HCV and schistosomiasis by 6BH2D9

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									                           HCV and schistosomiasis
Introduction
 Infection with HCV has become the most important public health problem in Egypt
   with complications ranging from chronic inflammatory disease to hepatic cirrhosis
   and end stage liver failure or hepatocellular carcinoma (HCC).
 Hepatitis C virus (HCV) infection and schistosomiasis are major public health
   problems in the Nile Delta of Egypt.
 Patients coinfected with HCV and schistosomiasis exhibit a unique clinical,
   virological and histological pattern.

Epidemiology

HCV

 It is estimated that 170 millions world wide are infected with HCV.
 Approximately 20% of Egyptian blood donors are seropositive for HCV antibodies.
 Seroprevalence of HCV antibodies were detected in 10–30% of the Egyptian
  population.
 In most Egyptian patients, HCV genotype 4 is highly prevalent.
Schistosomiasis

 Schistosomiasis is a chronic helminthic disease that infects more than 200 million
   people worldwide.
 Infection with Schistosoma mansoni is endemic in Egypt, with a prevalence of 17.5–
   42.9%.
Co-infection

 In Egypt epidemiological studies reported a high prevalence and incidence of HCV
  within families in rural areas endemic for schistosomiasis.
 This high association could be attributed to the transmission of the viruses via sharing
  contaminated syringes used to inject tarter emetic, which was prescribed to treat
  patients with bilharziasis about 25 years ago.
 HCV infection is probably acquired after S. mansoni infection was established,
  through parenteral antischistosomal therapy and/or blood transfusions.
 Seroprevalence of HCV (12.9%) among Egyptian patients with schistosomiasis was
  higher than that observed among blood donors.




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Impact of Schistosomiasis on HCV

Immunological

Background of immunological defense
Schistosomiasis
 S. mansoni causes liver pathology through an immune-mediated mechanism, rather
   than through direct hepatic injury.
 S. mansoni ova are trapped in the liver, evoking a highly skewed Th2 immune
   response profile with granuloma formation that progresses to periportal fibrosis with
   preserved hepatic ultrastructure.
 This is coupled with a defect in Th1-cell effect or function.
HCV
 The host immune response probably plays a critical role in the control of both HCV
   replication and liver injury.
 In acute HCV: Th1& Th0 with its typical cytokine milieu consisting of (IL2, IFN,
   TNF-α  clearance of virus infected cells.
 In chronic HCV: Th2 & Th0 dominate with its typical cytokine milieu consisting of
   IL-4, 5,6,9,10,13  high titer of antibody of antibody and increase in IL-10 
   inhibition of Th1 response.
Coinfected
 In coinfected patients, HCV infection was probably acquired after the establishment
   of S. mansoni infection, possibly via parenteral antischistosomal therapy and/or blood
   transfusions.
 Thus, in the first encounter of HCV with the host immune system, it was confronted
   with:
           o Prevailing Th2 pattern.
           o Cytokine shift pattern.
                    Reduced IFN-γ, IL-4 and IL-10 secreted by HCV-specific T cells.
           o Cytotoxic T lymphocyte response.
 This Th2 profile, induced by S. mansoni infection, has probably antagonized and
   downregulated the antiviral activities of Th1 cytokines  cannot clear viremia 
   increased viral replication and more aggressive progression to fibrosis
 It has been shown that soluble egg antigen possesses a potent in vitro proliferative
   activity on peripheral blood mononuclear cells and directly stimulates HCV
   replication in vitro.
Clinical
 Patients with hepatitis C and Schistosoma mansoni coinfection show markedly
   accelerated hepatic fibrosis.
 This may be reflected on the coinfected patient by an early onset of:
           o Portal hypertension.
           o Bleeding oesophageal varices.
           o Huge splenomegaly.
           o Hypersplenism.


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Virological
 Patients with concomitant HCV and schistosomiasis infection are characterized by:
          o Higher HCV RNA titers explained by:
                  The lack of viral control due to defective HCV-specific CD4 T cell
                    response.
                  Abrogation of the HCV-specific Th1 response antagonized by the
                    S. mansoni–induced Th2 response.
                  High initial virus load may cause immune exhaustion thereby
                    aggravating HCV infection.
          o Predominance of HCV genotype 4.
          o Inverse relationship between virus load and CD4 T cell count.

Histological
 Periportal fibrosis is a typical pathologic feature in advanced schistosomiasis.
 Patients with hepatitis C and Schistosoma mansoni coinfection show markedly
   accelerated hepatic fibrosis with:
          o Higher histologic activity index.
          o Higher necroinflammatory and fibrosis scores.
 Progression of fibrosis may be mediated by an initially increased inflammatory
   response caused by:
          o Elevated TNF-α and subsequent activation of hepatic TGF-β.
          o Alterations of cytokine patterns in the form of:
                   Insufficient intrahepatic Th1 responses.
                   Augmented Th2 responses.
 This result in
          o Predominance or up-regulation of the collagen-inducing cytokine IL-4.
          o Down-regulation of the collagen-suppressing cytokine IFN-γ.

Therapeutic
 Poor response to IFN therapy due to high fibrosis score.
Impact of HCV on Schistosomiasis

Clinical
 In pure and uncomplicated schistosomiasis, hepatocellular function is preserved.
 Since HCV is a hepatic parenchymal disease it is a major cause of decompensation of
   schistosomal hepatic disease (mesenchymal).
 Clinical consequences of HCV on schistosomiasis infection:
           o Cirrhosis with hepatic decompensation manifested by:
                  Jaundice.
                  Bleeding tendency.
                  Ascites and lower limb oedema.
                  Hepatic encephalopathy.
           o Hepatocellular carcinoma.
           o Higher mortality rate.


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Biochemical
 Features of parenchymal injury and hepatic decompensation:
         o Elevated serum total and direct bilirubin.
         o Elevated liver enzymes AST, ALT.
         o Decreased serum albumin and total proteins.
         o Prolonged prothrombin time and low concentration.

Histological
 Patients infected with schistosomiasis alone had very low inflammatory scores (2)
   with no piecemeal necrosis and preserved lobular architecture.
 Coinfected patients have higher necroinflammatory and fibrosis scores that may
   evolve into cirrhosis with loss of normal hepatic lobular architecture.

Management
 Treat schistosomiasis.
 Then treatment of HCV.




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