one of the patients on peritoneal dialysis was positive for HCV. A liver biopsy was obtained from 17 patients, who consented to the procedure. All the cases were.
Nephrol Dial Transplant (1996) 11: 2265-2268
Nephrology Dialysis Transplantation
Original Article
Liver disease in dialysis patients with antibodies to hepatitis C virus J. Al-Wakeel1, G. H. Malik1, S. Al-Mohaya1, A. Mitwalli1, F. Baroudi2, H. El Gamal1 and M. Kechrid1 'Division of Nephrology, 2Division of Gastroenterology, Department of Internal Medicine, Security Forces Hospital, Riyadh, Saudi Arabia
Abstract Eighty-three patients with chronic end-stage renal failure, including 65 on haemodialysis and 18 on intermittent peritoneal dialysis, were evaluated for hepatitis B virus profile and antibodies to hepatitis C virus (HCV). All those positive for HBsAg were excluded from the study. Nineteen patients were found to be positive for antibodies to HCV by the ELISA II test. Eight cases were already positive for HCV antibody when they started dialysis in our unit, the other 11 became positive during dialysis in our unit. Only one of the patients on peritoneal dialysis was positive for HCV. A liver biopsy was obtained from 17 patients, who consented to the procedure. All the cases were evaluated for the number of blood transfusions received, HIV infection and the approximate time of contracting the HCV infection. Liver enzymes were determined every month. Only three patients had abnormally raised serum aminotransferase at the time of biopsy. The various histopathological lesions detected were chronic active hepatitis (« = 3, including one with changes consistent with cirrhosis), chronic persistent hepatitis (« = 4), non-specific hepatitis (« = 3) and haemosiderosis (« = 3); four biopsy samples were normal. There was no correlation between the biochemical and histopathological changes. Moreover, patients with normal serum aminotransferase levels had abnormal histopathological changes. All were negative for HIV and none of the patients had received a renal graft. Twelve patients had received blood transfusions varying from 2 to 12 units, four had not received any blood, and in one the history of blood transfusion could not be confirmed. The four patients with anti-HCV antibodies who had not received blood transfusion had relatively mild disease—non-specific hepatitis (« = 2) or normal biopsy (« = 2).
of liver disease, and liver biopsy is a definitive way of evaluating the patients of dialysis with positive HCV antibodies for prognosis. Key words: antibodies to hepatitis C virus; haemodialysis; peritoneal dialysis; liver disease; blood transfusion; liver biopsy
Introduction A significant increase (12%) of antibodies to hepatitis C virus (anti-HCV) was initially noted in haemodialysis patients by Jeffers et al. [1]. These findings were subsequently confirmed by various reports from different countries with prevalences varying from 10 to 68% [2-4]. In contrast, zero prevalence has been reported among maintenance peritoneal dialysis patients [5]. Up to 60% of HCV-positive patients develop chronic liver disease in the post-transplant period, and worsening of liver disease has been observed [6,7]. Hypertransaminasaemia was noted in only about 31% of patients with chronic active hepatitis due to HCV infection and a need for liver biopsy has been stressed [7]. In addition, some patients on haemodialysis are candidates for renal transplantation. In the few studies performed, a poor correlation has been found between biochemical liver function tests and histopathological changes in dialysis patients with positive anti-HCV antibodies [7,8]. It seems imperative to have more data on these observations. We undertook the present study to determine the patterns of liver pathology in our dialysis patients with HCV infection and correlate these findings with biochemical liver function tests.
One patient with cirrhosis died 30 months after liver biopsy from hepatic insufficiency and three received renal transplants. Others are continuing on dialysis and their biochemical tests are within normal limits Subjects and methods 12-45 (30± 14) months after biopsy. In conclusion, biochemical tests are poor indicators Correspondence and offprint requests to: Dr Jamal Al-Wakeel, Consultant and Head, Division of Nephrology, Security Forces Hospital, PO Box 3643, Riyadh 11481, Saudi Arabia.
Since January 1990 all the patients on maintenance haemodialysis and chronic intermittent peritoneal dialysis were included in the present study. Number of transfusions of blood or its products and history of homosexuality and drug
© 1996 European Renal Association-European Dialysis and Transplant Association
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abuse were noted. All were screened for the presence of hepatitis B virus and those positive for the hepatitis B surface antigen were excluded from the study. All cases were also evaluated for the presence of HIV. Antibodies to HCV were assessed by ELISA II using hepatitis C virus encoded recombinant antigen (Abbott HCV EIA 2nd generation), and confirmed by detection of HCV RNA by polymerase chain reaction (PCR). Nineteen patients were found to be positive for the presence of anti-HCV antibodies. Seventeen of them consented to undergo liver biopsy. The causes of end-stage renal failure in these 17 patients were glomerulonephritis (« = 6), bilateral small kidneys of unknown cause (n = 6), diabetes mellitus (n = 2), hypertension («=1), chronic pyelonephritis (n=l), and obstructive uropathy due to long standing bladder neck obstruction («=1). A liver biopsy was obtained from nine patients, 4-16 months (average = 8+4.1 months) after acquiring the infection and from eight patients, 7-16 (10.5+4.0) months after the onset of dialysis in our unit (the latter group was already positive for Anti HC antibody when dialysis was initiated). Transcutaneous liver biopsy was performed using Menghini's aspiration biopsy needle. Formalin-preserved, paraffin-embedded sections of liver were stained with haematoxylin and eosin, PAS, reticulin, silver, pearl's iron stain, Masson chrome, Von-Gieson, hepatitis B surface and core antigen. All the anti-HCV-antibody-positive cases were assessed by monthly measurements of liver enzymes. Any patient with serum ALT level 1.5 times above the normal range of 0-40 u/1 was regarded as hypertransaminasaemic.
J. Al-Wakeel et al.
(108 + 36) units/ml. At the time of biopsy the enzymes were normal in 14 of 17 (82.3%) cases, and an abnormal increase was noted in three (17.6%). Histopathology changes
Of the 17 patients who underwent liver biopsy, three showed evidence of chronic active hepatitis including one with cirrhosis (17.64%), four had chronic persistent hepatitis (23.52%), three had non-specific hepatitis (17.64%), three had changes suggestive of haemosiderosis (17.64%), and four had normal histology (23.52%). Twelve of 17 (70.5%) had received blood transfusion. Of the four patients who had no history of blood transfusion, two had non-specific hepatitis, and no histological abnormalities were noted in the other two. One patient who had changes consistent with chronic active hepatitis and cirrhosis developed ascites and portal hypertension and died 30 months after biopsy from hepatic insufficiency. Three received renal transplants; the remaining 13 patients had no clinical evidence of liver disease and their biochemical tests were within normal limits 12-45 (30+14) months after biopsy. Discussion
Nineteen of 83 patients in the present study were positive for anti-HCV antibody; an overall prevalence of 22.9%. The prevalence in an earlier study from the A total of 83 patients with chronic end-stage renal same dialysis unit was 30.7% [9]. This difference could failure, including 65 on haemodialysis and 18 on be attributed to the adoption of standard precautions peritoneal dialysis were evaluated. Nineteen were found and isolation of HCV patients in our unit while perto be positive for anti-HCV antibody, and a liver forming haemodialysis [10] and reduction in the number of blood transfusions required by our patients biopsy was taken from 17. Of the 17 patients who underwent liver biopsy, eight due to the widespread use of erythropoietin [11]. were males and nine females, with ages ranging from Twelve of our 17 patients (70.5%) with positive HCV 14 to 55 and with a mean age of 42 years. Only one antibodies had received blood transfusion while on patient who had cirrhosis (on biopsy) developed dialysis. haemoperitoneum after biopsy and needed blood transOnly one of the 18 (5.5%) on chronic peritoneal fusion. None of the other patients had any complica- dialysis was positive for anti-HCV antibodies and none tions after biopsy. of them had received blood transfusion. Many studies Eight of the 17 patients who underwent liver biopsy have reported a direct relationship between the number were already positive for anti-HCV antibodies at the of blood transfusion and the prevalence of anti-HCV time of initiating dialysis, whereas nine became anti- antibodies among haemodialysis patients [1,3,4,12]. HCV-antibody positive while on dialysis in our unit. This low prevalence is in agreement with the zero The latter group had liver biopsy 4-16(8 + 4.1) months prevalence reported by Besso et al. in 24 patients on after they became positive for anti-HCV antibody. In continuous ambulatory peritoneal dialysis [5]. The eight patients who were already positive for anti-HCV marked difference in the prevalence of anti-HCV antibody, we do not know the length of the period of among peritoneal and haemodialysis patients seems mainly related to the increased number of blood transHCV positivity. Twelve of 17 patients had a history of blood transfu- fusions required by the patients on haemodialysis sion varying from 2 to 12 units; four had not received compared to those on peritoneal dialysis. any blood or its products, and in one patient a history Serum aminotransferases were abnormally increased of blood transfusion could not be confirmed. None of in only three of 13 patients who had abnormal histothese patients had received a kidney graft and all were logical changes on liver biopsy. One of these three HIV negative. patients had chronic active hepatitis, one had chronic Significantly raised levels of aminotransferases were persistent hepatitis, and one had haemosiderosis. Thus noted in seven cases—ALT ranging from 65 to 516 76.9% cases with abnormal liver biopsy findings had (153 + 160) units/ml and AST ranging from 62 to 303 normal serum aminotransferases, clearly indicating the
Results
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Liver disease in dialysis patients with antibodies to hepatitis C virus
low sensitivity of liver enzymes to detect liver disease due to HCV. Pol et al. [7] found that only 16 of 52 (31%) patients with HCV RNA in the circulation had abnormal liver function tests; furthermore only four of 15 (26.6%) with histological evidence of chronic hepatitis had elevated liver enzymes. Chan et al. observed that only 33% of anti-HCV-positive haemodialysis patients were hypertransaminasaemic, and eight of 10 (80%) patients with HCV-positive antibodies with normal liver enzymes were HCV RNA positive [2]. Van Ness and Diehl [13] have also advocated the higher diagnostic accuracy of liver biopsy compared with non-invasive methods. Previous series of non-A, non-B hepatitis in non-dialysis patients have also reported a similar lack of correlation between biochemical and histological findings [14,15]. In a study similar to ours, the various histopathological patterns reported by Caramelo et al. [8] were chronic active hepatitis, cirrhosis, chronic persistent hepatitis, haemosiderosis, and reactive hepatitis. The results are comparable; however, chronic active hepatitis was present in 14 of 33 (42.4%) compared to three of 17 (17.6%) in our study. A similar histological pattern was reported in a survey of otherwise healthy blood donors who tested positive for HCV [16]. Pol et al. [7] described chronic active hepatitis in 16 of 17 liver biopsies, and Al-Meshari et al. [17] found this lesion in 70% of cases from the same geographical region. This discrepancy in results could be explained in part by the fact that a real distinction between chronic active hepatitis and chronic persistent hepatitis is difficult in most cases [18]. In the present study, four of our 17 (23.5%) HCV antibody-positive patients had normal histology on liver biopsy, consistent with the observation that hepatitis C viraemia is not always associated with liver disease [19]. Three of 17 patients (17.6%) who received multiple blood transfusions had haemosiderosis and this figure corresponds to that of Caramelo et al. [8] wherein five of 33 (15%) liver biopsies had features of haemosiderosis. Of the four patients who had no history of blood transfusions, two had non-specific hepatitis and two had normal histology. Other authors [17] believe that HCV-positive patients with non-specific histological changes in the liver may represent resolving HCV hepatitis, and therefore we infer that patients who contact HCV via non-transfusion methods develop a milder disease. Lau et al. detected a higher viraemia in health workers and intravenous drug abusers who acquired HCV infection by blood transfusion [20]. However, as the number of such patients in our study was small, further studies are needed to confirm this observation. Despite claims that increasing use of erythropoietin and better blood-donor screening has resulted in a decrease in post-transfusion hepatitis [21], the risk of nosocomial HCV transmission persists. At least four of 17 (23.5%) of our patients had not received a blood transfusion, were not drug abusers, and were HIV negative, and yet were HCV antibody positive. This is
true even though we isolate HCV-positive dialysis patients in our unit, which has been shown to decrease the incidence of anti HCV in at least one study [22], and have adopted universal precautions [10]. Clearly a search for unknown modes of transmission is needed, a view held by others [12,23]. In conclusion, there is a poor correlation between the biochemical liver tests and liver pathology in dialysis patients with positive antibodies to HCV, and liver biopsy is the only definitive way of diagnosing liver disease in such cases. Acknowledgements. The authors are grateful to Ms Laura S. QuiaposRozario and her team for management of the cases during dialysis. We also express our gratitude to Ms Estrella C. Mosuela-Lazaro for her secretarial assistance.
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Received for publication: 16.2.96 Accepted in revised form: 9.7.96
