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February 1994, Volume 44, Issue 2

Original Article

Hepatitis-C Virus Antibodies (Anti HCV) in Haemodialyzed vs Non-Dialyzed Patients

Haren Kumar  ( The Kidney Centre, stadium Road, Karachi. )
S. A.J. Naqvi  ( Department of Nephrourology, Jinnah Postgraduate Medical centre, stadium Road, Karachi. )
Aasim Ahmed  ( Department of Medicine, Aga Khan University Hospital, stadium Road, Karachi. )
Saeed Hamid  ( Department of Medicine, Aga Khan University Hospital, Stadium Road, Karachi. )

Abstract

Anti HCV was checked using Enzyme Immuno assay (EIA) (C100-3- Abbott) in 68 patients with chronic renal failure (CRF) who were on maintenance haemodialysis and 48 patients on conservative management. Mean age of the patients was 50 years. The duration of illness ranged from 3 months to 18 years (mean 3 years). All patients were Hepatitis B surface antigen (HBs Ag) negative. In haemodialyzed group 31(46%) and in conservative group only 3(6%) were Anti HCV positive. High Frequency of Anti HCV positivity In haemodialyzed group was related to period on dialysis (1 year) and number of blood transfusions (>4 units). Patients in whom dialyzer was re-used showed 60% positivity as compared to only 17% in those with single use. Anti HCV positivity predominated in females as compared to males, 42.6% vs 20.3%. Nine out of 10 patients with a history of jaundice and six out of 8 patients with raised transaminase levels were Anti HCV positive. Fifteen of 37 Anti HBc (igG) positive cases were Anti HCV +ve (JPMA 44 : 28, 1994).

Introduction

Parenterally transmitted hepatitis virus infection has always been a major health problem in patients with chronic renal failure especially in those on haemodialysis. Epidemics of hepatitis B (HBV) was a major cause of morbidity and mortality in these patients1. Lately the incidence of HBV infections in dialysis patients has been controlled to a great extent following universal precautions2. Inspite of this sporadic outbreaks of post transfusion hepatitis continued to occur and with con­tinuous search parenterally transmitted Hepatitis C virus (HCV) was identified3,4. It appears to be the major cause of hepatitis in haemodialysis units because of repeated transfusions, use of common equipments and the im­muno compromised status of these patients5,6. Majority of the HCV positive cases are asymptomatic showing moderate rise in transaminases with characteristic, fluc­tuations throughout the course of the disease and a higher rate of progression to chronicity7-9. The HCV antibody assay based on recombinant viral antigen (C100- 3) is now available for detection of HCV. This study reports the frequency of Anti HCV in chronic renal failure managed conservatively and by haemodialysis.

Patients and Methods

One hundred and sixteen, Hepatitis B surface antigen negative chronic renal failure patients seen between 1st March to 30th September, 1992 were studied. Patients were divided - into two groups, 68 patients on maintenance haemodialysis (selected from The Kidney Centre) and 48 non-dialyzed patients on conservative management (from Jinnah Postgraduate Medical Centre and Aga Khan University Hospital). All patients were dialyzed on SPS 450 and SPS 550 Baxter haemodialysis machines using only hollow fibre dialyzer. Twenty three patients were on single use of dialyzer and 45 were on 4 times re-use. Patients were selected on the basis of history, clinical examination and specific renal investigations. Other tests included standard LET’s, hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody and hepatitis C virus antibody using Auszyme monoclonal 3rd generation EIA, Ausab EJA and Corzyme EJA (Abbott) and 2nd generation EIA (C100-3 Abbott). The dialyzer for re-use was prepared manually after flushing with 4 litres of water and sterilization with 3% formaldehyde at the end of dialysis and cleaned with 4 litres of 0.9% normal saline before the start of each dialysis. Only purffied and treated water obtained from Reserve Osmosis water treatment plant was used for the preparation of acetate dialy sate in the ratio of 1:34. The statistical analysis were carried out with students ‘t’ test.

Results

Of 116 hepatitis B surface antigen negative patients with chronic renal failure, 68 were on maintenance haemodialysis and 48 on conservative management. There were 69 males and 47 females whose ages ranged between 18-77 years (mean 50 years). Chronic glomerulonephritis was the commonest etiology, 39 (33.5%) followed by diabetes mellitus 31 (26.7%), hyper­tension 12(10.3%), calculus disease 10(8.6%), polycystic kidneys 8 (6.8%) and others 16(13.7%). Of 68 patients in haemodialysis group, 31 (46%) and in non- dialyzed group of 48, only 3 (6%) were anti HCV positive (P= <0.001). Anti HCV positivity predominated in females 20 (42.6%) as compared to males 14 (20.3%) (P= <0.005). In haemodialyzed group the frequency of blood transfusion, duration on dialysis and the type of dialyzer used showed strong association to Anti HCV positivity (Table I).


Table II shows an overall association of Anti HO! to the history of jaundice, transaminases and Anti HBc IgG. Of 3 Anti HCV positive patients in the conservative group, all were females. One had biopsy proven cirrhosis and two received multiple blood transfusions. There were three patients, two in haemodialysis and one in conservative group who were never transfused and yet were Anti HO! positive.

Discussion

Hepatitis C infections have assumed an alarming  proportion in haemodialysis units10, especially after the adequate control of hepatitis B. HCV is now the leading cause of post-transfusion hepatitis worldwide11. The present study shows a HCV positivity of 46% in haemodialysis population. Similar results were reported from Singapore (45%)12 Taiwan (50.2%)13, Indonesia (46.8%)14 and Brazil (50%)7. These figures are significantly higher when compared with those from Europe (Germany 10.1%15, Italy 17.3%16, Hungary 20%17) and USA 12%6 to 15.7%18. Majority of patients in this study had ESRD secon­dary to chronic glomerulonephritis of unknown etiology. It is possible that hepatitis C might be playing an etiological role in the development of immune complex nephritis leading to renal failure19,20. High Anti HO! positivity in female patients in the present study is different from studies conducted abroad5,8,21. The pos­sible explanation might be a higher pregnancy rate with poor obstetric and gynaecological care requiring fre­quent blood transfusion at the time of delivery. A definite correlation of Anti HO! positivity was found between the frequency of blood transfusion and the duration on dialysis. Similar results are reported in other studies2,5,7. Similarly the percentage of Anti HCV positivity increases as the duration on dialysis increases reaching to almost 100% in those who are on dialysis for more than 3 years. Our figures are higher than those reported from Germany (14%)15, Japan (14%)22 and Italy (26%)23. Various factors implicated for this high frequency are the cross infection through the use of common equipment, extracorporeal hemocirculation, immune compromised state contact with an infected person and contamination of environmental surfaces gloves, clamps and dress­ing5,22,24. Three patients (two in haemo dialysis and one in conservative group) who had never received trans­fusion and yet were Anti HCV positive. suggest com­munity transmission of HCV5,25,26. For the first time we have found a strong correlation between the reuse of dialyzer and Anti HCV positivity. Though the mean pore size of the dialyzer membrane is much smaller than that of viral particle (and is considered a safe barrier against the passage of virus) but it is possible that during the procedure of reuse and cleaning especial­ly when performed manually micro fractures occur lead­ing to contamination of machine27,28. It was seen that most of the patients (although the number is small) with a history of jaundice or raised transaminase levels were Anti HCV positive but at the same time, a significant number of patients had no history of jaundice or raised transaminases and yet they were Anti HCV positive. This points towards the milder course of the disease with characteristic waxing and waning of transaminase levels5,7,18,29. Anti HBc IgG has long been considered as a surrogate marker for HCv30,31. In this study 24% patients were Anti HCV positive without and 40.5% with evidence of past HBV infection. Anti HBc IgG as a surrogate marker for HO! is less convincing in our study when compared to others6,18. There is a need to conduct further studies in high risk group26 and blood donors32,33 so that true incidence is established. We recommend routine estimation of showing persistently raised levels and are anti HCV positive to be dialyzed separately. Confirmatory assay like recombinant Immunoblot assay (RIBA) and Polymerase chain reactions (PCR) should be made available34,35. Instead of discontinuing reuse of dialyzer which has its own benefits like cost effectiveness and better biocom­patibility36, we recommend adaptation of strict disinfec­tion protocols and universal precautions in every dialysis unit27,28. Automation in dialyzer reprocessing can go a long way in limiting the spread of hepatitis C viral infection.

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