Study of incidence of hepatitis C virus infection in hemodialysis patients

The present study was undertaken to determine the prevalence of hepatitis C virus (HCV) infection by antibody testing in hemodialysis (HD) patients. A total of 102 chronic renal failure patients on HD was studied. All the patients were tested for antiHCV. The overall prevalence of HCV infection was 23.5%. The longer a patient is on HD, the more susceptible he/she is to HCV acquisition. It is recommended that HD patients should be monitored in order to determine the full risk factors for HCV contamination observed in this study.

Keywords: Chronic renal failure, hemodialysis, hepatitis C virus Key messages: Strict adherence to universal precautions without isolating HCV-infected dialysis patients seems to be enough to control disease spread in HD units.

Hepatitis C virus (HCV) infection in patients undergoing hemodialysis (HD) is an emerging condition and constitutes a major problem complicating the dialysis process in dialysis units worldwide. The prevalence of HCV among the HD patients varies in different countries worldwide from 1% to 85%. ^[1] The prevalence of HCV is particularly high in developing countries like India and is a major cause of increased morbidity and mortality in patients with terminal stage of renal disease. Cirrhosis, higher rate of graft loss, glomerulonephritis, and hepatocellular carcinoma are some of the far-reaching effects of HCV positivity in HD patients. The mode of transmission of this virus is still not conclusively defined. Factors such as blood transfusion and frequent parenteral interventions have been shown to be associated with increased risk for this HCV infection. ^[2] The duration of HD treatment and the possibility of nosocomial HCV transmission have also been suggested as additional contributing factors for this emerging HCV infection in India.

It is with this background that this scientific work was taken up in order to know the incidence of HCV infection with a view to control the HCV infection among HD undergoing patients to reduce morbidity and mortality due to HCV infection.

Study design and patients

The study was performed in the Department of Microbiology in collaboration with Department of Nephrology of Alluri Sitaramaraju Academy of Medical Sciences (ASRAM) Hospital, Eluru. The study protocol was approved by the Ethics Committee of ASRAM. A total of 102 chronic renal failure patients on HD was studied. Patients who tested HCV positive at the starting of HD were excluded from the study.

Serum collection and serology

With the informed consent, blood samples were collected of a total 102 HD undergoing patients who constituted the test group. By following all the standard necessary precautions, 5 ml of whole blood was drawn from each of the suspected HCV patients undergoing HD under strict aseptic conditions. All the blood samples were transported to the Department of Microbiology, and all the samples were allowed to clot. The clear serum was transferred into sterile test tubes. It was then centrifuged, and the clear supernatant was transferred into Lax Brow vials for preservation at 4°C in the refrigerator. All 102 blood samples sera were tested periodically for the incidence of HCV infection by determining the presence of antiHCV antibodies using a third generation ERBA ELISA Hepatitis C test kit manufactured by Transasia Bio-Medicals Ltd., S.A. in Germany.

Hemodialys unit

The HD unit has one routine HD area and two isolated areas, one for HBsAg positive patients and other for antiHCV positive patients. The routine HD area has seven HD machines, HBsAg-positive area has one machine, and antiHCV positive area has one machine. All the patients who were proved negative for antiHCV before initiating dialysis were dialyzed in routine HD unit. Patients who were positive for antiHCV before initiating the dialysis were dialyzed on concerned machines in the respective isolated areas of HD unit. All the 102 patients received regular dialysis of 2-3 sessions/week.

Maximum number of cases in this study were in the age group between 41 and 60 years (49.1%) and least number of cases were in the age group up to 20 years (2.9%) [Table 1] with a male preponderance [Table 2]. Hypertensive nephropathy with chronic renal failure constituted the commonest disease group with the incidence of 73.5% [Table 3]. About 24 patients out of 102 screened tested positive for antiHCV antibodies, an incidence of 23.5% [Table 4]. Majority of the seropositive cases belonged to the 41-60 age group [Table 5].

Alanine aminotransferase (ALT) level of 1.5 times the normal level (40 U/l) was considered as abnormal. Levels were raised in 10 out of the 24 seropositive patients (41.6%). Levels were normal in the rest of the 14 seropositive patients. None of the patients in seronegative group had abnormal ALT levels [Table 6].

The mean value of ALT in the seropositive group was 75.0 ± 77.0 U/l. The mean value of ALT in seronegative group was 23.9 ± 12.0 U/l. This difference between the two groups was found to be statistically significant (P = 0.004, <0.01, Student’s t-test) [Table 7].

The mean number of sessions in the seropositive group was 85.4 ± 23.7 and in seronegative group was 60.1 ± 14.2 [Table 7]. There was significant difference in the number of sessions between seropositive and seronegative patients (P = 0.0001, <0.01, Student’s t-test) [Table 7].

The mean average values of ALT levels and HD sessions were significantly high in HCV-positive patients (P < 0.01) [Table 7].

Hemodialysis patients are at high risk for the development of hepatitis C infection. However, the data of prevalence of HCV infection among Indian HD patients are inadequate. Salunkhe et al.^[3] reported 45%, Chadha et al.^[4] reported 12.1%, Sumathi et al. ^[5] reported 37.5%, Agarwal et al. ^[6] reported 42% and Jaiswal et al. ^[7] in a study from 1992 to 2000 reported prevalence of 30%. The prevalence of HCV infection among the HD patients at our institute is 23.5%.

Nosocomial transmission, prolonged vascular access, potential for exposure to infected patients and contaminated equipment and sharing of multi-dose heparin vials are some factors responsible for the high risk in HD patients.

Historically, the number of blood transfusions received were consistently reported in the literature to be associated with an increased prevalence of HCV positive dialysis patients. ^[8] However, several recent studies could not recognize blood transfusions as an independent risk factor in HCV spread among HD subjects. ^[9]

The prevalence of antiHCV was 13.3% in patients who had HD for <1 year in comparison to 69.9% in patients who had HD for >10 years ^[10] indicating that the duration of HD is related to the risk of developing HCV infection.

Hepatitis C virus does not penetrate the membrane pores of dialyzer; the size of the virus is 10 times more than the dialysis membrane pores. ^[11] Hence, although the potential sources of nosocomial transmission could be dialyzer reuse, internal contamination of HD monitors, environmental aerosols, droplets contaminated with the virus and contaminated hands and articles, the two former mechanisms are almost unlikely. ^[12]

The performance parameters of the testing method used have a direct impact on the detection of hepatitis C and thus can lead to differences in the prevalence data. In the early 1990s, the first generation HCV antibody testing kits were introduced using NS4 antigen. These tests were further improvised with the addition of NS3 and the core regions of the viral genome. This second generation ELISA assay had a higher sensitivity and specificity over the earlier one. ^[13],[14] At present, the third generation ELISA assays use highly purified antigens with addition of NS5 region of HCV genome and have the highest sensitivity and specificity. ^[15] The kit used by us has a combination of recombinant and synthetic peptides as antigens with 100% sensitivity and 67% specificity.

With the advent of molecular techniques, the circulating virus can now be detected by HCV RNA measurement using polymerase chain reaction (PCR) test. ^[16] This testing is used for early detection (before seroconversion) and is also essential for confirmation of active HCV infection and monitoring of antiviral therapy. However, the limitation of this test is the cost effectiveness and nonavailability in most of the laboratories.

In our study, only antiHCV was taken as criteria to diagnose HCV infection. PCR test is required if the patients are planned to be put on antiviral therapy. This was definitely not the aim of the present study. Thus, although the limitation exists for the use of single antiHCV test, considering all factors, it is still a test of choice for HCV screening as recommended by Centers for Disease Control (CDC). The current CDC recommendations for HCV screening in HD patients include testing for antiHCV and serum ALT on admission, ALT every month, and antiHCV semiannually.

Lack of strict adherence to universal precautions by staff and sharing of articles like multi-dose drugs might be the main mode of nosocomial HCV spread among HD patients. ^[17] since use of separate dialysis machines for HCV-positive patients was the norm at our center, the prevalence rate which we had indicates the importance of the role of nosocomial transmission through cross-contamination via gloves, personnel or heparin vials.

Although some studies found that nosocomial spread of HCV declined when HCV-infected patients were treated in dedicated HD units, other investigators could control nosocomial spread by strict application of hygienic precautions without isolation of HCV-infected subjects or machine segregation. ^[18]

Centers for Disease Control recommend that special precautions should be observed in dialysis units. These include wearing and changing of gloves and water-proof gowns between patients, systematic decontamination of the equipment circuit and surfaces after each patient treatment, and no sharing of instruments (e.g., tourniquets) or medications (e.g., multi-dose vials of heparin) among patients. ^[19]

To promote more efficient biosafety controls, quality programs must be implemented in dialysis centers addressing methodology training of technical teams and constant monitoring by epidemiological authorities.

It is recommended that HD patients should be monitored in order to determine the full risk factors for HCV contamination observed in this study.

Hepatitis C virus infection is more prevalent among HD patients in the developing countries. HCV infection prominently increases the burden of disease in the HD population. The longer a patient is on HD, the more susceptible he/she is to HCV acquisition. HD patients should be routinely screened for HCV infection, preferably using serological methods. Strict adherence to universal precautions along with isolating HCV-infected dialysis patients might help to control disease spread in HD units.

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.149499

[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]