This study was undertaken to determine a correlation between HCV and schistosomiasis infection in relation to hepatic fibrosis stages and antiviral treatment response.
Our findings showed a correlation of positive schistosomal serology in reference to sex, with the predominance involving males. HCV patients with positive schistosomal serology were also found to be older than those with negative serology. This finding is suspected to be due to the reservoir of HCV infection in Egypt, for which intravenously administered tartar emetic was used as a primary treatment[11
While this study showed no significant difference between the two groups in terms of fibrosis staging, other studies report HCV/schistosomiasis coinfected patients have more rapid progression of hepatic fibrosis than those with HCV monoinfection[12
], as evidenced by increased fibrosis scores for the liver biopsies taken at 96.0 ± 4.6 mo of follow-up. Moreover, another study demonstrated that serum transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) levels are higher in coinfected groups[13
Ahmad et al[14
] showed that schistosomiasis coinfection with HCV and/or non-alcoholic steatohepatitis had no significant impact on fibrosis stage. Results involving differences in fibrosis stages may be explained by several factors. Genetic predisposition may play a role, whereby only a minority of the individuals infected with Schistosoma mansoni
may develop hepatic fibrosis or be more sensitive to infection(s). Moreover, frequency of exposure is directly correlated with the presence and amount of fibrosis[15
]. In addition, several clinical and pathological studies have shown that schistosomal hepatopathy is a reversible condition and that resolution of the schistosomiasis disease is accompanied by subsequent fibrosis resorption[16,17
Moreover, HCV patients with evidence of coinfection or previous exposure to schistosomiasis received oral antischistosomal treatment of PZQ prior to starting the anti-viral therapy. PZQ is believed to exert antifibrotic effects by affecting (decreasing) activation of hepatic stellate cells through inhibition of profibrotic gene expression[18
]. Morcos et al[19
] demonstrated that PZQ treatment could induce resolution of schistosoma-induced pathology, showing partial reversal of liver fibrosis in Schistosoma mansoni
infected mice. Improvements and/or resolutions of schistosomal-induced periportal thickening/fibrosis in PZQ treated models have also been demonstrated by Berhe et al[20
] and Frenzel et al[21
]. It is theorized that the beneficial effects are likely related to the clearance of schistosomal worms and subsequent reduction of egg deposition.
Other limiting issues for the use of liver biopsy as a clinical tool for assessing fibrosis in schistosomiasis include ethical considerations and the risk of sampling errors, which may be especially evident for small-volume biopsies[22
In our current study, the EVR, virological response at week 24, and SVR were significantly higher in patients with negative schistosomal serology. This finding may be attributed to coinfected patients with a down-regulated immune response to HCV leading to reduced IFNγ, interleukin (IL)-4 and IL-10 secreted by HCV-specific T cells. Early reports by Kamal et al[23
] using standard IFN in the treatment of chronic HCV patients reported that Egyptian patients with coinfections have higher HCV RNA titers, more advanced liver disease, more hepatic complications and greater mortality rates than those infected with HCV alone.
In light of the previous real time PCR findings from Bahgat et al[24
], soluble egg antigen (SEA) should be considered as a potential stimulatory factor for HCV RNA that may have influenced the early detection of HCV RNA as SEA can stimulate viral replication. The higher morbidity that is observed in patients coinfected with schistosomiasis and HCV is related, at least in part, to direct stimulation of viral replication by SEA[25
It is interesting to consider that Derbala et al. found no significant difference in the treatment responses of patients treated with and without bilharziasis[26
]. This finding might be explained by phenotypic variations in Egyptian patients infected with HCV genotype 4, whereby some patients may mount HCV-specific T cell responses, both CD4+ and CD8+, despite the prevalence of concomitant schistosomiasis[27
A major limitation of this study was the need to diagnose schistosomiasis in patients by using an antischistosomal serology approach with a commercially available indirect hemagglutination test (IHAT). While the IHAT is sensitive in detecting bilharziasis, it cannot differentiate between past and current infection status nor between Schistosoma mansoni
and Schistosoma haematobium
species. While rectal snips are the preferred method of schistosomiasis diagnosis, this approach was not possible in our study population due to the large number of participants. Finally, genotyping for HCV was not performed on the patients in our study, since approximately 90% of infections in Egypt are due to genotype 4[9
] and the Egyptian National Committee for Control of Viral Hepatitis does not recommend routine genotyping.
In conclusion, positive schistosomal serology has no effect on fibrosis stage but it is significantly associated with failure of response to HCV treatment despite antischistosomal therapy.