Changes in Serum Interferon Gamma and Interleukin-10 in Relation to Direct-Acting Antiviral Therapy of Chronic Hepatitis C Genotype 4: A Pilot Study.

Introduction: This study analyzes the changing levels of circulating inflammatory cytokines Interferon gamma (IFN-γ) and interleukin (IL)-10 (as the main cytokines of T-helper-1 and T-helper-2 immune responses) in patients with chronic hepatitis C virus (HCV) infection undergoing therapy with direct-acting antivirals (DAAs) and to correlate them with laboratory markers. Methods: This Pilot study included 50 HCV monoinfected patients who received DAAs for 12 or 24 weeks. They were followed up monthly during therapy and 3 months after the end of the treatment. Liver disease was determined by transient elastography, in addition to FIB-4 indices. Analysis of IFN-gamma and IL-10 was carried out using an enzyme-linked immunosorbent assay. Results: All patients carried HCV genotype 4. The Sustained virological response was 100% and 92% in cirrhotics and noncirrhotics, respectively. There was no significant difference between groups in baseline IL-10 or IFN-gamma. In noncirrhotics, IL-10 showed a significant reduction at Week 4 after treatment start. In cirrhotics, IL-10 showed a significant reduction at Week 4 after treatment starts and a significant reduction at Week 12 after the end of the treatment. At Week 12 after the end of the treatment, serum IL-10 levels were significantly lower in cirrhotics. IFN-γ showed nonsignificant changes in noncirrhotics. A significant increase of IFN-γ occurred in cirrhotics from Week 4 after treatment starts to 12 weeks after the end of the treatment. IFN-γ was significantly higher in cirrhotics at Week 12 after the end of the treatment. IFN-γ and IL-10 showed different correlations with laboratory markers. Conclusion: Viral eradication induced by DAAs caused a significant change in IL-10 and IFN-gamma.

Assessment of circulating levels of microRNA-326, microRNA-424, and microRNA-511 as biomarkers for hepatocellular carcinoma in Egyptians.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer. Differential expression of microRNAs (miRNAs)-326, miRNA-424, and miRNA-511 has been associated with the diagnosis and prognosis of HCC in different populations. However, limited information is available regarding their expression in Egyptian HCC patients. AIM: To assess the role of circulating miRNAs-326, miRNA-424, and miRNA-511 in Egyptian HCC patients. METHODS: This prospective observational study included 70 HCC patients and 25 healthy controls. The circulating levels of these three miRNAs were evaluated by real-time PCR. Receiver operating characteristic curve analysis was used to test the diagnostic accuracy of microRNA expression levels. RESULTS: All miRNAs were differentially expressed in HCC patients; miRNAs326 and miRNA-424 were upregulated, while miRNA-511 was downregulated. Both miRNA-326 and miRNA-424 showed sensitivity and specificity of 97%, 71.4%, and 52%, 60%, respectively, to differentiate HCC from controls. Moreover, miRNA-326 was associated with survival and could differentiate between Child grades (A vs B); miRNA-424 significantly differentiated early vs intermediate stages of HCC; while miRNA-511 was significantly correlated with response to modified Response Evaluation Criteria in Solid Tumors (mRECIST). CONCLUSION: We conclude that miRNA-326, miRNA-424, and miRNA-511 have diagnostic and prognostic roles in Egyptian patients with hepatitis C virus-related HCC and should be considered for better disease management.

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.

Relation of ALT and AST levels to the histopathological changes in liver biopsies of patients with chronic hepatitis C genotype 4.

BACKGROUND AND STUDY AIMS: Worldwide, Egypt has a high prevalence of adult hepatitis C virus (HCV) infection. Serum alanine aminotransferase (ALT) activity is most commonly measured to assess hepatic disease. The revision of the definition of the normal limits for the ALT level is advisable. The aim of this work was to compare the histopathological changes in the liver tissue biopsies of HCV-infected patients, clinically presenting with ALT levels below normal, based on the conventional, previously used upper limit of normal (ULN) of ALT (40U/L for men and 30U/L for women) with the proposed new ULN (30U/L for men, and 19U/L for women). PATIENTS AND METHODS: This is a retrospective cross-sectional study. A total of 668 cases of chronic hepatitis C genotype 4 were included. Patients were classified according to grades of histological activity and fibrosis stages (by the Metavir scoring system). They were also classified into normal and high groups according to the old and new cutoffs of both aspartate transaminase (AST) and ALT levels. RESULTS: The results of our study showed that the serum AST level in our study showed a better correlation with the histopathological changes in liver biopsy rather than ALT, especially when using the old cutoff of the ULN for AST. The serum ALT level in our study (both the old and the new cutoffs) did not show a significant correlation with the histopathological status in the liver biopsies of our patients. CONCLUSION: This study concluded that the old cutoff of the ULN AST is a better predictor of fibrosis.

Effect of vitamin D therapy on interleukin-6, visfatin, and hyaluronic acid levels in chronic hepatitis C Egyptian patients.

OBJECTIVES: We aimed to compare serum levels of interleukin-6, visfatin, and hyaluronic acid in chronic hepatitis C Egyptian patients who received standard of care (SOC) therapy for chronic hepatitis C virus (HCV) consisting of pegylated interferon (PEG-IFN) and ribavirin (RBV) and in those who received SOC with vitamin D (vit D) for 48 weeks in HCV genotype 4a subjects. DESIGN AND METHODS: One hundred chronic HCV patients were classified into two groups: study 50 patients received SOC therapy PEG-IFN/RBV + vit D and control 50 patients received SOC PEG-IFN/RBV without vit D. Both groups were followed up at 12 weeks, 24 weeks, and 48 weeks of treatment. RESULTS: Results showed a significant elevation in vit D levels in the group treated with SOC and vit D compared to SOC group and a reduction in HCV RNA from the 12th week to reach zero level in the 24th week. Interleukin-6, visfatin, and hyaluronic acid levels were also reduced significantly. Alanine transaminase and aspartate transaminase biomarkers were significantly reduced, indicating decreased liver injury. CONCLUSION: SOC PEG-IFN/RBV + vit D therapy for chronic HCV led to reduced interleukin-6, visfatin, and hyaluronic acid levels and follow up liver biochemical biomarkers as aspartate transaminase and alanine transaminase indicates proper liver healing and monitoring.

Molecular detection of monocyte chemotactic protein-1 polymorphism in spontaneous bacterial peritonitis patients.

AIM: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP). METHODS: Fifty patients with post-hepatitis C liver cirrhosis and ascites were categorized into two groups; group I included 25 patients with SBP and group II included 25 patients free from SBP. In addition, a group of 20 healthy volunteers were included. We assessed the MCP-1 gene polymorphism and gene expression as well as interleukin (IL)-10 levels in both blood and ascitic fluid. RESULTS: A significant MCP-1 gene polymorphism was detected in groups I and II (P = 0.001 and 0.02 respectively). Group I was associated with a significantly higher frequency of AG genotype [control 8 (40%) vs SBP 19 (76.0%), P < 0.001], and group II was associated with a significantly higher frequency of GG genotype when compared to healthy volunteers [control 1 (5%) vs cirrhotic 16 (64%), P < 0.001]. Accordingly, the frequency of G allele was significantly higher in both groups (I and II) [control 10 (25%) vs SBP 27 (54%), P < 0.001 and vs cirrhotic 37 (74.0%), P < 0.001, respectively]. The total blood and ascetic fluid levels of IL-10 and MCP-1 gene expression were significantly higher in group I than in group II. Group I showed significant reductions in the levels of MCP-1 gene expression and IL-10 in the whole blood and ascetic fluid after therapy. CONCLUSION: MCP-1 GG genotype and G allele may predispose HCV infected patients to a more progressive disease course, while AG genotype may increase the susceptibility to SBP. Patients carrying these genotypes should be under supervision to prevent or restrict further complications.