Chronic Hepatitis C Virus Egyptian Patients Research Articles

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.

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.

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.

Comparison of hepatic and splenic stiffness in chronic hepatitis C infection with and without schistosomal infection; correlation with hepatic histopathological changes.

Aim of the studyTo assess the degree of liver and spleen stiffness in chronic hepatitis C virus (HCV) patients co-infected with schistosomiasis, and chronic HCV mono-infected patients.Material and methodsThe present study was conducted on 50 Egyptian chronic HCV patients, categorized into two groups: group A (25 patients with chronic HCV mono-infection) and group B (25 patients with chronic HCV and schistosomiasis coinfection). Also, 25 age- and sex-matched healthy subjects with no evidence of liver disease were included in the study as a control group. Stage of fibrosis was assessed invasively by histopathological examination of liver biopsies (patients only) and non-invasively by acoustic radiation force impulse imaging (ARFI) (all subjects).ResultsARFI of liver (ARFI L) and ARFI of spleen (ARFI S) in group A patients who had significant fibrosis were 1.82 ±0.24 and 2.72 ±0.26, respectively, while in group B, ARFI L and ARFI S in patients with significant fibrosis was 1.99 ±0.53 and 3.10 ±0.57, respectively.ConclusionsThe current study demonstrated insignificantly higher values of liver stiffness and significantly higher values of spleen stiffness assessed by ARFI in patients co-infected with HCV and schistosomiasis than mono-infected with HCV.

The Value of Iron Metabolism Dynamic Changes in Response to Direct Anti-Viral Agents among Egyptian Chronic HCV Patients

Background: Like other viruses, hepatitis C virus (HCV) needs constituents of host cells to proliferate and iron is considered as one of the most important constituents. So, chronic HCV often appears to be associated with disturbances in iron homeostasis. Objective: The aim of this study was to evaluate the iron metabolism dynamic changes in response to direct antiviral agents (DAAs) among Egyptian chronic HCV patients. Patients and Methods: This prospective cohort study was conducted on 180 subjects, 150 of them had chronic HCV whom received different DAAs regimens at one of the specialized HCV treatment facilities (Group A), as well as another 30 healthy volunteers (Group B), in the period from January 2017 to September 2018. The study was approved by the medical ethics committee of Al-Azhar University Hospitals and a written informed consent was obtained from all patients. Result: Before treatment, serum iron, ferritin, transferrin saturation and triglycerides were significantly higher among HCV patients when compared to controls (p<0.001), while serum TIBC, transferrin, hepcidin, hepcidin/Ferritin ration, cholesterol were significantly lower in HCV patients in comparison with controls (p<0.001). Following treatment with DAAs, serum iron, ferritin, transferrin saturation and triglycerides were significantly decreased. On the other hand, serum TIBC, transferrin, hepcidin, hepcidin/Ferritin ration and serum cholesterol were significantly increased. The improvement of HbA1c was associated with an improvement in iron overload parameters. Conclusion: Rapid decrease in serum ferritin during IFN/RBV free treatment may reflect a quick regression of inflammation after inhibition of viral replication. The improvement in the iron parameters associated with improvement in triglyceride and glucose metabolism may also suggest an improvement of metabolic functions of the liver following HCV eradication.

The Value of Iron Metabolism Dynamic Changes in Response to Direct Anti-Viral Agents among Egyptian Chronic HCV Patients

Background: Like other viruses, hepatitis C virus (HCV) needs constituents of host cells to proliferate and iron is considered as one of the most important constituents. So, chronic HCV often appears to be associated with disturbances in iron homeostasis. Objective: The aim of this study was to evaluate the iron metabolism dynamic changes in response to direct antiviral agents (DAAs) among Egyptian chronic HCV patients. Patients and Methods: This prospective cohort study was conducted on 180 subjects, 150 of them had chronic HCV whom received different DAAs regimens at one of the specialized HCV treatment facilities (Group A), as well as another 30 healthy volunteers (Group B), in the period from January 2017 to September 2018. The study was approved by the medical ethics committee of Al-Azhar University Hospitals and a written informed consent was obtained from all patients. Result: Before treatment, serum iron, ferritin, transferrin saturation and triglycerides were significantly higher among HCV patients when compared to controls (p<0.001), while serum TIBC, transferrin, hepcidin, hepcidin/Ferritin ration, cholesterol were significantly lower in HCV patients in comparison with controls (p<0.001). Following treatment with DAAs, serum iron, ferritin, transferrin saturation and triglycerides were significantly decreased. On the other hand, serum TIBC, transferrin, hepcidin, hepcidin/Ferritin ration and serum cholesterol were significantly increased. The improvement of HbA1c was associated with an improvement in iron overload parameters. Conclusion: Rapid decrease in serum ferritin during IFN/RBV free treatment may reflect a quick regression of inflammation after inhibition of viral replication. The improvement in the iron parameters associated with improvement in triglyceride and glucose metabolism may also suggest an improvement of metabolic functions of the liver following HCV eradication.

Evaluation of Serum Level of IL-6 in Chronic Hepatitis C Virus Infected Egyptian Patients

Background: Hepatitis C virus (HCV) infection is a worldwide public health problem. The highest prevalence is in Egypt and constitute about 10-20% of the general population. IL-6 is a plieotropic cytokine that plays a role in the acute phase response; it is released from various cells, such as, Leukocytes, fibroblasts, macrophages and endothelia cells. IL-6 is produced by kupffer cells in the liver and leads to production of the acute phase proteins. Aims: This study was conducted to evaluate serum level of IL-6 as a marker of liver fibrosis in chronic hepatitis C virus infected Egyptian patients and to assess its correlation with the stages of liver fibrosis. Methods: A case control study was conducted on 40 Egyptian patients with chronic HCV infection (group1). Studied patients were divided according to the stage of fibrosis assessed by fibroscan into two sub-groups: Group Ia: 22 Patients with early fibrosis (F0, F1, F2) and Group Ib: 18 Patients with late fibrosis (F3, F4) compared to age matched 40 healthy controls (group 11). Routine laboratory investigations, Hepatitis markers including (HBsAg), HCV antibody and HCV RNA by real time polymerase chain reaction (PCR) and, serum Interleukin-6 and Abdominal ultrasonography were done for all studied groups and assessment of liver fibrosis by APRI score & FIB-4for patients and control but Fibro scan for patients only. Results: There were highly significant Elevation of serum level of IL-6 in group1 when compared to the control and This elevation was more significant in (group Ib) when compared to (group Ia) and There was highly significant positive correlation between serum IL-6 and each of serum ALT, AST and Fibro scan in group 1. Conclusion: The study concluded that a highly significant elevation of serum level of IL-6 in chronic HCV Egyptian patients and there was a highly significant positive correlation between IL-6 and stages of liver fibrosis assessed by fibroscan.

Real-life results of sofosbuvir based therapy in chronic hepatitis C -naïve and -experienced patients in Egypt.

BackgroundMore than ten million Egyptians are infected with HCV. Every one of them is going to infect about three to four persons every year. Treating those patients is a matter of national security. A dramatic improvement in hepatitis C virus (HCV) infection treatment was achieved in the last five years. A new era of direct-acting antivirals is now dawning in Egypt.Objective(s)We share in this report our clinical experience in treating chronic HCV Egyptian patients with Sofosbuvir based regimens to evaluate its safety and efficacy on real life practical ground.MethodsA total of 205 chronic HCV patients (195 naive and 15 experienced) were enrolled in the study. Patient were treated with Sofosbuvir+Ribavirin 24 weeks as standard of care. Two interferon eligible patients were treated with PEG-INF+ Sofosbuvir+Ribavirin for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response at 24 weeks after cessation of therapy.ResultsThe overall response rate was 97.1%. Sustained virological response rate did not differ among treatment-naive patients and patients with previous history of IFN-based therapy. Portal hypertension, prediabetes, and lack of early virologic response were predictors of non response. No clinically significant treatment-emergent adverse effects were noted. No treatment discontinuation was encountered.ConclusionIn the real-life setting, Sofosbuvir based regimens for 24 weeks has established an efficacious and well tolerated treatment in naïve and experienced patients with chronic HCV genotype 4 infection; although shorter treatment durations may be possible. However, patient follow up should extent to at least 6 months post-treatment and verifying viral load on yearly basis is warranted to track any late relapse.

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement.

BackgroundLiver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 pre-dominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM) improvement after successful HCV eradication.Patients and methodsThe study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA) treatment and after achieving sustained virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified into F0–F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4), p-value <0.05 was statistically significant.ResultsFollowing DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%), mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m2. Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of −5.8 occurred in F4 versus −2.79, −1.28 and +0.08 in F3, F2 and F0–F1 respectively (p<0.0001). At baseline, 41 patients were in the F4 group; only 16 (39%) regressed to non-cirrhotic range (<12.5 kPa), while 25 (61%) were still cirrhotic despite achieving SVR-24 (p<0.0001). Patients who achieved LSM improvement (n=64) have had significantly higher baseline aspartate transferase (AST) and alanine transaminase (ALT). Also, those patients showed significant improvement in AST, AST/platelets ratio index (APRI) and fibrosis-4 index (Fib-4) after achieving SVR; 91% showed AST improvement (p=0.01) and APRI improvement (p=0.01) and 81% showed Fib-4 improvement (p=0.04). Females, diabetics, patients with S3 steatosis and patients older than 50 years showed less LSM improvements than their counterparts. Baseline LSM ≥9 kPa, bilirubin ≥1 mg/dl, ALT ≥36 U/L and AST ≥31 U/L were significant predictors for LSM improvement.ConclusionSuccessful HCV genotype-4 eradication results in significant LSM improvement; the best improvement occurs in F4 patients. But as the majority of cirrhotics are still at risk for liver decompensation and hepatocellular carcinoma development despite achieving SVR-24, early detection and treatment are highly recommended.

The genetic association of cytokine genes, single nucleotide polymorphisms, and the incidence of liver cirrhosis in chronic hepatitis C Egyptian patients

Cytokines play a central role in regulating the anti-viral responses against hepatitis C virus (HCV). The objective of this study were to evaluate the effect of proinflammatory cytokines (IL-18 − 607 C/A, rs 1946518; IL-18 − 137 G/C, rs 187283; INF-γ + 874 T/A, rs 240561), SNPs, and the anti-inflammatory cytokine (IL-10 + 1082 G/A, rs 1800896) SNPs on the risk of development of hepatic cirrhosis in Egyptian patients and to evaluate the combined effect of the polymorphic variants that show an interrelation with the risk of hepatic cirrhosis. The study included 63 chronic HCV patients. The patients were stratified into two groups. Group 1 consisted of 33 cirrhotic chronic hepatitis C patients while the second group consisted of 30 non-cirrhotic chronic hepatitis C patients that were taken as a control group. Genotyping of IFN-γ (+ 874 T/A) and IL-10 (− 1082 G/A) SNPs was performed by allele-specific PCR technique (AS-PCR). Genotyping of IL-18 (− 607 C/A) and IL-18 (− 137 G/C) SNPs was determined by PCR-RFLP technique. Analysis of IFN-γ (+ 874 T/A) SNP revealed that the T allele and the TT genotype were significantly higher in cirrhotic patients’ group compared to non-cirrhotic group (P < 0.001 and P = 0.004, respectively). Analysis of IL-10 (− 1082 G/A) SNP revealed that the A allele and AA genotype were significantly higher in the cirrhotic patients’ group (P = 0.001 and P = 0.047, respectively). Regression analysis revealed that IFN-γ Hi/IL-10 Lo combined genotypes were significantly higher in liver cirrhosis patients compared to non-cirrhotic patients (P = 0.002). INF-γ (+ 874 T/A) and IL-10 (+ 1082 G/A) SNPs might be associated with occurrence of hepatic cirrhosis in chronic HCV Egyptian patients.

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

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.

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

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.

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

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.

Association of Myxovirus Resistance Gene Promoter Polymorphism with Response to Combined Interferon Treatment and Progression of Liver Disease in Chronic HCV Egyptian Patients.

To evaluate the frequency of single-nucleotide polymorphism at the -88 myxovirus resistance (MxA) gene promoter region in relation to the status of hepatitis C virus (HCV) progression and response to combined interferon (IFN) in chronic HCV Egyptian patients. One hundred ten subjects were enrolled in the study; 60 HCV genotype 4-infected patients who underwent combined IFN therapy and 50 healthy individuals. All subjects were genotyped for -88 MxA polymorphism by the restriction fragment length polymorphism technique. There was an increasing trend of response to combined IFN treatment as 34.9% of GG, 64.3% of GT, and 66.7% of TT genotypes were sustained responders (P=0.05). The T allele was significantly affecting the response rate more than G allele (P=0.032). Moreover, the hepatic fibrosis score and hepatitis activity were higher in GG genotypes compared with the GT and TT genotypes. The multivariate analysis showed that the MxA GG genotype was an independent factor increasing the no response to IFN therapy (P=0.04, odds ratio [OR] 3.822, 95% confidence interval [CI] 1.056-11.092), also MxA G allele (P=0.0372, OR 2.905, 95% CI 1.066-7.919). MxA -88 polymorphism might be a potential biomarker to predict response to IFN and disease progression in chronic HCV-infected patients.

Insulin resistance as a predictor of early virologic response to HCV therapy among chronic HCV Egyptian patients.

Prior assessment of insulin resistance by HOMA-IR is emerging as an important milestone in the treatment of patients with chronic hepatitis C. This cost-effective tool is recommended to individualize treatment duration, or to exclude those with low insulin sensitivity from being treated until ameliorating their state of insulin resistance (IR). The present work aims to elucidate further the effect IR state on early viral kinetic response to Chronic hepatitis C virus (HCV) therapy and the impact of HCV treatment and viral eradication on insulin sensitivity. Insulin sensitivity was assessed using the HOMA-IR method. All enrolled patients were treated with a dual therapy (pegylated interferon-alpha plus ribavirin) for 48 weeks and evaluated using qRT-PCR for early virologic response as well as the impact of treatment on insulin sensitivity throughout the early period of therapy. Of a total 392 chronic HCV cases, early virologic response was achieved by 318 (81.1%). IR was detected in 241 (61.5%) chronic HCV patient of which 73.4% responded to treatment. Early virologic response among patients with > 2.18 HOMA-IR value were significantly lower than those with HOMA-IR values ≤2.18 (P < 0.0001). IR was significantly associated with high baseline BMI. Steatosis and fibrosis correlated with IR but neither independently predicted early virologic response. Pretreatment IR < 2.18, low fasting blood glucose, low and intermediate HCV viral load, normal BMI, and non-smoking were independent factors associated with early virologic response. IR interferes with early virologic response to the antiviral care. Clinical application of pretreatment HOMA-IR assessment could help in predicting early treatment outcome and thus enable treatment regimens to be optimized and individually tailored.

Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis

BackgroundChronic hepatitis C virus (HCV) represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphisms is associated with high rates of sustained virological response to pegylated interferon and ribavirin in HCV genotype-1 patients. Data on other genotypes are more limited. ObjectiveWe aim to evaluate the predictive power of the rs12979860 IL28B single nucleotide polymorphisms for treatment response at 3 and 6months in chronic HCV genotype 4 Egyptian patients in relation to other predictors. Patients and methodsThe study included 60 chronic HCV Egyptian patients receiving pegylated interferon and ribavirin therapy. Patients were classified into 2 groups; 30 patients with compensated cirrhosis, and 30 patients without cirrhosis. We analyzed selected pretreatment factors such as age, sex, HCV viral load, anti-schistosomal antibodies, insulin resistance, alpha fetoprotein, low and high density lipoproteins and single nucleotide polymorphisms of IL28B and tried to find out which of them influence sustained virological response. ResultsIn univariate analysis, CC genotype showed a significant association with sustained virological response at 6months among the cirrhotic patients (81.8% responders had the CC genotype, 58.3% had the CT/TT genotype) (p=0.009). While in multivariate analysis, the presence of cirrhosis showed higher risk of failed response at 3 and 6months (p=0.016 and 0.020 respectively). Also, positive schistosoma serology was an important negative predictor of response at 3 and 6months in both groups (p=0.003 and 0.001 respectively). ConclusionIn Egypt, where chronic HCV genotype 4 and schistosoma coinfection predominate, both schistosoma infection and cirrhosis are more potent than IL28B polymorphisms as strong baseline negative predictors of hepatitis C treatment response.

Genotype characterization of occult hepatitis B virus strains among Egyptian chronic hepatitis C patients

Chronic hepatitis C virus (HCV) infection combined with occult hepatitis B virus (HBV) infection has been associated with increased risk of hepatitis, cirrhosis and hepatocellular carcinoma. This study aimed to determine the prevalence of occult HBV infection among Egyptian chronic HCV patients, the genotype and occurrence of surface gene mutations of HBV and the impact of co-infection on early response to treatment. The study enrolled 162 chronic HCV patients from Ismailia Fever Hospital, Egypt, who were HBV surface antigen-negative. All patients were given clinical assessment and biochemical, histological and virological examinations. HBV-DNA was detectable in sera from 3 patients out of the 40 patients who were positive for hepatitis B core antibody. These 3 patients were responsive to combination therapy at treatment week 12; only 1 of them had discontinued therapy by week 24. HBV genotype D was the only detectable genotype in those patients, with absence of "a" determinant mutations among those isolates.

The impact of clinicopathological parameters in predicting response to pegylated interferon and ribavirin in chronic hepatitis C patients

ObjectivesThis study aimed to investigate the impact of clinical and histopathological changes in liver tissue of responders and nonresponders to standard pegylated interferon (Peg-IFN) and ribavirin (RBV) therapy and to determine whether they could predict treatment outcome or not.BackgroundHepatitis C virus (HCV) infection is a major health problem worldwide. Combination therapy of Peg-IFN and RBV has been recognized as a standard treatment for HCV infection. Unfortunately, this standard therapy produces a sustained virological response in only 50% of HCV-infected patients. Clinical and histological findings may play a role in predicting response to standard Peg-IFN/RBV therapy.Patients and methodsThis retrospective study included 64 patients with chronic HCV who were treated with Peg-IFNa/RBV. According to their response to treatment, they were classified into responders (n = 34) and nonresponders (n = 30). Pretreatment liver biopsies were evaluated histopathologically for necroinflammatory grade and fibrosis stage according to the modified Ishak and Metavir scoring systems for chronic hepatitis. Other pathological findings were also reported. Demographic, laboratory, and histopathological results were subjected to a statistical analysis.ResultsThe current study showed that the age of the patients (P = 0.003), sex (P = 0.027), and serum a-fetoprotein level (P = 0.046) were the parameters that showed a statistically significant difference between responders and nonresponders to interferon therapy. However, the grade of necroinflammation, stage of fibrosis as well as other pathological changes did not show a statistically significant difference between both groups.ConclusionThe current study showed that young age, female sex, and the baseline serum level of a-fetoprotein are the parameters that favored response to interferon and RBV therapy in chronic HCV Egyptian patients, whereas histopathological changes played no role in predicting response to treatment.

Association of liver inflammation with alpha-fetoprotein and treatment response in hepatitis C virus genotype 4 patients

Objectives: Chronic hepatitis C (CHC) or liver inflammation resulting from infection with hepatitis C virus (HCV) is the cause of chronic liver disease and leads to cirrhosis and hepatocellular carcinoma. The burden of chronic HCV-related liver disease in Egypt continues to rise and the interaction of liver inflammation with biomarkers and response to therapy is scarcely discussed. Moreover, serum alanine transaminase (ALT) is considered as a moderately accurate test for indicating liver inflammation. This study aims to evaluate the correlation of liver inflammation with response to therapy and with alpha-fetoprotein (AFP), and to assess the potential efficiency of AFP as a marker for liver inflammation. Methods: The study included 134 consecutive Egyptian chronic HCV patients. Sustained virological response (SVR) was assessed by the detection of HCV by reverse polymerase reaction (PCR). Furthermore, fibrosis and necroinflammation were assessed before treatment. Results: Severe liver inflammation was significantly associated with higher pretreatment levels of ALT, aspartate aminotransferase (AST) and AFP. AFP overcomes ALT as marker of inflammation by ROC curve analysis. Early virologic response (EVR), end-of-treatment response (ETR) and SVR was significantly higher in patients with mild inflammation than those with moderate and severe inflammation. Conclusion: Pretreatment AFP levels should be considered as a surrogate marker in predicting liver inflammation. Mild liver inflammation was more prevalent than moderate and severe inflammation in responders by means of EVR, ETR and SVR. d be considered as a surrogate marker in predicting liver inflammation. The response to therapy is more apparent in mild than moderate and severe liver inflammation by means of EVR, ETR and SVR.