Hepatitis C Virus Antibody in Patients on Chronic Hemodialysis in Fukuoka, Japan

Anti-HCV was examined in 454 patients on chronic hemodialysis(HD) in Fukuoka in 1990. The anti-HCV positive rate was significantly greater in those with than in those without blood transfusion (40.5% vs 11.7% for males, p<0.01, and 29.4% vs 5.6% for females, p<0.01). The anti-HCV positive rate increased with the duration of HD treatment among all patients except for the non-transfusion female patients. Blood transfusion thus appeared to be a major route of HCV infection in HD patients as had been reported previously. The anti-HCV positive rate was 2.6 times higher in those who had less than 5 years HD treatment but had never received a blood transfusion than found in the blood donors of Kitakyushu Red Cross Blood Center, adjusted by age. These results suggest that HD treatment might increase the exposure to HCV infection apart from blood transfusion. J Epidemiol, 1991 ; 1 : 31-36.

There have been many patients on chronic hemodialysis (HD) who used to suffer from anemia until recombinant erythropoietin became clinically available.
They were often at a high risk of posttransfusion hepatitis due to frequent blood transfusions for anemia1).
Although more than 90% of posttransfusion hepatitis are non-A non-B hepatitis2), infections due to non-A non-B hepatitis virus have only been suggested by epidemiologic arguments3). Recently,Choo et al.4) and Kuo et al.5) isolated the gene products of the hepatitis C virus (HCV) and a test for antibodies to HCV has become available.
Very recently, Yamaguchi et al.6) reported that the anti-HCV positive rate was high in HD patients even in those without undergoing blood transfusions and the positive rate of HCV infection increased with the duration of HD in Kumamoto prefecture, Japan. However no detailed analysis by sex and age group was given in this paper.
The present study intends to evaluate the effect of The ratio of the observed number of cases to the expected number(O/E ratio) was calculated to see the effect of blood transfusion and conditions of renal failure with HD treatment on the anti-HCV positive rate. The expected number was calculated based on the anti-HCV positive rate among blood donors at the Kitakyushu Red Cross Blood Center7). Table 1, the anti-HCV positive rate in patients with a history of blood transfusions was greater than in those without (male p<0.01, and female p<0.01).

As shown in
Similarly, the rate was also greater in patients with anti-HBs positive (male p<0.01, and female p<0.1) than those without it regardless of sex. Among females, the anti-HCV positive rate was significantly greater in those with a habit of drinking (p< 0.05) than those without such a habit.
The anti-HCV positive rate increased with the duration of HD treatment in both males who had blood transfusions (p<0.001) as well as in those who did not(p<0.05).
Among females, however, the rate increased only in those with blood transfusions (p< 0.001) but not in those without transfusions ( Table 2). As shown in Table 3, the anti-HCV positive rate did not increase with age for patients either with or without blood transfusions regardless of sex.
The anti-HCV positive rate increased with the duration of HD treatment in both anti-HBs positive and negative patients with blood transfusions (p<0.005 and p<0.005) but did not increase in those without transfusions (Table 4). The positive rate of anti-HCV was significantly higher in blood transfusion positive patients than in blood transfusion negative patients among either anti-HBs positive (p<0.05) or anti-HBs negative patients (p<0.05).
After correction by duration of HD treatment, the positive rates of anti-HCV were similar between patients with anti-HBs positive and those without it regardless of blood transfusions.
As shown in Table 5, O/E ratio of anti-HCV positive patients was 15.6 (p<0.001) in HD patients with blood transfusions, 3.5 (p<0.005) in those without blood transfusions or 2.6 (p<0.05) in those without blood transfusions and with less than 5 years' HD treatment.

DISCUSSION
In the present study, 103 (23%) of the 454 HD patients were anti-HCV positive. This rate was similar to that among HD patients in both Kumamoto prefecture (22%)6) and Nagano prefecture (21%)8), while it was slightly higher than that in Ishikawa prefecture (16%)9). There was no difference in the mean age of HD patients between the present study and other studies6, 8,9). The anti-HCV positive rate among HD patients was much higher than that among blood donors throughout Japan (1.3%)10) as well as among those from Fukuoka prefecture (2.1%)10). This crude rate of 23% in the present study was also similar to the rate among HD patients in Spain (20%)1), while it was much higher than that in either West Germany (10%)11) or the United Kingdom (1%)12). The far lower rate of positive anti-HCV among HD patients in United Kingdom seems due to the very low rate among blood    Table 4, the study subjects consisted only of patients from one hospital in Kitakyushu City , because at the hospital in Fukuoka City, the HBs antibody test was done only on patients with HBs antigen positive .   This result may be explained by the two following possibilities.
Firstly, HD patients with longer duration of HD treatment may receive more units of blood transfusion.
Secondarily, screening program for blood donors to avoid posttransfusion hepatitis was improved with time. The hepatitis B virus (HBV) is horizontally transmitted by either blood transfusion or sexual contact, and vertically transmitted during child birth16). HBsAg disappears after recovery from the symptoms and signs of HBV infection, followed by the appearance of anti-HBs within 1-3 months in the majority of patients with HBV infection. In infants, however, HBsAg positivity continues and anti-HBs fails to appear in the serum17). In our study, the positive rate of anti-HCV was similar between HBsAg positive and negative patients, suggesting that HCV might not be transmitted vertically. After correction by duration of HD treatment, the positive rates of anti-HCV were similar between anti-HBs positive patients and negative patients, and increased with the duration of HD treatment only in patients with blood transfusion regardless of anti-HBs positivity. These results suggest that HCV may be transmitted horizontally, mainly by blood transfusion. Screening program of blood donors for HBsAg from 1971 may explain the reason why blood transfusion did not affect the incidence of coinfection of HCV and HBV.
Compared to blood donors, the positive rate of anti-HCV was 3.5 times higher in HD patients without blood transfusion, and 2.6 times higher even in blood transfusion negative patients with a short duration of HD treatment.
These results suggested that the condition of end-stage renal failure may increase the chance of HCV infection apart from the effect of blood transfusion. The anti-HCV positive rate among HD patients is reported to be higher than that among continuous ambulatory peritoneal dialysis patients (30% vs l5%)18). In HD units, patients may have a chance of exposure to blood spills or parenteral routes of contamination.
In Taiwan, where HD patients have the very high anti-HCV positive rate of 34% or 47%14,15) the rate in patients with blood transfusion (43%) is not higher than that in those without it (51%)'s). In our study, anti-HCV positive rate of male patients without blood transfusion increased with HD duration but female did not. Small number of female patients in the present study might explain the reason why their anti-HCV positive rate failed to show the relationship between the duration of HD treatment and anti-HCV positive rate. Further investigations using patients just before starting HD treatment should be carried out to clarify whether or not end-stage renal failure patients in Japan have an increased risk of HCV infection apart from any influence of HD treatment.
The positive rate of anti-HCV among blood donors is reported to increase with age7,10) but did not do so in our HD patients. The positive rate even among elderly blood donors is about 3.5%, which is half of that among HD patients without blood transfusion.
The much increased positive rate during HD treatment may conceal the relationship between the positive rate and age.
Erythropoietin treatment for anemia may decrease the total amount of blood transfusion, and an improved screening program of blood donors for anti-HCV will decrease the incidence of HCV infection after blood transfusion.
However, even blood transfusion negative HD patients had a high positive rate of anti-HCV in the present study. Since HCV plays an extremely important role in the pathogenesis of hepatocellular carcinoma and liver cirrhosis in Japan19) and anti-HCV positive HD patients are at a high risk of chronic liver disease20), it is important to establish the best protocol for reducing the incidence of HCV infection among HD patients.