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Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease.

ABSTRACT: BACKGROUND:IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance. OBJECTIVES:In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined. PATIENTS AND METHODS:Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals. RESULTS:A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD. CONCLUSIONS:Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.

SUBMITTER: El-Awady MK

PROVIDER: S-EPMC3360937 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease.

El-Awady Mostafa K MK Mostafa Lotiaf L Tabll Ashraf A AA Abdelhafez Tawfeek H TH Bader El Din Noha G NG Zayed Naglaa N Shenawy Reem El RE El Abd Yasmin Y Hasan Reham M RM Zaghlol Hosam H El Khayat Hesham H Abdel Aziz Ashraf O AO

Hepatitis monthly 20120430 4

<h4>Background</h4>IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.<h4>Objectives</h4>In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined.<h4>Patients and methods</h4>Frequencies of the protective genotype C/C of SNP, rs12979860 were ...[more]

PMID: 22690235

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Project description:IntroductionWe have assessed the utility of autologous mesenchymal stem cell (MSC) peripheral vein infusion as a possible therapeutic modality for patients with end-stage liver diseases.MethodsForty patients with post-hepatitis C virus (HCV) end-stage liver disease were randomized into two groups: Group 1 (GI): 20 patients who received granulocyte colony-stimulating factor (G-CSF) for 5 days followed by autologous MSCs peripheral-vein infusion and group 2 (GII): 20 patients who received regular liver-supportive treatment only (control group).ResultsIn MSC-infused patients (GI), 54% showed near normalization of liver enzymes and improvement in liver synthetic function. Significant changes were reported in albumin (P = 0.000), bilirubin (P = 0.002), increased international normalized ratio (INR) (P = 0.017), prothrombin concentration (P = 0.029) and alanine transaminase (ALT) levels (P = 0.029), with stabilization of clinical and biochemical status in 13% of cases. None of the patients in GII showed any significant improvement. Hepatic fibrosis was assessed in GI by detection of procollagen IIIC peptide level (PIIICP) and procollagen III N peptide level (PIIINP). The pretreatment values of s-PIIICP and s-PIIINP were 9.4 ± 4.2 and 440 ± 189, respectively, with a decrease to 8.1 ± 2.6 and 388 ± 102, respectively, 3 months after MSC therapy. However, the difference was statistically nonsignificant (P = 0.7). A significant correlation coefficient was reported after 3 months between the s-PIIINP and prothrombin concentration (P = -0.5) and between s-PIIICP and ascites (P = 0.550).ConclusionsFirst, autologous MSC infusion into a peripheral vein is as effective as the previously reported intrahepatic infusion. Second, MSCs have a supportive role in the treatment of end-stage liver disease, with satisfactory tolerability and beneficial effects on liver synthetic functions and hepatic fibrosis. Third, IV infusion of MSCs after G-CSF mobilization improves s-albumin within the first 2 weeks and prothrombin concentration and alanine Taransaminase after 1 month. According to the data from this current study and those previously reported by our group, we recommend further studies on patients' infusion with pure CD133 and CD34 followed by IV infusion of in vitro-differentiated MSCs within 1 week and another infusion after 3 months.Trial registrationClinicalTrials.gov NCT01729221. Registered 17 November 2012.

Project description:AIM:To test whether the status of positive cytomegalovirus (CMV) DNA detection adds to the predictive value of IL28B and to further categorize C/T allele carriers. METHODS:This study included 166 chronic hepatitis C (CHC) patients who received combined interferon and ribavirin therapy for 48 wk, 84 spontaneous hepatitis C virus (HCV) resolvers who were positive for IgG anti-HCV antibody and negative for HCV RNA, and 100 healthy subjects who were negative for both HCV antibodies and RNA as controls. Genomic DNA from peripheral blood was used for IL28B rs.12979860 single nucleotide polymorphism (SNP) and CMV DNA detection. A 139 bp fragment containing IL28B SNP was amplified in all subjects by polymerase chain reaction using a specifically designed primer. Then the IL28B rs.12979860 SNP was detected by restriction fragment length polymorphism (RFLP) genotyping. The presence of CMV DNA was tested by amplification of the gB1 gene using nested polymerase chain reaction. The role of CMV and IL28B rs.12979860 SNP genotypes in determining the response rate to combined interferon therapy and clinical status of patients were statistically analyzed. RESULTS:Current data showed that 67% of patients carrying the IL28B 12979860 C/C allele had a sustained viral response (SVR) while the genotypes C/T and TT were associated with lower SVR rates, 50% and 48%, respectively. SVR rates for the C/C allele were lower than other HCV genotypes and/or other populations. Genotype CC was associated with the response to interferon (P = 0.025). Genotype C/C was reduced from 48% in controls to 14% in CHC patients suggesting its protective role against progression to chronicity. The majority of spontaneously cleared subjects (86%) were C/C, confirming its protective role. The C/T allele was present in 71% of CHC patients compared with 38% of controls, so the use of IL28B SNP genotyping only in these patients may be of little value as a predictor of response. CMV reactivation occurred in 40% of CHC patients. Co-infection with CMV seriously diminished the response to interferon (IFN) therapy, with SVR rates in C/C genotypes 87.5% in CMV-negative patients and 12.5% in CMV-positive patients (P < 0.0001). SVR rates among C/T carriers were reduced to < 50% in patients with positive CMV DNA while the non-response rate doubled. These data indicate that a supplemental assay for CMV viremia adds to the prognostic value of IL28B genotyping. CONCLUSION:The results suggest that both genetic (i.e., spontaneous) and therapeutic (IFN-based therapy) arms are complementary in the battle against HCV. CMV DNA testing may be of value to better predict the response to IFN, particularly in IL28B C/T carriers.

Dataset Information

Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease.

Publications

Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease.

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