Anti-C1q antibody as a predictor of chronic HCV genotype 4 response to treatment in Egyptian children

Background: Hepatitis C virus [HCV] infection has been reported to be the most common blood born pathogen all over the world. The prevalence of HCV in children in developed countries ranges between 0.1 and 0.4%, and is generally lower than in adults. Combinedpegylated interferon and ribavirin is still the only standard of care treatment in spite of its side effects, high costs and low sustained virological response [SVR] rates. Hence, this provides a compelling reason for the identification of biomarker predictors of disease response to treatment

Objective: To evaluate anti-C1q antibody as a predictor of chronic HCV response to treatment with combined pegylated interferon alpha-2b and ribavirin in Egyptian children

Methodology: This study was conducted on forty-four chronic HCV-infected children [Male/Female: 30/14; aged 12.02 +/- 3.1 years] from the outpatient clinic, Pediatric Hepatology Department, National Liver Institute, Menoufiya University. They were given combined pegylated interferon alpha-2b [Peg-IFN-alpha-2b] and ribavirin [RBV] for 48 weeks and a quantitative polymerase chain reaction [PCR] for hepatitis C virus Ribonucleic acid was performed at 12, 24, 48 weeks during treatment and after another 24 weeks post-treatment. Anti-HCV antibody and Real-time PCR for HCV-RNA was performed [the detection limit was 15 IU/mL]. Anti-C1q antibodies were performed by enzyme-linked immunosorbent assay [ELISA]

Results: Serum levels of Anti-C1q antibodies were significantly higher [P = 0.001] in the Non-responders group [mean = 14.61 +/- 6.749ng/ml] compared to the SVR one [mean = 2.27 +/- 3.77ng/ml]. No statistically significant difference [P > 0.05] had been found between SVR and Non-responders regarding the age, ALT, viral load, or hepatic necroinflammatory activity and liver fibrosis. Anti-C1q at a cutoff value of 9.05 ng/ml, had sensitivity and specificity of 84.6% and 75% respectively and 92% positive predictive value. No significant correlation between the serum level of anti-C1q antibodies and the age, sex or HCV viral load, liver enzymes, and the degree of fibrosis and necroinflammatory activity was found [P> 0.05] for all parameters

Conclusion: Anti-C1q could be a good predictor for HCV treatment and should be included in pretreatment laboratory assessment for proper choice of chronic HCV children patients who will benefit from combination therapy

Human leukocyte antigen DRB1 and the response to pegylated interferon/ribavirin therapy with chronic hepatitis C in children

Background: Egypt has the highest prevalence of hepatitis C virus [HCV] infection in the world [15%-25%] and the main [90%] genotype is type 4. Prevalence in Egyptian children was found to be 3% in Upper Egypt and 9% in Lower Egypt. Various human leucocytic antigen [HLA] alleles have been linked either persistence or clearance of the hepatitis C virus [HCV]. Several studies have aimed to identify the involvement of HLA with different outcomes of HCV infection, but the results have not been consistent

Aim of the work: To identify HLA association with different outcomes as regard treatment of chronic HCV [CHC] in Egyptian children with pegylated interferon-alpha2b [Peg-IFN-alpha-2b] and ribavirin [RBV]

Patients and methods: Forty clinically and laboratorial children diagnosed as CHC genotype 4 [ages 3-18 years, 14 females and 26 males]. Patients were treated using Peg-IFN-alpha 2b [Peg Intron] at a dosage of 60 ug/m[2] per week subsutaneously and RBV 15 mg/kg per day orally for 48 weeks. Serum HCV ribonucleic acid [RNA] was measured at the baseline, at the 12[th], 24[th] and 48[th] weeks during treatment, and after 24 weeks of post-treatment [study weeks 72]. Sustained virologic responders [SVR] were defined as patient with undetectable HCV-RNA in the serum at 24 weeks post-treatment, while non-responders defined as HCV-RNA remains detectable throughout the treatment phase. Genomic DNA was extracted from 1 ml peripheral blood in tubes containing EDTA. HLA typing was performed by polymerase chain reaction followed by detection using sequence-specific oligonucleotides probes

Results: Twenty-nine out of forty patients [72.5%] showed a sustained virological responders to Peg-IFN/RBV therapy, whereas eleven [27.5%] non-responders did not. The frequencies of DRB1[asterisk]11 was significantly higher in sustained virological responders than non-responders. On the other hand, DRB1[asterisk] 07 allele was significantly higher in non-responders than SVR. We also found that no statistically significant difference between SVR and non-responders as regards the demographic, laboratory and liver histopathology characteristics of patients

Conclusion: There is a trend of association between certain HLA alleles and the response to Peg-IFN/RBV in HCV infected children and a study on large number of patients to confirm this association is worthy