| Abstract|| |
We present a patient with hepatitis C virus (HCV) infection who developed chronic active hepatitis (CAH) after renal transplantation. Alpha-interferon (a-IF) therapy was administered in view of deteriorating liver biochemistry. Liver histology at this stage showed features suggestive of chronic active hepatitis (CAH). The patient had stable graft function. Therapy with a-IF resulted in noticeable biochemical response within two weeks of commencement. An episode of steroid resistant renal allograft rejection occurred after 10 weeks of a-IF therapy which responded well to anti-lymphocyte globulin. Since then, the CAH has gradually progressed on to the development of cirrhotic changes and hepato-cellular carcinoma after 10 years following transplantation. Our case indicates that liver disease in antiHCV positive patients can follow a serious course following renal transplantation.
Keywords: Hepatitis C virus, Renal transplantation, Chronic active hepatitis, Hepato-cellular carcinoma, Alpha-interferon.
|How to cite this article:|
Abdalla AH, Mousa DH, Rassoul Z, Al Hawas F, Al Sulaiman MH, Al-Khader AA. Progression of Hepatitis C Infection in a Renal Transplant Recipient: A Case Report. Saudi J Kidney Dis Transpl 1995;6:206-10
|How to cite this URL:|
Abdalla AH, Mousa DH, Rassoul Z, Al Hawas F, Al Sulaiman MH, Al-Khader AA. Progression of Hepatitis C Infection in a Renal Transplant Recipient: A Case Report. Saudi J Kidney Dis Transpl [serial online] 1995 [cited 2020 Jul 5];6:206-10. Available from: http://www.sjkdt.org/text.asp?1995/6/2/206/40867
| Introduction|| |
Chronic liver disease (CLD) is a major cause of morbidity and mortality among the late survivors following renal transplantation ,, . Hepatitis C virus (HCV) appears to be responsible for 60-90% of cases of posttransfusion hepatitis , . Many centers have reported a high prevalence of HCV infection in hemodialysis (HD) patients and renal transplant recipients. In immunocompetent patients, persistent HCV infection is associated with the development of chronic active hepatitis (CAH), cirrhosis and hepato-cellular carcinoma  . The course of HCV infection in renal transplant recipients is currently unknown . They could be at greater risk because of their immuno suppressed state. We present the course of HCV infection in a patient with end-stage renal disease, both while on dialysis as well as following renal transplantation.
| Case History|| |
Our patient is a 60 year old Saudi male. He was started on reg'ular HD in 1979, when he was 44 years old, at another center for end-stage renal disease of unknown etiology. His past history was otherwise unremarkable. In 1982, he was referred to our center to be assessed for a possible cadaveric renal transplantation. He gave a history of having received at least four units of blood during the year preceding admission at our center. He was negative for hepatitis B surface antigen (HBsAg) and his liver function tests (LFT) were normal.
In June 1985, he received a cadaveric renal allograft in the USA. He returned to us five months later. His immunosuppressive therapy consisted of azathioprine, 100 mg once daily and prednisolone 10 mg once daily. Blood tests showed mildly elevated serum aspartate transaminase (AST) level to 70 U/L, (normal 11-55 U/L) with normal serum levels of albumin, alkaline phosphatase and bilirubin. HBsAg was negative.
The liver enzyme levels remained static for seven years post-transplant and in May 1992, he developed progressive elevation of serum AST levels. He tested positive for anti-HCV by second generation ELISA. A liver biopsy was performed which showed moderate CAH with mild cholestasis [Figure - 1]. Immunoperoxidase staining for HBsAg was negative. Azathioprine was discontinued to protect the liver against further damage and he was commenced on cyclosporine-A. His graft function remained stable with a serum creatinine level at 100 umol/L.
The liver biochemistry continued to deteriorate gradually with alanine transaminase (ALT) level reaching 300 U/L. In early 1993, abdominal computerized tomography (CT) scan was performed which showed a diffusely enlarged liver with no focal lesions. Serum alpha-fetoprotein (AFP) level was within normal limits. A repeat liver biopsy at this stage showed CAH with heavier mononuclear cell infiltrate than in the previous biopsy with the development of fibrotic changes and early cirrhosis [Figure - 2]. The liver acinar architecture was preserved. In view of the deteriorating liver biochemistry and histology, alpha-interferon (a-IF) therapy (Interon A, Schering-Plough) was instituted after informed consent and counselling regarding the possible risk of precipitating kidney rejection. The patient received 5 million units (mu) of a-IF, administered subcutaneously three times a week, as an inpatient, with frequent monitoring of his renal function, blood counts and LFT. The serum ALT and bilirubin levels began to fall within two weeks of starting treatment [Figure - 3].
Ten weeks after starting a-IF, the patient's serum creatinine rose from 100 to above 300 nmol/L. His cyclosporin level was in the therapeutic range at 445 nmol/L. Ultrasound and isotope renography were consistent with acute rejection which was confirmed by graft biopsy, that showed acute cellular rejection with features of vascular rejection [Figure - 4],[Figure - 5],[Figure - 6]. He received two consecutive courses of methylprednisolone, each of three boluses of 500 mg daily, but with no positive response. Graft biopsy was repeated which showed persistent cellular rejection with some tubular atrophy. He was then commenced on antilymphocyte globulin (ALG) 15 mg/kg/day which was given for 14 days. He tolerated this well. There was noticeable improvement in his renal functions from the fourth day and gradually his serum creatinine dropped to 180 umol/L.
He continued regular follow-up in the renal transplant clinic. His renal functions remained stable with serum creatinine around 140 umol/L. The LFT also remained stable. In December 1993, a small mass measuring about 2 cm x 1.8 cm, was noticed in the right lobe of the liver on ultrasonography and was initially reported as a possible hemangioma. A four-monthly monitoring of the mass by ultrasound and measurement of serum AFP levels, was made. One year later, (December 1994), the mass appeared to have increased slightly in size and the AFP level rose to 900 ug/L. A biopsy of the mass was performed under CT guidance; the histopathology revealed well differentiated adenocarcinoma [Figure - 7]. He was evaluated further by means of magnetic resonance imaging, CT scan of the chest and abdomen, angiography and bone scintigraphy. There was no evidence of other lesions in the liver, or any distant metastases. He was treated with local percutaneous ethanol injections to necrotize the tumor mass. Resection and hepatic transplantation were considered inappropriate in this patient. He received five ethanol injections over a twoweek period with no adverse effects. Repeat CT scan showed evidence of necrosis in the tumor mass. Serial monitoring showed a drop in the serum AFP level from 700 to 400 µ-g/L. He was subsequently discharged to be followedup as an out-patient.
| Discussion|| |
This patient is a tragic example of the seriousness of HCV infection in renal transplant recipients. It is difficult to find out when he acquired the HCV infection, since he was transplanted long before the establishment of specific HCV serological assays.
The natural history of HCV infection in the immunosuppressed allograft recipients and its impact on long-term patient outcome are still being analysed  . Most of the available evidence suggests that HCV infection in posttransplant patients can be a serious problem. Morales and co-workers showed that 60% of their HCV positive transplant patients have CLD and can exhibit, on biopsy, a severe histological pattern  . The possible role of immunosuppressive therapy in aggravating liver pathology is, as yet not clearly defined. It was reported that progression to severe disease tends to occur more often in patients on azathioprine  . Our patient was on azathioprine for five years before switching over to cyclosporin-A.
There is little data on the efficacy of a-IF therapy in transplant recipients with chronic HCV infection. Since a-IF has been incriminated in precipitating renal allograft rejection among patients shortly after renal transplantation, there is more reluctance to use it on such patients ,,, .
Our patient showed good response to a-IF therapy, which he tolerated well initially. However, 10 weeks after starting this drug, the patient developed steroid resistant renal allograft rejection. It is to be noted that he had good graft function for seven years before a-IF therapy was started. The exact mechanism by which a-IF precipitates rejection is unknown, but it could be due to the induction of class III histocompatibility antigen expression  . The prophylactic use of a-IF immediately after renal transplantation against cytomegalovirus infections also was associated with a high incidence of steroid resistant rejections and graft loss  . Similarly, Chan and co-workers reported a renal transplant recipient who developed steroid responsive rejection nine months after starting a-IF  . It has therefore been recommended, that a-IF therapy is best avoided in the early post-transplant period and, in patients with unstable renal function  .
Relapse of liver disease frequently occurs in immunocompetent patients after cessation of a-IF therapy. However, the transaminase levels in our patient remained stable after discontinuation of a-IF.
We have recently reported two renal transplant patients who developed hepatocellular carcinoma eight and 12 years post-transplantation, both of whom were HBsAg positive, and HCV negative (in press, Saudi Medical Journal). However, HCV may be more important than hepatitis B in the etiology of hepato-cellular carcinoma  . There is a four-fold higher incidence of liver cancer among anti-HCV positive persons than among HBsAg carriers  . A report from the Cincinnati transplant tumor registry shows that there is a three-fold higher relative risk for hepato-cellular carcinoma following renal transplantation among anti-HCV positive patients  .
Treatment of hepatomas depends on the extent and rate of growth. The results with hepatic transplantation are generally unsatisfactory; recurrence and metastases are usual and may be enhanced by the immunosuppression necessary to prevent rejection  . The overall prognosis of such patients remains poor.
Further studies are needed to clarify the natural history of HCV infection in renal transplant patients and to assess the progression of liver disease and its impact on long term patient outcome. We suggest that anti-HCV positive renal transplant recipients who have abnormal transaminase levels should have a liver biopsy to morphologically characterize the extent of the liver disease, and those with evidence of chronic hepatitis should be closely monitored with regular ultrasound and measurement of serum AFP levels.
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Abdalla H Abdalla
Department of Renal Medicine, Riyadh Armed Forces Hospital P.O. Box 7897, Riyadh 11159
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7]