Minocycline Administration During Human Liver Transplantation

Liver transplantation is the sole therapy for end-stage liver diseases in children and
adults. However, use of this life-saving technique is limited due to a severe shortage of
donor livers and, consequently, over 1500 patients/year on waiting lists die prior to
transplantation due to organ shortages. Also, poor immediate graft function remains a
persistent problem especially in recipients of marginal livers, and biliary strictures
evolving from reperfusion injury cause prolonged hospital stay, increased health care costs,
and increased mortality. Furthermore, hepatic cold storage and reperfusion in transplantation
settings cause mitochondrial dysfunction in liver cells, which constitutes a great risk for
primary nonfunction and initial poor function after liver transplantation. The tetracycline
derivative minocycline is a safe and widely used antibiotic that possesses cytoprotective
effects through prevention of mitochondrial dysfunction in a variety of disease models.
Recently, we showed that minocycline also protects against graft dysfunction and failure
after orthotopic rat liver transplantation and against cell death after ischemia-reperfusion
to cultured rat hepatocytes. Minocycline treatment specifically prevented mitochondrial
dysfunction and increased graft and animal survival by blocking necrotic and apoptotic death
pathways. Clinical studies indicating severe deterioration of mitochondrial function in
livers during preservation provide a strong impetus to investigate minocycline as an
effective agent to decrease injury and improve graft function after human clinical
transplantation.

Inclusion Criteria:

- All adult primary transplant recipients of solitary orthotopic liver transplants are
considered for this study

Exclusion Criteria:

- Pediatric patients, fulminant hepatic failures, split livers, living donor liver
transplants, multiple organs, known tetracycline hypersensitivity, and re-transplant
patients are excluded.