Impact of Hepatitis C Virus/Schistosoma mansoni Coinfection on the Circulating Levels of HCV-NS4 Protein and Extracellular-Matrix Deposition in Patients with Different Hepatic Fibrosis Stages

Abstract

Hepatitis C virus (HCV)/Schistosoma mansoni coinfection is common in Egypt and other developing countries. This study aimed to investigate the influence of HCV/S. mansoni coinfection on the concentration of HCV-nonstructural protein-4 (NS4) in addition to collagen III and matrix metalloproteinase-1 (MMP-1) in different hepatic fibrosis stages. We found that coinfected patients (N = 186) showed significantly (P < 0.05, Mann-Whitney U test) higher concentrations of HCV-NS4, collagen III, and collagen III/MMP-1 ratio (CMR) than those with HCV monoinfection (N = 104) in different fibrosis stages. Conversely, coinfected patients showed significantly lower concentrations of MMP-1 when compared with HCV monoinfection. The elevated levels of CMR in case of HCV monoinfection yielded an estimated odds ratio of 1.8 and 2.6 for developing significant fibrosis (F2-F4) and cirrhosis (F4), respectively. HCV/S. mansoni coinfection increased the risk for developing F2-F4 and F4 several fold yielding an estimated odds ratio of 11.1 and 5.2, respectively. This means that coinfected patients have a 6-fold and 2-fold increased risk of developing F2-F4 and F4, respectively, over HCV-monoinfected patients. Thus, elevated levels of HCV-NS4 and CMR in HCV/S. mansoni coinfection suggest increased susceptibility of coinfected patients, compared with those with HCV monoinfection, for accelerating hepatic fibrosis progression.

Figure 1.

A flowchart showing the selection process of patients included in this study. Hepatitis C virus (HCV) diagnosis was based on a positive test for anti-HCV antibodies. Patients were then confirmed for the presence of HCV-RNA using polymerase chain reaction assay. HCV-monoinfected patients had no history or laboratory evidence of previous or current Schistosoma mansoni infection. The diagnosis of S. mansoni was based on detecting vital or dead schistosomal ova in stools or rectal biopsy with seropositivity to schistosomal antibodies. Patients with serological evidence of active hepatitis A or B viruses, history of habitual alcohol consumption, hepatocellular carcinoma, previous interferon treatment, and liver transplantation were excluded from the present study.

Figure 2.

Impact of hepatitis C virus (HCV)/Schistosoma mansoni coinfection on HCV–nonstructural protein-4 (NS4) concentration and extracellular-matrix deposition. (A) Number of patients, (B) levels of S. mansoni antigens in different hepatic fibrosis stages, (C) levels of HCV-NS4, (D) levels of collagen III, (E) levels of matrix metalloproteinase-1 (MMP-1), and (F) levels of collagen/MMP-1 ratio (CMR) in different hepatic fibrosis stages in HCV-infected patients with and without schistosomiasis. Statistically significant differences between groups were determined using the nonparametric Mann–Whitney U test.

Figure 3.

Levels of collagen/matrix metalloproteinase-1 (MMP-1) ratio (CMR) in relation to hepatitis C virus–nonstructural protein-4 (HCV-NS4) concentration in absence and presence of schistosomiasis and its impact on the progression rates of liver fibrosis. (A) Levels of CMR in patients with significant fibrosis (F2-F4), (B) levels of CMR in patients with cirrhosis (F4), and (C) the risk of elevated CMR on the progression rates of liver fibrosis. Statistically significant differences between groups were determined using the nonparametric Mann–Whitney U test.