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

Abstract

After orthotopic liver transplantation (OLT), patients with chronic hepatitis C virus (HCV) infectionshow nearly universal persistence of viremia and reinfection of the liver, but identifying the point at which the liver is reinfected morphologically can be difficult. One tool that may potentially be useful to detect reinfection is reverse transcriptasepolymerase chain reaction (RT-PCR), which has proven to be highly sensitive for detecting HCV RNA in formalin-fixed paraffin-embedded liver tissue. Our purpose was to gain insight into the time frame of HCV reinfection by assaying for HCV RNA in serial posttransplant liver biopsy specimens. Our study population consisted of 14 patients who underwent liver transplantation for hepatitis C and had confirmed HCV RNA in pretransplant serum, absence of HCV RNA in donor livers, and available consecutive posttransplant liver allograft specimens. We performed RT-PCR for HCV RNA in serial posttransplant liver biopsy specimens, beginning at 1 week until at least one biopsy from each tested positive. HCV RNA was detected in liver tissue by RT-PCR in 1-week post-OLT liver samples in 6 of 14 (42.8%) patients, the earliest being 5 days post-OLT. Eventually, each of the remaining eight samples became RT-PCR positive as well; the first detections occurred in these at 3 weeks (three cases), 4 weeks (three cases), 48 weeks (one case), and 144 weeks (one case). Histologic identification of hepatitis C recurrence was relatively insensitive in relation to these molecular data. These data suggest that (1) HCV RNA reinfection is nearly universal after liver transplantation in patients with chronic hepatitis C infection, (2) molecular reinfection by HCV occurs at a variable interval post-OLT, with the majority of allograft livers reinfected as early as 1 week, and (3) morphologic features of hepatitis C are usually appreciable at the time of "molecular" recurrence.

Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patients

“…The disease is known to recur after liver transplantation, [18][19][20][21][22] resulting in hepatic dysfunction, which can further impair the metabolism of tacrolimus. 23,24 In this event, extreme caution is necessary to avoid overimmunosuppression.…”

Impact of immunosuppression on immunopathogenesis of liver damage in hepatitis C virus-infected recipients following liver transplantation

“…In addition, it is difficult to detect histological differences between HCV-and non-HCVinfected allografts in the early posttransplantation period. 7 A more distinguishable biochemical and histological hepatitis picture usually is detected between 1 and 3 months posttransplantation. 6 At this stage, all patients are HCV polymerase chain reaction positive in serum, and HCV core antigen can be detected in more than 90% of allograft biopsy specimens.…”

A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C

“…[1][2][3][4][5] However, hepatic replacement does not cure the disease, and the virus recurs in the transplanted liver. 2,6,7 The administration of immunosuppressive agents for the prevention and treatment of rejection results in acceleration of viral replication. Quantitative viral loads post-LT are much greater than they are pre-LT. 8 Reinfection of the transplanted liver allograft is almost uniform, leading to recurrent hepatitis in up to 75% of patients.…”