الفهرس 
HCV INFECTIONOnly 14 pages are availabe for public view
 |  | from | 151 |  |  |
| | | from | 151 | | |
Abstract
H
epatitis C virus (HCV) infection is an important public health problem. In more than 80% of infected person HCV infection can induce persistent hepatic injury which leads to disease progression from periportal inflammation to chronic hepatitis with bridging fibrosis to frank cirrhosis and hepatocellular carcinoma.
Combination treatment of pegylated interferon alpha and ribavirin has become the standard therapy for patients with chronic hepatitis C infection .Patient with chronic hepatitis C infection receiving combination treatment develop anaemia because of ribavirin induced hemolysis and interferon induced bone marrow suppression. Conversely, interferon directly suppresses the bone marrow synthesis of granulocytes, erythrocytes and megakaryocytes. In paticular, hematological abnormalities and ribavirin induced hemolytic anaemia often necessitate dose reduction and premature withdrawal from therapy.
The aim of the study:
The present study was conducted to evaluate the clinical significance of ITPA gene variants in protection against sever anaemia induced by pegylated interferon and ribavirin therapy in Egyptian hepatitis C patient.
Patient and method:
This retrospective study was carried out on 50 subjects recruited from Kafr El Shiekh Liver Center Internal Medicine Department and Outpatients clinics on treatment by interferon and ribavirin. During the period from October 2012 to April 2013 and subject were classified into two groups:
Group (A):25 HCV-positive patients developed sever anaemia (Hb<10mg) during course of treatment with interferon and ribavirin.
Group (B):25 HCV-positive patients didnot developed anaemia during course of treatment with interferon and ribavirin.
Patients of the studied groups were subjected to full history taking, clinical examination, laboratory investigations, abdominal ultrasonography , liver biopsy and Genetic Analysis of ITPA SN PS (rs 1127354) and (rs 7270101) by means of Real Time PCR using Taqman SNP Genotyping assays.
Result:
In this study, patients were matched in age, sex and body weight.
In this retrospected study, there were no significant difference between the studied groups according to baseline WBCs, Platelet, PCR, ALT, Biopsy (A) (F) {accoding to Metavir score}, Type of interferon and ribavirin dose.
In this study, there were highly significant difference between the studied groups according to baseline Hb level and Hb level at end of treatment .
Also, there were highly significant difference between Hb level before and after treatment of patient in each group .
In this study, there were no significant difference between studied groups according to ITPA SNP RS 1127354 major and minor genotyping but there is tendency {major genotype (non protective) in group A [21 patient (84%)] > group B [16 patient(64%)] and minor allele (protective) in group B
[9 patient (36%)] > group A [4 patient (16%)] so this may be due to small sample.
In this study, there were no significant difference between studied groups according to ITPA SNP RS 7270101 major and minor genotyping.
In this study, there were no significant difference between baseline WBCs, Platelet, PCR, ALT, Biopsy (A) (F) {accoding to Metavir score}, Type of interferon and ribavirin dose of patient and ITPA SNP (RS 1127354) and (RS 7270101) major and minor genotyping.
In this study, there were significant difference between ITPA SNP (RS 1127354) major and minor genotyping in baseline Hb of patient in group (A) {mean Hb of major genotype [21 patients (84%)] was 13.357<mean Hb of minor genotype [4 patients (16%)] was 14.625.
There were no significant difference between ITPA SNP (RS 1127354) major and minor genotyping in Hb level during and at end of treatment of patient in group (A) but mean Hb of major genotype [21 patients (84%)] was 8.714<mean Hb of minor genotype [4 patients (16%)] was 9.000.
In this study, there were no significant difference between ITPA SNP (RS 1127354) major and minor genotyping in baseline Hb of patient in group (B) but mean Hb of major genotype [16 patients (64%)] was 14.825>mean Hb of minor genotype [9 patients(36%)] was 14.456.
There were highly significant difference between ITPA SNP (RS 1127354) major and minor genotyping in Hb level at end of treatment of patient in group (B) {mean Hb of major genotype [16 patients (64%)] was 12.056<mean Hb of minor genotype [9 patients(36%)] was 12.681}.
In this study, ITPA SNP (RS 1127354) major genotyping patient was in group A (21)>group B (16) and their mean baseline Hb was in group A (13.357)<group B (14.825).
In this study, ITPA SNP (RS 1127354) minor genotyping patient was in group A (4)<group B (9) and their mean baseline Hb was in group A (14.625)>group B (14.456).
In this study, there were no tendency or difference between ITPA SNP (RS 7270101) major and minor genotyping in baseline Hb and Hb level at end of treatment between patient in group (A) and in group (B).
In this study, the mean baseline Hb of ITPA SNP (RS 7270101) major genotyping patient was in group A(13.341) <group B (14.025).
In this study, the minor alleles of both SNPS never occurred on the same chromosome.
The patient with sever ITPase activity in group A [19 patients (76%)] > group B [11 patients (44%)] and patients with mild to moderate ITPase activity in group B [14 patients (56%) > group A [6 patients (24%)].
Conclusion:
Inosine triphosphatase (ITPA) SNP (rs 1127354) variant reduce incidence of anemia induced by pegylated interferon-and ribavirin therapy in Egyptian hepatitis C patients.