Brief Reports Open Access
Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 15, 2000; 6(6): 888-892
Published online Dec 15, 2000. doi: 10.3748/wjg.v6.i6.888
Follow-up study of hepatitis C virus infection in uremic patients on maintenance hemodialysis for 30 months
Nian Song Wang, Department of Nephrology, Shanghai Sixth People’s Hospital, Shanghai 200233, China
Lu Tan Liao, Yan Juan Zhu, Department of Nephrology, Zhang Shan Hospital, Shanghai Medical University, Shanghai 200032, China
Wei Pan, Fang Fang, Department of Microbiology, The Second Military Medical University, Shanghai 200433, China
Nian Song Wang, got a doctorate degree in 1997 in Shanghai Medical University, now associate professor of internal medicine, having 19 papers published.
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Nian Song Wang, Department of Nephrology, Shanghai Sixth People’s Hospital, Shanghai 200233, China. Email: Niansong@public8.sta.net.cn
Telephone: 0086-21-64369181 Ext. 8335
Received: July 5, 2000
Revised: July 19, 2000
Accepted: July 21, 2000
Published online: December 15, 2000

Abstract
Key Words: hepatitis C virus; hemodialysis; blood transfusion; cross infection; polymerase chain reaction; risk factors; follow-up studies



INTRODUCTION

A high prevalence of antibodies to hepatitis C virus (HCV) (range from 3.3%-80%) has been reported in hemodialysis (HD) patients[1-20], and worrisome as it often becomes chronic and induces chronic liver disease[7,14,15], therefore the nephrologists face a major challenge of how to prevent it. The main route of HCV transmission is parenteral, and most cases of HCV infection are thought to be related to blood transfusion, intravenous drug addiction, or HIV infection[1,6,9-10,21-24], but an increased prevalence of anti-HCV has also been reported in non-transfused HD patients without identifiable risk factors[1,2,5,6,10-12,15,18,25,26]. In fact, some recent reports and our report outline that HCV-negative patients who shared dialysis machines with HCV-positive patients were seroconverted within HD period[1,5,8,12-16,25-35]. We undertook a prospective study to assess the incidence and the risk factors for HCV infection in HD patients.

MATERIALS AND METHODS
Subjects

A total of 346 patients at our HD center followed up from June 1, 1995 to December 1, 1997, and 63 patients in June 1995 were included in the study. They were dialyzed for 1 to 92 (mean 23.4) mo. Their age ranged from 20-76 years (mean 44.7 years).

From June 1995 to November 1995, December 1995 to May 1996, June 1996 to November 1996, December 1996 to May 1997, June 1997 to November 1997, additional 42, 39, 45, 65 and 71 new patients were included, respectively. Of these 262 patients, 226 had recently started HD, 15 resumed HD after a transplantation failure and 21 had been transferred from other units. Their age range was similar to that of previously included patients. In December 1997, 21 patients who recently started HD, were included, their age range was similar to that of previously included patients.

In June 1996, the sera of 62 patients were tested for anti-HCVIgM, anti-HCVIgG and HCV RNA. Among them, 38 were males and 24 females, their age ranged from 16-71 years (mean 44.6 years), mean duration of HD was 16.1 ± 7.6 mo (1-96).

Anti-HCV antibodies

All patients at our HD center were tested every 3 mo for the presence of anti-HCV antibodies during the follow-up period. All blood samples were obtained before HD, and were centrifuged, serum stored at -80 °C until testing. The kits for examining anti-HCVIgM and anti-HCVIgG were purchased from Shanghai Chang Zhang Chemical Reagent Company, and were tested by the Laboratory of Microbiology, The Second Military Medical University.

HCV RNA

Primers were designed from the conserved 5’-noncoding (5’-NC) region of the HCV genome. S1: 5’-CACTCCACCATGAATCACTC-3’, AS1: GGTG-CACGGTCTACGAGACC-3’, S2: 5’-ACTCCCCTG-TGAGAAGCTAC-3’, AS2: 5’-CTCGCAAGCACCC-TATCAGG-3’. A RT-PCR assay procedure was per formed as previously described[1].

Risk factors for seroconversion (SC) for HCV

All data of risk factors for HCV were collected by using special questionnaire, including the sex, age, renal function, HBV marker, EPO, infection at hospital, history of CAPD and kidney transplantation, duration of dialysis, history of transfusion, ALT abnormality, dialyzer reused.

Dialysis and disinfection procedue

HD was performed using dialysis machines from Baxter, Fresenius. We used bicarbonate dialysis fluid (flow 500 mL/min). Water quality and bacterial count were monitored regularly. HD patients have been dialyzed with Cuprophan, polysulfone or hemophan dialyzer. A strict chemical disinfection using Citrosteril, run at 85 °C for 35 min after each dialysis session, was adopted before using the machine for the next patient. It was hoped that both the high temperature bath and the low pH offered by Citrosteril would be enough to combat HCV. But our patients shared machines indiscriminately.

Statistical analysis

Results are expressed as mean ± SEM as indicated. Unpaired Student’s t test, χ² and Fisher’s exact test were used. P values < 0.05 were considered as significant.

RESULTS
Prevalence of HCV marker in June 1996

In June 1996, the total positivity of HCV marker (HCVM) was 59.7% (37/62), 27 patients (43.6%) were anti-HCVIgM positive, 29 (46.8%) anti-HCVIgG positive, 34 (54.8%) HCV RNA positive, 22 (35.5%) anti-HCVIgM, anti-HCVIgG and HCV RNA positive, 27 were anti-HCVIgM and HCV RNA positive, 22 were anti-HCVIgM and anti-HCVIgG positive, 26 anti-HCVIgG and HCV RNA positive, 34 patients at least one of anti-HCVIgM and anti-HCVIgG positive, 3 each were anti-HCVIgG positive or HCV RNA positive only.

Sixty-two patients were divided into two groups, GI: 43 HD patients with histories of transfusion, ALT abnormality, kidney transplantation and HBV markers positive; GII: 19 HD patients without the history and abnormality as those of GI. Comparison of detection of HCVM in GI and GII is shown in Table 1.

Table 1 Comparison of detection of HCVM in GI and GII.
ParameterGI (%) (n = 43)GII (%) (n = 19)P value
anti-HCVIgM (+)21 (48.8)6 (31.6)> 0.05
anti-HCVIgG (+)25 (58.1)4 (21.1)< 0.05
HCV RNA (+)27 (62.8)7 (36.8)> 0.05
All three (+)18 (41.9)4 (21.1)> 0.05
At least one (+)29 (67.4)8 (42.2)> 0.05

When comparing the clinical manifestation between HCVM positive and negative groups, no significant differences were found with respect to the sex, age, renal function, HBV marker, EPO and history of CAPD; but there were significant differences with regard to the duration of dialysis, history of transfusion, ALT abnormality and kidney transplantation (Table 2).

Table 2 Comparison of clinical manifestation in HCV positive and negative group of HD patients.
Clinical manifestationHCVM positive group (n = 37)HCVM negative group (n = 25)P value
M/F22/1516/9> 0.05
Mean age (years)49.6 ± 16.848.4 ± 14.4> 0.05
Range16-7126-67
Mean duration of HD (months)31.2 ± 8.68.1 ± 4.7< 0.01
Range2-961-24
History of transfusion29 (78.4%)11 (44.0%)< 0.01
EPO12 (32.4%)8 (32.0%)> 0.05
History of kidney transplantation (n = 6)6 (16.2%)0 (0.0%)< 0.05
History of CAPD (n = 8)6 (16.2%)2 (8.0%)> 0.05
HBVM positive18 (48.6%)10 (40.0%)< 0.01
ALT abnormality10 (27.0%)1 (4.0%)< 0.01
BUN (mmol/L)24.6 ± 8.628.4 ± 10.2> 0.05
Cr (μmol/L)1154.4 ± 402.61164.8 ± 468.5> 0.05

Relationship between dialysis times and HCV markers is shown in Table 3. The risk of HCV marker positivity increased significantly as the duration on HD increased (χ² = 9.23, P < 0.01). Seven patients were dialyzed for more than 3 years (mean 5 years) and 100% HCVM positive.

Table 3 Relationship between dialysis times and HCV markers.
HD time (Year)nIgM
IgG
HCV RNA
Only one marker positive
n%n%n%n%
< 132928.1825.01237.51443.8
1-218950.01055.61161.11266.7
2-35360.0480.0480.0480.0
> 37685.77100.07100.07100.0

Relationship between number of transfusion and HCV markers is shown in Table 4. The risk of HCV marker positivity increased significantly as the number of transfusion increased (χ² = 21.14, P < 0.01).There were 8 patients with positive HCV markers in 22 patients without histories of transfusion. Among them, 6 (27.3%) were anti HCVIgM positive, 7 anti-HCVIgG positive, and 6 HCV RNA positive. When comparing the clinical manifestation between HCVM positive and HCVM negative groups in 22 patients without transfusion, no significant differences were found with respect to the sex, age, renal function, HBV marker, EPO and history of CAPD and kidney transplantation; but there were significant differences in the duration of dialysis and ALT abnormality (Table 5).

Table 4 Relationship between number of transfusion and HCV markers.
Transfusion (U)nIgM
IgG
HCV RNA
Only one marker positive
n%n%n%n%
022627.3731.8627.3836.4
1-58225.0225.0450.0450.0
6-1016743.8637.51062.51168.8
11-206466.7583.3583.3583.3
> 3010880.0990.0990.0990.0
Table 5 Comparison the clinical manifestation between HCVM positive and negative group in 22 patients without transfusion.
Clinical manifestationPositive groupNegative groupP value
Cases814
M/F5/38/6> 0.05
Mean age (Years)53.1 ± 14.249.6 ± 12.5> 0.05
Range30-7130-67
Mean duration of HD (months)24.2 ± 6.43.4 ± 1.6< 0.01
Range4-361-6
History of kidney transplantation00
History of CAPD00
EPO35> 0.05
ALT abnormality30< 0.01
BUN (mmol/L)25.7 ± 7.826.4 ± 6.8> 0.05
Cr (μmol/L)1132.6 ± 482.61182.4 ± 464.3> 0.05
Positive prevalence of anti-HCV antibodies in consecutive six-month period

Positive prevalence of anti-HCV antibodies was found in six consecutive period of 6 mo as shown in Table 6.

Table 6 Positive prevalence of anti-HCV antibodies in six consecutive periods of 6 mo.
TimeCasesPositive (%)Negative (%)
1995.66337 (58.7)26 (41.3)
1995.126736 (53.7)31 (46.3)
1996.66234 (54.8)28 (45.2)
1996.126432 (50.0)32 (50.0)
1997.67640 (52.6)36 (47.4)
1997.128344 (53.0)39 (47.0)

Positive prevalence of anti-HCV antibodies was found in uremic patients when they entered into our HD center as shown in Table 7. Among the 283 new patients admitted to our HD center, 11 (3.9%) were positive for anti-HCV. Of the 11 patients, 6 had histories of kidney transplantation, and 3 were transferred from other units, they all had histories of transfusion, only 2 patients with positive anti-HCV antibody started HD recently.

Table 7 Positive prevalence of anti-HCV antibodies in uremic patients when they were admitted to our HD center.
TimeNew patientPositive (%)Negative (%)
1995.6-1995.11422 (4.8)40 (95.2)
1995.12-1996.5391 (2.6)38 (97.4)
1996.6-1996.11453 (6.7)42 (93.3)
1996.12-1997.5653 (4.6)62 (95.4)
1997.6-1997.11712 (2.8)20 (97.2)
1997.12210 (0.0)21 (100.0)
Total283?11 (3.9)273 (96.1)
Adequacy of serologic follow-up

Out of 346 patients followed up from June 1995 to December 1997, 48 did not complete the study as a result of death (n = 22), kidney transplantation (n = 24), transfer to other dialysis units (n = 1), and transfer to peritoneal dialysis (n = 1).

Incidence of SC for HCV

During the follow-up period (1-30 mo), 80 patients had seroconversion (SC) for anti-HCV positive; 298, 167, 87, 48 and 11 were followed up for 6, 12, 18, 24, and 30 mo; and their positive seroconversion rates were 6.4%, 11.9%, 20.7%, 35.4% and 54.5%, respectively. Of the 80 seroconverted patients, 57 patients had histories of transfusion, mean number of transfusion being 12.5 U ± 6.2 U.

ALT level in seroconverted patients

ALT determinations obtained every one month from the onset of HD were reviewed in 23 (28.8%) patients with SC. SC was preceded (1 to 6 mo) by an unexplained, sustained (5 cases) or interrupted (18 cases) elevation of ALT level. This rise was not accounted for by hepatitis B virus infection or hepatotoxic drugs, and was noted for the first time since the initiation of HD. During the follow-up period, 4 patients had liver cirrhosis, 8, 3, 4 and 5 mo after HD, respectively, 1 died after SC for 10 mo, others remained in our HD center.

Serologic follow-up of seroconverted patients

All 80 seroconverted patients remained positive throughout the follow-up.

DISCUSSION

Non-A, non-B hepatitis is a major worldwide health problem. It accounts for more than 90% of transfusion associated hepatitis cases[21], and was associated with a high incidence of chronic carrier state and subsequently progressive liver disease[7,21]. In 1989, HCV was isolated from most cases of blood-borne non-A, non-B hepatitis by Choo et al[36], the HCV was considered as the major cause of such disease, and HCV has evoked great interest, a plethora of reports have appeared in the literature for HD patients. Different prevalence rates of anti-HCV have been reported from different countries and the reported rates varied from as low as 3.3% in Newzland[14], 39% in South America[6], 44%-60% in the Far-Eastern countries[29] to as high as 80.0% in Egypt[16]. By contrast, the country-wide anti-HCV prevalence among volunteer blood dono rs is 0.86%[31]. Our results showed that the positivity of anti-HCVIgM was 43.6% (27/62), anti-HCVIgG 46.8% (29/62) and HCV RNA 54.8% (34/62), the total positivity was 59.7% (37/62). By excluding the HD patients with histories of transfusion, ALT abnormality, history of kidney transplantation and positive HBV markers, the positivity of HCVM was 42.2% (8/19). So HCV infection in our HD center is a very serious problem.

Our findings that 3 HD patients had detectable serum HCV RNA despite their anti-HCV negativity confirms previous observations, although figures vary considerably, ranging from 1% to 15%[3,4,37]. Fern-ndez et al[37] reported that 53 anti-HCV negative blood donors were examined for HCV RNA, and within the study group 4 patients (12.9%) were HCV RNA positive. The existence of HCV viremia without specific antibody expression in HD patients differs significantly when compared with blood donors who represent a control population. One explanation to account for the difference is that HCV RNA positivity precedes anti-HCV SC in an acute infection[3]. Another possible explanation is that the immunosuppression that characterizes HD patients may be responsible for the inability to express detectable amount of serum anti-HCV in the same way as is observed in kidney and liver transplantation recipients[19,38]. Therefore, detection of HCV RNA can improve positivity of HCV infection, as the compensation of inadequacy of anti-HCV.

Prospective studies of HCV infection in HD patients were fewer and the conclusions were not consistent[8,22,28,29,32-34,39]. Dentico et al[11] using a less sensitive ELISA I test reported in 115 Italian HD patients, a yearly incidence of SC for HCV falling from 6.1% to 2.2% between 1984 and 1990. Two small prospective studies relying on the ELISA I test in 35 and 62 HD patients followed for 12 and 18 mo, reported a yearly incidence of 11.4%[23] and 6%[40], respectively. Chan et al[4] using ELISA II test prospectively reported a yearly incidence of 4.9% in 39 HD patients followed for 19 mo. Jadoul et al[28] reported prospectively the SC for HCV in 401 HD patients, the SC rate averages 1.7% per year. More recently, in a prospective study relying on the ELISA II test in 187 HD patients followed for 36 mo, a yearly incidence of SC for HCV was 22.6%[29]. Our study defined prospectively the SC using the sensitive ELISA II in a large series of 346 HD patients. During the 1-30 mo follow-up period, a total of 80 patients had SC for anti-HCV positive; 298, 167, 87, 48 and 11 patients were followed up for 6, 12, 18, 24, and 30 mo; their positive SC was 6.4%, 11.9%, 20.7%, 35.4% and 54.5%, respectively.

Our study confirms that blood transfusion is an important risk factor for the transmission of HCV in HD patients. We have demonstrated a positive correlation between the two which increased with the increase in the number of transfusion units. Similar results have been reported by many other investigators[1,2,8,9,12,15,19,21-23,31]. In addition, the introduction of screening of blood products for anti-HCV has led to a decline in the incidence of post-transfusion hepatitis[24].

However, factors other than transfusion contribute to the transfection of HCV as demonstrated by the absence of blood transfusion in 23 of the 80 patients with SC. Interestingly, other studies have detected HCV antibodies in up to 19%-39% of HD patients who never received blood transfusion[9,25,41]. The span of dialysis was significantly longer in anti-HCV positive patients than in anti-HCV negative patients[1,5,12,19,25,31]. The risk of acquiring HCV infection on HD has been estimated to be 10% per year[29]. These facts raised the possibility of nosocomial transmission. This hypothesis is supported by our observations that patients dialyzed in a bed adjacent to that of an anti-HCV positive patients had significantly higher risk of SC than the others in our unit[1,8,12,15,23,31]. But until recently, the route of nosocomoal transmission is not very clear. Transmission of infection to dialysis staff by needle-stick injury[1,25,26], breakdown in standard infection control practices[1,23,26,28,42,43], physical proximity to an infected patient[1,8,25,28], through dialysis machines[1,25,26], dialyzer membranes[44], hemodialysis ultrafiltrate[13,44] and reprocessing of dialyzers[14,19] implicated a variety of potential modes of HCV transmission.

Several studies advocated the segregation of HCV (+) from HCV (-) patients to prevent nosocomial transmission[9,22,25,29]. Implementation of a rigorous separation between patients according to their HCV status is rather cumbersome. Also in treating HBV positive patients, this would imply up to four separate facilities (B+C+, B+C-, B-C+ and B-C-). However, there are strong arguments against a policy of isolating anti-HCV positive patients because: HCV is not as infective as HBV, circulates in low titers in infected serum and is rapidly degraded at room temperature[45]; and Currently licenced anti-HCVtest detects non-neutralizing antibodies, does not distinguish between current and post infection, and a negative test does not exclude HCV infection[42]; although isolation may protect uninfected patients, it might also increase the risk of superinfection in patients originally infected with a single strain[46]. Infection with two or more different HCV genotypes has been observed in HD patients and 13% of patients referred for renal transplantation[47]. Grouping of anti-HCV positive patients in dialysis units might thus increase their risk acquiring multiple HCV strains.

In view of the above debate, the centers for Disease Control and Prevention in the U.S. (CDC) recommend dedicated machines, patient isolation or a ban on reuse in HD patients with HCV infection[48,49]. Such measures are detailed in the universal precautions for prevention of transmission of blood borne pathogenes in health care settings[47,49] and recommended precautions for patients undergoing hemodialysis who have AIDS or non-A non-B hepatitis delineated by the CDC[48]. They include cleaning and disinfection of instruments, machines and environmental surfaces that are routinely touched, avoidance of sharing of articles between patients, frequent handwashing and use of glove.

In conclusion, the status of HCV infection in HD patients was a very serious problem, contamination appears to be both transfusion and nosocomial. Strict adhesion to the ‘CDC guidelines’ and isolation of HCV positive patients during dialysis sessions are recommended. Further long-term studies are needed to confirm these conclusions.

ACKNOWLEDGEMENTS

The authors would like to thank Professor Wu Zhao-Long for improving the English language in this paper.

Footnotes

Edited by You DY and Ma JY

Project supported by Scientific Research Foundation, State Health Commission, No. 96-2-128

References
1.  Wang NS, Zhu YJ, Pan W, Fang F, Liao LT. Hepatitis C virus infection rate in patients on maintenance hemodialysis. Shanghai Yike Daxue Xuebao. 1999;26:313-317.  [PubMed]  [DOI]  [Cited in This Article: ]
2.  Simon N, Couroucé AM, Lemarrec N, Trépo C, Ducamp S. A twelve year natural history of hepatitis C virus infection in hemodialyzed patients. Kidney Int. 1994;46:504-511.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 87]  [Cited by in F6Publishing: 88]  [Article Influence: 2.9]  [Reference Citation Analysis (0)]
3.  Dussol B, Berthezène P, Brunet P, Roubicek C, Berland Y. Hepatitis C virus infection among chronic dialysis patients in the south of France: a collaborative study. Am J Kidney Dis. 1995;25:399-404.  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Chan TM, Lok AS, Cheng IK, Chan RT. Prevalence of hepatitis C virus infection in hemodialysis patients: a longitudinal study comparing the results of RNA and antibody assays. Hepatology. 1993;17:5-8.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Hardy NM, Sandroni S, Danielson S, Wilson WJ. Antibody to hepatitis C virus increases with time on hemodialysis. Clin Nephrol. 1992;38:44-48.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  Boero R, Martina G, Bosio P, Devos S, Bertolo P, Forneris G, Giachino O, Quarello F, Piccoli G. HCV viremia in hemodialysis patients: detection by a DNA enzyme immunoassay for amplified HCV sequences. Ren Fail. 1995;17:565-573.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 12]  [Article Influence: 0.4]  [Reference Citation Analysis (0)]
7.  Hung KY, Chen WY, Yang CS, Lee SH, Wu DJ. Hepatitis B and C in hemodialysis patients. Dialysis Transplantation. 1995;24:135-139.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  Wang NS, Zhu YJ, Tang LQ, Liao LT. Analysis of hepatitis B virus and hepatitis C virus infection in patients with maintenance hemodialysis. Zhonghua Shenzangbing Zazhi. 1998;14:376-379.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Muller GY, Zabaleta ME, Arminio A, Colmenares CJ, Capriles FI, Bianco NE, Machado IV. Risk factors for dialysis-associated hepatitis C in Venezuela. Kidney Int. 1992;41:1055-1058.  [PubMed]  [DOI]  [Cited in This Article: ]
10.  Al-Muhanna FA. Hepatitis C virus infection among hemodialysis patients in the eastern region of saudi arabia. Saudi J Kidney Dis Transpl. 1995;6:125-127.  [PubMed]  [DOI]  [Cited in This Article: ]
11.  Dentico P, Buongiorno R, Volpe A, Carlone A, Carbone M, Manno C, Proscia F, Pastore G, Schiraldi O. Prevalence and incidence of hepatitis C virus (HCV) in hemodialysis patients: study of risk factors. Clin Nephrol. 1992;38:49-52.  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Wang NS, Tang LQ, Pan W, Zhu YJ, Fang F, Liao LT. Clinical significance of anti-HCV IgM determination in hemodialysispatients. Shanghai Yixue Jianyan Zazhi. 1999;14:20-21.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Pol S, Thiers V, Carnot F, Zins B, Romeo R, Berthelot P, Bréchot C. Efficacy and tolerance of alpha-2b interferon therapy on HCV infection of hemodialyzed patients. Kidney Int. 1995;47:1412-1418.  [PubMed]  [DOI]  [Cited in This Article: ]
14.  Wang NS, Liao LT. Hemodialysis and hepatitis C virus. Guowai Yixue Liuxingbingxue Chuanranbingxue Fence. 1998;25:115-118.  [PubMed]  [DOI]  [Cited in This Article: ]
15.  Wang NS, Zhu YJ, Pan W, Fang F, Liao LT. Detection and significance of hepatitis C virus infection in uremic patient onmaintenance hemodialysis. Linchuang Gandanbing Zazhi. 1999;15:106-108.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Al-Faleh FZ. Hepatitis C virus infection: an update. Saudi J Kidney Dis Transpl. 1995;6:118-121.  [PubMed]  [DOI]  [Cited in This Article: ]
17.  An P, Yuan F, Han CF. Risk factos of hepatitis C virus infevtion in hemodialysis patients. Xin Xiaohuabingxue Zazhi. 1996;4:12-14.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Fabrizi F, Lunghi G, Guarnori I, Raffaele L, Di Filippo S, Erba G, Pagano A, Locatelli F. Virological characteristics of hepatitis C virus infection in chronic hemodialysis patients: a cross-sectional study. Clin Nephrol. 1995;44:49-55.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  Pereira BJ, Levey AS. Hepatitis C virus infection in dialysis and renal transplantation. Kidney Int. 1997;51:981-999.  [PubMed]  [DOI]  [Cited in This Article: ]
20.  El Shahat YI, Varma S, Bari MZ, Shah Nawaz M, Abdulrahman S, Pingle A. Hepatitis C virus infection among dialysis patients in United arab emirates. Saudi J Kidney Dis Transpl. 1995;6:157-162.  [PubMed]  [DOI]  [Cited in This Article: ]
21.  Esteban JI, González A, Hernández JM, Viladomiu L, Sánchez C, López-Talavera JC, Lucea D, Martin-Vega C, Vidal X, Esteban R. Evaluation of antibodies to hepatitis C virus in a study of transfusion-associated hepatitis. N Engl J Med. 1990;323:1107-1112.  [PubMed]  [DOI]  [Cited in This Article: ]
22.  Suliman SM, Fessaha S, El Sadig M, El-Hadi MB, Lambert S, Fields H, Ghalib HW. Prevalence of hepatitis C virus infection in hemodialysis patients in Sudan. Saudi J Kidney Dis Transpl. 1995;6:154-156.  [PubMed]  [DOI]  [Cited in This Article: ]
23.  Wang NS, Tang LQ, Zhu YJ, Zhou SS, Liao LT. A study on risk factors of hepatitis C virus infection for maintenancehemodialysis (HD). Xiandai Yufang Yixue. 1999;26:497.  [PubMed]  [DOI]  [Cited in This Article: ]
24.  Donahue JG, Muñoz A, Ness PM, Brown DE, Yawn DH, McAllister HA, Reitz BA, Nelson KE. The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med. 1992;327:369-373.  [PubMed]  [DOI]  [Cited in This Article: ]
25.  Calabrese G, Vagelli G, Guaschino R, Gonella M. Transmission of anti-HCV within the household of haemodialysis patients. Lancet. 1991;338:1466.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 36]  [Cited by in F6Publishing: 38]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
26.  Knudsen F, Wantzin P, Rasmussen K, Ladefoged SD, Løkkegaard N, Rasmussen LS, Lassen A, Krogsgaard K. Hepatitis C in dialysis patients: relationship to blood transfusions, dialysis and liver disease. Kidney Int. 1993;43:1353-1356.  [PubMed]  [DOI]  [Cited in This Article: ]
27.  Sampietro M, Badalamenti S, Salvadori S, Corbetta N, Graziani G, Como G, Fiorelli G, Ponticelli C. High prevalence of a rare hepatitis C virus in patients treated in the same hemodialysis unit: evidence for nosocomial transmission of HCV. Kidney Int. 1995;47:911-917.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 70]  [Cited by in F6Publishing: 72]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
28.  Jadoul M, Cornu C, van Ypersele de Strihou C. Universal precautions prevent hepatitis C virus transmission: a 54 month follow-up of the Belgian Multicenter Study. The Universitaires Cliniques St-Luc (UCL) Collaborative Group. Kidney Int. 1998;53:1022-1025.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 131]  [Cited by in F6Publishing: 139]  [Article Influence: 5.3]  [Reference Citation Analysis (0)]
29.  Souqiyyeh MZ, Shaheen FA, Huraib SO, Al-Khader AA. The annual incidence of seroconversion of antibodies to the hepatitis C virus in the hemodialysis population in saudi arabia. Saudi J Kidney Dis Transpl. 1995;6:167-173.  [PubMed]  [DOI]  [Cited in This Article: ]
30.  Wang NS, Tang LQ, Zhu YJ, Liao LT, Pan W, Fang F. Molecular epidemiology of nosocomial transmission of hepatitis C virus (HCV) infection in patients on maintenance hemodialysis. Linchuang Gandanbing Zazhi. 2000;16:24-25.  [PubMed]  [DOI]  [Cited in This Article: ]
31.  Wang N, Pan W, Zhu Y, Fang F, Liao L. [Nucleotide sequence analysis for high variance region of hepatitis C virus in patients with hemodialysis]. Zhonghua Yu Fang Yi Xue Za Zhi. 1999;33:146-148.  [PubMed]  [DOI]  [Cited in This Article: ]
32.  Medin C, Allander T, Roll M, Jacobson SH, Grillner L. Seroconversion to hepatitis C virus in dialysis patients: a retrospective and prospective study. Nephron. 1993;65:40-45.  [PubMed]  [DOI]  [Cited in This Article: ]
33.  Martin P, Friedman LS. Chronic viral hepatitis and the management of chronic renal failure. Kidney Int. 1995;47:1231-1241.  [PubMed]  [DOI]  [Cited in This Article: ]
34.  Jadoul M, Cornu C, van Ypersele de Strihou C. Incidence and risk factors for hepatitis C seroconversion in hemodialysis: a prospective study. The UCL Collaborative Group. Kidney Int. 1993;44:1322-1326.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 138]  [Cited by in F6Publishing: 131]  [Article Influence: 4.2]  [Reference Citation Analysis (0)]
35.  Zein NN, Rakela J, Krawitt EL, Reddy KR, Tominaga T, Persing DH. Hepatitis C virus genotypes in the United States: epidemiology, pathogenicity, and response to interferon therapy. Collaborative Study Group. Ann Intern Med. 1996;125:634-639.  [PubMed]  [DOI]  [Cited in This Article: ]
36.  Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359-362.  [PubMed]  [DOI]  [Cited in This Article: ]
37.  Fern-ndez JL, del Pino N, Lef L, Valtuille R, Berridi J, Rendo P, Viola L. Serum hepatitis C virus RNA in anti-HCV negativehemodialysis patients. Dialysis Transplant. 1996;25:14-18.  [PubMed]  [DOI]  [Cited in This Article: ]
38.  Pereira BJ, Natov SN, Bouthot BA, Murthy BV, Ruthazer R, Schmid CH, Levey AS. Effects of hepatitis C infection and renal transplantation on survival in end-stage renal disease. The New England Organ Bank Hepatitis C Study Group. Kidney Int. 1998;53:1374-1381.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 246]  [Cited by in F6Publishing: 250]  [Article Influence: 9.6]  [Reference Citation Analysis (0)]
39.  Abu-Aisha H, Mitwalli A, Huraib SO, Al-Wakeel J, Abid J, Yousif KI, Algayyar F, Ramia S. The effect of chemical and heat disinfection of the hemodialysis machines on the spread of hepatitis C virus infection: a prospective study. Saudi J Kidney Dis Transpl. 1995;6:174-178.  [PubMed]  [DOI]  [Cited in This Article: ]
40.  Wang NS, Liao LT, Zhu YJ, Pan W, Fang F. Prospective study on hepatitis C virus infection in chronic hemodialysis patients. Shanghai Yixue Zazhi. 1999;22:600-602.  [PubMed]  [DOI]  [Cited in This Article: ]
41.  Stuyver L, Claeys H, Wyseur A, Van Arnhem W, De Beenhouwer H, Uytendaele S, Beckers J, Matthijs D, Leroux-Roels G, Maertens G. Hepatitis C virus in a hemodialysis unit: molecular evidence for nosocomial transmission. Kidney Int. 1996;49:889-895.  [PubMed]  [DOI]  [Cited in This Article: ]
42.  Zeuzem S, Scheuermann EH, Waschk D, Lee JH, Blaser C, Franke A, Roth WK. Phylogenetic analysis of hepatitis C virus isolates from hemodialysis patients. Kidney Int. 1996;49:896-902.  [PubMed]  [DOI]  [Cited in This Article: ]
43.  Houghton M, Weiner A, Han J, Kuo G, Choo QL. Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease. Hepatology. 1991;14:381-388.  [PubMed]  [DOI]  [Cited in This Article: ]
44.  Wang NS, Zhu YJ, Pan W, Liao LT. A study on nosocomial transmission of hepatitis C virus infection on maintenancehemodialysis patients. Xiandai Yufang Yixue Zazhi. 1998;25:404-407.  [PubMed]  [DOI]  [Cited in This Article: ]
45.  Farci P, Alter HJ, Govindarajan S, Wong DC, Engle R, Lesniewski RR, Mushahwar IK, Desai SM, Miller RH, Ogata N. Lack of protective immunity against reinfection with hepatitis C virus. Science. 1992;258:135-140.  [PubMed]  [DOI]  [Cited in This Article: ]
46.  Okamoto H, Sugiyama Y, Okada S, Kurai K, Akahane Y, Sugai Y, Tanaka T, Sato K, Tsuda F, Miyakawa Y. Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources. J Gen Virol. 1992;73:673-679.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 859]  [Cited by in F6Publishing: 858]  [Article Influence: 26.8]  [Reference Citation Analysis (0)]
47.  No authors listed. Leads from the MMWR. Update: universal precautions for prevention of transmission of human immunodeficiency virus, hepatitis B virus, and other bloodborne pathogens in health-care settings. JAMA. 1988;260:462-465.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 39]  [Cited by in F6Publishing: 30]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
48.  Alter MJ, Favero MS, Maynard JE. Impact of infection control strategies on the incidence of dialysis-associated hepatitis in the United States. J Infect Dis. 1986;153:1149-1151.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 81]  [Cited by in F6Publishing: 83]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]
49.  Wang NS, Liao LT. Suggestion on how to prevent hepatitis C virus infection in uremic on maintenance hemodialysis. Ganzhang. 1998;3:234-235.  [PubMed]  [DOI]  [Cited in This Article: ]