The use of hepatitis C-infected grafts in liver transplantation

Abstract

O rthotopic liver transplantation (OLT) has become the definitive procedure for management of end-stage liver disease, with survival rates greater than 80% at 1 year. Therefore, as absolute contraindications have progressively decreased, the number of indications has proportionately increased. Unfortunately, mortality on the waiting list has increased because of the disparity between number of donors and the rapid growth in number of candidates. According to the United Network for Organ Sharing (UNOS), the number of patients on the waiting list increased from 1,527 patients in 1991 to 16,874 patients in 2000, and the number of deaths while waiting increased from 515 to 1,661 deaths in the same period. 1 Patients with hepatitis C make up the largest segment of the candidate pool, continuing to stress the ability to provide grafts to those in need. In North America, most centers report hepatitis C virus (HCV) infection in greater than 40% of their candidates.To solve the problem of donor organ availability, several approaches have been explored. One approach is the use of organs from less-than-perfect donors, also called marginal donors. These could include nonheart-beating donors, older donors (age Ͼ 65 years), donors with morbid obesity, and last, donors infected with hepatotropic viruses, specifically HCV and hepatitis B virus. This review focuses on the development of the latter practice and its virological consideration, and we suggest recommendations on how these organs should be allocated. HCV-Infected Grafts Transmission of HCV by Donor OrgansIn 1990, the first report of HCV transmission from organ donor to recipient was made, followed by several successive reports. 2,3 With more sensitive and specific techniques, Pereira et al 4 reported that virtually all organ recipients from anti-HCV-positive (HCV ؉ ) donors become infected with the virus. Another study from the United Kingdom by Wreghitt et al 5 found a transmission rate of 93%, in which 50% of recipients of HCV ϩ organs had evidence of HCV-related liver disease after OLT. HCV seroprevalence in their donor pool was 1.08%. 5 The New England Organ Bank retrospectively evaluated clinical outcomes of recipients of organs from HCV ϩ and HCV-negative (HCV ؊ ) donors. 6 Between 1986 and 1990, a total of 29 patients received organs from 13 HCV ϩ donors (determined by a first-generation enzyme-liked immunosorbent assay). They were compared with 74 recipients of grafts from 35 HCV Ϫ donors. Median posttransplantation follow-ups for the HCV ϩ and HCV Ϫ groups were 42 and 49 months, and relative risk for the development of hepatitis in the HCV ϩ group was 4.37. 6 Using the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database, Everhart et al 7 prospectively evaluated 702 liver transplant recipients and 604 donors who were tested for antibody to HCV, followed by recombinant immunoblot and HCV RNA confirmation by polymerase chain reaction. Fifteen donors were HCV ϩ by either antibody to HCV or polymerase chain reaction. Eig...

Impact of donor age on survival and fibrosis progression in patients with hepatitis C undergoing liver transplantation using HCV+ allografts

“…Previous studies have demonstrated equivalent incidence of recurrence in recipients of HCVϩ donor grafts, [7][8][9][10][11][12] and, most recently, equivalent time to biopsy-proven HCV recurrence. 14 Our results suggest that patients receiving HCVϩ donor organs develop more fibrosis over time than those receiving HCVϪ grafts.…”

“…[7][8][9][10][11][12][13] Saab et al 14 recently reported no difference in patient survival, graft survival, or time to HCV recurrence in 59 recipients of HCVϩ grafts com-pared to matched recipients of HCV-negative (HCVϪ) grafts. The authors did not comment on whether the donor age or allograft features impacted survival.…”

Viral Hepatitis in Solid Organ Transplant Recipients

“…While early reports suggested a higher rate of recurrence following LDLT, subsequent data have dispelled these concerns(Garcia-Retortillo, Forns et al 2004;Terrault, Shiffman et al 2007). The use of HCV+ donors (without fibrosis) for HCV+ recipients also does not appear to impact recurrence rates (Arenas, Vargas et al 2003;Peek and Reddy 2007). The use of genotype 1 HCV+ donors into nongenotype 1 recipients is, however, not recommended.…”

Trasplante hepático

“…Los donantes con anticuerpos frente al antígeno del core del virus B (antiHBcpositivos), que suponen hasta el 15% de los donantes hepáticos en nuestro medio, tienen integrado el genoma del virus B en el genoma de sus hepatocitos En la última década, se ha comenzado a utilizar como donantes hepáticos a los donantes con hepatitis C. Obviamente, estos injertos se utilizan solamente en receptores con cirrosis hepática por virus C y después de comprobar que el injerto hepático no tiene un daño histológicamen-te relevante. De esta forma, la supervivencia de los pacientes que reciben estos injertos es comparable a la de los pacientes que reciben injertos de donantes con serología de virus C negativa 24 .…”