Clinical Study Am J Nephrol 1992;12:288-291

Ahmed Mitwallia Suleiman Al-Mohaya* Jamal Al Wakeel3 Hazem El Gama!a Vincent Rotimic Abdulkarim Al-Zebend Abdulkarim Al-Askab

Hepatitis C in Chronic Renal Failure Patients

Division of Nephrology, Department of Medicine, Division of Clinical Microbiology and Laboratory. Security Forces Hospital, Riyadh, Kingdom of Saudi Arabia

Abstract The occurrence of hepatitis C virus (HCV) infection amongst chronic renal failure (CRF) patients in our Nephrology Unit was investigated over a period of 1 year. A total of 71 patients was studied comprising 26 chronic haemodialysis (CHD) patients, 6 acute haemodialysis patients. 4 peritoneal dialysis patients and 35 CRF patients not on dialysis. Patients were screened before and after haemodialysis, and their baseline and postdialysis values of liver enzymes were determined. Eleven (15.5%) of the total 71 patients were HCV antibody posi­ tive. Analysis of the individual patient groups showed that 8 (30.7%) of the 26 CHD patients were positive for HCV. Our data showed a statistically signifi­ cant relationship between seroconversion and duration of dialysis (p < 0.05). A high statistically significant (p < 0.0001) correlation was observed between the HCV antibodies and CRF. The relative risk of hepatitis C was about 22 times greater for those with CRF compared with the normal controls, which makes CRF an important risk factor. A high proportion of the HCV seroconverters had elevated liver enzyme (serum glutamic pyruvic transaminase). The data presented show a positive correlation between HCV seroconversion, CRF. duration on dialysis and elevated serum liver enzymes.

Introduction Non-A, non-B (NANB) hepatitis, whose antigenic de­ terminant is designated hepatitis C virus (HCV), remains the most common serious consequence of blood transfu­ sion. There is evidence which shows that chronic infec­ tion by NANB hepatitis virus is a frequent cause of chronic liver disease [1]. Studies conducted before 1980 indicated that the risk of posttransfusion hepatitis due to NANB infection was 7-12% [2], Thereafter, published data gave figures as high as 70% of posttransfusion hepa­ titis due to HCV infection [3]. Other reports have simi­ larly stressed the significance of HCV antibody in post­ transfusion hepatitis C [4, 5]. Reports of HCV (formerly called NANB) hepatitis in dialysis units are few, probably because in units with widespread hepatitis B virus (HBV) infection, NANB

Received: September 6. 1991 Accepted: June 3,1992

hepatitis may pass unnoticed. In HBV-free units, on the other hand, clusters of patients with abnormal serum glu­ tamic pyruvate transaminase (SGPT) levels have been reported [6-8], These reports pointed to a frequent ten­ dency to progression towards chronic hepatitis, as in other transfused patients [9-11], Since 1980, the Euro­ pean Dialysis and Transplant Association (EDTA) re­ ports have analytically distinguished among the renal incidence of HBV, hepatitis A virus and HCV hepatitis in European dialysis units [12,13]. In the year 1980, the pro­ portion of HCV hepatitis was 17% of proven 2,235 cases of hepatitis patients and 9% among the staff [ 14], During the subsequent 5 years, the progressive decrease in HBV infection in dialysis units, due to extensive vaccination programmes in several European countries [14], has been offset by a growing number of cases of HCV hepatitis, with a mean incidence of more than 700 new cases per

Dr. Ahmed Mitwalli Security Forces Hospital PO Box 3643 Riyadh 11481 (Kingdom of Saudi Arabia)

© 1992 S. Karger AG. Basel 0250-8095/92/0125-0288 $2.75/0

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Key Words Dialysis Hepatitis C acquisition Renal failure

year [ 14], Recently, a portion of the genome of an NANB hepatitis virus, designated as HCV, was cloned, and a spe­ cific immunoassay for anti-HCV antibodies was devel­ oped [15]. This study was undertaken to investigate the occur­ rence of HCV infection among renal patients in the Secu­ rity Forces Hospital.

Material and Methods

Table 1. Occurrence rate of hepatitis C in the different studygroups Patient group

CRF not requiring dialysis Chronic HD Acute HD Peritoneal dialysis Blood donors

Total patients 35 26 6 4 730

HCV-positive patients n


3 8 0 0 6

8.5 30.7 0 0 0.8


Screening for H C V Antibody

Scrum specimens were tested either immediately or were refriger­ ated at 4 °C for a maximum of 5 days until tested. Antibodies to HCV were detected using the Abbott HCV enzyme immunoassay microtitre kits, which detect antibodies to a recombi­ nant protein antigen expressed by the C 100-3 clone region of the HCV genome (Abbott Laboratories, Chicago, III., USA).

Liver Enzym e Estimation

The liver enzyme levels of each patient were recorded on a monthly basis. The relationship between elevated SGPT and the presence of HCV antibody were meticulously noted. These liver enzymes were estimated in our routine Biochemistry Laboratory using the automated Boehringcr Hitashi 711 (Bochringer Mannheim GmbH. Mannheim, FRG). The association between CRF, duration on dialysis, number of blood transfusions and acquisition of hepatitis C was investigated by the x2 test and Fisher’s exact test with the significance level set at 5 %.

Results Out of the 71 patients studied, 11 (15.5%) were HCV antibody positive of the 26 patients who were on CHD. for periods ranging from 1 month to 8 years with a mean stay on HD of 48.5 months; 8 were HCV antibody posi­ tive, and none was HBsAg positive. Sixteen of the 26 patients on CHD had received blood transfusion for severe anaemia before starting dialysis in our unit. Seven of the 8 HCV-antibody-positive CHD patients had received transfusion. The remaining patient had no blood transfusion. Four of the 8 patients were HCV antibody positive on first screening at the start of dialysis. The fifth seroconverted to be HCV antibody positive 1 month after starting dialysis; this patient was inadvertently placed on the HD machine used for HCVantibody-positive patients before knowing the former re­ sult. The last 3 patients of this group seroconverted to be HCV antibody positive in 6,8 and 8 months, respectively, after starting HD. These 3 patients were sharing a ma­ chine with a female patient who continued to be seronega­ tive for HCV antibody on follow-up (even after 2 months following seroconversion of the other 3 patients) but had high liver enzymes from the moment she was started on


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Seventy-one patients were screened for HCV over a period of 1 year comprising the following: 26 receiving chronic haemodialysis (CHD). 6 receiving acute haemodialysis (HD). 4 receiving peritoneal dialysis plus 35 predialysis patients with chronic renal failure (CRF) being supervised by the Nephrology clinic. Thirty females and 41 males with ages ranging between 13 and 19 years, with a mean age of 51.5 years were included. The underlying causes of renal failure in these patients were unknown in 24 patients: diabetes mellitus in 16 patients, glomerulonephritis in 13 patients, hypertension in 4 pa­ tients, chronic pyelonephritis in 6 patients, polycystic kidney in 2 patients, obstruction uropathy in 2 patients, analgesic nephropathy in 2 patients, and 1 patient each had chronic rejection and acute tubular necrosis. For the glomerulonephritis patients, focal glomeru­ losclerosis was seen in 6 patients, a further group of 6 patients was divided equally between membranoproliferative glomerulonephritis, IgA nephropathy and mesangioproliferative glomerulonephritis, and 1 patient had membranous glomerulonephritis. The following information was recorded for each patient: age, sex, duration of treatment, number of blood transfusions, underlying aetiology of renal failure and identification number of dialysis machine used for treatment. In addition 730 healthy volunteer blood donors were used as controls (table 1). Sixteen of the 26 CHD patients had received blood transfusion to correct severe anaemia (haemglobin range of 4-7 g/1; 3 of the 16 patients had blood transfusions at least 16-24 months prior to the seroconversion). The Dialysis Unit operates a policy of screening all patients for HCV antibody and HBV full profile, prior to commenc­ ing dialysis. All patients arc commenced on haemofiltration until their serol­ ogy is established. Two isolation machines, one each for hepatitis B surface antigen (HBsAg)-positive patients and HCV-antibody-positive patients are available. The patients therefore receive permanent HD on a machine appropriate to their status. Every CHD patient followed in our unit received repeat tests every 2 months for the HCV antibody. Those at higher risk (elevated serum transaminases, or those who had the occasional dialysis out­ side our unit during the study period) had their HCV serology tested monthly.

Duration of dialysis

Total of HCV patients n %

1 year 1-3 years 3-5 years 5 years Total

12 9 4 1 26

i 4 2 1 8

8 44 50 100 30.7

dialysis. None of those 3 patients had a history of blood transfusion in the last 16-24 months. The duration of dialysis appeared to be important with respect to the acquisition of HCV antibody. This observa­ tion is highlighted in table 2. Data analysis showed a sta­ tistically significant relationship between duration on di­ alysis and occurrence of hepatitis C (p < 0.05). The lon­ ger the patient was on dialysis, the greater the chances of seroconversion. In the group of the 35 patients with CRF who were not yet on dialysis, only 3 patients (8.5%) were HCV antibody positive (all the patients were HBsAg negative), and there was a significant statistical relationship between the oc­ currence of HCV antibody and CRF (p < 0.0001). The relative risk of hepatitis C is about 22 times greater for those with CRF when compared to controls. The 6 patients who received acute HD for varying lengths of time (2-12 weeks) and the 4 patients on perito­ neal dialysis were negative for HCV. Relationship between Blood Transfusion and HCV Seroconversion The relationship between units of blood transfusion and the acquisition of HCV antibody was investigated in all patients. Of the 4 HCV-positive CHD patients who all had a recent history of blood transfusion, 2 patients received 1-4 units of blood, while 2 patients received 5 units or more. However, this was not statistically signifi­ cant at the 5% level. Of the 3 patients who were HCV antibody positive in the CRF group and who were not yet on dialysis, 2 had no history of transfusion, while the third had had several transfusions to correct severe anaemia. Among the peritoneal dialysis group only 1 of the 4 patients had a previous history of blood transfusion; this patient was HBsAg positive, but none was HCV antibody positive.


In the CHD group it was observed that 6 out of 8 (75%) HCV-positive patients had a high SGPT level (3-5 times the upper limit of normal), while only 3 of the 18 (16.7%) HCV-negative patients had a high SGPT level (2-3 times the upper limit of normal); this was a statistically signifi­ cant difference (p < 0.001).

Discussion The data analysis generated from this study has given the overall occurrence rate of HCV in this study group as 15.4%. The rate is much higher among the patients on CHD (30.7%). This finding is compatible with the obser­ vations of others [16-19], The risk of cross-infection through the HD machine could be present despite the routine use of heat disinfec­ tion following each individual dialysis. This was sug­ gested by the pattern of seroconversion of the last 3 patients in the CHD group. These 3 were seronegative on arrival at the unit (with a history of the last blood transfu­ sion 16-24 months prior to seroconversion) but seroconverted between 6 and 8 months after the start of dialysis, all having shared the same dialysis machine with a patient seronegative for HCV but who had elevated liver enzymes throughout her stay in the unit and has remained so. Regarding the fourth patient, who was inadvertently placed on the HD machine used for HCV-positive pa­ tients, seroconversion occurred 4 weeks later. It is there­ fore inconceivable that the seroconversion occurred sec­ ondary to cross-infection through the machine or due to the blood transfusion she had received 12 weeks before starting dialysis in our unit. Available evidence showed that the mean interval for seroconversion is about 21.9 weeks (range 10-38 weeks) after contact or transfusion with contaminated blood [3]. Nosocomial transmission may have played a part in the 3 patients who had inadvertently shared the same machine (their last trans­ fusion was at least 16-24 months prior to seroconver­ sion). It is of interest to note that the occurrence of HCVpositive serology increased with time on dialysis (table 2). This appears to be an important risk factor. This type of linear relationship agrees with a previous study [16] which reported that the prevalence of HCV antibody rises with time on dialysis, reaching 36% after more than 6 years. Evidence from our study also showed that there was a positive correlation between the number of units of blood transfused and the risk of HCV positivity. It is therefore

Mitwalli/Al-Mohaya/Al Wakeel/ El Gamal/Rotimi/Al-Zeben/Al-Aska

Hepatitis C in Chronic Renal Failure Patients

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Table 2. Relationship between the dura­ tion of dialysis and acquisition of hepatitis C in the HD group

possible that the acquisition of HCV in about one half of or patients is transfusion related. Reports elsewhere have strongly supported this finding [20, 21 ]. The lack of a positive HCV anibody titre in the group of patients who had acute HD could be explained by the minimal risk of exposure to HCV, as none of those patients had required blood transfusion. The relatively short period of follow-up and the limited number of patients involved could also explain this observation. A longer period of follow-up and more patients would be necessary to support this finding. The occurrence rate of HCV infection was zero in the peritoneal dialysis group. This could be due to the absence of two main risk factors, HD with a possibly contami­ nated machine and blood transfusion, as this was not required. In the predialysis CRF group the occurrence of HCV of 8.5% was considered very high when compared to 0.8% amongst the control group (blood donors). It is notewor­ thy that only 1 out of 3 HCV-positive patients in the CRF group received blood transfusion. It is possible that CRF could predispose to acquisition of HCV. This observation requires further studies.

The marked increase in SGPT levels in the HCV-posi­ tive patients in the CHD group when compared to the HCV-negative patients in the same group is similar to that reported by Alter et al. [3, 22] who demonstrated a positive correlation between elevated liver enzyme (SGPT) and HCV infection. In conclusion, analysis of our data has shown that the occurrence of HCV increases with time spent on HD; the number of blood transfusions and cross-infection through the HD machine could be another considerable risk fac­ tor. We also conclude that elevated serum SGPT is much more common among patients with positive HCV com­ pared to the negative subjects. Whether CRF is a definite risk factor for HCV infection or not is a question that needs to be answered. Peritoneal dialysis appeared to carry little risk of HCV infection, a larger number of cases will have to be studied to substantiate this speculation. Acknowledgements W e would like to thank Leen V ercaemst and C atherine H unter,

Head Nurses. Renal Dialysis Unit, for their assistance and JojoSalbibia for her secretarial work.

References 8 Galbraith RM. Dienstag JL, Purcell RH, et al: Non-A, non-B hepatitis associated with chronic liver disease in a haemodialysis unit. Lancet 1979;i:951—953. 9 Berman M, Alter HJ. Ishak KG. et al: The chronic sequelae of non-A, non-B hepatitis. Ann Intern Med 1979;91:1-6. 10 Knodell RG, Conrak ME, Ishak KG: Develop­ ment of chronic liver disease after acute non-A, non-B posttransfusion hepatitis. Gastroenter­ ology 1977;72:902-905. 11 Rakela J, Redeker AG: Chronic liver disease after acute non-A. non-B viral hepatitis. Gas­ troenterology 1979;77:1200-1202. 12 Broyer M. Brunner FP. Brynger H, et al: Com­ bined report on regular dialysis and transplan­ tation in Europe. XII, 1981. Proc Eur Dial T ransplant Assoc 1982; 19:4-7. 13 Wing AJ, Broyer M, Brunner FP, et al: Com­ bined report on regular dialysis and transplan­ tation in Europe, XIII, 1982. Proc Eur Dial Transplant Assoc 1983;20:5-8. 14 Jacobs C, Broyer M, Brunner FP, et al: Com­ bined report on regular dialysis and transplan­ tation in Europe. XI, 1980. Proc Eur Dial Transplant Assoc 1981;18:2-5. 15 Choo QL. Kuog Weiner AJ, Oberly LR. et al: Isolation of cDNA clone derived from a blood borne non-A. non-B viral hepatitis genome. Science 1989;244:359-362.

16 Jadoul M. Cornu Ch, Lamy ME, et al: Preva­ lence and clinical significance of hepatitis C virus antibodies in haemodialysis patients (ab­ stract). XXVllth EDTA Congr, Vienna. Sept 1990, p 141. 17 Leimenstoll G. Rautenberg P, Loose G, et al: Hepatitis C virus (HCV) in patients on renal replacement therapy (abstract). XXVllth EDTA Congr, Vienna, Sept 1990, p 147. 18 Esteban JL Viladomiu L. Gonzales A. et al: Hepatitis C virus antibodies among risk groups in Spain. Lancet 1989;ii:294—296. 19 Kallinowski B, Theilmann L, Gmelin K, et al: Prevalence of HCV antibodies in haemodialy­ sis and kidney transplant patients (abstract). XXVllth EDTA Congr, Vienna. Sept 1990, p 142. 20 Prischl F, Mayr H, Mitter G, et al: Hepatitis C, a new problem in patients on haemodialysis? (abstract). XXVllth EDTA Congr, Vienna, Sept 1990,p 161. 21 Terucl JL, Marcen R. Gamez C, et al: Antibody to hepatitis C virus in patients on haemodialy­ sis and after kidney transplantion (abstract). XXVllth EDTA Contr, Vienna, Sept 1990, p 170. 22 Alter HJ, Purcell RH, Holland PV, Aling DW, Kozial DE: Donor transaminase and recipient hepatitis: Impact on blood transfusion services. JAMA 1981;246:630-634.


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1 Alter HJ: Chronic consequences of non-A. nonB hepatitis; in Seed LB, Lewis JH (eds): Cur­ rent Perspectives in Hepatology. New York, Plenum Medical. 1989. pp 83-97. 2 Dienstag JL: Non-A, non-B hepatitis, recogni­ tion, epidemiology, and clinical features. Gas­ troenterology 1983;85:439-462. 3 Alter HJ. Purcell RH, Shih JW, et al: Detection of antibody to hepatitis C virus in prospec­ tively followed transfusion recipients with acute and chronic non-A. non-B hepatitis. New Engl J Med 1989;321:1494-1500. 4 Kno G. Choo QL, Alter HJ, et al: An assay for circulation antibodies to a major aetiologic vi­ rus of human non-A, non-B hepatitis. Science 1989;244:362-364. 5 Kranuledat PB: Report of the proceedings of the First International Symposium on Hepati­ tis C virus. Rome, Sept 1989. 6 Galbraith RM. Portman B. Eddleston ALWF, et al: Chronic liver disease developing after outbreak of HBsAg-negative hepatitis in hae­ modialysis unit. Lancet 1975;ii:886—890. 7 Avran MM. Feinfeld DA, Gan AC: Non-A, non-B hepatitis: A new syndrome in uraemic patients. Proc Eur Dial Transplant Assoc 1979; 16:141-143.

Hepatitis C in chronic renal failure patients.

The occurrence of hepatitis C virus (HCV) infection amongst chronic renal failure (CRF) patients in our Nephrology Unit was investigated over a period...
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