Incidence Of Steroid-resistant Rejection Research Articles

Calcineurin Inhibitor Free De Novo Immunosuppression in Liver Transplant Recipients With Pretransplant Renal Impairment: Results of a Pilot Study (PATRON07).

Renal impairment and high model of end-stage liver disease scores before liver transplantation (LT) are increasingly common. This was a single-arm, 2-step prospective trial of bottom-up calcineurin inhibitor (CNI)-free de novo immunosuppressive treatment (mycofenolate mofetil, steroids, basiliximab) with delayed introduction of sirolimus in patients with renal impairment. Primary endpoint was immunologic safety assessed by the incidence of steroid-resistant rejection within the first 30 days after liver transplantation. Twenty-seven patients were included with a median age of 56 years and labMELD of 28. Baseline glomerular filtration rate was 38 (Cockroft-Gault) and 24 mL/min (modification of diet in renal disease). No steroid-resistant rejections occurred within 30 days. Incidence of biopsy proven acute rejection was 18.5%. Sirolimus was started on day 10 (range, day 1 to day 48). The rate switched to CNI treatment by 1 year was 44%; 1-year overall survival was 93%. Renal function improved significantly, reflected by a Δglomerular filtration rate of 31 mL/min from baseline to 1 year (P = 0.006). Per protocol analysis revealed freedom from CNI, but not presence of sirolimus within the first 30 days, as critical for renal recovery. Initial de novo CNI-free immunosuppressive bottom-up treatment is safe in selected patient groups. The critical period for relevant recovery of renal function seems to be the early period (first 30 days), independent from presence of sirolimus.

Basiliximab Improves Graft Survival in Renal Transplant Recipients With Delayed Graft Function

The aim of this study was to evaluate the use of basiliximab in first renal transplant recipients with delayed graft function, defined by the need for dialysis in the first week posttransplantation. Among 148 patients in the study, 90 received basiliximab (60.8%) with 58 comprising the control group. There were no significant differences between the 2 groups related to the evaluated variables, except that the control group received more blood transfusions pretransplantation. There was a lower incidence of steroid-resistant rejection (6% vs 20.9%; P = .017) and humoral rejections (0% vs 7%; P = .038) in the basiliximab group. Also, graft survival was significantly higher in basiliximab group compared with the control one (92.8% vs 80.4%; P = .028). There were no significant differences in the other outcomes. In conclusion, this study confirmed the beneficial effects of addition of basiliximab to the immunosuppressive schema of patients with delayed graft function.

Long‐term results of basiliximab induction immunosuppression in pediatric liver transplant recipients

It has been shown that an induction therapy with the monoclonal anti-interleukin-2 receptor antibody basiliximab (Simulect) is capable to reduce the incidence of acute graft rejection in adult and pediatric liver transplantation (Ltx). However, data on long-term results using basiliximab in children post-Ltx are still pending. Therefore, the objective of our study was to report on the long-term results of basiliximab induction therapy in pediatric liver transplant recipients. A total of 54 children received two single doses of basiliximab in addition to cyclosporine and prednisolone following Ltx. We analyzed the incidence of acute and chronic graft rejection that of post-transplant lymphoproliferative disease (PTLD), and patient and graft survival. The follow-up was 22-46 months. The historical control group (matched controls) consisted of 54 patients treated with a cyclosporine and prednisolone dual therapy. Patient survival was 53 of 54 in the treatment group and 51 of 54 in the controls. One patient was retransplanted in the treatment group vs. three patients in the control group. The incidence of acute graft rejection was 16.6% compared with 53.7% in the control group (p < 0.001), that of chronic rejection was comparable in both groups (one of 54 vs. one of 54). The incidence of steroid resistant rejection was four of 54 vs. six of 54 that of PTLD were one of 54 vs. zero of 54. There were no adverse effects observed, which could be related to the antibody treatment. We conclude that basiliximab provides safe and effective induction immunosuppression in pediatric liver graft recipients. Short- and even long-term results are excellent.

Cyclosporine-Sparing Effect of Basiliximab in Renal Transplant Recipients With Mycophenolate Mofetil

Basiliximab added to a maintenance regimen consisting of cyclosporine microemulsion and mycophenolate mofetil was studied for its effectiveness in allowing early steroid withdrawal in renal transplantion. Furthermore, the cyclosporine-sparing effects between groups with and without basiliximab induction therapy were compared. Patients Between September 2001 and June 2003, 90 patients underwent renal transplants with cyclosporine-based immunosuppression, namely, cyclosporine, mycophenolate mofetil, and methylprednisolone, (group 1; n = 25). During the latter half of the study basiliximab was administered during the induction phase (group 2; n = 65). In group 2, steroids were completely withdrawn on postoperative day 14 in 57 patients. Results The incidence of acute rejection was significantly higher among group 1 patients ( P = .005). The incidence of steroid-resistant rejection in group 1 patients was significantly higher ( P = .025). At each time point cyclosporine levels in group 1 patients were significantly higher ( P < .01). The incidence of infection was comparable between the groups. Patient and graft survival rates in group 1 were 100% and 100%; in group 2, they were 99% and 99%, respectively. In group 2, steroids were discontinued in 57 patients with permanent withdrawal achieved in 32 patients (56%). Conclusion The use of basiliximab, together with mycophenolate mofetil allowed for a significant reduction in the cyclosporine dose without increasing the risk of acute rejection. Although further follow-up is necessary to confirm the effect, this regimen may attenuate cyclosporine nephrotoxicity thereby affecting the long-term outcomes of renal transplantation.

ROLE OF HLA MATCHING IN LIVER TRANSPLANT

A2 Aims: Whereas the role of HLA matching in renal transplantation is more or less established, its role in liver transplant is still very much a matter of debate. Methods: We conducted a search on various databases like PUBMED, EMBASE, and OVID using various combinations of key words like liver transplant, HLA, Major Histocompatibility Complex (MHC) etc. to locate all the studies on role of HLA matching in liver transplantation published in peer-reviewed journals in English language. The heterogeneity of the studies and lack of properly conducted randomized controlled trials did not lend the subject to a meta-analysis. The studies identified in this manner were hence subjected to a systematic review. Results: Opinions are split nearly in the middle on whether HLA matching is beneficial for liver transplant patients with nearly half the authors on either side. However most studies, including a number of those that concluded an adverse impact, have showed some immunological benefit for HLA matching. Amongst the beneficial outcome shown are decreased acute rejection, decreased incidence of steroid resistant rejection and chronic rejection, prolonged graft survival, prolonged patient survival, and higher chances of immunosuppression withdrawal. Whereas some found class I matching to be beneficial, others identified class II matching as useful. Matching could be harmful in two subgroups of patients with autoimmune diseases and viral infections. In these patients matching could worsen the outcome by some other not yet fully described HLA restricted mechanism. These patients could also account for the detrimental effect of matching observed in some studies. Most large studies on this topic, which have analysed these two groups of patients separate from the rest, have failed to show any substantial harm caused by matching in the remaining patients. Conclusions: Liver transplant can be performed with reasonable safety across major HLA incompatibilities and evidence is lacking to support any role for routine pretransplant matching. In patients with autoimmune disease and viral disease, matching may be harmful but whether an active effort should be made to avoid matching for these remains to be more fully elucidated.

Increasing incidence of steroid resistant rejection in kidney transplantation

Increasing incidence of steroid resistant rejection in kidney transplantation

Pediatric renal transplantation under tacrolimus-based immunosuppression.

Tacrolimus has been used as a primary immunosuppressive agent in adult and pediatric renal transplant recipients, with reasonable outcomes. Methods. Between December 14, 1989 and December 31, 1996, 82 pediatric renal transplantations alone were performed under tacrolimus-based immunosuppression without induction anti-lymphocyte antibody therapy. Patients undergoing concomitant or prior liver and/or intestinal transplantation were not included in the analysis. The mean recipient age was 10.6+/-5.2 years (range: 0.7-17.9). Eighteen (22%) cases were repeat transplantations, and 6 (7%) were in patients with panel-reactive antibody levels over 40%. Thirty-four (41%) cases were with living donors, and 48 (59%) were with cadaveric donors. The mean donor age was 27.3+/-14.6 years (range: 0.7-50), and the mean cold ischemia time in the cadaveric cases was 26.5+/-8.8 hr. The mean number of HLA matches and mismatches was 2.8+/-1.2 and 2.9+/-1.3; there were five (6%) O-Ag mismatches. The mean follow-up was 4.0+/-0.2 years. The 1- and 4-year actuarial patient survival was 99% and 94%. The 1- and 4-year actuarial graft survival was 98% and 84%. The mean serum creatinine was 1.1+/-0.5 mg/dl, and the corresponding calculated creatinine clearance was 88+/-25 ml/min/1.73 m2. A total of 66% of successfully transplanted patients were withdrawn from prednisone. In children who were withdrawn from steroids, the mean standard deviation height scores (Z-score) at the time of transplantation and at 1 and 4 years were -2.3+/-2.0, -1.7+/-1.0, and +0.36+/-1.5. Eighty-six percent of successfully transplanted patients were not taking anti-hypertensive medications. The incidence of acute rejection was 44%; between December 1989 and December 1993, it was 63%, and between January 1994 and December 1996, it was 23% (P=0.0003). The incidence of steroid-resistant rejection was 5%. The incidence of delayed graft function was 5%, and 2% of patients required dialysis within 1 week of transplantation. The incidence of cytomegalovirus was 13%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 12%. The incidence of early Epstein-Barr virus-related posttransplant lymphoproliferative disorder (PTLD) was 9%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 4%. All of the early PTLD cases were treated successfully with temporary cessation of immunosuppression and institution of antiviral therapy, without patient or graft loss. These data demonstrate the short- and medium-term efficacy of tacrolimus-based immunosuppression in pediatric renal transplant recipients, with reasonable patient and graft survival, routine achievement of steroid and anti-hypertensive medication withdrawal, gratifying increases in growth, and, with further experience, a decreasing incidence of both rejection and PTLD.

A PROSPECTIVE, RANDOMIZED TRIAL TO COMPARE TACROLIMUS AND PREDNISONE WITH AND WITHOUT MYCOPHENOLATE MOFETIL IN PATIENTS UNDERGOING RENAL TRANSPLANTATION: FIRST REPORT

Purpose Between September 20, 1995 and September 20, 1996, 120 patients were entered into a prospective, randomized trial comparing tacrolimus and prednisone with (61) and without (59) ± gm. mycophenolate mofetil daily to determine whether mycophenolate mofetil was associated with a lower incidence of rejection. Materials and Methods Mean recipient age plus or minus standard deviation was 50.8 +/− 14.1 years (range 18.8 to 84.1). Mean donor age was 34.3 +/− 21.7 years (range 0.01 to 76). Of the donors 18 (15%) were older than 60 years. Mean cold ischemia time was 30.9 +/− 8.4 hours (range 14.2 to 49). Median followup was 8.6 +/− 0.5 months. Results The 6-month actuarial patient survival was 95%, 92% in the double therapy group and 98% in the triple therapy group (not significant). The 6-month actuarial graft survival was 88%, 84% in the double therapy group and 92% in the triple therapy group (not significant). The overall incidence of rejection and steroid resistant rejection was 34.2 and 4.2%, respectively. There was a strong trend toward less rejection in the mycophenolate mofetil group than in the double therapy group (26.2 versus 42.4%). Crossover was common, and was 42.6% from triple to double therapy and 18.6% from double to triple therapy. The reasons for discontinuation of mycophenolate mofetil were gastrointestinal toxicity, primarily diarrhea, or less commonly hematological toxicity, primarily neutropenia or thrombocytopenia. Gastrointestinal toxicity was ameliorated by separating the doses of tacrolimus and mycophenolate mofetil by 2 to 4 hours, and reducing the dose to 1 gm. daily. Conclusions Mycophenolate mofetil appears to be a useful third agent with tacrolimus in patients undergoing renal transplantation, and is associated with a reduction in the rate of rejection and a low incidence of steroid resistant rejection. There is a high incidence of gastrointestinal toxicity associated with the 2 gm. daily dose but this complication is relatively straightforward to manage.

PEDIATRIC RENAL TRANSPLANTATION UNDER TACROLIMUS-BASED IMMUNOSUPPRESSION

21 Between December 14, 1989, and December 31, 1996, 82 pediatric renal transplantations alone were performed under tacrolimus-based immunosuppression without induction antilymphocyte antibody therapy. Patients undergoing concomitant or prior liver and/or intestinal transplantation were not included in the analysis. The mean recipients age was 10.6±5.2 years (range 0.7-17.9). 18(22%) cases were retransplantations, and 7(9%) were in patients with panel reactive antibody levels over 40%. 34(41%) cases were with living donors, and 48(59%) were with cadaveric donors. The mean donor age was 27.3±14.6 years (range 0.7-50), and the mean cold ischemia time in the cadaveric cases was 26.5±8.8 hours. The mean number of HLA matches and mismatches was 2.8±1.2 and 2.9±1.3; there were 5 (6%) O-Ag mismatches. The mean follow-up was 4.0±0.2 years. The 1 and 4 year actuarial patient survival was 99% and 94%. The 1 and 4 year actuarial graft survival was 98% and 84%. The mean serum creatinine was 1.1±0.5 mg/dl, and the corresponding calculated creatinine clearance was 88±25 ml/min/1.73m2. 66% of successfully transplanted patients were withdrawn from prednisone. In children off steroids, the mean standard deviation height scores (Z-score) at the time of transplantation and at 1 and 4 years were -2.3±2.0, -1.7±1.0, and +0.36±1.5. 86% of successfully transplanted patients were not taking anti-hypertensive medications. The incidence of acute rejection was 44%; between 12/89 and 12/93, it was 63%, and between 1/94 and 12/96, it was 23% (p=0.0003). The incidence of steroid-resistant rejection was 5%. The incidence of delayed graft function was 5%, and 2% of patients required dialysis within one week of transplantation. The incidence of cytomegalovirus was 13%; between 12/89 and 12/92, it was 17%, and between 1/93 and 12/96, it was 12%. The incidence of early EBV-related PTLD was 9%; between 12/89 and 12/92, it was 17% and between 1/93 and 12/96, it was 4%. All of the early PTLD cases were treated successfully with temporary cessation of immunosuppressive and antiviral therapy without patient or graft loss. These data demonstrate the short- and medium-term efficacy of tacrolimus-based immunosuppression in pediatric renal transplant recipients, with reasonable patient and graft survival, routine achievement of steroid and anti-hypertensive medication withdrawal, gratifying increases in growth, and, with further experience, a decreasing incidence of both rejection and PTLD.

A randomized, double-blind study of Neoral vs. Sandimmune in primary liver transplant recipients with two year follow up.

46 A double-blind, multi-center, randomized, two-year trial was conducted to compare the Neoral formulation (NEO) of cyclosporine to the traditional Sandimmune formulation (SIM) in de novo liver transplant patients.Aim: The primary purpose of the study was to assess the safety of NEO relative to SIM. Methods: 325 patients from 15 centers were randomized(1:1) and received either NEO (n=161) or SIM (n=164) as primary immunosuppressive therapy. Following initial IV cyclosporine therapy, patients were started on oral cyclosporine at 10 mg/kg/day and dose titrated to target trough levels according to study protocol. Steroid and azathiprine were administred according to local protocol. No antilymphocyte preparations were used for induction. Frequent study visits to assess vital sign, laboratory values and other safety and efficacy parameters were scheduled at specified intervals. Key endpoints being patient and graft survival, acute cellular rejection episodes (ACR) and adverse event profiles. Patients who discontinued from study medication were asked to participate in a follow-up phaseof data collection to complete the two years duration of the study: These data were used for an ITT analysis. Results: Key patient demographics were comparable between the two groups. One and two year patient survival rates also did not differ between groups, (Actual 1yr patient SR = NEO 93.6%vs SIM 90.8%. Retransplantation with in 1 year: N -6.5% vs S- 6.8%. Actual 2 yr patient SR was identical N- 84.2% vs S-86.6%. Retransplantation by the end of the second year occurred in N- 9.3% vs S-7.7% (p=ns). The number of patients experiencing biopsy-confirmed ACR was comparable in the two groups - NEO = 98(62.7%) vs. SIM = 94 (59.1%), with the severity of the rejection and the incidence of steroid resistant rejection (18.5% for NEO and 20.0% for SIM) also being comparable. The incidence of major adverse events, i.e., hypertension, hyperlipidemia, renal insufficiency, infections, and neurologic symptoms were also comparable for the two groups. Patients randomized to the NEO group were weaned off cyclosporine I.V. more rapidly, median days 6 vs 7(p =0.02). Patients discontinued from study medications during the follow-up period totaled 129, 66 in the NEO group vs. 63 in the SIM group; primary reasons for discontinuations were adverse events including patient death,(N-14% vs. S-13%). Discontinuation for treatment failurewasN- 15.5% vs. S-15.8%. Mean cyclosporine doses after 24 months in study were 3.7 ±1.7 vs. 3.9 ± 2.1 mg/kg/day and trough cyclosporine levels 202 ± 95 vs. 213 ± 101 ng/mL for the NEO and SIM groups respectively.Conclusion: Excellent patient and graft survival were seen in both NEO and SIM treatments arms, with less IV. cyclosporine use in the NEO treated group. This is as good or better than any other liver recipient patient and graft survival published to date. In spite of the greater exposure provided by the NEO formulation, there were no more adverse events in the NEO group.

Tacrolimus in pediatric renal transplantation.

Tacrolimus was used as the primary immunosuppressive agent in 69 pediatric renal transplantations between December 17, 1989, and June 30, 1995. Children undergoing concomitant or prior liver and/or intestinal transplantation were excluded from analysis. The mean recipient age was 10.3+/-5.0 years (range, 0.7-17.5 years). Seventeen (24.6%) children were undergoing retransplantation, and six (8.7%) had a panel reactive antibody level of 40% or higher. Thirty-nine (57%) cases were with cadaveric kidneys, and 30 (43%) were with living donors. The mean donor age was 28.0+/-14.7 years (range, 1.0-50.0 years), and the mean cold ischemia time for the cadaveric kidneys was 27.0+/-9.4 hr. The antigen match was 2.7+/-1.2, and the mismatch was 3.1+/-1.2. All patients received tacrolimus and steroids, without antibody induction, and 26% received azathioprine as well. The mean follow-up was 32+/-20 months. One- and 4-year actuarial patient survival rates were 100% and 95%. One- and 4-year actuarial graft survival rates were 99% and 85%. The mean serum creatinine level was 1.2+/-0.8 mg/dl, and the calculated creatinine clearance was 82+/-26 ml/min/1.73 m2. The mean tacrolimus dose was 0.22+/-0.14 mg/ kg/day, and the level was 9.5+/-4.8 ng/ml. The mean prednisone dose was 2.1+/-4.9 mg/day (0.07+/-0.17 mg/kg/day), and 73% of successfully transplanted children were off prednisone. Seventy-nine percent were not taking any antihypertensive medications. The mean serum cholesterol level was 158+/-54 mg/dl. The incidence of delayed graft function was 4.3%. The incidence of rejection was 49%, and the incidence of steroid-resistant rejection was 6%. The incidence of rejection decreased to 27% in the most recent 26 cases (January 1994 through June 1995). The incidence of new-onset diabetes was 10.1%; six of the seven affected children were able to be weaned off insulin. The incidence of cytomegalovirus disease was 13%, and that of posttransplant lymphoproliferative disorder was 10%; the incidence of posttransplant lymphoproliferative disorder in the last 40 transplants was 5% (two cases). All of the children who developed posttransplant lymphoproliferative disorder are alive and have functioning allografts. Based on this data, we believe that tacrolimus is a superior immunosuppressive agent in pediatric renal transplant patients, with excellent short- and medium-term patient and graft survival, an ability to withdraw steroids in the majority of patients, and, with more experience, a decreasing rate of rejection and viral complications.

Incidence, risk factors, and outcome of antithymocyte globulin treatment of steroid-resistant rejection after liver transplantation.

We retrospectively analyzed the incidence and outcome of steroid-resistant rejection (SRR) during the first 6 months after OLT in 126 patients receiving triple immunosuppression. A total of 95 patients either did not experience acute rejection at all or had acute rejection that subsided without additional treatment. A total of 31 patients had biopsy-proven acute rejection that required therapy: 18 patients had acute rejection that responded to steroid therapy (steroid-sensitive rejection, SSR); the remaining 13 patients had SRR and received ATG. At the onset of acute rejection, no differences in clinical, biochemical, or immunological parameters were present between patients with SSR and SRR. However, the histological grade of acute rejection in the initial biopsy was higher in patients with SRR (P = 0.05). ATG treatment was effective in 10 of the 13 patients and was not associated with an increased incidence of opportunistic infections. Patient and graft survival rates at 2 years were comparable in the three groups. These data show that the incidence of SRR during the first 6 months after OLT is low, and that its treatment with ATG is both effective and well tolerated.

Incidence, risk factors, and outcome of antithyrnocyte globulin treatment of steroid-resistant rejection after liver transplantation

Abstract We retrospectively analyzed the incidence and outcome of steroid-resistant rejection (SRR) during the first 6 months after OLT in 126 patients receiving triple im-munosuppression. A total of 95 patients either did not experience acute rejection at all or had acute rejection that subsided without additional treatment. A total of 31 patients had biopsy-proven acute rejection that required therapy: 18 patients had acute rejection that responded to steroid therapy (steroid-sensitive rejection, SSR); the remaining 13 patients had SRR and received ATG. At the onset of acute rejection, no differences in clinical, biochemical, or immunological parameters were present between patients with SSR and SRR. However, the histological grade of acute rejection in the initial biopsy was higher in patients with SRR (P= 0.05). ATG treatment was effective in 10 of the 13 patients and was not associated with an increased incidence of opportunistic infections. Patient and graft survival rates at 2 years were comparable in the three groups. These data show that the incidence of SRR during the first 6 months after OLT is low, and that its treatment with ATG is both effective and well tolerated.

The release of cytokines, adhesion molecules, and extracellular matrix parameters during and after reperfusion in human liver transplantation.

Poor initial graft function may increase postoperative morbidity including the risk of early allograft rejection. Various mediators, including immunostimulatory cytokines, may be released during reperfusion in relation to the extent of preservation and reperfusion injury. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines, adhesion molecules, extracellular matrix (ECM) parameters, and neopterin at predefined time-points during and after transplantation. To estimate the origin of cytokine release, blood was obtained central and hepatic venously for the first 48 hr after reperfusion and subsequently from a peripheral vein. One-year patient survival was 88.9%; no relation to initial graft function was observed. Poor initial graft function failed to increase the risk for subsequent infectious complications but was associated with an increased risk of early allograft rejection. The incidence of steroid-resistant rejection was significantly increased in patients with poor initial graft function (35.7% versus 12.7% in patients with good and moderate initial graft function; P < or = 0.05). Various cytokines, adhesion molecules, and ECM parameters including sTNF-RII, sIL-2R, IL-8, IL-10, sVCAM-1, E-selectin, hyaluronic acid, sialic acid, and laminin correlated significantly with the extent of preservation and reperfusion injury. Although none of these parameters was more appropriate in determining the extent of preservation and reperfusion injury than currently established parameters (AST, ALT, and color and amount of bile production), the combined increase in these parameters may not only promote tissue repair but may also perpetuate liver allograft injury and thereby cause significant morbidity. Besides cytokines and adhesion molecules, the ECM may play a pivotal role in determining repair or ongoing tissue injury. Ongoing changes at the microvasculature and basement membrane may result in an increase of local and circulating cytokines and adhesion molecules, which increase the risk of subsequent early allograft rejection. Furthermore, the increase in sTNF-RII, E-selectin, and laminin during reperfusion was predictive of subsequent development of acute allograft rejection. These observations may be of value for further strategies to decrease reperfusion injury and prevent early allograft rejection.

Hepatitis C: indication for anti-viral therapy?

Hepatitis C infection is a frequent indication for liver transplantation. In general, recurrent graft hepatitis is assumed to be mild, but may be the cause of lethal postoperative complications in a small patient population. Out of 500 transplants in 458 patients, 123 patients were transplanted due to hepatitis C infection (26.7%) between September 1988 and April 1994. Cumulative 1- to 6-year patient survival was similar for patients transplanted due to hepatitis C (87.0%) and those transplanted for other indications (86.0%). In patients with hepatitis C virus (HCV), death, in 50% of the cases, was related to HCV recurrence and chronic rejection. Four patients (25.0%) died because of severe infection and multiple organ failure syndrome unrelated to HCV recurrence and chronic rejection. The incidence of retransplantation was similar in HCV (9.8%) and other patients (8.4%). In HCV patients, 6 of 12 retransplantations (50.0%) were performed due to HCV recurrence and chronic rejection. Of 123 HCV patients, 45 experienced histologically proven recurrent graft hepatitis between 2 weeks and 5.5 years after transplantation. The incidence of acute rejection was similar in both groups. The incidence of steroid-resistant rejection was, however, higher in HCV patients (29.3%) than in those transplanted for other indications (14.5%; P < or = 0.05). Furthermore, there was a significant association between acute rejection and the development of recurrent graft hepatitis. In conclusion, patients with hepatitis C may be transplanted with as good patient and graft survival rates as patients transplanted for other indications. However, the combination of recurrent graft hepatitis and chronic rejection remains the most limiting factor for some of these patients, which strengthens the necessity for a specific anti-viral therapy.