الفهرس 
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Abstract
Globally, hepatitis C is a global public health problem where about 130 to 150 million people suffer from chronic HCV. It is estimated that HCV related deaths are 350,000 to 500,000 annually. Mapping the prevalence of HCV all over the world showed that Africa, Central and East Asia have the highest prevalence rate.
In Egypt, Hepatitis C disease burden is substantially increasing in Egyptian communities, and it is estimated that its prevalence in Egyptian communities has reached 22% of the total population. This high prevalence of HCV is not the only problem, the high incidence of HCV is another important issue which reflects the new HCV infections that occurs annually.
Growing evidence, however, has moved HCV infection from the traditional picture of a localized, liver-focused disease, to the concept of a systemic disease capable of producing extrahepatic manifestations, so HCV-infected individuals have increased risks of developing immune-related disorders, metabolic alterations, neurological/psychiatric disorders and cardiovascular alterations.
The replication of the HCV may result in myocarditis, which progresses to cardiomyopathy in subjects with genetic susceptibility. The HCV associated myocarditis would progress to chronic persistent myocarditis via the direct (viral) effect, and via the indirect (immune) effect, which would lead to the activation of proinflammatory and profibrogenic environments in the liver as well as systemically enhancing the development of cardiovascular alterations.
NT-pro BNP is a hormone that is secreted predominantly by the ventricles, and reaches very high plasma concentrations in subjects with congestive heart failure. It is synthesized in the heart as a reaction to cardiac wall distension and stretching, and neurohormonal activation. The cardiomyocytes synthesize a pre-propetptide (preproBNP 134 amino acids) which is split into a signal peptide and a propeptide (pro BNP 108 amino acids). During secretion from the cardiomyocytes, pro BNP is split at a ratio of 1:1 into the physiologically active BNP (32 amino acids) which corresponds to the C-terminal fragment, and the biologically inactive N-terminal fragment (NT-pro BNP, 76 amino acids).
Of all investigated neurohormones and natriuretic peptides, B type natriuretic peptide and NT-pro BNP are the best markers for ruling out left ventricular dysfunction and to detect the degree of severity.
NT-pro BNP was suggested to be a valuable tool for screening asymptomatic individuals to prevalent subclinical cardiovascular disease and/or incident cardiovascular events, including heart failure and cardiovascular death.
This study aims to evaluate the level of N-terminal pro-B type natriuretic peptide as a predictor of myocardial dysfunction in patients with chronic hepatitis C virus infection.
To achieve this goal, it was conducted on 45 patients with chronic HCV infection with positive HCV antibody and detectable HCV RNA for > 6 months, selected from outpatient clinic of hepatology department, National Liver Institute. In addition to 35 apparently healthy subjects matching age and gender were used as a control group.
The studied subjects were grouped as follow:
group 1 chronic HCV infection group: It included 45 patients. Their ages ranged from 25 to 63 years with mean age of 45.6±7.3, they were 22 males and 23 females.
group 1 was subdivided into 2 subgroups: I. According to the cutoff value of NT pro BNP as follow:
-Group1a: It included 9 patients with NT pro BNP value ≤ 65pg/ml.
-Group1b: it included 36 patients with NT pro BNP value >65pg/ml.
II. According to NT-pro BNP level at 125 pg/ml, the proposed cutoff value for heart failure as follow:
- Group1 : It included 32 patients with NT pro BNP value ≤ 125pg/ml.
- group 1 : It included 13 patients with NT pro BNP value >125pg/ml.
group 2 control group: It included 35 apparently healthy subjects, their age ranged from 22 to 65 years with mean age of 45.9±7.4, they were 18 males and 17 females.
All patient and control groups were subjected to the following:
1. Complete history taking.
2. Complete clinical examination.
3. Abdominal US, Electrocardiography (ECG).
4. Laboratory investigation including:
i. Liver function tests:
Serum transaminases (aspartate transaminase (AST) and alanine transaminase (ALT), gamma glulamyl transpeptidase (GGT), serum bilirubin (total bilirubin and direct bilirubin), serum albumin (Alb), serum alkaline phosphatase (ALP), serum total proteins (TP).
ii. Viral markers (HBsAg, HCV-Ab)
iii. Fasting blood sugar.
iv. Renal function test (urea ,creatinine) v. Lipid profile (cholesterol, HDLC , LDLC and triacylglycerol)
vi. HCV RNA quantification for cases only
vii. Fibroscan for cases only
viii. Serum level of NT pro-BNP measured by ELISA .
The results from the current study can be summarized in the following:
There is no significant difference between patient and control group regarding age, gender and BMI.
Regarding the different liver function tests, there is a significant increase of ALT, AST, ALP, γ-GT, TB and TP, while there is asignificant decrease of albumin level in patient group compared to control group.
There is no significant difference between patient and control groups regarding cholesterol, TG, LDL-c and HDL-c.
Regarding ECG changes, the control group had normal ECG but ECG abnormality was present in 15.6% of patients and in 10 patients (76.9%) from the 13 patients with high NT-proBNP >125pg/ml. None of the studied participants had ECG changes suggestive of ischemic, valvular and hypertensive heart disease.
On testing the value of NT-pro BNP in this study, the NT-pro BNP concentration was significantly higher for the HCV patients (mean 120.62±72.602 pg/ml) than for the controls (mean 36.11±28.07 pg/ml) (P=0.001).
By using ROC curve, the cutoff point of NT-pro BNP at which sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 80%, 83%, 86%, 76% and 81% respectively was 65 pg/ml.
BMI and albumin were significantly lower in the NT-pro BNP >65 pg/ml group than in the ≤65 pg/ml group (P=0.01 and P=0.027 respectively). No significance between group differences were found in age, gender, ECG, TC, LDL, HDL, TG, ALT, AST, ALP, γGT, TP, urea, creatinine, HCV RNA level or liver fibrosis level.
Multivariate analysis of independent parameters related to a NT-pro BNP level >65 pg/ml, of all studied participants, identified HCV infection, body mass index (BMI), albumin and AST (P=<0.0001, P =0.025, P=0.004 and P=0.036 respectively). In our study, HCV-RNA level, and liver fibrosis did not have a significant influence on high NT-pro BNP. The immune reaction toward HCV varies; thus, the difference might be caused by individual immune response.
We also divided the patient group with chronic HCV infection according to whether or not they had a high NT-pro BNP level, >125 pg/ml, the proposed cutoff value for heart failure. No statistically significant difference between the two groups was found.
This suggests that HCV infection influences cardiac function asymptomatically and that testing for NT-pro BNP would be helpful in identifying patients in an asymptomatic state of cardiac failure.