Background. Recurrence of hepatitis C (HCV) infection after orthotopic liver transplantation (OLT) in HCV-positive patients is almost universal. Severity of graft hepatitis increases during the long-term follow-up, and up to 30% of patients develop severe graft hepatitis and cirrhosis. However, there are still no clear predictors for severe recurrence. The aim of this study was to examine the 10-year outcome and risk factors for graft failure caused by HCV recurrence.
Methods. In a prospective analysis, 234 OLTs in 209 HCV-positive patients with a median age of 53 years were analyzed. Immunosuppression was based on cyclosporine A or tacrolimus in different protocols. Predictors for outcome were genotype, viremia, donor variables, recipient demographics, postoperative immunosuppression, and human leukocyte antigen (HLA) compatibilities.
Results. Actuarial 5-, and 10-year patient survival was 75.8% and 68.8%. Eighteen of 209 (8.7%) patients died because of HCV recurrence, which was responsible for 35.9% of the total 53 deaths. Significant risk factors for HCV-related graft failure in an univariate analysis were multiple steroid pulses, use of OKT3, and donor age greater than 40. However, in a multivariate analysis, multiple rejection treatments with steroids and OKT3 treatment proved to be significantly associated with HCV-related graft loss.
Conclusions. The analysis of causes leading to graft failure in patients with HCV showed that HCV recurrence is responsible for one of three deaths in HCV-positive patients. Rejection treatment contributed significantly to an enhanced risk for HCV-related graft loss. New antiviral treatments, as well as adapted immunosuppressive protocols, will be necessary to further improve the outcome of HCV-positive patients after liver transplantation.
Hepatitis C virus (HCV) infects an estimated 170 million people worldwide and thus represents a viral pandemic. In the past, transfusion-associated hepatitis decreased to a negligible level, but new cases occur mainly as a result of injection-drug use and, to a lesser degree, through other means of percutaneous or mucous-membrane exposure. Subsequently, chronic HCV has emerged as the most common indication for orthotopic liver transplantation (OLT) (1).
The availability of antibody testing, and more recently the introduction of polymerase chain reaction (PCR) amplification, led to a more accurate diagnosis of HCV infection. With this improvement of diagnostic techniques, it became evident in recent years that HCV recurrence occurred very early, within the first 4 weeks after liver transplantation (2). Molecular analysis has shown that postoperative viral strains are identical to isolates detected before transplantation (3).
After liver transplantation, the virus load increased up to more than 10-fold compared with pretransplant levels (4), which is thought to reflect suppression of those host-effector immune responses usually controlling HCV replication. This resulted in severe HCV-related graft hepatitis in nearly 50% of HCV-positive patients after OLT. Fifteen to 30% of all HCV-positive patients developed cirrhosis during the course of the disease; however, less than 10% required retransplantation within 5 years after OLT (5-7). In contrast with an analysis of the United Network of Organ Sharing (UNOS) database (8), recent large, single-center studies showed no differences in HCV-positive patients compared with HCV-negative patients (9,10). One possible reason for these results may be the inaccurate definition of study endpoints. To predict the outcome of HCV-positive patients after OLT, several risk factors for the development and severity of graft hepatitis have been reported in the past. A relationship between HCV viremia levels, genotype 1b, rejection treatment, recipient age older than 52 years, and serum creatinine level greater than 1 mg/dL before OLT has been suggested to be involved in the pathogenesis of severe recurrent hepatitis, but the matter remains controversial (10-14). In this study, we prospectively evaluated our HCV-positive patients for predictors of fatal outcome and HCV-related graft failure after OLT.