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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
LETTER TO THE EDITOR  
Year : 2012  |  Volume : 23  |  Issue : 6  |  Page : 1268-1273
Infection with the hepatitis C virus as a risk factor of cardiovascular events in the early years after renal transplantation: A single center study from Egypt


1 Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
2 Nasser Institute Hospital, Faculty of Medicine, Ain Shams University, Cairo, Egypt
3 Internal Medicine and Nephrology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

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Date of Web Publication17-Nov-2012
 

How to cite this article:
Morcos NS, Medhat AM, Ahmed AE, El Sharkawy MS. Infection with the hepatitis C virus as a risk factor of cardiovascular events in the early years after renal transplantation: A single center study from Egypt. Saudi J Kidney Dis Transpl 2012;23:1268-73

How to cite this URL:
Morcos NS, Medhat AM, Ahmed AE, El Sharkawy MS. Infection with the hepatitis C virus as a risk factor of cardiovascular events in the early years after renal transplantation: A single center study from Egypt. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2019 Sep 16];23:1268-73. Available from: http://www.sjkdt.org/text.asp?2012/23/6/1268/103574
To the Editor,

Infection with the hepatitis C virus (HCV) and chronic renal disease are common and potentially serious medical problems throughout the world. These two conditions are linked in several important ways; some forms of renal disease are precipitated by HCV infection, while patients with end-stage renal disease (ESRD) are at increased risk for acquiring HCV infection. [1]

Kidney transplantation (KTx) offers the best and most cost-effective option for most individual patients, with improved quality of life and survival. [2] Nevertheless, cardiovascular complications remain important factors for morbidity and mortality after KTx, and contribute most prominently to the yet unsolved problem of death with a functioning allograft, [3] although some studies have recognized that patients who lack identifiable risk factors had a low incidence of cardiac events after transplantation. [4]

Infection with HCV is the main cause of chronic liver disease among renal transplant recipients (RTR), being the fourth most prevalent cause of mortality. [5] The proportion of anti-HCV antibodies in RTR varies from 6 to 64%, depending on the geographic area. [6] In Egypt, this proportion was reported to be higher than most other countries found in the literature, and is around 60%. [6],[7] Renal transplantation remains the best form of treatment for patients with HCV with ESRD and has been the subject of a number of trials with inconsistent and sometimes paradoxical results. [8],[9] The reason for this controversy is related to the natural history of HCV in ESRD involving complex host-virus interactions.

We conducted this cross-sectional study on 42 male renal transplant recipients who were admitted to the renal clinic at the Nasser Institute Hospital. All study patients had stable renal functions (serum creatinine <2 mg/dL and absence of proteinuria) during the early years (up to three years), and were treated with cyclosporine A. Patients who were diabetic, hepatitis B virus (HBV) positive, cirrhotic (by routine biopsy), smokers, obese or older than 50 years were excluded. Of the 42 patients studied, anti-HCV antibodies were detected in 22 patients, while 20 were anti-HCV negative. Twenty healthy volunteers were included and served as reference controls. Pre-transplant data were available and obtained from only nine patients. All patients provided written informed consent as stated in the Declaration of Helsinki of 1979.

All hematological tests were done immediately after sample collection. Testing for anti-HCV was carried out using a commercial Ortho HCV 3.0 enzyme-linked immunosorbent assay test system. The following tests were carried out on all study candi-dates: fasting blood sugar, creatinine (Cr), blood urea nitrogen (BUN), cyclosporine A (CsA), alanine aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP), total (T. Bil) and direct bilirubin (D. Bil). The lipid profile tested included total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL), non-HDL (non-HDL = TC - HDL), [10] very low density lipoprotein (VLDL) (VLDL = TG/5) [11] and low-density lipoprotein-cholesterol (LDL) (LDL-C = non-HDL-C - TG/5). [11],[12] Testing for liver fibrosis was calculated from AST/platelets ratio (APRI) and AST/ALT ratio, [13] and the atherosclerosis index was calculated as TC/HDL; LDL/HDL; TG/HDL; or non-HDL/HDL. [14] The glomerular filtration rate (eGFR) was estimated using the abbreviated Modification of Diet in Renal Disease (MDRD) equation. [8]

Continuous variables are presented as mean values ± standard deviation, while categorical variables are presented as absolute number and frequencies. Associations between categorical variables were tested by the use of contingency tables and the calculation of chi-squared test. Differences between groups were evaluated by the calculation of Student's t-test and one-way ANOVA. Paired t-test was used to calculate differences before and after KTx. Correlations between biochemical markers and other continuous variables were tested using the Spearman or the Pearson's correlation coefficients. All reported P-values are based on two-sided tests and compared with a significance level of 5%. SPSS 17.0 software (Statistical Product and Services Solutions, version 17.0, SPSS Inc., Chicago, IL, USA) was used for all the statistical calculations.

The participants were categorized as RTR anti-HCV negative, RTR anti-HCV positive and control reference groups. Patients were then classified by their eGFR status (with a cut-off value of 60 mL/min/1.73 m 2) or by duration of KTx (1 year; >1 year). The results revealed that the eGFR did not differ between the HCV groups, but was significantly lower in the RTR when compared with the reference control group. [Table 1] illustrates the various characteristics of the participants.
Table 1: Demographic and clinical data of the participants (one-way ANOVA).

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The anti-HCV positive RTRs had slightly lower ALP and higher ALT activities along with lower red blood cell count when compared with the anti-HCV negative group. No other statistical significance was observed in the studied parameters between the two groups. [Table 2] illustrates the various biochemical data of the participants.
Table 2: Comparative biochemical data in post-renal transplant patients with and without anti-HCV antibodies and the reference group (one-way ANOVA).

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Correlation analysis revealed that none of the lipid parameters correlated with the eGFR values; however, the LDL levels decreased with the increase of KTx duration, and a significant inverted correlation (P <0.009) was observed between liver fibrosis (presented as APRI index) and HDL levels. Consequently, there was a positive correlation with the atherosclerotic indices (presented as non-HDL/HDL and LDL/HDL). [Figure 1] illustrates the significant correlations of the lipid parameters with (a) duration of KTx and (b and c) liver fibrosis (APRI).
Figure 1: The significant correlations of the lipid parameters with (A) duration of KTx and (B and C) liver fibrosis (APRI).

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Pre-transplant data were obtained from only nine patients, of whom five were anti-HCV positive. Their lipid profile was within the normal reference range. However, after transplantation, the paired t-test statistical analysis revealed that there was a significant increase inthe atherogenic profile.

The main outcome of the results in the present study is that anti-HCV positive RTRs had significantly lower ALP and higher ALT activities along with lower RBC count when compared with the HCV-neg group. No other statistical significance was observed in the studied parameters between the two groups. Both RTR groups had considerable dyslipidemia and the calculated cardiac risk factors were significantly higher in RTRs when compared with the reference group. These results were found equally in patients with and without anti-HCV antibodies. The pathogenesis of dyslipidemia in RTR is poorly understood and appears to be multi-factorial, and includes age, body weight, gender, pre-transplant lipid level, renal dysfunction, proteinuria, concomitant use of diuretics or beta blockers, diabetes mellitus, steroid and cyclosporine use. [16],[17],[18] We did not find any favorable distinctive lipid pattern in patients with chronic HCV infection. Also, none of the lipid parameters correlated with the CsA level. Kidney transplantation corrected the anemia in both HCV groups equally, which is consistent with what has been demonstrated elsewhere. [19]

In the present study, no severe liver toxicity was seen in either of the two HCV groups. The anti-HCV positive patients had slightly higher levels of ALT, which could not be considered a marker for liver toxicity in renal recipient patients. Additionally, HCV-pos patients showed a better bone turnover than the HCV-neg ones as their ALP was lower.

It has been suggested that CsA might have beneficial effects on the natural course of HCV infection after renal transplantation.[20] This may be because host cell cyclophilins play an important role in the replication of HCV. Inhibition of cyclophilins caused by CsA causes profound inhibition of HCV replication, although the underlying mechanisms are not yet known. [21]

Male renal transplant recipients had an atherogenic lipid profile, which was not related to the presence of HCV, the eGFR value or CsA levels during the first three years after transplantation. Differences in the results of the other published studies may be explained by confounding factors including differences in immunosuppressive protocols, study design and differences in HCV genotypes. Other factors that should be considered are duration of pre-transplant dialysis, age, general health of recipients and history of liver toxicity.

 
   References Top

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3.Leite D, Campos AH. A strategy to improve the cardiovascular risk factor profile in renal transplant patients. Arq Bras Cardiol .2010;94: 738-46.  Back to cited text no. 3
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14.Kimura T, Itoh T, Fusazaki T, et al. Low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol ratio predicts lipid-rich coronary plaque in patients with coronary artery disease - integrated-backscatter intravascular ultrasound study. Circ J 2010;74:1392-8.  Back to cited text no. 14
    
15.Raszeja-Wyszomirska J, Szymanik B, £awniczak M, et al. Validation of the BARD scoring system in Polish patients with nonalcoholic fatty liver disease (NAFLD). BMC Gastroenterol 2010;28;10:67.  Back to cited text no. 15
    
16.Marcén R. Cardiovascular risk factors in renal transplantation-current Controversies. Nephrol Dial Transplant 2006l;21 Suppl 3:iii3-8.  Back to cited text no. 16
    
17.Fernández-Fresnedo G, Gómez-Alamillo C, Ruiz JC, de Francisco AL, Arias M. Chronic renal disease in renal transplant patients: Management of cardiovascular risk factors. Transplant Proc 2009;41:1637-8.  Back to cited text no. 17
    
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20.Fernandes F, Ansari IU, Striker R. Cyclosporine inhibits a direct interaction between cyclophilins and hepatitis C NS5A. PLoS One 2010;5:e9815.  Back to cited text no. 20
    
21.Kaul A, Stauffer S, Berger C, et al. Essential role of cyclophilin A for hepatitis C virus replication and virus production and possible link to polyprotein cleavage kinetics. PLoS Pathog 2009;5:e1000546.  Back to cited text no. 21
    

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Correspondence Address:
Nadia Youssef Sadek Morcos
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo
Egypt
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DOI: 10.4103/1319-2442.103574

PMID: 23168863

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