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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2001  |  Volume : 12  |  Issue : 1  |  Page : 14-20
Hepatitis C Virus Sero-status in Hemodialysis Patients Returning from Holiday: Another Risk Factor for HCV Transmission


1 King Abdulaziz University Hospital, Jeddah, Saudi Arabia
2 Prince Sultan Dialysis and Transplantation Center, North Western Armed Forces Hospital, Tabuk, Saudi Arabia

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   Abstract 

Hepatitis C virus (HCV) infection is an endemic disease in most hemodialysis (HD) units in Saudi Arabia. We observed that many of our HD patients seroconvert shortly after returning from "holiday dialysis" in other units. We investigated this issue together with other possible factors related to HCV transmission. During the study period, 56 patients were being dialyzed in our unit. Systematic screening was performed on all patients for anti-HCV antibody utilizing ELISA 2.0 and/or RIBA 3.0 and HBsAg every three months together with aminotransferases activity. The same tests were carried out on patients returning from "holiday dialysis" in other units. Test for HCV-RNA was performed in patients with elevated aminotransferases and negative HCV serology. HCV-antibody was positive in 32 patients (57%) of whom 15 (27%) were already positive at the time of starting HD and 17 (30%) seroconverted after starting HD. A total of 24 patients (43%) remained sero-negative. Comparing the sero-converters (SC) to the remained sero-negatives (RSN), the SC had been out for "holiday dialysis" more than the RSN with a mean number of such HD treatments of 16 versus 4 (P= 0.006). The SC had longer duration on dialysis, 38 versus 19 months for the RSN. The two groups did not have significant difference in their age, sex, number of blood transfusions or prior kidney transplantation. Fourteen out of 17 SC (82%) had seroconverted after a mean duration of 100 days from leaving our unit for "holiday dialysis". Eight out of 24 (33%) of the RSN had dialysis outside our unit and remained sero-negative; HCV-RNA confirmed infection in three of them, all of whom had high amino transferase levels. Our study suggests that patients who have "holiday dialysis" in units with high prevalence of HCV-antibody, run a high risk of sero-conversion and may play a role in unit to unit transmission of HCV.

Keywords: Hepatitis C virus, Dialysis, Aminotransferase, Sero-conversion.

How to cite this article:
Al-Ghamdi SM, Al-Harbi AS. Hepatitis C Virus Sero-status in Hemodialysis Patients Returning from Holiday: Another Risk Factor for HCV Transmission. Saudi J Kidney Dis Transpl 2001;12:14-20

How to cite this URL:
Al-Ghamdi SM, Al-Harbi AS. Hepatitis C Virus Sero-status in Hemodialysis Patients Returning from Holiday: Another Risk Factor for HCV Transmission. Saudi J Kidney Dis Transpl [serial online] 2001 [cited 2020 May 29];12:14-20. Available from: http://www.sjkdt.org/text.asp?2001/12/1/14/33880

   Introduction Top


Hepatitis C virus (HCV) is a major problem in patients with renal disease and is prevalent both in the pre-dialysis population [1] and more significantly so, in patients on maintenance hemodialysis (HD). [2],[3],[4],[5],[6],[7],[8] The reported prevalence of anti-HCV in HD population has however, varied widely among different countries [2],[3],[4],[5],[6] and even between different regions in a particular country. [8],[9],[10] The prevalence is reported to be around 1.7% in Ireland, [2] and 10% in the USA. [5] This figure is considerably higher (70%) in the Middle and Far East [7],[8] . The reported prevalence in Saudi Arabia ranges between 35-90%. [8],[9],[10] The transmission of the virus was thought to be related to the dialysis environment per se, [11],[12] as attempts to isolate the virus from the ultrafiltrate yielded no success. [13],[14] The nosocomial route of transmission has been advocated by many observers. [12],[15],[16] Multiple risk factors have been recognized for HCV sero­conversion. These include longer duration on dialysis, blood transfusion, kidney trans­plantation, and loose application of universal precautions (CDC, Atlanta). [11],[12],[17],[18],[19],[20] Using PCR sequencing, Allander et al [21] have demonstrated the transmission of the virus by transfer of an infected individual to a new dialysis unit. Other authors have previously reported HCV sero-conversion in patients returning from holidays, having been dialyzed in units with high anti-HCV antibody prevalence. [22] We observed the same phenomenon, as many of our patients leave the unit during holidays for dialysis in other parts of the country. Many of these dialysis units are known to have high prevalence of HCV. We evaluated "holiday dialysis" as a risk factor for HCV transmission in this study.


   Patients and Methods Top


Patients survey

Systematic anti-HCV antibody screening for our dialysis patients was introduced in 1992, utilizing ELISA 2.0 assay (HCV antibody ELISA test system; Ortho, Raritan; NJ, USA). Since February 1996, Recombinant Immunoblot Assay (RIBA HCV 3.0, Chiron Corporation) has been introduced. All study patients were subjected to monthly alanine aminotransferase (ALT) and aspartate aminotransferase (AST) assays. Patients underwent HBsAg and HCV-Ab screening on admission to the unit and every three months thereafter, irrespective of liver enzyme status. Patients returning from "holiday dialysis" underwent estimation of ALT and AST along with HBsAg and HCV-Ab. If the liver enzymes were found to be elevated, and their antibody status was negative, HCV-RNA (Ampiclor Monitor; Roche, Basel Switzerland) was looked for. Patients who were found to be positive for HBsAg were excluded from the study.

During the months of July and August 1997, all patient records were studied and the patients were interviewed. Special emphasis was put on the relation between timing of sero-conversion and risk factors for HCV transmission. Leaving the unit for "holiday dialysis" or receiving blood transfusion in the six months prior to sero­conversion were considered risk factors for HCV transmission. Similarly, kidney trans­plantation antedating sero-conversion was also considered a risk factor.

Since July 1995, we have assigned dedicated machines for the anti-HCV antibody positive patients; however, we do not physically isolate the positive patients from the negative ones. Universal Health Precautions were strictly applied, which included changing gloves after handling each patient, avoiding sharing articles and instruments between patients, and disinfecting the surfaces of tables, chairs and other materials in contact with the patients. Hemodialysis machines were heat­disinfected after each use, while chemical disinfection was performed at the end of the day.


   Statistical Analysis Top


Statistical analysis was performed using SPSS 7.5 program. Age, duration on dialysis, number of holiday HD treatments, and level of ALT and AST were expressed as the mean value ± standard error. The unpaired Student's t-test was used to evaluate the difference between the normally distributed continuous variables, while discrete variables were tested by the non-parametric test, chi square. A P value of less than 0.05 was considered significant.


   Results Top


During the study period, 56 patients were dialyzed in our unit. Thirty-two of them (57%) were anti-HCV antibody positive, by both ELISA 2.0 and RIBA 3.0 assays. We divided the study patients into three groups according to their sero-status and the timing of their sero-positivity [Table - 1]. Group I included patients who were already positive for anti-HCV when they were started on dialysis (n = 5), or were transferred to our unit from other units and were found to be sero-positive (n = 10). These 15 patients (27% of our dialysis population), were collectively labeled "commenced positive".

Group II included the patients who were initially sero-negative with normal liver enzymes, but subsequently sero-converted to positive after starting HD. They totaled 17 patients (30% of our dialysis population) and were labeled "sero-converters". Group III were the 24 patients (43% of the dialysis population) who remained sero-negative and were labeled "remained sero-negative", [Table - 1]. Comparing the sero-converters (SC) to the remained sero-negatives (RSN), the SC had been out for "holiday dialysis" more often than the RSN (P= 0.001) with a mean number of HD treatments of 16 versus 4 for the RSN (P= 0.006). The SC, had longer dialysis duration of 38 months versus 19 months for the RSN (P= 0.028). There was no significant difference in the age, sex, number of blood transfusions or prior kidney transplantation between the groups [Table - 2].

Fourteen out of 17 SC (82%) had left the unit for holidays and received dialysis in other units mostly in the southern and western parts of the Kingdom. They sero­converted after a mean duration of 100 days from leaving our unit for "holiday dialysis".

Three patients (18%) sero-converted without ever being dialyzed outside our unit, but they had received HCV-screened blood transfusion in the six months preceding sero-conversion. Eight out of 24 (33%) RSN had left for dialysis outside our unit and remained sero-negative (by both ELISA 2.0 and RIBA 3.0). Three of these patients had high ALT and AST and all three tested positive for HCV-RNA.

The mean ALT was significantly higher at 241 IU (range 11-629) in SC versus 32 (range 5-32) for the RSN (P value < 0.0001). Similarly, the mean AST was elevated at 122 IU (12-357) for the SC versus 32 (3­290) for the RSN (P value < 0.001).


   Discussion Top


In our study, we found a high prevalence of anti-HCV positivity similar to other units in Saudi Arabia. [8],[9],[10] This is considerably higher than what has been reported in Europe and the USA. [2],[4],[5] Moreover, 27% of our dialysis patients were positive for anti­HCV even before starting HD, which may underline the significance of this problem in the pre-dialysis renal patients. This is especially true, because only 3.9% of healthy blood donors in Saudi Arabia are anti-HCV positive [20] . Similar results have been reported from Japan by Yonemura et al, [1] who found a high prevalence of HCV-Ab positivity (11%) in the pre-dialysis population compared to 0.9% among blood donors. Also, HCV has been strongly associated with glomerular diseases such as essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis and membranous neph­ropathy. [23] These findings should draw attention to HCV as a probable agent in the pathogenesis of glomerular diseases in areas with high prevalence of HCV infection in the pre-dialysis population.

We found a strong association between "holiday dialysis" and HCV-Ab sero­-conversion. Fourteen of the 17 sero-converters had "holiday dialysis" in the six months preceding sero-conversion. Three of these patients had elevated ALT and AST with negative anti-HCV. On subjecting this group to PCR-RNA, a detectable hepatitis C viremia was confirmed, further suggesting the risk of HCV transmission by the "holiday dialysis". The value of HCV-RNA in sero-negative patients with elevated aminotransferases has previously been shown by Caramelo et al. [24] They found that 28% of the anti-HCV antibody negative patients were HCV-RNA positive. The mean ALT and AST in the HCV-RNA positive patients was significantly higher than in the anti-HCV antibody and HCV-RNA negative patients.

Three of our patients sero-converted without receiving dialysis outside our unit; however, they had received HCV-screened blood transfusion. These patients acquired the infection from within the unit or contracted the infection via blood transfusion. It has been shown that HCV is a nosocomial infection, [12],[15],[16] and loose application of universal precautions could contribute to its spread within the unit. [11],[16],[19] Fabrizi et al [25] have demonstrated the de novo acquisition of HCV in units with no identifiable risk factors other than dialysis with HCV-Ab positive patients. In a study by dos Santos et al, [26] the incidence of HCV infection was significantly higher (35%) in units with high prevalence (> 60%) and low (2.5%) in units with low prevalence (< 19%). However, phylogenetic analysis of HCV isolates in HD patients has confirmed that the infection is probably related to parenterally administered products, as patient-to-patient transmission was found to be less common. [27] Collectively, these data suggest that nosocomial trans­mission and blood acquired transmission is responsible for most, if not, all of the sero­conversion in the HD units.

We found a significant correlation between duration on dialysis and HCV sero-positivity, which conforms with previously published data. [4],[5],[6],[8],[11],[17],[20],[23],[28] However, we did not find any significant association between previous blood transfusions or prior kidney transplantation and HCV sero-positivity.

There was no significant difference between the number of male and female patients and the rate of HCV sero-conversion in our study. This is similar to a previous report from Saudi Arabia. [20] Interestingly, a report from Japan has shown low prevalence of anti-HCV antibody in female patients in a population of HD patients who had never received blood transfusions. [29]

There is conflicting data regarding the role of aminotransferases activity in predicting HCV infection in dialysis population. [6],[24],[25],[30],[31] While some reports [6],[30] have questioned the sensitivity of ALT and AST in predicting HCV infection, there are other reports which suggest the contrary. Fabrizi et al [31] found that anti-HCV antibody positivity was significantly associated with elevated ALT and AST. Moreover, they found detectable HCV-RNA in the serum as a strong predictor of raised enzymes. This has been further confirmed by other reports. [17],[24],[25] We speculate that the timing of amino-transferase testing in relation to sero-conversion has produced this conflict. We found that routine surveillance in our patients had documented elevated ALT and AST in most of the SC compared to the RSN group (P< 0.0001 and 0.001 respec­tively). This demonstrates the significance and importance of these tests in predicting sero-conversion. As described earlier, three of the patients were found to be sero­negative and at the same time had elevated ALT and AST. HCV-RNA confirmed infection in these patients, further stressing the significance of elevated enzymes. Finally, we have incorporated the three tests (ELISA 2.0, RIBA 3.0 and HCV-RNA) together with ALT and AST to screen for the infection in our dialysis patients. We used ELISA 2.0 and aminotransferase activity as our routine testing for all patients in the unit. RIBA TM 3.0 was reserved for patients returning from holiday after having been dialyzed in other units, or patients who continued to have elevated enzymes and negative ELISA 2.0. This was because RIBA 3.0 has a better sensitivity and a better ability to predict early viremia. [17],[32] We believe that the usage of this screening methodology has contributed significantly in better surveillance of HCV in our HD unit.

In conclusion, we found that patients leaving for holidays to receive dialysis in units with high prevalence of HCV and possibly poor application of universal precautions, run the high risk of sero­conversion and transmission of the infection to the primary unit. This mechanism could have contributed to perpetuation of the high prevalence of HCV in Saudi dialysis population. We also conclude that increased aminotransferase activity predicts HCV infection in HD patients.

 
   References Top

1.Yonemura K, Hishida A, Yoneyama T, et al. High prevalence of hepatitis C virus antibody in patients with chronic renal failure at the start of hemodialysis therapy. Nephron 1996;73:484-5.  Back to cited text no. 1  [PUBMED]  
2.Conlon PJ, Walshe JJ, Smyth EG, McNamara EB, Donohoe J, Carmody M. Lower prevalence of anti-hepatitis C antibody in dialysis and renal transplant patients in Ireland. Ir J Med Sci 1993; 162(4):145-7.  Back to cited text no. 2    
3.Yamaguchi K, Nishimura Y, Fukuoka N, et al. Hepatitis C virus antibodies in hemo-dialysis patients. Lancet 1990;335:1409-10.  Back to cited text no. 3    
4.Jadoul M, Cornu C, van Ypersele de Strihou C. The UCL Collaborative Group. Incidence and risk factors for hepatitis C sero-conversion in hemodialysis: a pros­pective study. Kidney Int 1993;44:1322-6.  Back to cited text no. 4    
5.Niu MT, Coleman PJ, Alter MJ. Multi-center study of hepatitis C virus infection in chronic hemodialysis patients and hemodialysis center staff members. Am J Kidney Dis 1993;22(4):568-73.  Back to cited text no. 5    
6.Pujol FH, Ponce JG, Lema MG, et al. High incidence of hepatitis C virus infection in hemodialysis patients in units with high prevalence. J Clin Microbiol 1996;34(7):1633-6.  Back to cited text no. 6    
7.Soetjipto, Handajani R, Lusida MI, et al. Differential prevalence of hepatitis C virus subtypes in healthy blood donors, patients on maintenance hemodialysis, and patients with hepatocellular carcinoma in Surabaya, Indonesia. J Clin Microbiol 1996;34(12): 2875-80.  Back to cited text no. 7    
8.Huraib S, AL Rashed R, Aldrees A, Aljefry M, Arif M, Al-Faleh FA. High prevalence of and risk factors for hepatitis C in haemodialysis patients in Saudi Arabia: a need for new dialysis strategies. Nephrol Dial Transplant 1995;10:470-4.  Back to cited text no. 8    
9.Al-Muhanna FA. Hepatitis C virus among hemodialysis patients in the eastern region of Saudi Arabia. Saudi J Kidney Dis Transplant 1995;6(2):125-7.  Back to cited text no. 9    
10.Shaheen FAM, Huraib SO, Al­Rashed R, et al. Prevalence of hepatitis C antibodies among hemodialysis patients in the western province of Saudi Arabia. Saudi J Kidney Dis Transplant 1995;6(2):136-9.  Back to cited text no. 10    
11.Jadoul M. Transmission routes of HCV infection in dialysis. Nephrol Dial Transplant 1996;11(Suppl 4):36-8.  Back to cited text no. 11  [PUBMED]  
12.de Lamballerie X, Olmer M, Bouchouareb D, Zandotti C, De Micco P. Nosocomial transmission of hepatitis C virus in hemo-dialysis patients. J Med Virol 1996;49: 296-302.  Back to cited text no. 12  [PUBMED]  
13.Caramelo C, Navas S, Alberola ML, Bermejillo T, Reyero A, Carreno V. Evidence against transmission of hepatitis C virus through hemodialysis ultrafiltrate and peritoneal fluid. Nephron 1994;66(4):470-3.  Back to cited text no. 13    
14.Manzini P, Amore A, Brunetto MR, et al. Is hepatitis C virus RNA detectable in dialysis ultrafiltrate? Nephron 1996;72:102-3.  Back to cited text no. 14  [PUBMED]  
15.Stuyver L, Claeys H, Wyseur A, et al. Hepatitis C virus in a hemodialysis unit: molecular evidence for nosocomial transmission. Kidney Int 1996;49:889-95.  Back to cited text no. 15  [PUBMED]  
16.McLaughlin KJ, Cameron SO, Good T, et al. Nosocomial transmission of hepatitis C virus within a British dialysis centre. Nephrol Dial Transplant 1997;12:304-9.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]
17.Fabrizi F, Lunghi G, Raffaele L, et al. Serologic survey for control of hepatitis C in haemodialysis patients: third generation assays and analysis of costs. Nephrol Dial Transplant 1997;12:298-303.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]
18.Natov SN, Pereira BJ. Hepatitis C in dialysis patients. Adv Ren Replace Ther 1996;3(4):275-83.  Back to cited text no. 18    
19.Forns X, Ferndndez-Llama P, Pons M, et al. Incidence and risk factors of hepatitis C virus infection in a haemodialysis unit. Nephrol Dial Transplant 1997;12:736-40.  Back to cited text no. 19    
20.Ayoola EA, Huraib S, Arif M, et al. Preva-lence and significance of antibodies to hepatitis C virus among Saudi haemodialysis patients. J Med Virol 1991;35(3):155-9.  Back to cited text no. 20    
21.Allander T, Medin C, Jacobson SH, Grillner L, Persson MA. Transmission of hepatitis C virus by transfer of an infected individual to a new dialysis unit. Nephron 1996;73:110.  Back to cited text no. 21  [PUBMED]  
22.Al Shohaib S, Abunijem Z. Hepatitis C: is isolation essential? Nephron 1996;73:109.  Back to cited text no. 22  [PUBMED]  
23.Roth D. Hepatitis C virus: the nephrologist's view. Am J Kidney Dis 1995;25(1):3-16.  Back to cited text no. 23    
24.Caramelo C, Bartolome J, Albalate M, et al. Undiagnosed hepatitis C virus infection in hemodialysis patients: value of HCV RNA and liver enzymes levels. Kidney Int 1996;50:2027-31.  Back to cited text no. 24    
25.Fabrizi F, Martin P, Dixit V, et al. Acquisition of hepatitis C virus in hemodialysis patients: a prospective study by branched DNA signal amplification assay. Am J Kidney Dis 1998;31(4):647-54.  Back to cited text no. 25    
26.dos Santos JP, Loureiro A, Cendoroglo Neto-M, Pereira BG. Impact of dialysis room and reuse strategies on the incidence of hepatitis C virus infection in hemo-dialysis units. Nephrol Dial Transplant 1996;11:2017-22.  Back to cited text no. 26    
27.Zeuzem S, Scheuermann EH, Waschk D, et al. Phylogenetic analysis of hepatitis C virus isolates from hemodialysis patients. Kidney Int 1996;49:896-902.  Back to cited text no. 27  [PUBMED]  
28.Hardy NM, Sandroni S, Danielson S, Wilson WJ. Antibody to hepatitis C virus increases with time on hemodialysis. Clin Nephrol 1992;38:44-8.  Back to cited text no. 28  [PUBMED]  
29.Nakayama E, Liu JH, Akiba T, Marumo F, Sato C. Low prevalence of anti-hepatitis C virus antibodies in female hemodialysis patients without blood transfusion: a multi-center analysis. J Med Virol 1996;48:284-8.  Back to cited text no. 29  [PUBMED]  
30.Oliva JA, Maymo RM, Carrio J, Delgado O, Mallafre JM. Late sero­conversion of C virus markers in hemodialysis patients. Kidney Int Suppl 1993;41:S153-6.  Back to cited text no. 30  [PUBMED]  
31.Fabrizi F, Lunghi G, Andrulli S, et al. Influence of hepatitis C virus (HCV) viraemia upon serum aminotransferase activity in chronic dialysis patients. Nephrol Dial Transplant 1997;12:1394-8.  Back to cited text no. 31  [PUBMED]  [FULLTEXT]
32.Al Meshari K, Alfurayh O, Al Ahdal M, Qunibi W, Kessie G, De Vol E. Hepatitis C virus infection in hemodialysis patients: comparison of two new hepatitis C antibody assays with a second­generation assay. J Am Soc Nephrol 1995;6:1439-44.  Back to cited text no. 32  [PUBMED]  

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Correspondence Address:
Saeed M.G Al-Ghamdi
Department of Medicine, King Abdulaziz University Hospital, P.O. Box 6615, Jeddah 21452
Saudi Arabia
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