Viral dynamics of hepatitis C early after orthotopic liver transplantation: Evidence for rapid turnover of serum virions

Abstract

rum HCV-RNA levels in recipients before, during, and after The pathogenesis of hepatitis C virus (HCV) infectionOLT to obtain kinetic information on the dynamics of HCV is likely to be associated with viral replication in vivo, replication and clearance in vivo. Liver transplantation recipbut little is known concerning the dynamics of HCV ients are ideally suited to provide insights into the mechaturnover. We performed serial measurements of serum nisms of HCV pathogenesis, because hepatic HCV replication HCV-RNA levels following orthotopic liver transplantais terminated at the time of removal of the infected liver, and tion (OLT) in nine patients with HCV-positive cirrhosis.the clinical setting following reperfusion of the engrafted liver Serum HCV-RNA levels were determined by quantitaprovides a model for monitoring dynamic processes of graft tive polymerase chain reaction before, immediately reinfection. after, and for up to 1 month after OLT. There was a rapid decline in HCV-RNA levels from 3.1 { 1.3 1 10 5 copies/ PATIENTS AND METHODS mL (mean { SEM) preoperatively to 0.15 { 0.6 1 10 5 copies/mL on the first and 0.16 { 0.6 1 10 5 copies/mL on the therapy including steroid bolus administration. In mostAll patients received a quadruple immunosuppressive regimen for patients, serum virions continued to increase averaging the first week after OLT consisting of prednisolone, azathioprine, 11.6 { 2.8 1 10 5 copies/mL on the 30th postoperative day. antithymocyte globulin, and cyclosporin A or tacrolimus. Murine These findings indicate that the half-life of HCV is quite monoclonal antibody (OKT-3) was not used in any of the patients. short, and that extrahepatic viral replication contrib-Subsequently, patients underwent a triple immunosuppressive regiutes little to the total virus pool in serum. Furthermore, men for 3 weeks (prednisolone, azathioprine, and cyclosporin A or tacrolimus). Six of the nine patients developed histologically conthe marked HCV replication beginning as early as the firmed acute rejection and in five, steroid bolus injection was initithird postoperative day strongly suggests that the liver ated 8 or 9 days after OLT. Liver biopsy was performed in all patients graft is rapidly reinfected by HCV after OLT. (HEPATOLbetween 7 to 10 days after OLT. Serum samples were collected at 1 day before OLT and daily after OLT for a period of up to 30 days and stored at 080ЊC. In addition, for six of the nine patients, serum samples were also collected during Hepatitis C virus (HCV) reinfection after orthotopic liver the transplantation procedure, i.e., before starting the operation, transplantation (OLT) occurs in almost all patients with preduring the anhepatic phase, during reperfusion of the graft, and at transplantation viremia, and 50% to 70% of these patients regular intervals for the first day after reperfusion. develop graft hepatitis which is mild in most cases.1-6 How-The presence of antibody to HCV (anti-HCV) was tested for by ever, in some patients, graft hepatitis can be severe, with a secon...

Controversies in the management of hepatitis C virus infection after liver transplantation

“…[29][30][31][32][33][34] Over the next several weeks, the serum level of HCV RNA plateaus at a value 10-to 100-fold greater than that observed in the pretransplantation period and remains relatively stable thereafter. There appears to be no relationship between the serum HCV RNA level measured after 4 months and the histologic severity of recurrent HCV.…”

Hepatitis C viral infection in the immunosuppressed patient

“…27,28 HCV RNA levels begin to rise on day 2 reaching pretransplant levels on day 9 and become three times pre-transplant levels by day 28. 29 HCV RNA levels may ultimately reach 14 times pretransplant levels. 29 Early reports on HCV recurrence suggest that severe recurrent liver disease was uncommon; however, in a more close analysis of serial liver biopsies, with more extensive patient numbers and a longer follow-up, it is now clear that recurrent disease is more common than originally thought and may be more aggressive than that seen in the immunocompetent patient.…”

Prediction of liver allograft fibrosis after transplantation for hepatitis C virus: Persistent elevation of serum transaminase levels versus necroinflammatory activity

“…Previous reports have shown an association of CMV viremia, 27 HLA donor-recipient compatibility, 28 episodes of rejection, 19,29,30 use of OKT3, 31 and intensity of immunosuppression 15,32,33 with HCV-induced graft injury. These findings were not confirmed in this study and were likely caused by the relatively small number of subjects studied.…”