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Renal transplantation in anti–HCV-positive patients with end-stage renal disease
Renal Transplantation in Anti–HCV-Positive Patients With End-Stage Renal Disease F.A.M. Shaheen, I.A. Sheikh, A. Mutwalli, and A. Al-Khader
I
T TOOK many years for research workers to obtain answers to the mystery regarding non-A, non-B hepatitis1 (NANBH) in patients receiving frequent blood transfusions and in organ-transplant patients. Since 1989, new tests2,3 detecting the cause of NANBH have become available, with more sensitivity and specificity, which can confirm the presence of hepatitis C virus (HCV). Various modes of spread have been examined (eg, blood-borne, sexually transmitted, perinatally transmitted, transmitted via organ transplantation, nosocomially transmitted).4 – 8 See Table 1 for policy regarding patients who are anti– HCV-positive.
PATIENTS AND METHODS A total of 84 patients with known anti–HCV-positive status were transplanted between 1992 and 1996. Another 24 patients were enrolled in this study who were proven to be anti–HCV-positive after renal transplant, or were transplanted at some other center and had come to follow-up at our center. We used ELISA for screening of anti-HCV, whereas RIBA-2 was used to confirm it. Twenty-six of our patients had undergone liver biopsies prior to transplantation. All patients were followed-up for an average of 30 months at 4- to 6-week intervals. At each visit, renal graft function and liver function tests were done. The hepatitis C status was evaluated every 6 months. At posttransplantation follow-up, 25 patients were subjected to liver biopsies. The control group included 100 patients who were of the same gender and transplanted during the same time period. They were also followed-up 4 to 6 weeks in OPD for an average of 26 months. Hepatitis C status was also checked at 6-month intervals. Only six patients had liver biopsies done at posttransplantation, due to elevated transaminases.
RESULTS
The patients were divided into two groups. Group I included patients with HCV antibody (Ab)-positive status, whereas group II patients were persistently negative for HCV Ab at follow-up. In group I, 32 patients were found to have high transaminases in the immediate posttransplant period. Follow-up of group II revealed that 16 patients had high liver enzymes in the same period. In group I, a total of 26 patients had liver biopsies preoperatively and they were accepted for transplantation according to our criteria. Repeat biopsies of 15 of these patients at follow-up revealed a picture of mild chronic hepatitis; 10 other patients in this group had liver biopsies reported to be consistent with mild hepatitis in 8, whereas 2 developed acute fulminant hepatitis. They were also found to be positive for hepatitis B virus and subsequently died due to hepatic failure. In group II, 6 patients had liver biopsies due to persistently raised transminases, and histopathologic investigation revealed nonspecific hepatitis (n 5 3), chronic hepatitis (n 5 1), and drug-induced hepatitis (n 5 2). Graft survival in both groups was about 83% over 4 years. DISCUSSION
A 100% transmission of HCV, as determined by PCR, to the recipients when the donor was either PCR-positive or strongly RIBA-positive was noted in one study.9 Based on the results of another study10 in 1993, the New England From the King Fahd Hospital, Jeddah Kidney Center, Riyadh, Kingdom of Saudi Arabia. Address reprint requests to Dr S. Fam, PO Box 11076, Jeddah 21453, Saudi Arabia.
Table 1. Policy for Anti–HCV-Positive Patients Clinical Findings
Anti–HCV-positive with normal transaminases during previous 6 months Anti HCV Positive with raised transamines No cirrhosis or active hepatitis in pathology Anti–HCV-positive with raised transaminases; found to have liver cirrhosis in histopathology Anti–HCV-positive with active hepatitis
Remarks
Permitted transplantation Liver biopsy done Permitted transplantation Abandoned renal transplantation Delayed transplantation and repeat liver biopsy after 6 months
0041-1345/98/$19.00 PII S0041-1345(98)00969-5
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
3142
Transplantation Proceedings, 30, 3142–3143 (1998)
RENAL TX in Anti–HCV-Positive Patients
Organ Bank adopted a policy of restricting the use of HCV-Ab-positive donors to life-saving transplants (heart, liver, lung) only. Other investigators11,12 have also shown that the presence of anti-HCV at the time of renal transplantation does not adversely affect graft or patient survival after transplantation. In summary, much controversy has taken place over the question of whether anti–HCV-positive patients on dialysis should be offered renal transplantation. Because the incidence of anti–HCV-positivity was very high in our dialysis population, and was persistently rising, we had no choice but to start accepting these patients for transplantation. In our study, patients with anti–HCV-positive status did very well, but the two patients who died of fulminant hepatitis were found to have become positive for hepatitis B, indicating the unfavorable presence of HBV in the immunosuppressed patient. A similar observation was published in a study13 in which the investigators reported the prevalence and clinical course of hepatitis B and C liver disease in cyclosporinetreated renal allograft recipients, and there were no liverdisease-related deaths in the HCV group, whereas four cases progressed to fulminant hepatic failure in the hepatitis B–positive group. The average mortality in group I and group II patients was almost equal, and graft function was also comparable between groups. If we look back at the controversy regarding transplantation of HCV-positive patients in 1993 and at the experience up to 1997 it would seem to be a good decision to start
3143
transplanting these patients, but biopsies would be of great importance for exclusion of patients with significant irreversible liver disease. CONCLUSIONS ● ●
●
Short-term outcome of renal transplantation in anti– HCV-positive patient is excellent. Pretransplant liver biopsies and follow-up liver biopsies are important for detecting progression of liver disease during long-term follow-up. The combination of anti-HCV and hepatitis B suggests a poor clinical prognosis.
REFERENCES 1. Choo QL, Kuo G, Weiner AJ, et al: Science 244:358, 1989 2. Kuo G, Choo QL, Alter HJ, et al: Science 244:362, 1989 3. Evan CS, Tobler L, Polito A, et al: Transfusion 32:408, 1992 4. Alter MJ: N Engl J Med 330:784, 1994 5. Botte C, Janot C: Nephrol Dial Transplant 11(suppl 4):19, 1996 6. Pereira BJG, et al: Lancet 345:484, 1995 7. Dussol B, et al: Nephrol Dial Transplant 10:477, 1995 8. McLaughlin KJ, et al: Nephrol Dial Transplant 12:304, 1997 9. Aeder MI, Shield CF, Tegtneier GE, et al: Transplant Proc 25:1469, 1993 10. Pereira BTG, et al: Transplant Proc 5:1458, 1993 11. Stempel CA, et al: Transplantation 55:273, 1993 12. Klauser R, et al: Transplant Proc 24:286, 1992 13. Bang BK, et al: Nephron 70:397, 1995
I
T TOOK many years for research workers to obtain answers to the mystery regarding non-A, non-B hepatitis1 (NANBH) in patients receiving frequent blood transfusions and in organ-transplant patients. Since 1989, new tests2,3 detecting the cause of NANBH have become available, with more sensitivity and specificity, which can confirm the presence of hepatitis C virus (HCV). Various modes of spread have been examined (eg, blood-borne, sexually transmitted, perinatally transmitted, transmitted via organ transplantation, nosocomially transmitted).4 – 8 See Table 1 for policy regarding patients who are anti– HCV-positive.
PATIENTS AND METHODS A total of 84 patients with known anti–HCV-positive status were transplanted between 1992 and 1996. Another 24 patients were enrolled in this study who were proven to be anti–HCV-positive after renal transplant, or were transplanted at some other center and had come to follow-up at our center. We used ELISA for screening of anti-HCV, whereas RIBA-2 was used to confirm it. Twenty-six of our patients had undergone liver biopsies prior to transplantation. All patients were followed-up for an average of 30 months at 4- to 6-week intervals. At each visit, renal graft function and liver function tests were done. The hepatitis C status was evaluated every 6 months. At posttransplantation follow-up, 25 patients were subjected to liver biopsies. The control group included 100 patients who were of the same gender and transplanted during the same time period. They were also followed-up 4 to 6 weeks in OPD for an average of 26 months. Hepatitis C status was also checked at 6-month intervals. Only six patients had liver biopsies done at posttransplantation, due to elevated transaminases.
RESULTS
The patients were divided into two groups. Group I included patients with HCV antibody (Ab)-positive status, whereas group II patients were persistently negative for HCV Ab at follow-up. In group I, 32 patients were found to have high transaminases in the immediate posttransplant period. Follow-up of group II revealed that 16 patients had high liver enzymes in the same period. In group I, a total of 26 patients had liver biopsies preoperatively and they were accepted for transplantation according to our criteria. Repeat biopsies of 15 of these patients at follow-up revealed a picture of mild chronic hepatitis; 10 other patients in this group had liver biopsies reported to be consistent with mild hepatitis in 8, whereas 2 developed acute fulminant hepatitis. They were also found to be positive for hepatitis B virus and subsequently died due to hepatic failure. In group II, 6 patients had liver biopsies due to persistently raised transminases, and histopathologic investigation revealed nonspecific hepatitis (n 5 3), chronic hepatitis (n 5 1), and drug-induced hepatitis (n 5 2). Graft survival in both groups was about 83% over 4 years. DISCUSSION
A 100% transmission of HCV, as determined by PCR, to the recipients when the donor was either PCR-positive or strongly RIBA-positive was noted in one study.9 Based on the results of another study10 in 1993, the New England From the King Fahd Hospital, Jeddah Kidney Center, Riyadh, Kingdom of Saudi Arabia. Address reprint requests to Dr S. Fam, PO Box 11076, Jeddah 21453, Saudi Arabia.
Table 1. Policy for Anti–HCV-Positive Patients Clinical Findings
Anti–HCV-positive with normal transaminases during previous 6 months Anti HCV Positive with raised transamines No cirrhosis or active hepatitis in pathology Anti–HCV-positive with raised transaminases; found to have liver cirrhosis in histopathology Anti–HCV-positive with active hepatitis
Remarks
Permitted transplantation Liver biopsy done Permitted transplantation Abandoned renal transplantation Delayed transplantation and repeat liver biopsy after 6 months
0041-1345/98/$19.00 PII S0041-1345(98)00969-5
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
3142
Transplantation Proceedings, 30, 3142–3143 (1998)
RENAL TX in Anti–HCV-Positive Patients
Organ Bank adopted a policy of restricting the use of HCV-Ab-positive donors to life-saving transplants (heart, liver, lung) only. Other investigators11,12 have also shown that the presence of anti-HCV at the time of renal transplantation does not adversely affect graft or patient survival after transplantation. In summary, much controversy has taken place over the question of whether anti–HCV-positive patients on dialysis should be offered renal transplantation. Because the incidence of anti–HCV-positivity was very high in our dialysis population, and was persistently rising, we had no choice but to start accepting these patients for transplantation. In our study, patients with anti–HCV-positive status did very well, but the two patients who died of fulminant hepatitis were found to have become positive for hepatitis B, indicating the unfavorable presence of HBV in the immunosuppressed patient. A similar observation was published in a study13 in which the investigators reported the prevalence and clinical course of hepatitis B and C liver disease in cyclosporinetreated renal allograft recipients, and there were no liverdisease-related deaths in the HCV group, whereas four cases progressed to fulminant hepatic failure in the hepatitis B–positive group. The average mortality in group I and group II patients was almost equal, and graft function was also comparable between groups. If we look back at the controversy regarding transplantation of HCV-positive patients in 1993 and at the experience up to 1997 it would seem to be a good decision to start
3143
transplanting these patients, but biopsies would be of great importance for exclusion of patients with significant irreversible liver disease. CONCLUSIONS ● ●
●
Short-term outcome of renal transplantation in anti– HCV-positive patient is excellent. Pretransplant liver biopsies and follow-up liver biopsies are important for detecting progression of liver disease during long-term follow-up. The combination of anti-HCV and hepatitis B suggests a poor clinical prognosis.
REFERENCES 1. Choo QL, Kuo G, Weiner AJ, et al: Science 244:358, 1989 2. Kuo G, Choo QL, Alter HJ, et al: Science 244:362, 1989 3. Evan CS, Tobler L, Polito A, et al: Transfusion 32:408, 1992 4. Alter MJ: N Engl J Med 330:784, 1994 5. Botte C, Janot C: Nephrol Dial Transplant 11(suppl 4):19, 1996 6. Pereira BJG, et al: Lancet 345:484, 1995 7. Dussol B, et al: Nephrol Dial Transplant 10:477, 1995 8. McLaughlin KJ, et al: Nephrol Dial Transplant 12:304, 1997 9. Aeder MI, Shield CF, Tegtneier GE, et al: Transplant Proc 25:1469, 1993 10. Pereira BTG, et al: Transplant Proc 5:1458, 1993 11. Stempel CA, et al: Transplantation 55:273, 1993 12. Klauser R, et al: Transplant Proc 24:286, 1992 13. Bang BK, et al: Nephron 70:397, 1995