| Abstract|| |
Hepatitis C virus (HCV) infection, unrelated to blood transfusion is very common among hemodialysis patients with chronic renal failure. The positivity rate for anti-HCV varies from 18% to 91% among various countries. It is due not only to the past blood transfusions, but also to nosocomial transmission which is preventable. The main route of virus entry, is most likely, the two (arterial and venous) needle holes that are touched by the fingers of the physician and the nurse repeatedly. The recommended preventive measures include: the use of a sterile glove, finger sterilization with a disinfectant solution, immediately before touching the needle/needle hole. and repeated education of the staff. Whether the anti-HCV positive patients should be separated from the negative, largely depends on the prevalence of HCV infection within the dialysis unit.
|How to cite this article:|
Okuda K, Hayashi H. Hepatitis C virus infection among maintenance hemodialysis patients: A preventable problem of the world. Saudi J Gastroenterol 1996;2:1-7
|How to cite this URL:|
Okuda K, Hayashi H. Hepatitis C virus infection among maintenance hemodialysis patients: A preventable problem of the world. Saudi J Gastroenterol [serial online] 1996 [cited 2020 Jul 16];2:1-7. Available from: http://www.saudijgastro.com/text.asp?1996/2/1/1/34033
Hepatitis C virus (HCV) infection is very common among maintenance hemodialysis patients throughout the world. The prevalence seems to reflect the quality of medical practice being offered in the country as does the anti-HCV prevalence among the general population there. Hepatitis B virus (HBV) infection in patients and hospital staff at dialysis units was once rampant, but it has been steadily reduced in incidence with the separation of patients and adherence to other preventive measures. When the HCV was identified and the assay system for testing HCV antibodies (anti-HCV) became available, we began repeating the same past experience with HBV infection. There are a number of differences between HBV and HCV in infectivity and outcome of acute infection, however. HBV infection in normal adults rarely becomes chronic, whereas acute HCV infection turns into chronic hepatitis in the majority. If left untreated, chronic hepatitis C progresses to cirrhosis, and in certain countries, to liver cancer. Compared with HBV, the routes of HCV infection are less clearly known at the moment, particularly the mode of HCV transmission unrelated to blood transfusion among dialysis patients. This review attempts to put together the reported data and discuss the likely mode of HCV transmission among dialysis patients with a suggestion on its prevention.
| Prevalence of HCV antibodies among dialysis patients|| |
After the development of the assay system for anti-HCV by the Chiron Laboratories  , it did not take time to find out that anti-HCV positivity is high among maintenance hemodialysis patients with chronic renal failure ,,,,,,,,,,,,,,,,,,,,, . It was not unexpected from the past experiences with HBV infection ,,,,,,, . The early results obtained with the first generation test (C100-3) varied considerably among countries. They were reassessed with the subsequently-developed, more specific and sensitive second generation test  , and the positivity rates were further increased as shown in[Table - 1]. With the second generation test, the positivity rates ranged from 18% to 74.2% among various countries. In some eastern European countries, it exceeds 90%  . Clearly, the positivity rates are much higher than the control values in nondialysis patients and hospital staff members. In several studies, the first and the second generations tests were compared with the same sera , , and the latter was found to be more sensitive; antibody positivity corresponded well with the assay for HCV RNA ,, .
At the beginning of these studies, it was thought that the high prevalence of anti-HCV was due to frequent blood transfusions given to these patients who were anemic with chronic renal failure. After erythropoietin became clinically available, the number of blood transfusions has been much reduced. However, there is as yet, no sign of reduction of anti-HCV positivity among hemodialysis patients. Most of these studies noted that although the positivity rate increases with the number of blood transfusions they received in the past, the duration of hemodialysis is also correlated with the positivity rate ,,,,,,,,, ,and that some of the positive patients had never received blood transfusion ,,,,,,,,,,,, . There have been increasing numbers of reports on acute hepatitis C ,,,, and seroconversion ,,, as well, among dialysis patients.
| Hepatitis B infection associated with dialysis|| |
The epidemiology of HBV infection among hemodialysis patients and hospital staff is now well documented. In a 1967-68 survey conducted in the U.S.A. by the Center for Disease Control (CDC), 41% of the dialysis centers reported sporadic cases of hepatitis infection. The attack rate per 100 persons at risk was estimated to be 10% for patients and three percent for the medical staff  . According to another survey carried out in the United States, 53% of 65 centers reported cases of viral infection to the CDC in a four-year period  . The European experience was similar. In a survey jointly carried out in 24 countries in 1971, 47% of centers reported cases of hepatitis. Fatality was estimated at seven percent for patients, and one percent for the staff. Besides sporadic infections, a number of outbreaks have been reported at dialysis centers ,,, . In the survey conducted by Szmuness et al in the States in 1972-73  , HBsAg was positive in 16.1% of a total of 583 dialysis patients as against the positivity of 2.4% among the staff. Clearly, nosocomial infection was occurring in these dialysis centers. The subsequently-recommended strategies for prevention included separation of HBsAg positive patients from the negative, vaccination of seronegative patients  , routine serological screening for HBsAg and anti-HBs/HBc, and routine cleaning and disinfection procedures. During these years, the dialyzer also underwent changes, from the parallel-plate to coil, and to the current hollow-fiber dialyzers. Some of freestanding centers still reuse the disposable dialyzers, but in most centers, dialyzers are no longer reused. At least in Japan, reuse has not been practised because of the insurance restrictions. With rigorous enforcement of the preventive measures for nosocomial infection, the incidence of HBsAg among dialysis patients has been remarkably reduced in the States and elsewhere. According to Alter et al  , infection incidence was 3.0% among 33,875 patients in 1976, 1.0% in 1980, and in 1983 it was down to 0.5%. A similar reduction from 2.6% to 0.5% occurred in the staff. The prevalence rate for HBsAg also came down from 7.8% among patients in 1976 to 2.4% in 1983. During these years and while combatting hospital infection of HBV, the exact mode of infection remained obscure. In one hospital outbreak, all patients showed uniformity of antigenic subtypes  , suggesting patient-to- patient transmission. Based on these and other epidemiological data, it was suggested that nosocomial infection was due to both parenteral and nonparenteral exposures.
The environmental surveillance conducted in two centers with a high incidence of hepatitis in the States demonstrated HBsAg in 21% and 11% of swab samples, respectively. HBsAg was also found on the surfaces of gloved hands, needle clippers, furniture and external parts of dialyzers, even without visible traces of blood  . HBV survives drying for at least one week and surface contamination can be the source of infection, unless a disinfectant is used  .
| Routes of transmission of HCV|| |
While the epidemiology of HBV infection at dialysis centers was being investigated, it also became apparent that HBsAg hepatitis was occurring among dialysis patients ,,, . In 1968, Eastwood et al  reported an outbreak of non-A, non-B hepatitis in 14 of 27 patients in whom the illness was mild; no staff members were affected. In retrospect, these were more or less typical cases of acute HCV infection because of the clinically-mild presentation. Between January 1987 and October 1988,45% of 77 dialysis patients developed ALT elevation at one dialysis unit in Texas, and subsequently, it was attributed to HCV infection  . The authors postulated that inadequate infection control measures demonstrated by the lack of glove use and poor hand washing, were the causes of transmission. It is now known that the vast majority of non-A, non- B hepatitis cases in the past were due to HCV infection, as the stored sera tested positive for anti-HCV  . Since new cases of nosocomial infection of HBV became uncommon as a result of implementation of recommended preventive measures at dialysis centers, people were surprised when a high prevalence of anti-HCV among these patients was disclosed. Without seromarkers for the non-A, non-B hepatitis, no isolation of such patients was made, hence no positive preventive measure.
Oguchi et al  compared 607 patients on dialysis and 704 blood donors of comparable ages; anti-HCV was positive in 17.1%, anti-HBs in 18.1% and antiHBc 36.7% in the former, and in the latter, these figures were 0.9%, 8.9% and 16.6%, respectively, the differences being highly significant. In other words, during the long period of dialysis, patients contract HBV as well as HCV infection often in an inapparent way, and acquire antibodies more frequently compared with the control subjects. Although HCV is less contagious than HBV because of its lower blood levels and chemical instability of RNA molecules, there is no reason that the route of infection should differ.
From the early studies with the C100-3 test on antiHCV in dialysis patients, the investigators found that most, but not, all patients had blood transfusion in the past. Medin et al  postulated from the seroconversion that occurred in patients who never had blood transfusion, that HCV was transmitted through the dialysis equipment. Our study at a large dialysis center on 152 patients who had never received blood, showed that 31.6% were anti-HCV positive, and that the positivity was correlated with the duration of dialysis  [Table - 2]. In other words, the longer the patient undergoes dialysis, the greater is the risk of antibody acquisition. It indirectly, but clearly, suggests infection within the dialysis unit. In fact, Sampietro et al  analyzed the genomic sequences of HCV in 28 patients from a dialysis center and environmentally-unrelated patients, and found a very high prevalence of a rare type of HCV among the patients, unequivocally pointing to a nosocomial transmission.
It seems to be established that the main route of HCV infection is through a wound of the skin and mucosa  . This virus is not commonly transmitted sexually  . A number of reports on isolated areas of high anti-HCV prevalence  attributes the infection to unsanitary injection procedures by physicians  , tattooing, and other practices in which bleeding occurs, such as blood suctioning through the skin  . It is generally assumed that acute rise in antiHCV positivity in the population survey above age 50 in Japan  is related to the past mass vaccination program, particularly small pox vaccination, in which the skin was cut with the same poorly-cleaned lancet till blood oozed out. In global areas where unsanitary medical practice is executed, the antiHCV positivity in the general population (blood donors) exceeds 50%  .
In an outbreak of acute hepatitis C at a large dialysis center, several patients who were dialyzed side-by-side came down with acute hepatitis C almost at the same time. It was assumed that the nurse did not change the glove for each patient, because just to withdraw the needle while having the patient press a gauze over the needle hole is so simple and quickly done  . No new acute hepatitis C occurred after re-education of the staff for aseptic procedures, and after changing the gauze pad to a round adhesive with a central cotton pad to be used at the time of needle withdrawal. No blood oozing occurs through the adhesive. Earlier, two to four patients were coming down with acute hepatitis C per month at this center. The entry of the virus was most likely through the two needle holes which were touched at the beginning and the end of hemodialysis at least once, sometimes several times, when needle repositioning was required. In other words, a large skin wound is touched four times a day, three days a week, and nearly 1,000 wound touchings occur per year. It is highly probable that HCV is transmitted through one of these wound touchings because the physician/nurse can not exchange the glove for the same patient when the needle requires repositioning or retouching, for fixation on the skin, although they change the glove at the start of dialysis for each new patient.
| Diagnosis of acute hepatitis C among dialysis patients|| |
Patients with renal failure all have a sense of fatigue some time, and it seems that subjective symptoms of acute hepatitis such as anorexia and prostration are complained less severely, compared to normal individuals contracting acute viral hepatitis. Serum ALT elevations are less remarkable ,, and jaundice usually mild, bilirubin seldom rising above 10 mg/dl  . It is long known that serum aminotransferase levels in patients with chronic renal failure are lower than normal, and it was attributed to vitamin B 6 deficiency ,, . Our study, in which the coenzyme form of vitamin B 6 was quantified by high performance liquid chromatography demonstrated that low amino transferase levels are not due to vitamin B 6 deficiency  . It also showed that the average serum ALT level among dialysis patients was 7 IU/L, and that levels above 20 IU/L were clearly abnormal. Thus, serum ALT elevations are less distinct in dialysis patients, and aminotransferasemia may not be very diagnostic for acute hepatitis C. Therefore, demonstration of seroconversion is necessary. This again poses some problem because seroconversion from negative antiHCV to a positive test is much delayed from the time of clinical presentation, perhaps due to compromised immune responses known in chronic renal failure  . It is more desirable to determine HCV RNA when serum ALT rises in a patient in whom it was normal earlier. All new patients who are started on dialysis must be studied for HBV serology and anti-HCV (2nd or 3rd generation test ). Clearly, in these patients, periodic liver function tests are necessary, and whenever ALT rises above 50 IU/L or so, suspicion of acute hepatitis should be entertained and a closer follow-up of liver function tests and serological examinations are required. Thus, serum ALT which is more specific for the liver than AST, should be measured regularly at short intervals.
| How to prevent HCV infection within the dialysis unit|| |
1. Isolation of patients. This is mandatory for HBsAg positive patients, but for HCV, it depends on the policy of the unit, because of the psychological impact on the patients. In a center where anti-HCV positivity is very high among patients, isolation may not be very practical. As long as all patients are treated as if they were carriers of contagious viruses, it may have the same preventive effect. If the percentage of positive patients is small, they may be separated, but the psychology of the staff is such, that non-separated patients may get to be treated less carefully.
2. Glove wearing. A sterile, preferably a new pair of gloves should be used for each patient at the time of needle insertion for the dialyzer. However, for various reasons, the gloved hand has to touch various objects around the patient- the console, and the needle again; the hand surface can be contaminated and it can transmit the virus. It is very time- consuming and uneconomical to change the glove whenever it touches the needle. Therefore it is much more practical to just dip the fingers in a disinfectant solution nearby. To that end, a basin containing a disinfectant solution should be available within an arm's reach. It will be ideal to have one disinfectant solution per several consoles. HCV is an RNA virus which is labile chemically, and unlike HBV that requires a strong disinfectant such as hypochlorite, any disinfectant will destroy HCV on the glove quickly.
3. Surface cleaning and prevention of surface contamination. The area around the patient's forearm in use should be protected from blood contamination with cloth and/or paper sheets. If blood has spurted beyond the protected area, the blood stain should be immediately treated with the disinfectant solution. After each dialysis session, the surface of the console should be wiped with a disinfectant. The floor should also be cleaned, because it is frequently contaminated by blood.
4. Repeated education of the staff. The staff members tend to feel safe with the glove on, as a protection for themselves. They need to be educated that the surface of the glove is dirty, once it has touched any object. It should be repeatedly emphasized that when touching the needle or needle hole, the fingers must be absolutely sterile either by wearing a virgin glove, or by cleansing fingers with the disinfectant. It is perhaps more effective to use a video tape to educate the staff periodically. There may be new, untrained recruits on the staff, and the staff members tend to become complacent about the strict aseptic precaution, particularly at the time of needle withdrawal.
| Conclusion|| |
HCV infection unrelated to blood transfusion is very common among chronic hemodialysis patients. The major route of virus entry to the patient seems to be the two needle holes in the forearm which are repeatedly touched by the fingers of the physician and nurse. The recommendations are to use a sterile glove and disinfect the fingers before touching the needle and the needle hole.
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School of Medicine, Chiba University Hospital, 1-8-1 Inohana, Chuo- ku, Chiha, 260
Source of Support: None, Conflict of Interest: None
[Table - 1], [Table - 2]