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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
RENAL DATA FROM THE ARAB WORLD  
Year : 2014  |  Volume : 25  |  Issue : 6  |  Page : 1315-1320
Impact of hepatitis C infection on renal transplant patients: A single-center experience in Libya


1 Department of Medicine, Hamad General Hospital, HMC, Doha, Qatar
2 Department of Medicine and Pharmacology, Al-Arab Medical University, Benghazi, Libya
3 Nephrology Division, Department of Medicine, Central Hospital, Tripoli, Libya
4 Pediatric Hospital, Tripoli, Libya

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Date of Web Publication10-Nov-2014
 

   Abstract 

The objective of this study was to assess the effect of hepatitis C virus (HCV) infection on graft and patient survival in a cohort of Libyan renal transplant recipients. Medical records of 241 renal transplant (RT) patients who have been followed-up at the Benghazi Nephrology Center up to February 2010 were reviewed. Based on the presence or absence of anti-HCV antibodies and HCV-RNA in the serum, patients were divided into two groups: HCV-positives and HCV-negatives. Anti-HCV antibodies were detected by the enzyme-linked immunosorbent assay technique and HCV-RNA by the polymerase chain reaction. Of the 241 RT patients, 162 were male and 79 were female. One hundred and ten patients (45.6%) were HCV-positives and 131 (54.4%) were HCV-negatives. Acute graft rejection was significantly higher among HCV-negative than HCV-positive patients (42 patients versus 28 patients, respectively; P < 0.001). Conversely, chronic graft rejection was higher among HCV-positives than that among HCV-negative patients (35 patients versus 24 patients, respectively; P <0.05), and this difference became more significant after a 12-month period of transplantation (P <0.01). Seventeen patients died during the follow-up: Seven HCV-positives (6.3%) and 10 HCV-negatives (7.6%), and there was no significant difference in the death rate following RT between the two groups (P = 0.08). Among the seven deaths of HCV-positives, liver disease-related complications were the main cause of death in three (42.8%) HCV-positive patients compared with none in the HCV-negative patients. The presence of HCV infection influenced chronic graft survival in RT patients and a higher proportion of HCV-infected patients had hepatic dysfunctions after RT. An increase in fatal liver complications was noted in HCV-positive patients with RT. In addition to pre-RT-specific therapy of HCV infection, all measures should be taken to prevent HCV infection pre- and post-RT. HCV-infected RT recipients need close monitoring for graft and liver function to prolong allograft and patient survival.

How to cite this article:
Elzouki ANY, Gargoum HM, Habas EM, Rayani AA, Othman M. Impact of hepatitis C infection on renal transplant patients: A single-center experience in Libya. Saudi J Kidney Dis Transpl 2014;25:1315-20

How to cite this URL:
Elzouki ANY, Gargoum HM, Habas EM, Rayani AA, Othman M. Impact of hepatitis C infection on renal transplant patients: A single-center experience in Libya. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2018 Apr 23];25:1315-20. Available from: http://www.sjkdt.org/text.asp?2014/25/6/1315/144303

   Introduction Top


Chronic liver diseases related to viral hepa­titis are common problem in renal transplant patients. Hepatitis C virus (HCV) infection should be assessed before and after renal trans­plantation in both donors and graft recipients.

This infection is present in 20-50% of end-stage renal disease patients worldwide, and it contributes significantly to morbidity and mor­tality following renal transplantation. [1],[2],[3],[4],[5]

Liver disease is an important cause of morbi­dity and mortality among organ-transplanted recipients. A higher rate of abnormal liver func­tion in renal transplant recipients has been reported by Pereira and coworkers. The authors also reported a significant increase in the rate of liver failure leading to death in long-term survi­vors of renal transplantation patients. Renal-transplanted recipients with HCV have a higher rate of liver complications and lower survival rate after transplantation than HCV-negative recipients. [6],[7],[8],[9],[10]

HCV is associated with many kidney-related HCV complications. A higher level of HCV viremia leads to an alteration in the ratio of antibody-antigen immune complexes causing immune-mediated glumerulopathy. [11] The preva­lence of proteinuria was greater among HCV-positive kidney transplant recipients. [12] Proteinuria is mostly due to membranous and membrano-proliferative glomerulonephritis type I, minimal change disease and focal and segmental glomerulosclerosis. [12] Renal thrombotic micro-angiopathy and mixed essential cryoglobulinemia also occur more in HCV-infected renal transplant patients. [13] HCV infection has been associated with a greater incidence of diabetes mellitus, both in the general population and among renal transplant patients. [14] Post-trans­plant diabetes mellitus is associated with poorer short-term and long-term complications that can affect the patient and graft outcomes. [15]

The objective of the present study was to determine the effect of HCV infection on graft and patient survival in a cohort of Libyan renal transplant recipients followed-up at a single ter­tiary nephrology center in Benghazi, Libya.


   Materials and Methods Top


A retrospective cohort study was conducted in 241 renal transplant patients who were followed-up to February 2010. The patients were followed-up at the Benghazi Nephrology Center, Benghazi, to which all patients in the eastern part of Libya were referred after renal trans­plantation for continuation of follow-up at the renal transplant clinic. The patients were either transplanted in Libya or in other worldwide countries such as Egypt, China or India, or others.

Viral screen including anti-HCV antibodies was conducted to all patients at the first follow-up visit after transplantation. Detection of anti-HCV antibodies in the serum was carried out by enzyme-linked immunosorbent assay techniques and positive results were confirmed by the detection of serum HCV-RNA level of viremia by polymerase chain reaction techniques.

Patients were divided into two groups; HCV-positives (group 1) and HCV-negatives (group 2). Age, sex, date and type of allograft, type, time and causes of occurred allograft rejection and deaths and its causes were recorded in all patients. The two groups were compared for statistically significant differences. SPSS 19.0 Statistical software was used for the analysis. Descriptive statistics in the form of mean, stan­dard deviation and frequency with percentages were calculated for interval and categorical variables, respectively. The chi-square test was used for between-categorical variables and Stu­dent's t-test for interval variables was used as appropriate. P-value (two-tailed) <0.05 was considered as the statistically significant level.


   Results Top


Of the 241 renal transplanted patients enrolled in the study, 162 (67.2%) were male and 79 (32.8%) were female. There was a significant difference in the male to female ratio (P <0.001). One-hundred and ten (45.6%) patients were HCV-positive and 131 (54.4%) patients were HCV-negative. [Table 1] shows the demo­graphic and clinical data of the two groups.
Table 1: Demographics of renal transplant HCV-positive patients and HCV-negative patients.

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Acute graft rejection was significantly higher among HCV-negative than HCV-positive pa­tients (42 patients vs 28 patients, respectively; P <0.001) [Figure 1]. Conversely, the overall chronic graft rejection was higher among HCV-positive than HCV-negative patients [35 (32%) patients vs. 24 (18%) patients, respectively; P <0.05] [Figure 1], and this difference became more statistically significant after 12 months of the transplantation surgery [15 (13.6%) chronic rejections among HCV-positives compared with eight (6%) chronic rejections among HCV-negatives; P <0.01] [Figure 2]. The overall mortality during the follow-up was 17 (7%) transplanted patients. There was no significant difference in the death rate fol­lowing renal transplantation between the two groups [seven (6.3%) deaths among HCV-positives compared with 10 (7.6%) deaths among the HCV-negatives, P = 0.08]. Among the seven deaths of HCV-positives, liver disease-related complications were the primary cause of death in three (42.8%) HCV-positive patients compared with none among the HCV-negative patients.
Figure 1: Causes of graft loss (i.e., acute rejection, chronic rejection or death) in the renal transplanted patients with or without HCV infection.

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Figure 2: Duration of chronic allograft rejection in the renal transplanted patients with and without HCV infection.

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Graft loss due to drug toxicity and poor compliance of drugs significantly affect graft survival in the HCV-negative transplanted group than in the HCV-positive transplanted group (P = 0.009 and P = 0.025, respectively). Other causes such as recurrent urinary tract infection, obstructive uropathy, glumerulopathy recur­rence and acute tubular necrosis had caused graft loss in both groups, without a significant difference between the two groups.


   Discussion Top


In the present study, the frequency of HCV infection among transplanted patients in the Benghazi Nephrology Center was very high (45.6%). The prevalence of HCV infection in renal transplant patients is mainly determined by the rate of infection before transplantation. In one study, the prevalence of HCV infection was 18% in transplanted patients [2] and 14% in chronic hemodialyzed patients. [1],[16] In Libya, a sero-epidemiologic survey on a representative, random and community-based large sample size of 65,671 individuals from all distinct admi­nistrative regions of the country was recently published, [17] where the prevalence of HCV was found to be 1.3% among the general population. In another study conducted in the Benghazi Nephrology Center, the prevalence of HCV in 153 chronic renal dialysis patients was found to be 21%. [18] It is well known that renal trans­plantation could lead to a dramatic increase in the HCV infection prevalence rate considering the dramatic increase in the number of renal transplantations and use of potent immunosuppressive drugs. [19]

HCV infection can cause serious liver da­mage in patients with chronic kidney disease. [6] About 8-28% of HCV-infected renal trans­planted patients die due to chronic liver disease. [5] In the present study, liver disease-related complications were the primary cause of death in even a higher proportion (42.3%) in HCV-positive patients compared with 0% among the HCV-negative patients. In patients with chronic kidney disease, control and specific treatment of HCV infection prior to renal transplantation may affect graft and patient survival following transplantation. [7] It has been reported that the survival is better in HCV-positive transplanted patients compared with HCV-positive dialyzed patients on HCV treatment. [20] The aims of pre-transplantation HCV treatment, therefore, are to decrease the risk of HCV-associated liver di­sease progression, stabilize renal function in patients with HCV-related glomerulopathy and to prevent other HCV-associated complications after renal transplantation.

Immune-competent patients had HCV infec­tion and a slowly progressive indolent liver dys­function course, while in the renal transplant HCV-positive patients, the natural history of liver damage progression was not well declared. [21] Data on the prognosis of HCV-positive patients who received renal transplantation are still controversial. [8],[],[9],[22] In the present study, HCV infection influenced chronic graft survival in renal transplant patients and caused a higher proportion of hepatic dysfunction. In contrast, the higher proportion of acute allograft rejec­tion among HCV-negative compared with HCV-positive renal transplant patients could be attri­buted to many other factors such as drug toxicity and poor compliance of the patient to their maintenance immunosuppressive therapy.

In the present study, the overall mortality was similar in HCV-positive and HCV-negative groups. It had been reported in previous studies that patient survival was not different in HCV-positive and HCV-negative renal transplant recipients at five years. [23],[24] Einollahi and co-workers had also reported no difference in terms of survival rate between HCV-positive and HCV-negative recipients at seven years post-renal transplantation, [7] and in another study even up to 20 years after transplantation. [25] On the contrary, other studies showed that positive HCV status was an independent and significant risk factor for death and graft failure after renal transplantation. [26]

In conclusion, the presence of HCV infection influences chronic graft survival in renal trans­plant patients and a higher proportion of HCV-infected patients had hepatic dysfunctions after renal transplantation. An increase in fatal liver complications was noted in HCV-positive pa­tients with renal transplantation. In addition to pre-renal transplantation specific therapy of HCV infection, all measures should be taken to prevent HCV infection pre- and post-renal transplantation. HCV-infected renal transplant recipients need close monitoring for both graft and liver function to prolong allograft and pa­tient survival.

Abdel-Naser Elzouki and Muftah Othman were affiliated to the Department of Medicine, Al-Arab Medical University, Benghazi, Libya, when the study was conducted.

 
   References Top

1.
Jadoul M, Cornu C, Van Yperselle De Strihouu C. Incidence and risk factors for hepatitis C seroconversion in hemodialysis: A prospective study. The UCL Collaborative Group. Kidney Int 1993;44:1322-6.  Back to cited text no. 1
    
2.
Goffin E, Pirson Y, Cornu C. Geubel A, Squiffiet JP, Van Ypersele de Strihou C. Out­come of HCV infection after renal transplan­tation. Kidney Int 1994;45:551-5.  Back to cited text no. 2
    
3.
Pereira BJ, Levey AS. Hepatitis C virus infection in dialysis and renal transplantation. Kidney Int 1997;51:981-99.  Back to cited text no. 3
    
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Mathurin P, Mouquet C, Poynard T, et al. Impact of hepatitis B and C virus on kidney transplantation outcome. Hepatology 1999;29: 257-63.  Back to cited text no. 6
    
7.
Einollahi B, Hajarizadeh B, Bakhtiari S, et al. Pretransplant hepatitis C virus infection and its effect on the post-transplant course of living renal allograft recipients. J Gastroenterol Hepatol 2003;18:836-40.  Back to cited text no. 7
    
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Kokado Y, Takahara S, Ichimaru N, et al. Clin­ical outcome of HCV infection after renal trans­plantation. Transplant Proc 2000;32:1940-3.  Back to cited text no. 8
    
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Fabrizi F, Martin P, Lunghi G, Ponticelli C. Nosocomial transmission of hepatitis C virus infection in hemodialysis patients: Clinical perspectives. Int J Artif Organs 2000;23:805-16.  Back to cited text no. 9
    
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11.
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12.
Romero E, Galindo P, Bravo JA, et al. Hepatitis C virus infection after renal transplantation. Transplant Proc 2008;40:2933-5.  Back to cited text no. 12
    
13.
Cruzado JM, Carrera M, Torras J, Grinyo JM. Hepatitis C virus infection and de novo glomerular lesions in renal allografts. Am J Transplant 2001;1:171-8.  Back to cited text no. 13
    
14.
Alavian SM. Re. Posttransplant Diabetes Mellitus in Kidney Allograft Recipients at Shaheed Hasheminejad Hospital. Iran J Kidney Dis 2008;2:110-1.  Back to cited text no. 14
    
15.
Saleem TF, Cunningham KE, Hollenbeak CS, Alfrey EJ, Gabbay RA. Development of dia­betes mellitus post-renal transplantation is associated with poor short-term clinical out­comes. Transplant Proc 2003;35:2916-8.  Back to cited text no. 15
    
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Fabrizi F, Messa P, Basile C, Martin P. Hepatic disorders in chronic kidney disease. Nat Rev Nephrol 2010;2:395-403.  Back to cited text no. 16
    
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Elzouki AN, Esmeo MN, Samod M, et al. Prevalence of Hepatitis B, C infection and its risk factors in Libya: A national seroepidemiological Survey. East Mediterr Health J 2014;19:589-99.  Back to cited text no. 17
    
18.
Elzouki AN, Bushala M, Tobgi RS, Kafifi M. Prevalence of anti-hepatitis C virus antibodies and hepatitis C virus viraemia in chronic haemodialysis patients in Libya. Nephrol Dial Transplant 1995;10:475-6.  Back to cited text no. 18
    
19.
Terrault NA, Adey DB. The kidney transplant recipient with hepatitis C infection: Pre- and posttransplantation treatment. Clin J Am Soc Nephrol 2007;2:563-75.  Back to cited text no. 19
    
20.
Knoll GA, Tankersley MR, Lee JY, Julian BA, Curtis JJ. The impact of renal transplantation on survival in hepatitis C-positive end-stage renal disease patients. Am J Kidney Dis 1997;29:608-14.  Back to cited text no. 20
    
21.
Natov SN. Transmission of viral hepatitis by kidney transplantation: Donor evaluation and transplant policies (Part 1: hepatitis B virus). Transpl Infect Dis 2002;4:124-31.  Back to cited text no. 21
    
22.
Sezer S, Ozdemir FN, Akcay A, Arat Z, Boyacýoglu S, Haberal M. Renal transplantation offers a better survival in HCV-infected ESRD patients. Clin Transplant 2004;18:619-23.  Back to cited text no. 22
    
23.
Roth D, Zucker K, Cirocco De Mattos A, et al. The impact of hepatitis C virus infection on renal allograft recipients. Kidney Int 1994;45:38-44.  Back to cited text no. 23
    
24.
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25.
Hanafusa T, Ichikawa Y, Kishikawa H, Kyo M, Fukunishi T, Kokado Y. Retrospective study on the impact of hepatitis C virus infection on kidney transplant patients over 20 years. Transplantation 1998;66:471-6.  Back to cited text no. 25
    
26.
Fabrizi F, Martin P, Dixit V, Bunnapradist S, Dulai G. Hepatitis C virus antibody status and survival after renal transplantation: Meta-analysis of observational studies. Am J Transplant 2005;5:1452-61.  Back to cited text no. 26
    

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Correspondence Address:
Prof. Abdel-Naser Y Elzouki
Department of Medicine, Hamad General Hospital, Hamad Medical Corporation, P.O. Box 3050, Doha
Qatar
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DOI: 10.4103/1319-2442.144303

PMID: 25394459

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