Hepatitis C, Acute Humoral Rejection, and Renal Allograft Survival JOHN P. FORMAN,* †‡ NINA TOLKOFF-RUBIN, †‡ MANUEL PASCUAL, § and JULIE LIN* ‡ *Renal Division, Department of Medicine, Brigham and Women’s Hospital, † Renal Unit, Department of Medicine, Massachusetts General Hospital, and ‡ Harvard Medical School, Boston, Massachusetts; and § Transplant Center, CHUV and Faculty of Medicine, Lausanne, Switzerland. Abstract. The effect of recipient hepatitis C virus (HCV) in- fection on renal allograft loss and acute rejection in kidney transplantation remains controversial. We studied 354 renal allograft recipients transplanted during 1996 to 2001 who had HCV antibodies (Ab) measured before transplantation. The primary outcome was death-censored allograft loss and the secondary outcome was acute humoral rejection (AHR). Com- pared with HCV Ab–negative patients, those with positive HCV Ab had longer time on dialysis before transplantation, higher percentage of panel-reactive antibodies (PRA), were more likely to receive a cadaveric transplant, and were more likely to develop delayed graft function (DGF). In univariate analyses, predictors of renal allograft loss included HCV, ca- daveric graft, PRA 20%, HLA mismatch 5, retransplanta- tion, DGF, induction therapy, and AHR. When adjusted for PRA 20%, HLA mismatch 5, and multiple transplant sta- tus, HCV was not a statistically significant predictor of allo- graft loss. HCV was also associated with AHR but lost signif- icance when adjusted for PRA 20%. HCV Ab–positive patients were more likely to have longer duration of dialysis before transplantation prior to kidney transplants, higher PRA, and to receive cadaveric transplants. These characteristics likely resulted in more DGF and AHR after transplantation. After adjusting for these confounding factors, the association between HCV Ab positivity and renal allograft loss was nota- bly attenuated and no longer statistically significant. Considerable controversy persists regarding the effect of hep- atitis C virus (HCV) on the outcomes of kidney transplantation (1,2). Numerous studies have reported a deleterious effect, with higher rates of acute rejection and allograft loss (3–9). In contrast, an equal number of studies report outcomes that are comparable to those seen in recipients who are not infected with HCV (10 –14). In this study, we examined the effect of HCV Ab status on death-censored allograft survival and acute rejection in kidney transplant recipients. Given the recent advances in the diagno- sis of acute humoral rejection (AHR) with specific pathologic criteria outlined by Racusen and others (15) in 1999, and our own interest in this field (16 –18), we also specifically asked whether HCV imposed an increased risk of antibody-mediated rejection. Notably, in 1996, Cosio et al. (19) reported that “acute vascular rejection” (possibly due to anti-donor antibod- ies) was more common in HCV-positive recipients, but this has not been studied in recent years. Materials and Methods Study Design We performed a retrospective study of 361 patients who received a kidney transplant between January 1, 1996, and December 31, 2001, at Massachusetts General Hospital, where the study was performed. The study cohort was restricted to 354 subjects who had HCV Ab measured before transplantation. This study was approved by the Massachusetts General Hospital Institutional Review Board. Data Collection Demographic and clinical data were extracted from review of the medical records. Serum creatinine measures were taken at 1, 3, 6, and 12 mo. After 12 mo, the creatinine was recorded if the test was performed within 3 mo of a predetermined time point of 24, 36, 48, 60, and 72 mo or at end of the study period. Follow-up continued until allograft loss, patient death, or end of the study period on December 31, 2002. Transplant Operation and Patient Management The individual surgeons and nephrologists caring for the patients directed perioperative and long-term management. Decisions regard- ing specific immunosuppression were generally at the discretion of the treating physicians. Beginning in 1997, the majority of patients (85%) were treated with triple immunosuppression consisting of a calcineurin inhibitor, corticosteroids, and mycophenolate mofetil. Be- fore 1997, azathioprine was used rather than mycophenolate mofetil; 42 transplants (11%) were performed before 1997. Sirolimus therapy was used in only 3% of recipients. Antibody induction therapy was generally given if the recipient had an elevated panel-reactive anti- body (PRA) (20%), was undergoing retransplantation, or developed delayed graft function (DGF). Beginning in 2000, recipients of ca- Received March 1, 2004. Accepted September 7, 2004. Correspondence to Dr. Julie Lin, Brigham and Women’s Hospital/Renal Di- vision, 75 Francis Street, MRB-4, Boston, MA 02115. Phone: 617-732-6432; Fax: 617-975-0840; E-mail: jlin11@partners.org 1046-6673/1512-3249 Journal of the American Society of Nephrology Copyright © 2004 by the American Society of Nephrology DOI: 10.1097/01.ASN.0000145896.16153.43 J Am Soc Nephrol 15: 3249–3255, 2004