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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 1995  |  Volume : 6  |  Issue : 2  |  Page : 144-150
Hepatitis C Virus Infection in Patients on Maintenance Dialysis in Kuwait: Epidemiological Profile and Efficacy of Prophylaxis

1 Department of Medicine, Kuwait University, Ministry of Public Health, Kuwait
2 Department of Community Medicine, Kuwait University, Ministry of Public Health, Kuwait
3 Faculty of Medicine, Kuwait University, Ministry of Public Health, Kuwait

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Data on hepatitis C virus (HCV) infection in patients undergoing maintenance hemodialysis (HD) in Kuwait were collected retrospectively in December 1994. Ninety three of 232 patients (40%) studied had hepatitis C antibodies (anti-HCV) when tested by a second generation enzyme linked immuno-sorbent assay (ELISA-II). Since October 1992, all HD patients who tested positive for anti-HCV were dialysed on separate machines and blood transfusions were limited to acute life-threatening emergencies through regular use of recombinant human erythropoeitin. The prevalence of anti-HCV positivity among dialysis patients who received treatment during the "HCV-prophylaxis period" was 33/163 (20.2%), as compared to 46/55 (83.6%) of those who received HD during the 27 months prior to October 1992 (p< 0.0001), and had similar average duration on dialysis (12 + 7 and 13 + 7 months, respectively). Excluding the 15 patients who had anti-HCV on entry to HD during "HCV­prophylaxis period", the estimated incidence of positive anti-HCV seroconversion was 11.5 per 100 patients per year on HD. In the 93 anti-HCV positive patients, alanine aminotransferase (ALT) levels were elevated for more than six months in 32 (34.4%), elevated in multiple peaks in 22 (23.7%) and showed combined variation of the latter two abnormalities in 16 (17.2%). Histological evidence of chronic active hepatitis was present in five of six patients who manifested persistent ALT abnormalities. Vaccination against hepatitis B virus produced positive seroconversion in 76.1% patients, and those with positive anti-HCV were not at a disadvantage. In conclusion, HCV infection is common in patients undergoing HD in Kuwait.Improvement in screening assays, isolation of anti-HCV positivepatients during dialysis and limitation of blood transfusions may decrease the transmission of this disease in this patient population.

Keywords: Dialysis, Kuwait,Hepatitis C.

How to cite this article:
El-Reshaid K, Kapoor M, Sugathan T, Al-Mufti S, Al-Hilali N. Hepatitis C Virus Infection in Patients on Maintenance Dialysis in Kuwait: Epidemiological Profile and Efficacy of Prophylaxis. Saudi J Kidney Dis Transpl 1995;6:144-50

How to cite this URL:
El-Reshaid K, Kapoor M, Sugathan T, Al-Mufti S, Al-Hilali N. Hepatitis C Virus Infection in Patients on Maintenance Dialysis in Kuwait: Epidemiological Profile and Efficacy of Prophylaxis. Saudi J Kidney Dis Transpl [serial online] 1995 [cited 2020 Jun 6];6:144-50. Available from: http://www.sjkdt.org/text.asp?1995/6/2/144/40856

   Introduction Top

The cloning of an agent, designated hepatitis C virus (HCV), from the plasma of a chronic non-A, non-B (NANB) hepatitis chimpanzee led to the development of multiple assays which were used to identify HCV [1] . Those assays aided the study of the HCV infection and confirmed that patients on maintenance hemodialysis (HD) were at a high risk [2],[3],[4],[5],[6],[7],[8],[9],[10] . The first report on HCV in HD patients in Kuwait appeared in 1992 [2] . Using non­structural recombinant antigens (C100-3), the authors reported 35% prevalence rate in the dialysis population, and indicated that such prevalence was 10 times higher than that observed in random blood donors in Kuwait. In mid-1992, the "HCV-infection control committee" was established by the ministry of public health. This committee suggested certain measures to control the disease transmission in the high-risk groups, and recommended guidelines for the care of HCV­infected patients. Since October 1992, all dialysis patients and staff have been periodically screened for anti-HCV. Patients who tested positive for anti-HCV were dialysed on separate machines. Precaution, similar to those previously recommended for hepatitis B infectious patients, were applied to anti-HCV positive patients during dialysis. Blood transfusions were limited through regular use of recombinant human erythropoetin (rHuEPO).

The present study was conducted to examine the latest epidemiological profile of HCV infection in patients on maintenance dialysis in Kuwait, and the efficacy of prophylactic measures in the control of infection in this patient population.

   Subjects and Methods Top

Data on HCV infection in patients under­going HD in Kuwait were collected retro­spectively in December 1994. A total of 232 patients, who remained on the dialysis program at that time, were included in the study. There were 113 males and 119 females, with a median age of 50 years and an age range of (2-86) years. The median duration on dialysis was 18 months and the duration range was (6-176) months. The patients had received HD in two hospital-based dialysis units and one outpatient dialysis facility. Medical records of the study patients were examined for history of hepatitis, blood transfusions, hepatotoxic drug intake, hepatitis B vaccination, as well as the results of monthly ALT activity, and quarterly testing for anti­HCV status. Three patients were excluded from the study due to insufficient viral work­up for the etiology of their transient liver enzyme abnormalities. Diagnosis of acute viral infections other than HCV was made by testing for specific markers for hepatitis B (HBsAg, HBcAB-IgM), and Cytomegalovirus (CMV-IgM), or demonstration of four-fold increase in viral antibody titres (compliment fixation method) in case of suspected infection by Epstein Barr and Herpes Virus.

Since October 1992, all the HD patients in Kuwait were periodically tested for anti-HCV. Those who tested positive for anti-HCV were dialysed on separate machines. Furthermore, blood transfusions were limited to acute life threatening emergencies. In all patients, hemoglobin levels were maintained, between 9-10 g/dl, by treatment with rHuE-PO. The" efficacy of these prophylactic measures in the control of HCV infection, in this patient population, was assessed by comparing the prevalence of anti-HCV positivity among patients who received HD during the last 27 months (HCV-prophylaxis period), with the prevalence in the patients who received HD during the 27 months, prior to October 1992 (control period).

Liver biopsy was done in six patients who had persistent liver function abnormalities, positive anti-HCV and negative viral serology.

   Screening for Anti-HCV Top

In the last 27 months, screening for anti­HCV was done using second generation enzyme linked immuno-sorbent assay (The Abbott HCV ELISA 2nd generation). The assay detects antibodies to proteins expressed by putative structural and non-structural regions of the HCV genome (C-100-3, C-33c and C-22). The assay was reported by the manufacturing company (Abbott GmbH Diagnostika) to have 95% sensitivity and specificity, in detection of acute as well as chronic NANB hepatitis.

   Statistical Analysis Top

The data were analyzed using the SPSS statistical package. Chi-squared test was used to test the differences among proportions. Assessment of differences of the duration on dialysis between any two parameters was done using Mann-Whitney U test, and among more than two parameters using Kruskal-Wallis H test. Cumulative probability of HCV infection­free dialysis was determined by using Kaplan-Meier technique.

   Results Top

Epidemiological profile of HCV infection

The Epidemiological profile of HCV infection in the patients studied and the impact of the duration of dialysis on its prevalence is summarized in [Table - 1]. At the end of the study, 93 of the 232 patients (40%) were found to be anti-HCV positive. The prevalence of anti-HCV, was significantly higher among patients who received hemodialysis as compared to those on peritoneal dialysis (P < 0.0001). The prevalence of anti-HCV was also higher in patients who received blood transfusions (P < 0.005). The high prevalence of anti-HCV in the hemodialysis patients and those with a history of blood transfusions was not mediated by a longer duration on dialysis [Table - 1]. On the other hand, a higher prevalence of anti-HCV was observed among patients who received dialysis treatment in the outpatient unit as compared to those who received treatment in the hospital-based facilities (P < 0.0001). However, the duration on dialysis was longer in the former group (P < 0.001). The prevalence of anti-HCV was relatively higher in non-Kuwaiti patients of Arabic background, but did not reach, statistical significance (P =0.06).

   Efficacy of preventive measures Top

During "HCV-prophylaxis period", 154 new end-stage renal disease (ESRD) patients entered HD program in addition to nine patients who had received HD for more than 27 months and tested negative for anti-HCV on October 1992. Thirty three of those 163 (20.2%) patients were found to be anti-HCV positive at the end of "HCV-prophylaxis period", as compared to 46 of 55 (83.6%) patients who received HD during the control period (P < 0.0001). The average duration on dialysis was not different in patients who received HD during the "HCV-prophylaxis period" and those in the control period (12 + 7 and 13+7 months, respectively). After exclusion of 15 patients who had anti-HCV on entry to HD, only 18 of 145 patients (12.4%) developed anti-HCV during follow-up of whom five had frequent travel outside Kuwait during that period. Hence, the estimated incidence of positive anti-HCV seroconversion during "HCV-prophylaxis" was 11.5 per 100 patients per year on HD. In the last 27 months, 15 seropositive patients entered maintenance dialysis program, during the study, of whom seven were kidney-transplant patients who recently lost their grafts. Positive anti-HCV were detected in seven close family members of the remaining eight patients as compared to none in the 18 patients who developed anti­HCV during the last 27 months. None of the 98 dialysis staff, responsible for the immediate care of dialysis patients, developed anti-HCV at the end of the study.

HCV infection and duration on dialysis

During the "HCV-prophylaxis period", the cumulative probability of HCV infection-free dialysis in the 157 anti-HCV seronegative patients was 73.4% at the 27th months of follow-up [Figure - 1].

Anti-HCV and the liver enzymes

During the last 27 months, the initial development of anti-HCV was not associated with elevated ALT in 12/18 patients [Table - 2]. Seven patients had abnormal ALT for more than six months and remained seronegative for HCV, as well as for other viral studies. Two of the seven patients ultimately seroconverted after nine and 12 months of follow-up [Table - 2]. During the last 27 months of observation, ALT levels remained within the normal range in 36 (38.7%) of the 93 patients who were seropositive for anti-HCV, elevated, for more than six months in 32 (34.4%), elevated in multiple peaks in 22 (23.7%) and elevated in a combined fashion of the two latter abnormalities in 16 (17.2%).

Histopathological changes in liver in anti­HCV positive patients

Liver biopsies were performed in six patients who had anti-HCV, which manifested persistent liver abnormalities. Five patients showed evidence of chronic active hepatitis and cirrhosis [Table - 3].

Anti-HCV, HBsAg and response to recombi-nant hepatitis B vaccination

In December 1994, six HBsAg positive patients were receiving HD in Kuwait. All those patients tested positive for HBsAg on entry to HD. Since the application of the routine hepatitis B vaccination in 1989, none of our patients developed HBsAg or HBcAb. HBsAB were detected only in those who received successful vaccination. In our study, anti-HCV were present in three HBsAg­positive patients and absent in four. Two of the 3 patients who had both anti-HCV and HBsAg manifested abnormal ALT levels as well as histological evidence of progressive liver disease [Table - 3]. A total of 155 patients were found to be negative for HBsAg, HBcAb, HBsAb and had received 40 ug of recombinant hepatitis B vaccine administered intramuscularly at time 0, 1, 2 and 6 months [11] . Successful seroconversion (antibody concentration of >0.1 as tested by absorbance, Ausab, Abbott, N. Chicago, IL) was achieved in 118 patients i.e. 76.1%. The seroconversion after hepatitis B vaccination was 67/79 (84.8%) in patients with positive anti-HCV and 51/76 (67.1%) in those who tested negative for anti-HCV [Table - 4].

   Discussion Top

Non-A, non-B hepatitis is a major world­wide health problem. It accounts for more than 90% of transfusion associated hepatitis cases.It was associated with a high incidence of chronic carrier state and subsequent progressive liver disease [12] . Recently, HCV was isolated from most cases of blood-borne NANB hepatitis, and the HCV was considered the major cause of such disease [3] . Prior to the application of HCV prophylactic measures in our dialysis units, the prevalence of anti­HCV in this patient population was 83.6%, as compared to 2.4% in random blood donors in Kuwait [4] . This prevalence was clearly higher than that described in an earlier study from Kuwait [2] . In that study, screening of a limited number of dialysis patients and the use of insensitive (first-generation) anti-HCV assay [5] may have underestimated the true prevalence of this disease. The latter issue was confirmed by rescreening those p.atients shortly afterwards, using EIA-II, with a reported prevalence of 71% [4] . However, the prevalence of anti-HCV in our dialysis units was high when compared to that reported from Saudi Arabia (40%) [6] , USA (25%) [7] , Europe (17.7%) [8] , and Japan (22.2%) [9] . The longer duration of dialysis treatment in the patients included in our study, may have been a factor, but the high prevalence of anti-HCV among random blood donors in Kuwait and patients entering HD indicated a higher prevalence of HCV disease in our area.

In our study, a high prevalence of anti-HCV was noted in the hemodialysis patients and those who received blood transfusions. This observation confirmed the role of blood and blood-contaminated materials in the transmission of HCV in this patient population. On the other hand, failure to detect anti-HCV in close-family members of patients who developed anti-HCV during HD and in the. dialysis staff was a cogent argument against a major role of cross-infection in transmission of HCV [4],[10] .

Kuhns, et al detected HCV-RNA in 75% of anti-HCV seropositive patients indicating that high proportions of seropositive patients are potential sources of infection [7] . Furthermore, a large proportion of our patients did not manifest liver enzyme abnormalities during their initial positive seroconversion (66.7%) or during 27 months of follow-up (38.7%). These findings emphasize the need of periodic screening of patients on HD for anti-HCV, rather than limiting the test to those with abnormal liver functions. The late­development (> 6 months) of anti-HCV in some patients and the persistent liver abnormalities in patients who tested negative for anti-HCV (and other viruses) indicated chronic HCV infection not detected by current antibody assays, or the inability of these patients to mount or sustain a significant antibody response. These findings were consistent with previous reports in which HCV-RNA was detected in two (4.3%) of 47 anti-HCV negative patients [7] .

The prevalence of anti-HCV positive patients at the end of the HCV-prophylactic period was significantly lower than that observed in the control period. During the last 27 months of observation, 15 of the 154 (7%) new ESRD patients were found to be anti-HCV-positive on entry to HD program. Assuming a similar prevalence (9.7%) in those who entered HD during the control period, a total of 41 patients would have developed anti-HCV during 637 patients years of dialysis. The expected incidence of anti-HCV positive seroconversion would be 77.2 per 100 patients per year on HD, which is more than six times that observed during "HCV-prophylaxis. Application of the HCV-prophylactic measures led to dramatic decrease in the incidence of HCV infection in our dialysis units, but failed to prevent HCV infection. This observation could be attributed to the limited sensitivity of the available screening assays and their long "windowperiod' prior to development of anti-HCV. Inherent limitations of the available HCV-assays result in suboptimal screening of blood donors in Kuwait as well as new HD patients and those who had a recent travel abroad, and subsequently limit the efficiency of HCV-prophylaxis.

The role of HCV infection in progressive liver disease is currently being investigated worldwide. Previous experience with chronic hepatitis due to NANB disease, indicated that 10-20% of the infected patients, ultimately developed histological evidence of cirrhosis during the first 10 years of follow-up [12] . Despite the uncertain relationship between the severity of the histopathological findings and the extent of abnormalities in liver enzymes, five of the six anti-HCV positive patients who had undergone liver biopsies, because of persistent ALT abnormalities, showed clear evidence of aggressive inflammation. This subject is currently under investigation by our group, as well as the efficacy of treatment with alpha interferon.

Recently, suboptimal HBsAB titres following hepatitis B vaccination in patients who tested positive for anti-HCV were reported [13] . It was suggested that these patients were at risk of hepatitis B virus infection. The minimum level of HBsAb titres necessary to guarantee an effective protection is a matter of controversy. However, in the present study, 84.4% of our anti-HCV-positive patients achieved successful seroconversion according to our vaccination protocol [11] and prospective follow-up failed to confirm a single case of hepatitis B infection.

   References Top

1.Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a oDNA clone derived from a blood­borne non-A, non-B viral hepatitis genome. Science 1989;244:359-62.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Al-Nakib B, Koshy A, Kaloui M, et al. HepatitisC virus antibody in Kuwait. Vox Sang 1992;63:75-6.  Back to cited text no. 2  [PUBMED]  
3.Esteban JI, Esteban R, Viladomiu L, et al. Hepatitis C virus antibodies among risk group in Spain. Lancet 1989;2:294-7.  Back to cited text no. 3  [PUBMED]  
4.Kapoor M, El-Reshaid K, Al-Mufti S, Sanad NA, Koshy A. Is dialysis envirnment more important than blood transfusion in transmission of hepatitis C virus during hemodialysis? Vox Sang 1993;65:331  Back to cited text no. 4  [PUBMED]  
5.van der Poel CL, Reesink HW, Schaasberg W, et al. Infectivity of blood seropositive for hepatitis C virus antibodies. Lancet 1990;335:558-60.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Alfurayh O, Sobh M, Buali A, et al. Hepatitis C virus infection in chronic hemodialysis patients, a clinicopathologic study. Nephrol Dial Transplant 1992;7:327-32.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Kuhns M, de Medina M, McNamara A, et al. Detection of hepatitis C virus RNA in hemodialysis patients. J Am Soc Nephrol 1994;4:1491-7.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Schneeberger PM, Vos J, van Dijk WC. Prevalence of antibodies to hepatitis C virus in a Dutch group of haemodialysis patients related to risk factors. J Hosp Infect 1993;25:265-70.  Back to cited text no. 8  [PUBMED]  
9.Yamaguchi K, Nishimura Y, Fukuka N, et al. Hepatitis C virus antibodies in hemodialysis patients. Lancet 1990;335:1409-10.  Back to cited text no. 9    
10.Caramelo C, Navas S, Alberola ML, Bermejillo T, Reyero A, Carreno V. Evidence against transmission of hepatitis C virus through hemodialysis ultrafilterate and peritoneal fluid. Nephron 1994;66:470-3.  Back to cited text no. 10    
11.El-Reshaid K, Al-Mufti S, Johny KV, Sugathan TN. Comparison of two immunization schedules with recombinant hepatitis B vaccine and natural immunity acquired by hepatitis B infection in dialysis patients. Vaccine 1994;12:223-34.  Back to cited text no. 11  [PUBMED]  
12.Koretz RL, Stone O, Mousa M, Gitnick GL. Non-A, non-B post-transfusion hepatitis a decade later. Gastroenterology 1985;88:1251-4.  Back to cited text no. 12  [PUBMED]  
13.Navarro JF, Teruel JL, Mateos M, Ortuno J, Hepatitis C virus infection decreases the effective antibody response to hepatitis B vaccine in hemodialysis patients. Clin Nephrol 1994;41:113-6.  Back to cited text no. 13    

Correspondence Address:
Kamel El-Reshaid
Department of Medicine, Faculty of Medicine, P.O. Box 24923, 13110 Safar
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  [Table - 1], [Table - 2], [Table - 3], [Table - 4]


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