الفهرس 
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Abstract
Since its discovery in 1989, HCV has been recognized as a major
public health problem worldwide because of its high prevalence, the high
risk of progression to cirrhosis, liver failure and hepatocellular carcinoma.
So, HCV is a major challenge for treating physicians all over the world
especially in Egypt where it is highly prevalent.
Combination therapy of Peg-IFN-a / RBV is the standard of care
treatment for chronic hepatitis C. Although efficacy of therapy has
improved, sustained virological response is still not satisfactory. Moreover,
many patients are not able to tolerate the prolonged therapeutic course both,
physically and financially. So, identification of factors that determine
response before starting treatment is critical.
The outcome of antiviral treatment seems to depend on host and viral
factors. Host genetic diversity is believed to contribute in determining the
outcome. The 2’-5’ oligoadenylate synthetases are a family of interferon -
induced enzymes with antiviral action. Thus, any genetic variants that affect
2’5’OAS activity could be important in predicting response to treatment.
The study included 42 chronic HCV children. They were treated with
combined Pegilated Interferon a and Ribavirin therapy for 48 weeks. PCR
was done on weeks 12, 24, 48 to detect EVR, BT, ETR & w72 post
Summary and conclusion
treatment to determine SVR. Detection of single nucleotide polymorphism at
OAS 1 exon 7 using restriction fragment length polymorphisms technique
was done with identification of the genotype GG, AG, or AA.
Our results showed that:
Among risk factors of HCV infection acquisition, performing
different medical procedures represents the highest risk in our
patients (66.7%). Also, half of the cases had HCV infection
within the family.
Eighteen of the patients had genotype GG (42.9%), 23 were AG
(54.7%), and only one patient was AA (2.4%). This is an
empirical sample of HCV Egyptian children.
There was no difference in clinical data, laboratory,
radiological, and histological parameters among different
genotypes, except for pre-treatment viral load which increased
in ascending order through GG, AG, and AA genotypes. This
may suggest that the OASl with the A allele (at exon 7)
showed lower ability to inhibit virus replication than the OAS 1
with G allele.
Sustained virological response achieved by patients in the
current shtdy was 51.3%. The rates of ETR, Relapse, and
breakthrough were 6 1.9%, 7.6%, 14.3% respectively.
Summary and conclusion
Males tend to respond more to treatment than females. Also,
children with vertical transmission had lower SVR than those
with horizontal transmission yet the effect of both, sex and
mode of transmission did not reach statistically significant
values.
All of the patients who achieved SVR had cEVR (negative
PCR) at week 12. Children who achieved partial EVR (the
HCV RNA level decreased more than 2 logs relative to
baseline) had breakthrough later.
Factors like: sex, age, mode of transmission of HCV, grade of
histological activity, degree of fibrosis, LFTs or pre-treatment
viral load had no influence on treatment response in the current
sbdy.
Patients
with GG genotype showed SVR in 44.4% of them, those with
AG had SVR of 60%, and the only patient with AA genotype
was NR.
The
frequency of G allel, was 56 (half of them were found in
responders and half in non-responders). As for A allel, it was
22 (10 in NR & 12 in responders).
In conclusion, our results show that different genotypes at exon 7
of OASl were not found to influence treatment response in HCV infected
Summary and conclusion
children treated with combined therapy (Peg IFNI RBV). So, it cannot be
used as a biomarker for predicting treatment response before initiation of
therapy.