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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 1995  |  Volume : 6  |  Issue : 2  |  Page : 211-215
Hepatitis C Virus Infection in a Hemodialysis and Kidney Transplant Patient: An Eight Year Follow-up Report

1 Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
2 Department of Pathology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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We report our experience in the management of a hemodialysis (HD) patient who acquired hepatitis C virus (HCV) infection while on dialysis, and subsequently received a kidney transplant. The potential role of alpha-interferon in the management of HCV infection is discussed, as well as the potential for azathioprine to perpetuate HCV induced liver disease following kidney transplantation. The management of this patient summarizes our standard practice for the management of HCV infection during HD and following kidney transplantation.

Keywords: Hepatitis C virus, Hemodialysis, Kidney transplantation, Chronic liver disease.

How to cite this article:
Al Meshari K, Abutaleb N, Alfurayh OI, Ali MA. Hepatitis C Virus Infection in a Hemodialysis and Kidney Transplant Patient: An Eight Year Follow-up Report. Saudi J Kidney Dis Transpl 1995;6:211-5

How to cite this URL:
Al Meshari K, Abutaleb N, Alfurayh OI, Ali MA. Hepatitis C Virus Infection in a Hemodialysis and Kidney Transplant Patient: An Eight Year Follow-up Report. Saudi J Kidney Dis Transpl [serial online] 1995 [cited 2020 Jun 4];6:211-5. Available from: http://www.sjkdt.org/text.asp?1995/6/2/211/40868

   Introduction Top

Hepatitis C virus (HCV) is now considered the leading cause of chronic hepatitis in hemodialysis (HD) and renal transplant patients [1],[2] . This raises many questions related to the natural history of the infection and its impact on the renal allograft on the one hand, and the impact of dialysis and immunosuppression on the course of HCV associated liver disease on the other. We report an eight-year course of a patient who was HCV positive while on HD and subsequently underwent renal transplantation. Many of the clinically relevant issues which concern HCV infection in HD and renal transplant patients were observed during the course of his illness.

   Case Report Top

Our patient is a 23 year old Saudi male. At the age of 14 years he developed end-stage renal disease of unknown cause. He was started on HD in 1986, and he gave a history of having received blood transfusions two years previously. In 1987, his liver enzymes were found to be elevated. Serolohepatitis A and B viruses. After proper exclusion of other causes of liver disease, he was diagnosed as having non-A, non-B hepatitis and underwent a transcutaneous liver biopsy which demonstrated mild focal portal inflammation and piecemeal necrosis. His liver enzyme levels fluctuated over the course of the next three years.

In 1990, he tested positive for HCV antibody (anti-HCV) and was subjected to a second liver biopsy in preparation for a therapeutic trial with alpha-interferon (a-IF). The liver biopsy showed diffuse portal inflammation, focal piecemeal necrosis, focal lobular inflammation, and mild lobular and portal fibrosis. He received three million units of a-IF subcutaneously, three times a week, for six months. At the conclusion of this treatment, a follow-up biopsy (third) showed that the portal and lobular inflammation had subsided and the piecemeal necrosis had disappeared.

In 1991, he had his first relapse, with high liver enzymes. A fourth transcutaneous liver biopsy showed a recurrence of piecemeal necrosis and worsening of the portal and lobular inflammation [Figure - 1] as well as the development of focal interportal bridging fibrosis [Figure - 2]. He was started on a further course of a-IF which was continued for six months. He showed a good clinical response. After normalization of liver enzymes for a period of six months, he underwent a fifth liver biopsy which confirmed the remission of hepatic inflammation and the disappearance of interportal bridging fibrosis [Figure - 3].

The patient was cleared for kidney transplantation and received a cadaveric graft in December, 1993. At the time of transplantation, he was HCV RNA positive by polymerase chain reaction (PCR) and HCV RNA genotype analysis by line-probe assay (INNO LIPA) revealed that he was a carrier of subtype 1b. Following transplantation, there was delayed renal allograft function for which he received a three-week course of induction anti­lymphocyte globulin (ALG). The graft recovered eventually and the patient was discharged on a triple immunosuppressive regimen of cyclosporine A (CyA), azathioprine (Aza) and prednisone with a baseline serum creatinine that ranged between 160 to 190 umol/L.

In February 1994, he was noted to have asymptomatic, fluctuating, elevation of liver enzymes which had become persistent by May 1994. In August 1994, he underwent the first post-transplant liver biopsy. This demonstrated portal inflammation, mild piecemeal necrosis, and mild portal and peri­portal fibrosis [Figure - 4]. Azathioprine was gradually tapered off over the next three months. In March 1995, his liver enzymes became normal and remained so for the next two months. In April 1995, a second posttransplant liver biopsy demonstrated a marked improvement of hepatic inflamma­tion.

He was last seen in the clinic in April 1995. At that time, he had no complaints; blood pressure was 140/80 mm Hg and his weight was 75 kg. Clinical examination was unremarkable except for the presence of mild facial acne. Laboratory investigations revealed: serum creatinine 162 umol/L; alanine aminotransferase 35 U/L; aspartate amino-transferase 25 U/L; hemoglobin 110 g/L; CyA level 420 ng/ml; and normal urinalysis.

   Discussion Top

This case raised many important questions concerning the management of HCV infection in dialysis and renal transplant patients. How did our patient acquire the HCV infection? It is probable that he acquired the infection through a blood transfusion, although, nosocomial transmission during HD cannot be ruled out. It has been established that HD patients are at increased risk for developing HCV infection [1] and the high prevalence of anti-HCV in this patient population has been well reported throughout the world [1] . Blood transfusions, longer duration on HD and the dialysis procedure itself are thought to contribute to this high prevalence [3] . Since passive immunization and effective vaccination are not yet available, prevention assumes a critical role in the control of HCV infection. Efficient screening of blood and blood products for anti-HCV, proper use of erythropoietin, and strict adherence to infection control policies are important preventive measures. It is yet to be proven that segregation of HCV infected HD patients is beneficial in controlling the spread of the infection [3] .

What is the natural history of HCV infection in HD patients and what is the role of a-IF in the treatment of the infection? We, and others, have shown that the course of HCV-associated liver disease in HD patients is somewhat indolent [4],[5] . We have also shown that since liver enzymes are poor markers of the grade and stage of liver disease in such patients [6] , liver biopsy is the most accurate method of assessing the progression of HCV-associated liver disease [1],[4] . By means of serial liver biopsies during a six-year follow-up on HD, we were able to demonstrate the somewhat non-progressive course of mild' chronic hepatitis in our patient. It might be argued, however, that the a-IF treatment influenced the course of his liver disease. However, our observation in dialysis patients with HCV infection who did not receive a-IF and were followed-up by serial liver biopsies, have shown that inter­mittent worsening of the portal and lobular inflammation can reverse spontaneously [4] .

An important goal of a-IF treatment in dialysis patients is to clear serum HCV RNA in preparation for kidney transplantation. One recent multi-center trial of a-IF treatment in patients v/ith HCV infection on maintenance HD reported a relapse rate (recurrence of serum HCV RNA) of 36%, and side effects were reported to be higher than in non-uremic subjects [7] . Our patient clearly had a relapse after his first course of a-IF. Although the second course was successful in suppressing the hepatic inflammation he was serum HCV RNA positive at the time of transplantation. Several factors have been proposed as predictors of good response to a-IF [2] . They include young age, female gender, recent infection, low viremia and genotype other than type II (lb). It could be argued that male gender, old infection and HCV genotype lb in our patient, had resulted in an unsustained response to a-IF.

Furthermore, we have recently shown in a controlled study, that prior treatment with a­IF in HD patients with HCV-associated mild chronic hepatitis and positive serum HCV RNA at baseline, does not change either the course of liver disease or patient and graft survival following kidney transplantation, at least in the short-term [8] .

At present, the role of a-IF in the management of HCV infection in dialysis patients is not clear. Several important issues remain unresolved:

a) whom to treat?

b) what are the markers of response?

c) what is the ideal duration of therapy?

d) does treatment have any impact on future kidney transplantation especially with regard to long-term morbidity and mortality?

Answers to these questions will help to delineate the exact role of a-IF in the management of HCV-infected HD patients.

What is the impact of kidney transplantation on the course of HCV-associated liver disease and the impact of HCV infection on the renal allograft? Our patient clearly had a flare-up of HCV-associated hepatitis post kidney transplant. Immunosuppression, failure to clear HCV RNA and increased viremic load are thought to contribute to the worsening of hepatitis post-transplant [9] . One recent study [10] has shown that the cumulative dose of ALG administered as induction therapy was an independent predictor of post-transplant HCV-associated liver disease in a dose­response relationship. Our patient did receive a prolonged course of ALG as induction therapy and it can be argued that this contributed to the flare-up of his hepatitis. However, he demonstrated marked improvement of hepatic inflammation a few months after withdrawal of Aza. This suggests that Aza might act synergistically to worsen HCV-associated liver disease and argues for early withdrawal of this drug in HCV infected renal transplant recipients who develop chronic hepatitis post­transplantation.

Two important questions remain;

a) what is the long-term impact of kidney transplantation on HCV-associated

liver disease? and

b) what is the impact of HCV infection on patient and graft survival?

Early retrospective studies [9] gave a dismal prognosis for HCV-associated liver disease post-kidney transplantation. However, we have shown in a prospective study [11] that kidney transplantation of HCV-infected patients does not worsen liver disease, at least in the short-term. We believe that the poor prognosis reported in previous studies might have been due to the inclusion of patients with advanced HCV-associated liver disease at the time of transplantation. Furthermore, we and others have shown that anti-HCV status does not affect patient and graft survival over the short term [11],[12] . Prospective studies with longer duration of follow-up are clearly needed to answer these two important questions

The role of a-IF in the treatment of HCV­associated liver disease post-kidney trans­plantation is not yet established. Early studies have described an increased risk of irreversible rejection in renal transplant recipients treated for Cytomegalovirus infection with a-IF [2] . More- recent studies describe a relatively poor and inefficient response of HCV infection to a­IF therapy in renal transplant recipients [2] .

Based on our experience and on data from the literature, our current policy for the approach and management of HCV infection post-kidney transplantation is:

a) HCV-infected patients can be accepted for kidney transplantation if they demonstrate mild chronic hepatitis or normal tissue at baseline liver biopsy prior to transplantation. Mild chronic hepatitis is defined as hepatic inflammation devoid of severe piecemeal necrosis, bridging necrosis, bridging fibrosis and cirrhosis.

b) Prolonged courses of induction ALG are to be avoided in these patients.

c) Early withdrawal of Aza is mandatory if the patients develop persistent (> 4-6 months) elevation of liver enzymes.

d) Interferon alpha is not recommended for HCV infected renal transplant recipients.[17]

   Acknowledgment Top

The authors would like to thank Allelic S. Morse for her secretarial assistance in preparing the manuscript.

   References Top

1.Al Meshari K, Al Ahdal M, Alfurayh O, Ali A, De Vol E, Kessie G. New insights into hepatitis C virus infection of hetnodialysis patients. Am J Kidney Dis 1995;25(4):572-8.  Back to cited text no. 1    
2.Pol S. Hepatitis C virus infection in hemodialysed patients and kidney allograft recipients. Advances in Nephrology 1995;24:315-30.  Back to cited text no. 2  [PUBMED]  
3.Natov SN, Pereira BJG. Hepatitis C infection in patients on dialysis. Setnin Dial 1994;7(5):360-8.  Back to cited text no. 3    
4.Al Meshari K, Al Ahdal M, Alfurayh O, Qunibi W. Insights into the natural history of HCV infection in hemodialysis patients: A histopatholo gical study. Abstract. American Society of Nephrology Meeting, October 1994, Orlando, Florida, USA.  Back to cited text no. 4    
5.Simon N, Courouce AM, Lemarrec N, Tripo C, Ducamp S. A twelve year natural history of hepatitis C virus infection in hemodialysed patients. Kidney Int 1994;46:504-ll. Ross E. Abnormal liver function tests: I. Semin Dial 1993;6:355-8.  Back to cited text no. 5    
6.Koenig P, Vogel W, Umlauft F, et al. Interferon treatment for chronic hepatitis C virus infection in uremic patients. Kidney Int 1994;45:1507-9.  Back to cited text no. 6  [PUBMED]  
7.Al Meshari K, Alfurayh O, Al Shaibani K, Qunibi W. Hepatitis C virus infection post kidney transplantation: A prospective controlled study of patients with and without prior a-IFN therapy. Abstract. American Society ofTransplant Physicians Meeting, May 1995,  Back to cited text no. 7    
8.Chicago, USA. Pereira BJ, Milford EL, Kirkman RL, et al. Prevalence of hepatitis C virus RNA in organ donors positive for hepatitis C antibody and in the recipients of their organs. N Engl J Med 1992;327:910-5.  Back to cited text no. 8    
9.Roth D, Zucker K, Cirocco R, et al. The impact of hepatitis C virus infection on renal allograft recipients. Kidney Int 1994;45:238-44.  Back to cited text no. 9  [PUBMED]  
10.Al Meshari K, Al Shaibani K, Alfurayh O, Qunibi W. Kidney transplantation- in hepatitis C virus infected hemodialysis patients with mild hepatitis: A prospective controlled study of liver disease and graft function. Abstract. American Society of Nephrology Meeting, October 1994, Orlando, Florida, USA.  Back to cited text no. 10    
11.Kazi S, Prasad S, Pollak R, et al. Hepatitis C infection in potential recipients with normal liver biochemistry does not preclude renal transplantation. Dig Dis Sci 1994;39(5):961-4.Arabia - A preliminary survey. Saudi Med J 1990;4:331-2.  Back to cited text no. 11    
12.Pereira BJ, Milford EL, Kirkman RL, Levey AS. Transmission of hepatitis C virus by organ transplantation. N Eng J Med 1991;325:454-60.  Back to cited text no. 12    
13.Aeder MI, Shield CF, Tegtmeier GE, et al.Incidence and clinical impact of hepatitis C virus-positive donors in cadaveric transplantation. Transplant Proc 1993;25:1469-71.  Back to cited text no. 13  [PUBMED]  
14.Parfrey PS, Farge D, Forbes" RD, Dandavino R, Kenick S, Guttmann RD. Chronic hepatitis in end-stage renal disease: comparison of HBsAg­negative and HBsAg-positive patients. Kidney Int 1985,28:959-67.  Back to cited text no. 14    
15.Morales JM, Munoz MA, Castellano G, et al. Impact of hepatitis C in long­functioning renal transplants: a clinico­pathological follow-up. Transplant Proc 1993;25:1450-3.  Back to cited text no. 15  [PUBMED]  
16.Rao KV, Andersen RW. Value of liver biopsy in the evaluation of management of chronic liver disease in renal transplant recipients. Am J Med 1988;94:21-50.  Back to cited text no. 16    
17.Dhar JM, Al-Khader AA, Al-Sulaiman MH, Al-Hasani MK. The significance and implications of Hepatitis B infection in reral transplant recipients. Transplant Proc 1991;23:1785-6.  Back to cited text no. 17  [PUBMED]  

Correspondence Address:
Khalid Al Meshari
Department of Medicine, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211
Saudi Arabia
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