Severe or multiple rejection episodes are associated with early recurrence of hepatitis C after orthotopic liver transplantation

Abstract

Recurrent hepatitis C causes significant morbidity after liver transplantation. Because immunosuppression is associated with enhanced viral replication, we postulated that clinical recurrence of the disease may be associated with augmented immunosuppression for rejection. In 96 patients with hepatitis C who received liver transplants, we recorded the interval from transplantation to recurrence, the episodes of steroid-resistant rejection (SRR) requiring OKT3, the number of rejection episodes, and the use of OKT3 induction. Recurrence was diagnosed based on elevated transaminases and characteristic histology. Hepatitis C recurred in 43 of 96 patients. Fifteen of 21 patients (71.4%) who previously had SRR had recurrence, versus 28 of 75 patients (37.3%) who either had no SRR (72 patients) or had it after recurrence was diagnosed (3 patients) (P < .01). Mean time to recurrence was 127 +/- 31 days in the 15 patients who had had SRR versus 246 +/- 42 days in the other 28 patients (P = .02). Recurrence and number of rejection episodes were clearly associated: 6 of 33 patients (18.2%) with no rejection had recurrence (P < .05), versus 11 of 26 patients (42.3%) with one rejection episode (P < .05) and 26 of 37 (70.2%) with more than 1 episode (P < .05). OKT3 induction was used in 15 patients; 9 of 15 patients had recurrence (ns) at 337 +/- 95 days. Of 72 patients who initially received triple immunosuppression, 30 patients had recurrence at 186 +/- 25 days (P = .05). Nine patients received primary FK506; 4 had recurrence at 68 +/- 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus

“…Nevertheless, some authors have reported better outcomes in patients receiving CsA-ME. [14][15][16][17][18] Only 3 trials have enrolled over 100 patients per arm. [19][20][21] The observational study of 283 HCV-positive liver transplant recipients by Berenguer and colleagues showed that use of tacrolimus compared to CsA-ME was independently associated with development of cirrhosis by multivariate analysis (P ϭ 0.009).…”

Hepatitis C viral infection in the immunosuppressed patient

“…28 In a series of 96 patients, Sheiner et al reported an increase risk of HCV-related chronic hepatitis in patients who had more than one rejection episode or who required OKT3 for steroid resistant rejection following transplantation. 33 Furthermore, in their series of 10 patients who developed severe recurrent cholestatic hepatitis C following liver transplantation, 50% had required increased immunosuppressive therapy with OKT3 for steroid resistant rejection in the early posttransplant period. 31 It is likely that the high dose of immunosuppression contributed to the unusually aggressive recurrent disease observed in this small group of patients.…”

Early Detection of Hepatitis C Allograft Reinfection after Orthotopic Liver Transplantation: A Molecular and Histologic Study

“…A possible explanation for these observations could be the detection of HCV RNA in serum or peripheral blood mononuclear cells, which accompany the tissue specimen (34,35). Another observation that raises the possibility of tissue RT-PCR detection of circulating HCV RNA has been the discovery of HCV RNA in liver biopsy tissue as early as 7 to 12 days post-OLT (5,22). In a preliminary study, however, we failed to detect HCV RNA by RT-PCR in liver biopsies taken from HCV-positive individuals immediately posttransplant (14).…”

“…unpublished data). Others have reported histological evidence of onset as early as 4 weeks (4,15) to as late as 3 years post-OLT (22).…”

“…Although orthotopic liver transplantation has emerged as an effective treatment for end stage chronic hepatitis C, recurrent infection of the allograft occurs almost universally according to most authors (1,2,4,5,12,(15)(16)(17)(18)(19)(20)(21)(22)(23). The major supporting evidence has been the post-OLT persistence of HCV RNA in serum, detected using the PCR technique, in nearly all cases (3,4,18,19,24).…”