF-alpha) is thought to be a mediator in the development of viral hepatitis. Because HCV is epidemic in Egypt, this study aimed to characterize the distribution of TNF-alpha gene promoter polymorphisms and their relation to TNF-alpha expression in HCV patients.&#x0D; Methods: Four promoter polymorphisms; −1031T/C, −863C/A, −857C/T, and −308G/A, were studied by restriction fragment length polymorphism in a population of Egyptian HCV patients.&#x0D; Results: Compared to healthy subjects, none of these polymorphisms were associated with HCV infection. The wild-type −1031T, −863A, −857C, and −308G alleles were highly prevalent in the studied population. Sequencing the promoter region spanning the four studied polymorphisms in some subjects did not reveal any difference in the nucleotide variance pattern, compared with the TNF-alpha reference sequence. Relative TNF-alpha mRNA expressions in HCV patients and healthy subjects were statistically indifferent.&#x0D; Conclusion: Since previous studies confirmed an increase in TNF-alpha level in case of viral infections, this study focuses on mechanisms of post-transcriptional and posttranslational modifications of TNF-alpha gene in HCV patients, which decode the genetic factors linked to HCV infection and severity.&#x0D;

Rs2267531, a promoter SNP within glypican-3 gene in the X chromosome, is associated with hepatocellular carcinoma in Egyptians

Hepatocellular carcinoma (HCC) is a major health concern in Egypt owing to the high prevalence of hepatitis C virus (HCV) infection. HCC incidence is characterized by obvious male predominance, yet the molecular mechanisms behind this gender bias are still unidentified. Functional variations in X-linked genes have more impact on males than females. Glypican-3 (GPC3) gene, located in the Xq26 region, has lately emerged as being potentially implicated in hepatocellular carcinogenesis. The current study was designed to examine the association of −784 G/C single nucleotide polymorphism (SNP) in GPC3 promoter region (rs2267531) with HCC susceptibility in male and female Egyptian HCV patients. Our results revealed a significant association between GPC3 and HCC risk in both males and females, evidenced by higher C allele and CC/C genotype frequencies in HCC patients when compared to controls. However, no such association was found when comparing HCV patients to controls. Moreover, GPC3 gene and protein expression levels were significantly higher in CC/C than in GG/G genotype carriers in males and females. The CC/C genotype exhibited a significant shorter overall survival than GG/G genotype in HCC patients. In conclusion, GPC3 rs2267531 on the X chromosome is significantly associated with HCC, but not with HCV infection, in the Egyptian population.

Towards hepatitis C virus elimination: Egyptian experience, achievements and limitations.

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.

MiRNA-221 and miRNA-222 are promising biomarkers for progression of liver fibrosis in HCV Egyptian patients

BackgroundCurrent methodologies used to determine the progression of hepatic fibrosis rely heavily on liver biopsy, a dangerous and invasive procedure, with semi-subjective analysis of the results of the biopsy. Thus, a new approach is immensely needed for monitoring the progression of liver fibrosis in Hepatitis C virus (HCV) patients. Aim of workThe purpose of this study was to find highly specific and sensitive miRNA biomarkers that can be used to detect different stages of liver fibrosis. MethodologyThe study consisted of 42 cases of chronic hepatitis C (CHC) with early-stage fibrosis, 45 cases of CHC with late-stage fibrosis, and 40 healthy subjects with no CHC or fibrosis as controls. Expression patterns of 5 miRNAs (miR-16, miR-146a, miR-214-5p, miR-221, and miR-222) were analyzed in each group using TaqMan real-time PCR. ResultsSerum levels of miRNA-16, miRNA-146a, miRNA-221, and miRNA-222 were all significantly up-regulated in early and late stages of liver fibrosis. miRNA-222 had the highest sensitivity and specificity values in early and late fibrosis. miRNA-221 had the second highest sensitivity and specificity with the late-stage fibrosis group. Furthermore, miRNA-221 showed significant positive correlations with both miRNA-16 and miRNA-146a in the early- and late-stage fibrosis groups, with the early stage having a stronger correlation. ConclusionsThe results indicated that miRNA-16, miRNA-146a, miRNA-221, and miRNA-222 can be used to detect the presence of liver fibrosis. The high sensitivity and specificity of miRNA-222 and miRNA-221 in late-stage fibrosis indicate promising prognostic biomarkers for HCV-induced liver fibrosis.