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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 1995  |  Volume : 6  |  Issue : 2  |  Page : 179-182
Hepatitis C Associated Chronic Liver Disease in Renal Transplant Recipients

Department of Renal Medicine, Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia

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Infection with Hepatitis C Virus (HCV) is emerging as a major cause of morbidity and mortality in renal transplant recipients. We studied three hundred and forty stable renal transplant recipients on follow-up in our transplant clinic. Anti-HCV, tested by second generation ELISA, was positive in 185 patients (54%) of whom 52 (28%) had evidence of chronic liver disease. Six of the study patients were positive for anti-HCV and hepatitis B surface antigen. Twenty-three patients consented to undergo liver biopsy of whom eight had normal histology or fatty changes. Five patients had chronic non-specific hepatitis; four each had chronic lobular and chronic active hepatitis (CAH) and two had CAH with cirrhosis. All 15 patients with significant abnormalities on liver histology had elevated serum transaminase levels. Repeat liver biopsies were performed in seven patients after a mean period of 23.8 months following the first biopsy which showed worsening of the disease in four while three retained the same pattern. These results suggest that the prevalence of anti-HCV in our renal transplant recipients is high and that these patients have a high prevalence of chronic liver disease associated with major changes on liver histology. It is therefore recommended that caution is exercised while considering transplantation in patients who are anti-HCV positive.

Keywords: Hepatitis C virus, Renal transplantation, Chronic liver disease, Liver biopsy.

How to cite this article:
Abdalla AH, Al Sulaiman MH, Mousa DH, Rassoul Z, Rahman MA, Al-Khader AA. Hepatitis C Associated Chronic Liver Disease in Renal Transplant Recipients. Saudi J Kidney Dis Transpl 1995;6:179-82

How to cite this URL:
Abdalla AH, Al Sulaiman MH, Mousa DH, Rassoul Z, Rahman MA, Al-Khader AA. Hepatitis C Associated Chronic Liver Disease in Renal Transplant Recipients. Saudi J Kidney Dis Transpl [serial online] 1995 [cited 2020 Jun 1];6:179-82. Available from: http://www.sjkdt.org/text.asp?1995/6/2/179/40863

   Introduction Top

Hepatic failure is an important cause of death in long-term survivors following renal transplantation [1],[2],[3],[4],[5] . Hepatitis C virus (HCV) appears to be responsible for 60­90% of cases of post-transfusion hepatitis [6],[7],[8] and up to 80% of cases of cryptogenic cirrhosis [9] . The course of HCV infection in renal transplant recipients is currently unknown [10] . In this study, we assessed the prevalence of anti-HCV antibodies, the clinical course of anti-HCV positive patients, the histologic abnormalities and their correlation with the biochemical changes and the influence of co-existing hepatitis B virus (HBV) infection among renal transplant recipients.

   Patients and Methods Top

This study was performed over a three month period and comprised 340 stable renal transplant recipients being followed-up in the transplant clinic at the Riyadh Armed Forces Hospital, Riyadh. All the study patients were subject to investigations including anti-HCV antibody tested by second generation enzyme linked immunosorbent assay (ELISA), hepatitis B surface antigen (HBsAg) and liver function tests. In addition, 23 of the antiHCV positive patients who did not have any evidence of chronic liver disease (CLD) before transplantation and who consented to liver biopsy, were subjected to this procedure regardless of whether or not they had raised liver enzymes. These patients were further tested for hepatitis A-IgM, Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Schistosoma and  Brucella More Details serology, anti­mitochondrial, anti-smooth muscle and nuclear antibodies as well as ultrasound of the liver and biliary tree. Nine of these patients had received cadaveric transplants and 14 were recipients of live donor kidneys. None of these 23 patients were on azathioprine. The mean interval between transplantation and liver biopsy was 49 + 7.83 months, (range 3 to 144 months). Repeat liver biopsies were performed on seven patients who showed progression of their liver disease clinically and/or biochemically. The mean interval between the two biopsies was 23.8 + 15 months (range 6 to 48). All these patients were followed-up for a mean period of 53 ± 7.84 months (range 6 to 148).

The diagnosis of CLD was based on the presence of persistently abnormal liver function tests for more than six months or an" abnormality on hepatic histology.

   Statistical Method Top

To assess the value of the serum enzymes in predicting the histological diagnosis, the levels of alanine transaminase (ALT), aspartate transaminase (AST) and gamma­glutamyl transferase (GGT) obtained at the time of the liver biopsy were plotted against each morphologic entity. The statistical difference in the mean values of each biochemical test among the different histologic groups was assessed using one­way analysis of variance.

   Results Top

Three hundred and forty renal transplant patients were studied of whom 185 (54%) were anti-HCV positive. Fifty-two of these 185 patients (28%) had evidence of CLD. There were 33 males (63.5%) and 19 females (36.5%) in this group of whom, 33 (63.5%) were recipients of live donor kidneys and 19 (36.5%) had received cadaveric kidneys. Three patients were on azathioprine (AZA), 41 on cyclosporine-A and eight were on both drugs. Six of 185 anti-HCV positive patients were positive for HBsAg also, and all six had evidence of CLD. On the other hand, 46 of the 179 (25.7%) patients who were anti-HCV positive and HBsAg negative had CLD. In these patients, there was no other cause to account for hepatitis and therefore HCV infection was identified as the major cause of CLD. None of the HBsAg positive patients were delta antigen positive.

Twenty-three of the 185 anti-HCV positive patients consented to liver biopsy. The histological diagnosis in them is given in [Table - 1]. One striking feature was that all the 15 patients with significant abnormalities on liver histology had raised serum transaminase levels. In contrast, all the eight patients with either normal histology or only fatty changes, had normal transaminase levels.

Repeat biopsies performed in seven patients showed progressive worsening of liver disease in four; development of cirrhotic changes in two patients who had chronic active hepatitis (CAH) in their first biopsy (six and 32 months after the first biopsy); development of portal fibrosis in one (48 months after the first biopsy) and progression of mild chronic hepatitis to CAH (35 months after the first biopsy) in one other patient. Two patients with moderate CAH and one with normal liver histology retained the same pattern on second biopsy performed after 12, 14 and 20 months respectively.

At the time of liver biopsy, the mean ALT level in the eight patients with normal histology or fatty changes was 22.6 U/L. In patients with chronic non-specific and lobu-lar hepatitis (nine patients) the mean ALT level was 79.7 U/L and in patients with mild to advanced CAH (six patients) the mean level was 102.1 U/L. There was no significant difference in the ALT or GGT level among the different histologic groups (P > 0.1) and as such, there was no statistical correlation between the serum enzyme levels and the histologic diagnosis.

   Discussion Top

The prevalence of anti-HCV positivity in our transplant population is 54% (185 out of 340). This is much higher than the 1.5% reported among voluntary blood donors in Riyadh [11] , but consistent with our finding of 75% prevalence of anti-HCV positivity among dialysis patients [12] .

It has been reported earlier that 42 to 52% of patients positive for HCV RNA had biochemical evidence of liver disease. Fifty-two (27%) of the anti-HCV positive patients in our study had evidence of CLD after transplantation. However, all the six patients who were anti-HCV and HBsAg positive developed CLD.

The pathological studies demonstrated that 15 (65%) of the biopsied patients had significant histological abnormalities. Repeat liver biopsies performed in seven patients showed progressive worsening of the liver disease in four (57%) over a period ranging between 6 to 48 months. These results suggest that hepatitis C in transplant recipients can be more aggressive than that found by Parferey, et al in patients with non A, non B hepatitis. It has also been reported that progression to severe disease tends to occur more often in patients on AZA , but none of our patients on this drug showed evolution to severe liver disease and further, CLD progressed in three patients despite discontinuing AZA.

Other findings of interest were that all the 15 patients with histologic evidence of CLD had raised serum transaminase levels; in contrast, the eight patients whose biopsies showed normal histology or only fatty changes had normal transaminase levels. Statistical analysis showed that the abnormal histological diagnosis cannot be predicted from the level of the enzymes as there was no significant difference in the ALT, AST, and GTT levels among the different abnormal histological groups. Other investigators have also reported that the majority of transplant recipients with major histological abnormalities in the liver, have only mild to moderate abnormalities in liver function tests .

The severe nature of HCV infections in renal transplant recipients coupled with the high prevalence of anti-HCV among our dialysis population have prompted us, in recent months, to do liver biopsy in all patients with anti-HCV who are being considered for transplantation and excluding all those with significant abnormality on histology. We are also planning to treat such patients with interferon and repeat the biopsy and consider transplantation only if histological improvement occurs. Also, patients with anti­HCV, even if they have normal liver histology, are not given AZA post-transplantation.

The findings described in this paper show that patients with HCV infection appear to have more rapid course of their liver disease following transplantation especially if they are also HBsAg carriers. This, contrasts with our previous findings that HBsAg positive, delta antigen negative patients, have good hepatic prognosis following renal transplantation.

It is therefore strongly recommended that caution is applied when considering transplantation in patients who are positive for anti-HCV and more so if they are also positive for HBV.

   References Top

1.Rao KV, Anderson WR, Kasiske BL, Dahl DC. Value of liver biopsy in the evaluation and management of chronic liver disease in renal transplant recipients. Am J Med 1993;94:241-50.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.irkman RL, Strom TB, Weir MR, Tilney NL. Late mortality and morbidity in recipients of long-term renal allografts.Transplantation 1982;34:347-51.  Back to cited text no. 2  [PUBMED]  
3.Le Froncois N, Elmaghabbar N, Chossengros P, et al. Long term results in kidney transplantation: patients and graft survival, causes of graft failure and mortality, renal function and complication after 10 years. Transplant Proc 1987;19:3767-8.  Back to cited text no. 3    
4.Rao KV, Andersen RC. Long-term results and complications in renal transplant recipients. Observations in the second decade. Transplantation 1988;45:45-52.  Back to cited text no. 4    
5.Sengar DP, Couture RA, Lazarovits Al, Jindal SL. Long-term patient and renal allograft survival in HBsAg infection: a recent update. Transplant Proc 1989;21:3358-9.  Back to cited text no. 5    
6.Mosley JW, Aach RD, Hollinger FB, et al. Non-A, non-B hepatitis and antibody to hepatitis C virus. JAMA 1990;263:77-8.  Back to cited text no. 6  [PUBMED]  
7.Esteban JI, Gonzalez A, Hernandez JM, et al. Evaluation of antibodies to hepatitis C virus in a study of transfusion-associated hepatitis. N Engl J Med 1990;323:1107-12.  Back to cited text no. 7    
8.Alter HJ, Purcell RH, Shih JW, et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med 1989;321:1494-500.  Back to cited text no. 8  [PUBMED]  
9.Read AE, Donegan E, Lake J, et al. Hepatitis C in patients undergoing liver transplantation. Ann Intern Med 1991;114:282-4.  Back to cited text no. 9  [PUBMED]  
10.Stempel CA, Lake J, Kuo G, Vincenti F. Hepatitis C - its prevalence in end-stage renal failure patients and clinical course after kidney transplantation. Transplantation 1993;55:(2):273-6.  Back to cited text no. 10    
11.Saeed AA, Ahmed AM, Al-Karawi MA, Mohamed AE, Al-Saud AA. The association between hepatitis C virus antibody and hepatocellular carcinoma in relation to hepatitis B viral infection. Ann Saudi Med 1992;12:3:283-5.  Back to cited text no. 11    
12.Saeed AA, Fairclough D, Al-Admawi AM, et al. Hepatitis C virus in Saudi  Back to cited text no. 12    

Correspondence Address:
Abdullah A Al-Khader
Director of Renal Medicine, Riyadh Armed Forces Hospital, P.O. Box 7897, Riyadh 11159
Saudi Arabia
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PMID: 18583861

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