Brief Article
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World J Hepatol. Aug 27, 2013; 5(8): 445-451
Published online Aug 27, 2013. doi: 10.4254/wjh.v5.i8.445
Serum complement C4a and its relation to liver fibrosis in children with chronic hepatitis C
Behairy E Behairy, Ghada M El-Mashad, Ragab S Abd-Elghany, Enas M Ghoneim, Mostafa M Sira
Behairy E Behairy, Mostafa M Sira, Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
Ghada M El-Mashad, Ragab S Abd-Elghany, Department of Pediatrics, Faculty of Medicine, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
Enas M Ghoneim, Department of Microbiology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
Author contributions: Behairy BE, El-Mashad GM, Abd-Elghany RS and Sira MM designed research, helped in diagnosis and patients recruitment, and shared in writing and revision of the manuscript; Abd-Elghany RS and Sira MM performed data collection; Sira MM performed statistical analysis; Ghoneim EM performed laboratory analysis, shared in writing and revision of the manuscript.
Supported by National Liver Institute, Menofiya University, Egypt
Correspondence to: Dr. Mostafa M Sira, Department of Pediatric Hepatology, National Liver Institute, Menofiya University, POBox 32511, Gamal Abdel Nasser St., 32511 Shebin El-koom, Menofiya, Egypt. msira@liver-eg.org
Telephone: +20-48-2222740 Fax: +20-48-2234586
Received: June 10, 2013
Revised: July 29, 2013
Accepted: August 4, 2013
Published online: August 27, 2013
Processing time: 101 Days and 17.2 Hours
Abstract

AIM: To evaluate serum complement C4a and its relation to liver fibrosis in children with chronic hepatitis C virus (HCV) infection.

METHODS: The study included 30 children with chronic HCV infection before receiving antiviral therapy. Chronic HCV infection was defined by positive anti-HCV, a positive polymerase chain reaction for HCV-RNA for more than 6 mo with absence of any associated liver disease. A second group of 30 age- and sex-matched healthy children served as controls. Serum C4a levels were measured by enzyme-linked immunosorbent assay. Liver fibrosis stage and inflammatory grade were assessed using Ishak scoring system. Serum C4a levels were compared according to different clinical, laboratory and histopathological parameters. Statistical significance for quantitative data was tested by Mann-Whitney U non-parametric tests. For qualitative data, significance between groups was tested by χ2 test. Correlation was tested by Spearman’s test. Results were considered significant if P value ≤ 0.05.

RESULTS: The age of the patients ranged from 3.5 to 18 years and that of controls ranged from 4 to 17 years. C4a mean levels were merely lower in patients (153.67 ± 18.69 mg/L) than that in the controls (157.25 ± 11.40 mg/L) with no statistical significance (P = 0.378). It did not differ significantly in patients with elevated vs those with normal transaminases (152.25 ± 16.62 vs 155.36 ± 21.33; P = 0.868) or with different HCV viremia (P = 0.561). Furthermore, there was no statistical significant difference in serum levels between those with no/mild fibrosis and those with moderate fibrosis (154.65 ± 20.59 vs 152.97 ± 17.72; P = 0.786) or minimal and mild activity (155.1 ± 21.93 vs 152.99 ± 17.43; P = 0.809). Though statistically not significant, C4a was highest in fibrosis score 0 (F0), decreasing in F1 and F2 to be the lowest in F3. When comparing significant fibrosis (Ishak score ≥ 3) vs other stages, C4a was significantly lower in F3 compared to other fibrosis scores (143.55 ± 2.33 mg/L vs 155.26 ± 19.64 mg/L; P = 0.047) and at a cutoff value of less than 144.01 mg/L, C4a could discriminate F3 with 76.9% sensitivity and 75% specificity from other stages of fibrosis.

CONCLUSION: Serum complement C4a did not correlate with any of transaminases, HCV viremia or with the histopathological scores. Although C4a decreased with higher stages of fibrosis, this change was not significant enough to predict individual stages of fibrosis. Yet, it could predict significant fibrosis with acceptable clinical performance.

Keywords: Children; Hepatitis C virus; Complement C4a; Liver biopsy; Liver fibrosis

Core tip: Non-invasive prediction of liver fibrosis is a challenging issue especially in pediatric population. Complement C4a was found, by proteomic analysis, to be associated with liver fibrosis and therefore proposed as a candidate for fibrosis prediction. In adults, serum C4 was found to decrease in hepatitis C virus (HCV) patients with moderate fibrosis and cirrhosis compared to healthy controls. In addition, in advanced HCV-induced liver fibrosis, the net production of C4a was found to be down-regulated. Furthermore, it was found to correlate negatively with alanine transaminase and the histological activity index of the Knodell scoring system. The issue has never been investigated in children before.