Kidney Transplantation From Donors With Viral B and C Hepatitis

Kidney Transplantation From Donors With Viral B and C Hepatitis P. Veroux, M. Veroux, V. Sparacino, G. Giuffrida, C. Puliatti, M. Macarone, P. Fiamingo, D. Cappello, M. Gagliano, M. Spataro, M. Di Mare, M.A. Cannizzaro, and V. Severino ABSTRACT Introduction. The success of renal transplantation as a treatment for end-stage renal disease has created a chronic shortage of donor organs. We present our experience in transplanting kidneys from donors with hepatitis B virus (HBV) or hepatitis C virus (HCV) among matched serology-positive recipients. Materials and Methods. From January 2002 to November 2005, 44 patients with end-stage renal disease and HCV seropositivity underwent kidney transplantation. In 28 transplants in HCV⫹ recipients, the donor was HCV⫹ (DC⫹/RC⫹) and in 16 of these cases the donor (one living donor) was HCV⫺ (DC⫺/RC⫹). In the same period 14 patients with HBV infection and HbsAg seropositivity underwent kidney transplantation: eight received their graft from a cadaveric HbsAg-positive donor (DB⫹/RB⫹), while six patients received their graft from an HbsAg-negative donor. Results. Viral reactivation was higher among DC⫹/RC⫹ (21.4%) than DC⫺/RC⫹ patients (6%). Graft survivals were 90% and 88% for DC⫹/RC⫹ and DC⫺/RC⫹, respectively; patient survivals were 100% for DC⫹/RC⫹ and 94% for DC⫺/RC⫹. Among the group of DB⫹/RB⫹, all the patients developed an HBV-DNA positivity in the early postoperative period. Patient and graft survivals were 100% in both groups. Conclusions. Our results suggest that HBV- and HCV-positive donors can be considered as an alternative donor source, because their kidneys are allocated to the matched serology-positive recipients, shortening their time on the waiting list. I N ITALY there are about 7000 patients on the waiting list for a kidney transplantation, with a median time on the waiting list of 3 years. Every year only about the 20% of patients receive a transplant. As the disparity between the number of patients awaiting kidney transplants and the number of available cadaveric renal allografts continues to increase, we have tried to supply our long waiting list by using organs from donors with special clinical situations. We have recently introduced the utilization of kidney donors with known hepatitis B virus (HBV) or hepatitis C virus (HCV),1,2 with particular care regarding the rate of clinical progression of hepatic disease. In this study we present the medium-term results of kidney transplantations performed with organs from cadaveric donors with HBV or HCV. PATIENTS AND METHODS After informed consent, 44 patients with end-stage renal disease and HCV seropositivity underwent kidney transplantation from January 2002 to November 2005. In 28 transplants in HCV⫹ 0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.03.049 996 recipients, the donor was HCV⫹ (DC⫹/RC⫹) and in 16, the donor (one living donor) was HCV⫺ (DC⫺/RC⫹). One DC⫹/ RC⫹ patient received a double transplant. In the same period after informed consent, 14 patients with an HBV infection and HbsAg seropositivity underwent kidney transplantation; eight from a cadaveric HbsAg-positive donor (DB⫹/RB⫹), while six patients, from an HbsAg-negative donor (one living donor). The inclusion criteria and the immunosuppressive regimen have been detailed in two previous studies.1,2 The median follow-up was 23 months (range 4 to 46 months) (Table 1). From the Department of Surgery, Transplantation and Advanced Technologies (P.V., M.V., G.G., C.P., M.M., P.F., D.C., M.G., M.S., M.D.M.), Organ Transplant Unit, University Hospital, Catania, Italy, and Nephrology and Transplantation Unit (V.S.), Civico Hospital, Palermo, Italy. Address reprint requests to Massimiliano Veroux, MD, PhD, Department of Surgery, Transplantation and Advanced Technologies, Organ Transplant Unit, University Hospital, Via S. Sofia, 86, 95123 Catania, Italy. E-mail: veroux@unict.it © 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 38, 996 –998 (2006) DONORS WITH VIRAL B AND C HEPATITIS RESULTS All DC⫹/RC⫹ patients had HCV-RNA positivity at followup. Six patients had clinical signs of viral replication and HCV reactivation. Median time of reactivation from transplant was short: 3 months (range 1 to 8 months). There was a low rate of acute rejection episodes (10%). One D⫹/R⫹ patient experienced an acute vascular rejection, which finally resulted in graft loss, due to the insurgence of severe infectious disease. In terms of renal function, the serum creatinine level at 1 year posttransplant was similar in both groups. Graft survivals were 90% and 88% for DC⫹/RC⫹ and DC⫺/RC⫹, respectively; patient survivals were 100% for DC⫹/RC⫹ and 94% for DC⫺/RC⫹. Among the group of DB⫹/RB⫹, all patients developed HBV-DNA positivity in the early postoperative period; however, only one patient showed clinical reactivation of viral hepatitis. In the DB⫺/RB⫹ group there were two cases of reactivation, requiring treatment with lamivudine with clinical regression of liver disease. Patient and graft survivals were 100% in both groups. DISCUSSION Infections with HBV or HCV are of particular importance due to the risk of progression to chronic liver disease as well as to the capacity of these viruses to be reactivated under immunosuppression.3 There are an estimated 150 million patients infected with HCV worldwide.4 The rates of HCV positivity among cadaveric donors vary from 1% to 11.8% in various parts of the world.5 The utilization of HCV-positive cadaveric donors is still controversial. HCV-positive recipients show worse graft and patient survivals compared with HCV-negative recipients,6 with a greater incidence of acute rejection episodes and proteinuria, which are both traditionally associated with a greater incidence of chronic transplant nephropathy.7–9 However, the survival of HCV-positive patients with end-stage renal disease is better after transplantation than if they remain on dialysis.10,11 Therefore, shortening the waiting time for end-stage renal disease patients with HCV infection appears beneficial. Morales et al12 first reported the results of a prospective study in which they demonstrated that there were no differences in the posttransplant prevalence of liver disease and graft and patient survivals among 24 anti-HCV-positive recipients who received kidney from anti-HCV-positive donors when compared with 40 HCV-positive recipients who received a kidney from an HCV-negative donor. Moreover, only 11% of HCV-RNA-positive patients who received an HCV-RNA-positive kidney developed liver disease after transplantation. We have previously demonstrated1 that transplanting kidneys from HCV-positive donors into HCV-positive recipient did not affect patient or graft survival in the early posttransplant period. With the present study we have demonstrated that at a longer follow-up transplantation of kidneys from HCV-positive donors into HCV-positive do- 997 nors recipients did not affect overall patient and graft survival, liver function, or rejection episodes when compared to HCV-positive recipients of kidneys from an HCV-negative donor. The results of this study, in addition, demonstrated a potential benefit in the transplantation of kidney from cadaveric HCV-positive donors into HCV-positive recipients, by the shortening their time on the transplant waiting list. Interestingly, clinical reactivation of viral hepatitis was more frequent and precocious in the DC⫹/RC⫹ group than DC⫺/RC⫹ group. This could be explained by the fact that in most HCV-positive donor organs, HCV-RNA was not available. The risk for development of chronic hepatitis following transmission of the virus from the graft appears to be increased among donors with high viral loads and HCV-RNA positivity compared with those without detectable viral loads.10,13–15 One may speculate that the viral reactivation was higher among kidney recipients of grafts from an HCV-RNA donor. Although this has not been demonstrated, we have actually adopted the policy to refuse kidneys from HCV-positive, HCV-RNA-positive donor organs. Despite that HCV-positive renal transplant recipients are considered to show high immunological risk, we have adopted an immunosuppressive regimen, with rapid taper of steroids to 5 mg within 3 months posttransplant, resulting in a low rate of rejection and infectious disease. Graft and patient survivals were similar between the two groups, with a slight benefit in the DC⫹/RC⫹ group. The high prevalence of HBV infection in some endemic area have stimulated the utilization of HbsAg-positive donors for transplantation. A few small studies have demonstrated that these patients can receive kidney allografts from HbsAg donors with no or minimal risk of acquiring an HBV infection from the donor.16,17 Consequently, some transplant centers have adopted a policy to transplant the HbsAg-positive kidneys into recipients who are immune to HBV or in HbsAg-positive patients.18 Most studies have shown that the long-term prognosis of HbsAg-positive kidney recipients is worse than of HbsAg-negative recipients, despite some studies that have shown little difference.19,20 Up to 85% of all HbsAg⫹ renal transplant recipients develop biopsy-proven chronic active hepatitis by 10 years posttransplant. The results of the present study showed that there was no statistically significant differences between the two groups with respect to the number of episodes of hepatitis and graft and patient survivals. However, clinical reactivation of hepatitis was detectable in about one third of patients, and the time of onset of reactivation is longer than for patients with HCV infection. In conclusion, renal transplantation from donors with HBV or HCV into matched serology-positive recipients could be a safe way to expand the donor pool. Donors with a demonstrable high viral load should be refused, because of the high rate of reactivation in patients receiving their kidneys. A careful pre- and posttransplant evaluation of the 998 VEROUX, VEROUX, SPARACINO ET AL Table 1. Donor and Recipient Characteristics Donor characteristics Age in years (average) Cold ischemia in hours (average) Terminal creatinine in mg/dL (average) Recipient Age in years (average) Male/female Time on waiting list in months Acute rejection Viral hepatitis reactivation Liver failure Graft loss Death Serum creatinine in mg/dL at 1 year DC⫹/RC⫹ (n ⫽ 28) DC⫺/RC⫹ (n ⫽ 16) DB⫹/RB⫹ (n ⫽ 8) DB⫺/RB⫹ (n ⫽ 6) 47 23 1.2 51 21 1.43 41 22 1.1 39 24 1.3 48 4/2 8 1 (12%) 1 (12%) 0% 0% 0% 1.4 42 4/2 12 0 (0%) 2 (33.3%) 0% 0% 0% 1.0 51 18/10 9 1 (10%) 6 (21.4%) 0% 3 (10%) 0% 1.5 liver function eventually with multiple liver biopsies, and tailored immunosuppression may improve the outcome of such patients. REFERENCES 1. Veroux P, Veroux M, Puliatti C, et al: Kidney transplantation from hepatitis C virus-positive donors into hepatitis C viruspositive recipients: a safe way to expand the donor pool? Transplant Proc 37:2571, 2005 2. Veroux M, Puliatti C, Macarone M, et al: Kidney transplantation from hepatitis B surface antigen-positive donors into hepatitis B surface antigen-positive recipients: preliminary findings. Transplant Proc 37:2467, 2005 3. No authors: Viral hepatitis guidelines in hemodialysis and transplantation. Am J Transplant 4 (suppl 10):72, 2004 4. Lauer GM, Walker BD: Hepatitis C virus infection. N Engl J Med 345:41, 2001 5. Natov SN, Pereira BJ: Transmission of viral hepatitis by kidney transplantation: donor evaluation and transplant policies (part 2: hepatitis C virus). Transplan Infect Dis 4:124, 2002 6. Abbott KC, Bucci JR, Matsumoto CS, et al: Hepatitis C and renal transplantation in the era of modern immunosuppression. J Am Soc Nephrol 14:2908, 2003 7. Pereira BJ, Wright TL, Schmid CH, et al: The impact of pre-transplantation hepatitis-C infection on the outcome of renal transplantation. Transplantation 60:799, 1995 8. 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