Journal of Medical Virology 36271-273 (1992)

Prevalence of Four Blood-Borne Viruses (HBV, HCV, HTLV-I, HIV-1) Among Haemodialysis Patients in Japan

Ikuo Tamura, Tetsuzo Koda, Yasunori Kobayashi, Hiroshi Ichimura, Osamu Kurimura, and Takashi Kurimura Institute of Clinical Research (I.T., Te.K., HJ., O.K.), and Department of Internal Medicine (Y.K.), Kure National Hospital, Kure, and Department of Pathology, Research Institute for Microbial Diseases, Osaka University, Suita (Ta.K.), Japan

To investigate the prevalence of four blood- borne viruses among a cohort of haemodialysis (HD) patients in Japan, hepatitis B surface anti- gen (HBsAg), antibody to hepatitis C virus (anti- HCV), antibody to human T-cell lymphotropic vi- rus type-I (anti-HTLV-I), and antibody to human immunodeficiency virus type-I (anti-HIV-1) were studied in the sera from 393 consecutive HD pa- tients and in the sera from 786 age- and sex- matched healthy individuals from the general population (controls). The prevalence of anti- HCV and anti-HTLV-l was significantly higher in HD patients than in the controls (17.8% vs. 1.1% and 3.8% vs. 0.5%), but the prevalence of HBsAg showed no significant difference. No patients or controls were positive for anti-HIV-1. In HD pa- tients with no history of blood transfusion, anti- HCV was detected in only one (2.1%) of 48 pa- tients undergoing HD treatment for less than 3 years, and there was no significant difference between the prevalence of anti-HCV in these pa- tients and in the controls. In HD patients who had received blood transfusion, anti-HTLV-l was de- tected in only one (1.0%) of 103 patients under- going HD treatment for less than 3 years, and there was no significant difference between the prevalence of anti-HTLV-l in these patients and in the controls. These findings suggest that in re- cent years, the risk of HCV transmission by routes other than blood transfusion in HD pa- tients is low, and that of HTLV-I transmission by transfusion is very low or non-existent.

KEY WORDS: HBsAg, anti-HCV, anti-HTLV-I, anti-HIV-1

INTRODUCTION Severe anaemia in haemodialysis (HD) patients often

requires frequent blood transfusions. HD patients therefore constitute a possible high risk group for infec- 0 1992 WILEY-LISS, INC.

tion with blood-borne viruses, hepatitis B virus (HBV), hepatitis C virus (HCV) [Choo et al., 19891, human T-cell lymphotropic virus type-I (HTLV-I), and human immunodeficiency virus type-1 (HIV-1).

The prevalence of HBV infection among HD patients in Japan has decreased because of improved infection control, including surveillance and segregation of virus carriers, as in the United States [Alter et al., 19861, and HBsAg screening of blood donors using the reversed passive haemagglutination method since 1978. In order to prevent the spread of HTLV-I, HIV-1, and HCV in- fection by blood transfusion, antibody to HTLV-I (anti- HTLV-I) and antibody to HIV-1 (anti-HIV-1) in blood donors has been checked by gelatin particle agglutina- tion assay [Ikeda et al., 19841 since November 1987, and antibody to HCV (anti-HCV) in donors has been checked by enzyme immunoassay (EIA) lKuo et al., 19891 since November 1989. However, the effectiveness of anti-HTLV-I, anti-HIV-1, and anti-HCV screening in blood donors remains to be elucidated.

We report recent trends in the prevalence of four blood-borne viruses in HD patients, and the effective- ness of screening of blood donors for the prevention of these viral infections.

PATIENTS AND METHODS From May to October 1990, serum samples were ob-

tained from 393 consecutive HD patients with chronic renal failure (mean age 52.1 years; range 17-87 years) from five hospitals in Hiroshima Prefecture, Japan. The mean duration of HD treatment was 78.6 2 59.0 months (range 3 to 241 months). Of these patients, none were intravenous drug addicts, haemophiliacs, or ho- mosexuals. Sera obtained from 786 age- and sex- matched healthy subjects from the general population were used as controls. All serum samples were stored at -20°C until assayed.

Accepted for publication September 23, 1991. Address reprint requests to Ikuo Tamura, Institute of Clinical

Research, Kure National Hospital, Aoyama 3-1, Kure 737, Japan.

272 Tamura et al.

TABLE I. Frequency of Seropositivity for HBsAg, Anti-HCV, Anti-HTLV-I, and Anti-HIV-1 in Haemodialysis Patients and Controls*

Patients (n = 393) Control (n = 786) P value

HBsAg (%) 15 (3.8) 18 (2.3) NS"

Anti-HIV-1 (%) 0 0 NS *HBsAg, hepatitis B surface antigen; Anti-HCV, antibody to hepatitis C virus; Anti-HTLV-I, antibody to human T-cell lymphotropic virus type-I; Anti-HIV-1, antibody to human immuno- deficiency virus type-1; Control, healthy subjects from the general population. aNot significant.

Anti-HCV (%) 70 (17.8) 9 (1.1) <0.001 Anti-HTLV-I (%) 15 (3.8) 4 (0.5) <0.001

TABLE 11. Frequency of Seropositivity for Anti-HCV and Anti-HTLV-I in Haemodialysis Patients With and Without Blood Transfusion*

With transfusion Without transfusion (n = 306) (n = 87) P value

Anti-HCV (%) 62 (20.3) 8 (9.2) <0.05 Anti-HTLV-I (%) 13 (4.3) 2 (2.3) NSa *Anti-HCV, antibody to hepatitis C virus; Anti-HTLV-I, antibody to human T-cell lymphotropic virus type-I. aNot significant.

HBsAg and anti-HIV-1 were assayed by EIA (Ho- echst Corporation). HBsAg positivity was confirmed by radioimmunoassay (Abbott Laboratory). Anti-HTLV-I was assayed by EIA (Eisai Corporation) [Taguchi et al., 1983 1. Anti-HTLV-I positivity was confirmed by West- ern blot assay. The criterion for a positive Western blot assay was the presence of bands specific to the HTLV-I gag proteins p19 and p24 [Agius et al., 19881. Anti- HCV was assayed by EIA (Ortho Diagnostic Systems). Anti-HCV positivity was comfirmed by a recombinant immunoblot assay (RIBA, Ortho Diagnostic Systems) with recombinant HCV antigens immobilised on nitro- cellulose strips [Weiner et al., 19901. A sample was considered to be reactive if the two bands corresponding to the 5-1-1 and (3100-3 peptides were simultaneously present.

Statistical analysis was carried out by Chi-square test with Yates' correction factor. For all tests, a P value of less than 0.05 was considered statistically sig- nificant.

RESULTS The frequency of seropositivity for HBsAg, anti-

HCV, anti-HTLV-I, and anti-HIV-1 in HD patients and control subjects is shown in Table I. Seropositivity of anti-HCV and anti-HTLV-I was significantly higher in HD patients than in controls (17.8% vs. 1.1% and 3.8% vs. 0.5%, respectively, P < 0.001). There was no signifi- cant difference in HBsAg seropositivity between HD patients and controls (3.8% vs. 2.3%). No patients or controls were positive for anti-HIV-1.

The frequency of seropositivity for anti-HCV in pa- tients with blood transfusion was significantly higher than in patients without transfusion (20.3% vs. 9.2%, P < 0.05). However, there was no significant difference

in anti-HTLV-I between patients with and without transfusion (Table 11).

In HD patients with blood transfusion, anti-HCV positivity (55 of 203) and anti-HTLV-I positivity (12 of 203) in patients undergoing HD treatment for more than 3 years were significantly higher than in patients (seven and one of 103) dialysed for less than 3 years (27.1% vs. 6.8%, P < 0.001; 5.9% vs. l.O%, P < 0.05). In HD patients without blood transfusion, anti-HCV posi- tivity (seven of 39) in patients dialysed for more than 3 years was significantly higher than in patients (one of 48) dialysed for less than 3 years (18.0% vs. 2.18, P < 0.05), but there was no significant difference in anti-HTLV-I positivity between patients dialysed for more and less than 3 years (Table 111).

DISCUSSION This study demonstrated that the risk of HCV infec-

tion in HD patients without a history of blood transfu- sion has become low recently. In a previous study, we reported that although in HD patients the risk of HCV infection via blood transfusion was very high, seroposi- tivity may be acquired via routes of HCV transmission other than blood transfusion [Tamura et al., 19901. In this study, however, anti-HCV in HD patients without transfusions was detected in only one (2.1%) of 48 pa- tients dialysed for less than 3 years, and the prevalence of anti-HCV in these patients and controls (l.l%,) showed no significant difference. The reason for the low prevalence of anti-HCV in the last 3 years is unknown, but there have been recent improvements in the HD membrane of the haemodialyzer, which may have con- tributed to the prevention of the spread of HCV infec- tion, excluding via blood transfusion, in HD patients.

Blood-Borne Viruses and Dialysis Patients 273

TABLE 111. Relationships Between Anti-HCV and Anti-HTLV-I and Duration of Haemodialysis Treatment in Patients With and Without Blood Transfusion*

With transfusion Without transfusion <3 yra >3 yrb <3 yr >3 yr

(n = 103) (n=203) P (n = 48) (n =39) P Anti-HCV (%) 7 (6.8) 55 (27.1) <0.001 1 (2.1) 7 (18.0) <0.05 Anti-HTLV-I (%) l ( l .0) 12 (5.9) <0.05 1 (2.1) l(2.6) NSc *Anti-HCV, antibody to hepatitis C virus; Anti-HTLV-I, antibody to human T-cell lymphotropic virus type-I. aHaemodialysis treatment for less than 3 years. 'Haemodialysis treatment for more than 3 years. 'Not significant.

In the present study, we investigated the prevalence of anti-HCV in HD patients by screening EIA and sup- plementary RIBA. There was a correlation between the specificity of the RIBA and the EIA optical density (OD) reading; most false positives had OD readings of less than 1.0 (data not shown). These data support the re- sults of other studies [Aceti et al., 1990; Brind et al., 1990; Van der Poel et al., 19901.

In HD patients with a history of blood transfusion, anti-HTLV-I was detected in only one (1.0%) of 103 patients dialysed for less than 3 years, and the preva- lence of anti-HTLV-I in these patients and controls (0.5%) showed no significant difference. No patients were positive for anti-HIV-1. Therefore, in recent years the risk of HTLV-I infection in HD patients with blood transfusion seems to be very low or non-existent, and HIV-1 infection in these patients seems to have not existed up to present. We believe that these findings reflect the effectiveness of anti-HTLV-1 and anti-HIV-1 screening of blood donors in Japan.

In HD patients with a history of blood transfusion, anti-HCV was detected in two (7.1%) of 28 patients dialysed for less than 12 months, in spite of having received over 2 units of blood products since the first of December 1989 (data not shown). Thus, the risk of HCV transmission by transfusion is still present, and the current assay ((2100-3 EIA) may not have sufficient sensitivity as an anti-HCV screening test for blood do- nors. In the near future, a more sensitive and specific assay for screening blood donors may contribute to the prevention of the spread of HCV infection in HD pa- tients receiving blood transfusion, as well as preven- tion of HTLV-I and HIV-1 infection.

It is concluded that the risk of HCV infection in HD patients without history of blood transfusion is at present low, and the risk of HTLV-I infection in pa- tients with history of transfusion is very low or non- existent in Hiroshima Prefecture (western part of Hon- shu Island, Japan).

ACKNOWLEDGMENTS We thank Dr. T. Takasugi, Dr. N. Hamaguchi, Dr. J.

Kawai, Dr. K. Yasuda, and Dr. J . Tatsukawa for inter- viewing patients and for collecting blood samples. This work is supported in part by a grant-in-aid for AIDS Research from the Ministry of Health and Welfare, Japan.

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