| Abstract|| |
Hepatitis C virus (HCV) infection is a major health problem in hemodialysis patients. Identified risk factors include duration on dialysis and blood transfusion. A more important risk factor contributing to the high prevalence of anti-HCV, particularly in the developing countries, could be the non-adherence to the known universal infection control precautions. The factors that might help reduce and/or prevent the spread of HCV infection among patients on dialysis include: early screening of patients for anti-HCV, reduction of the number of blood transfusions given, strict application of universal infection control precautions and isolation of patients or machines which ever feasible. The issue regarding isolation of antiHCV positive patients is controversial and although it is not recommended by the Centers for Disease Control to isolate these patients, it may be advisable to do so, particularly in the developing countries, wherein a high prevalence of anti-HCV exists among the dialysis population.
Keywords: Hepatitis C virus, Hemodialysis, Blood transfusion, Peritoneal dialysis.
|How to cite this article:|
Huraib SO. Hepatitis C in Dialysis Patients. Saudi J Kidney Dis Transpl 2003;14:442-50
| Introduction|| |
Viral hepatitis remains a major hazard for patients on maintenance hemodialysis (HD) as well as for dialysis staff. The decline in the incidence of hepatitis B virus (HBV) infection and with the application of universal infection long control precautions, isolation and vaccination  has led to non A, non B hepatitis (NANBH) to be the major cause of hepatitis among patients on HD.
Although there is good evidence that NANBH is not a new disease, it was described for the first time by Prince, et al, only in 1974 . They retrospectively reported a group of patients who did not have serologic evidence of hepatitis B and had an incubation period that was too long for hepatitis A. Feinstone, et al, in 1975 reported 22 patients with transfusion associated hepatitis not due to viral types A or B . Since then, the term NANBH has been used and almost 15 years later the hepatitis C virus (HCV) was identified as the leading cause of NANBH by Choo and coworkers at Chiron Laboratories . Since then, this virus has evoked great interest and a plethora of reports have appeared in the literature.
Numerous reports are available regarding correlation between serum alanine aminotransferase (ALT) levels and anti-HCV positivity. Few earlier studies showed a good correlation between ALT elevation and anti-HCV positivity ,. However, more recent reports did not find any such correlation and elevated ALT levels were found in only 24-67% of dialysis patients with positive anti-HCV ,,,,,. When HCV RNA positive HD patients were studied, elevated ALT was found in only 31% of these patients and in only 30% of those who had biopsy proven hepatitis . Postulated reasons for this poor correlation are:
a) baseline ALT levels are depressed in patients on dialysis ,
b) some of anti-HCV positive patients may have cleared the infection and seropositivity may be the remnant evidence of past infection ,
c) anti-HCV positivity may be a reflection of viral replication occurring at extrahepatic sites , and/or d) infection caused by non-virulent HCV strains .
Also, serum ALT levels are poor predictors of liver disease ,,. However, it has been shown that the greater the elevation in liver enzymes the higher is the probability of histological evidence of liver disease (16). Nevertheless, elevated ALT could be due to causes other than HCV. Therefore, liver biopsy remains the only reliable method of confirming the presence of liver disease in HD patients.
| Epidemiology of HCV in dialysis patients|| |
Patients on long-term HD are considered to be a population-at-risk for developing HCV infection. The prevalence of anti-HCV among patients on HD is constantly higher than that seen in healthy population. Also, the prevalence varies from country to country and from one center to the other. In general, it is higher in the developing countries than in the developed countries.
Prevalence of anti-HCV in Saudi Arabia
The prevalence of anti-HCV in Saudi Arabia was reported for the first time by Saeed, et al in 1990, to be 34.8% . One year later, our group from the King Khalid University Hospital, Riyadh, reported a prevalence of 41.9% . Three more reports have appeared subsequently in the literature reporting prevalence rates between 30.7-53.7% ,,. However, all these studies had used first generation ELISA test and all were from the Riyadh area [Table - 1]. A national multi-center study  involving 1,147 patients from 22 HD centers was started in 1992 by the National Kidney Foundation (now renamed Saudi Center for Organ Transplantation) in collaboration with the King Khalid University Hospital. Anti-HCV was assessed using second generation ELISA (Abbott Laboratories). All anti-HCV positive samples were re-tested by the Abbott HCV ELISA supplement assay. An overall prevalence rate of 68% was found with a range of as low as 14.5% and as high as 94.7% [Figure - 1], which is the highest value reported among dialysis patients from any part of the world. Recently, three reports have appeared from the western province of Saudi Arabia and Madinah area reporting prevalence rates varying between 52-72.3% ,,.
Prevalence of anti-HCV in other Middle Eastern Countries
Varying prevalence rates have been reported from different Middle Eastern countries ,,,, and the figures have varied from as low as 26.5% from Oman  to as high as 80% from Egypt .
Prevalence of anti-HCV in other countries
Varying prevalence rates have been reported from other parts of the world as well. The reported rates are 1-29% in Western Europe, ,,,,, 8-36% in North America ,, 5.9% in Australia , 39% in South America  and 44-60% in the Far-Eastern countries ,. [Table - 2] summarizes some of the reports from different parts of the world.
Epidemiology of hepatitis C genotype
Recently several new types and subtypes of HCV have been discovered . While at the beginning of 1992 only types la, lb, 2a and 2b had been recognized, at least 12 genotypes have been discovered todate . In Saudi Arabia, the commonest genotype found was type IV . This is similar to that reported from Egypt  but different from that seen in Belgium, Scotland, Finland, The Netherlands and Australia  where types 1, 2, and 3 are the predominant genotypes. In Hungary, the predominant type is type 1 and in Japan it is types 1 and 2 .
| Risk factors for hepatitis C in dialysis patients|| |
Blood transfusion is an important factor in the transmission of HCV infection and we have demonstrated a positive correlation, between the two which increases with the increase in the number of units transfused  [Figure - 2]. Similar results have been reported by many other investigators ,,,,,,,,. In addition, the introduction of screening of blood products for anti-HCV has led to a decline in the incidence of post-transfusion hepatitis . Nevertheless, our study showed that 65 of the 97 patients on HD (67%) who had not received previous blood transfusions had positive anti-HCV, a finding which indicates that factors other than blood transfusion were contributing to the transmission of HCV infection. Few other investigators also found no correlation between blood transfusion and positive anti HCV and have suggested that the association between dialysis-associated-hepatitis and transfusion is not causal, but is rather related to the duration on dialysis ,,.
Duration on hemodialysis
The importance of duration on HD as an independent risk factor for hepatitis C have been shown by many investigators ,,,,,,,,,,,. The risk of anti-HCV positivity increases as the duration on HD increases with an estimated 10% increment risk per year on dialysis .
Mode of dialysis
a) Hemodialysis versus continuous ambulatory peritoneal dialysis (CAPD):
The prevalence of anti-HCV in CAPD patients is 0-5% ,,. A higher prevalence of 20.6% has been found in Saudi Arabia . Nevertheless, it is still much lower than the reported prevalence among HD patients from the same center . Also, the prevalence rates will become much lower (from 15.4% to 5.9%) when patients with prior HD are excluded which indicates that the majority of anti-HCV positive CAPD patients might have acquired the infection while on HD .
b) Home-dialysis versus in-center dialysis:
The prevalence of anti-HCV in home-HD patients is much lower than patients on incenter HD . This may be because homeHD offers an isolated environment thus preventing patient to patient transmission.
Anti-HCV is more prevalent among certain nationalities e.g., Egyptians, Pakistanis and Yemenis. This is true for both dialysis patients and general population ,,.
A higher prevalence of positive anti-HCV was found in males both by Dentico, et al  as well as our group . Possible reason for this, at least in Saudi Arabia, is that many of the labor force in this country are males and belong to nationalities which have a very high prevalence of HCV.
Non-adherence to universal infection control precautions
This is the most important independent risk factor contributing to the high prevalence of HCV in our country. When comparison was made between centers with anti-HCV prevalence of more than 80% and those with prevalence of less than 50%, non-adherence to universal infection control precautions stood as a major contributing factor .
The importance of this has been emphasized in the CDC recommendations ,. The significance of implementing the universal infection control precautions is further evident in the major reduction that has occurred in the incidence and prevalence of HBV infection among in-center HD patients in USA between 1976 and 1982 . Recently Garcia-Valdescasas, et al,  reported a decline in the prevalence of HCV infection after implementing the universal precautions. Gilli, et al,  reported an outbreak of hepatitis C in a dialysis unit due to sharing of a multi-dose heparin vial by the patients on the same shift. Another outbreak of HD associated NANBH was reported, caused by multiple breaks in infection control procedures in the dialysis unit which was eradicated after the implementation of vigorous infection control measures . Similarly, Okuda, et al reported a high (around 5%) yearly incidence of NANBH in their HD patients from 1987 until 1993. Upon inquiry, the authors became aware that the nurses did not change gloves between handling different patients at the completion of a HD session. Stringent use of gloves was enforced and no new cases were observed subsequently . In many of our HD centers studied, having prevalence rates > 80%, it was found that the nurses either do not wear gloves at the time of commencement of a HD session or, they do not change gloves in between handling patients .
Several other reports also have demonstrated the possible role of nosocomial transmission of the HCV ,. Thus, the importance of adherence to universal infection control precautions cannot be emphasized more strongly. Also, the correlation between the presence of infected patients on HD to newly seroconverted patients in the same unit have been shown by many investigators ,,. Sharing of dialysis machines has been shown by some workers to play a role in the transmission of HCV infection ,,. Garcia-Valdescasas, et al found that using separate machines for anti-HCV positive patients in addition to strict application of infection control precautions led to a decline in the incidence of serocon-version in their unit . At the King Fahad Specialist Hospital, Al Qassim area, Saudi Arabia, a lower prevalence was found in comparison to other centers from the same area (Alras and Buraydah General Hospital) because they use separate machines for anti-HCV positive patients in addition to stringent application of infection control precautions . Recently, Abu-Aisha, et al  found that chemical disinfection does not seem to be adequate to guard against HCV infection in HD patients and they recommend assigning specific HD machines for positive patients. Thus, if cross-infection is an important factor in the transmission of HCV, one should ask if patients with HCV should be isolated or not.
Studies in support of isolation
a) Calabrese, et al , have reported that in the year following the introduction of dedicated area and machines for HCV positive patients on HD, no patients were infected, as against a 20% infection rate in the preceding year.
b) Daporto, et al , have found that antiHCV positivity appeared in a group of patients who had never been transfused before, but who had all been dialyzed in the same ward and during the same session. c) Teruel, et al , studied their in-center HD patients and 29 home-HD patients over a two year period. They reported an incidence of nosocomial infection of 2.7 cases/100 patients/year among in-center HD patients, while none of their homeHD patients seroconverted.
d) Vagelli, et al , found no new cases of HCV in the 18 month period after isolation while they used to have an annual incidence around 20-25% preceding this.
e) Jadoul, et al , in a multi-center trial in Belgium, found that 39% of the HD patients that anti-HCV seroconverted had never been transfused and had no other obvious risk factors. They also found that clustering of seroconversion occurred only in dialysis units in which anti-HCV positive patients were being treated. In addition, a higher risk of seroconversion was found in patients dialyzed at stations adjacent to anti-HCV positive patients.
f) In the multi-center study conducted in Saudi Arabia , it was found that a lower prevalence was present at the King Khalid Hospital, Tabuk, where they isolated their antiHCV positive patients. Similarly, in a followup study  the overall seroconversion rate was found to be 7-9% and it was low in those centers where isolation of machines or patients is in practice.
g) The success of isolation of HBV positive patients on HD, in addition to other measures, could also be taken as a promising example .
| Problems with isolation|| |
a) There is considerable difficulty in the recognition and isolation of HCV infected patients in the early phase of the disease ,. This is because the currently available screening test (ELISA II) only detects the antiHCV antibodies, the appearance of which may be delayed for up to one year after infection, especially in immunodeficient HD patients . This will reduce the effectiveness of isolation in preventing crossinfection .In addition, up to 10% of HCV infected HD patients never develop antibodies detectable by ELISA II . Although, third generation test is more sensitive, it still has false negative results. Polymerase chain reaction (PCR) which, although is the most definitive test today, remains impractical for routine use .
b) There are many genotypes of HCV  and the lack of cross- immunity between the different strains limits the usefulness of isolation. In addition, grouping of anti-HCV positive patients together increases their exposure to various HCV strains and in turn, might increase the risk of multiple infections.
c) Unlike HBV, HCV is present in low concentrations in the serum and is probably destroyed within a few hours when the serum is stored at room temperature . The risk of nosocomial transmission of HCV is thus expected to be lower than that of HBV. This is supported by the demonstration that the risk after accidental puncture with an infective needle is only 5 to 10% for transmission of HCV versus > 30% for HBV .
d) Isolation of anti-HCV positive patients is cumbersome and unlike HBV, it requires four places for proper isolation, one each for: HBV and HCV positive, HBV positive .and HCV negative, HBV negative and HCV positive and HBV and HCV negative patients. As a result of these problems and as an alternative to isolation, majority of HD units strictly adhere to 'the universal infection control precautions. These precautions include cleaning and disinfecting instruments, machines and environmental surfaces that are routinely touched, avoiding sharing articles between patients, frequent hand washing and the systematic use of gloves . However, the high prevalence of anti-HCV among HD patients in the developing countries calls for drastic measures to reduce this high prevalence. Therefore, it is advisable and more practical to isolate HD patients who are antiHCV negative in those units with a high prevalence of anti-HCV. Although the CDC recommends only strict adherance to the universal infection control precautions and does not recommend isolation, this may not be applicable in the developing countries wherein adherance to infection control precautions may not be feasible, as in the Western world, because of limited resources.
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Sameer O Huraib
King Khalid University Hospital, P.O. Box 2925, Riyadh 11461
[Figure - 1], [Figure - 2]
[Table - 1], [Table - 2]