A prospective analysis of oxidative stress and liver transplantation

Background. Oxidative stress (OS) is a potential mechanism of injury in many deleterious complications of orthotopic liver transplantation (OLT). There. fore, we evaluated OS prospectively in a cohort of 50 adult patients before, during, and after OLT. Methods. Urine, collected preoperatively, perioperatively, and at intervals for the first postoperative year was analyzed for dinor-dihydro-isoprostane F-2alpha-III (dinor-dihydro iPF(2alpha)-III), a well-characterized in vivo indicator of OS. Clinical events were extracted from the clinical records. Results. One-year patient and graft survival were 86% and 80%, respectively. There were nine episodes o acute cellular rejection (ACR). Twenty patients each experienced at least one adverse event. Pretransplantation urinary dinor-dihydro iPF(2alpha)-III levels were elevated, compared to healthy volunteers, and rose significantly following reperfusion of the grafted liver Levels fell sharply following OLT but never reached those of control subjects. Urinary dinor-dihydro iPF(2alpha)-III levels steadily increased thereafter, reaching preoperative levels within 12 months of transplantation There was no significant difference in dinor-dihydro iPF(2alpha)-III excretion, with respect to hepatitis C virus (HCV) status, the development of ACR, or the presence or absence of a composite of predesignated adverse events. Conclusions. OLT recipients exhibit enhanced lipid peroxidation in vivo, which is augmented during intra-operative liver reperfusion. Although OS declines following OLT, it redevelops gradually, albeit without association with clinical events such as acute cellular rejection, organ failure, or infection of the allograft by HCV. We conclude that OS increases in the first year after liver transplantation, in a time-dependent fashion, but independent of clinical events affecting the allograft.