الفهرس 
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Abstract
About 180 million people are having hepatitis C
virus infection (HCV) worldwide. In addition to
progression to cirrhosis and hepato-carcinoma, HCV
patients may develop extrahepatic manifestations.
HCV infection is considered as one of the most
important health problems all over the world. Egypt is one
of the countries with a high prevalence of HCV infection,
with an estimated prevalence of 22 percent among the adult
population.
The prevalence of thrombocytopenia in HCV
patients ranges from 0.16 percent to 45 percent, and more
than half of the studies reported a prevalence of 24 percent
or more.
Anti-platelet glycoprotein antibodies are common
with HCV infection, even without thrombocytopenia.
Antiviral antibodies that are cross-reactive with GPIIIa,
have been identified in many cases. Production of
thrombopoietin may be decreased with advanced liver
disease. Infection of the megakaryocytes by the virus may
impair platelet production. There are many proposed theories and mechanisms
that explain the pathophysiology of autoimmunity in HCV
infection. HCV can facilitate lymphotropism causing clonal
B-lymphocyte expansion which causes a widespread
autoantibody production. The envelope protein E2 of the
virus can bind to CD81 molecule which is expressed on the
hepatocytes and the B-lymphocytes, leading to a cytokine
dysregulation with enhanced T-helper 1 immune response.
This may cause autoimmunity induced by the self-reactive
lymphocytes in the chronic HCV patient. Cross-reactivity
between cytochrome P2-E1 (CYP2E1) and specific
sequences in the HCV-NS5b protein has been recently
shown to be responsible for the production of numerous
auto-antibodies that can target the self-proteins.
Patients with fibrosis and thrombocytopenia have
attained >90% sustained virologic response (SVR) with
direct antiviral agents (DAAs), even if lower in respect to
patients with a normal platelet count. Thus, direct antiviral
agents can be continued in most patients without
interruption, and thrombopoietin mimetics should be used
only in cases with severe thrombocytopenia.
For immune reconstitution after DAA therapy, it is
likely that viral elimination will decrease the intrahepatic inflammation, and will reconstitute the innate immune
mediators such as natural killer cells (NK), but there will be
a minimal effect on Mucosal associated invariant T cells
(MAIT), and there are very limited data suggesting reduced
activation of the lymphocytes after DAA therapy. The
effect on tumor- associated antigens specific T (TAA-T)
cells is unknown, and preliminary studies suggest that T
regulatory cells (Treg) do not normalize in the blood after
DAA therapy. If DAA therapy does not significantly alter
the localization and suppressive activity of Treg cells, this
will create an immunosuppressive environment.
The aim of this work was to evaluate the effect of
DAA (sofosbuvir and daclatasvir) therapy on HCV
associated thrombocytopenia, and tracking the platelet level
changes during and after treatment of HCV infection.
To our knowledge this is the first study on this issue
in Egypt.
This was a prospective study on 104 patients with
HCV-associated thrombocytopenia receiving DAA
(sofosbuvir and daclatasvir) in Menoufia University
Hospitals and National Liver Institute.
Patients with any of the following were excluded from this
study:
- concomitant HBV or HIV infection
- History of IFN therapy.
- Hepatocellular carcinoma (HCC).
- Autoimmune and endocrinal diseases.
- H. pylori infection.
All patients were followed up every 4 weeks during
anti-viral therapy (for 12 weeks), and at SVR24 (at 24
weeks), clinically by weekly symptoms checklist, and by
CBC. PCR for HCV RNA was done at start of therapy, 12
& 24 weeks of therapy.
Patients were divided into several groups according
to presence or absence of splenomegaly, the child Pugh
class (A, and B), and Firbroscan score (F1, F2, and F3),
and comparison between similar groups regarding the
baseline platelet count and serial platelet counts during and
after the treatment was done.
The present study revealed that:
1- HCV associated thrombocytopenia is more common
in middle aged females.
2- The platelet count is expected to decrease initially on
starting the DAA antiviral treatment, then increases
gradually and steady during and after the treatment. 3- DAA therapy in patients with HCV-associated
thrombocytopenia and compensated liver disease is
safe with platelet count improvement in most cases.
4- Further large-scale studies, including studies of the
immune system reconstitution behavior with DAA
therapy are needed.
5- Further studies evaluating the effect of DAA therapy
on other extrahepatic HCV immune mediated
diseases are needed to understand the exact immune
system reconstitution and behavior with HCV