Liver transplant recipients and prioritization of anti-HCV therapy: an Italian cohort analysis.
OBJECTIVE
In patients with hepatitis C virus (HCV), recurrence of infection after liver transplant (LT) is universal and associated with worst survival. We present the results of an Italian cohort to compare the 3-year outcome of HCV-Ab-positive and HCV-Ab-negative LT recipients and to assess the potential interaction between HCV-Ab sero-status and other risk factors for LT failure.


METHODS
The study is a multicentre cohort including a sample of liver transplant centres. Participant's information was collected at the local level. The best functional form of variables was decided according to the objective methods based on information theory. Association between transplant failure and potential risk factors was assessed in univariate and multivariate Poisson regression model with random intercept.


RESULTS
Between June 2007 and May 2009, 1164 LT recipients were enrolled in 16 Italian transplant centres, of them 275 (23.63%) experienced LT failure. Incidence rates of LT failure was 0.32 and 0.23 per 1000 person-days in HCV-Ab-positive and HCV-Ab-negative recipients respectively (P = 0.003). Inferential models according to Akaike information criterion indicated that donor-recipient age difference and donor-recipient sex matching were more informative to predict LT failure than the age and the sex as separate variables. Multivariate analysis provided evidence that HCV-Ab sero-status, time after LT, donor-recipient age difference, donor-recipient sex matching and recipient's MELD score were significantly associated with LT failure. Moreover, the effect of HCV-Ab sero-status on LT failure was modified by the simultaneous action of time after LT and donor-recipient age difference. No interaction was found between recipient's HCV-Ab sero-status and either recipient's MELD or donor-recipient sex matching.


CONCLUSIONS
In view of the imminent introduction of new anti-HCV therapies, our study provides information to assess which LT recipients should be prioritized for receiving these highly effective, but expensive, new treatments. This is particularly relevant for those clinical settings where healthcare prioritization is endorsed by national authorities.
'Lazzaro Spallanzani' National Institute for Infectious Diseases IRCCS, Rome, Italy.
Simone
S
Lanini
Italian National Transplant Center (CNT), Italian National Institute of Health (ISS), Rome, Italy.
Alessandro
A
Nanni Costa
Department of Surgical and Morphological Sciences, University of Insubria-Ospedale di Circolo, Varese, Italy.
Paolo A
PA
Grossi
Italian National Transplant Center (CNT), Italian National Institute of Health (ISS), Rome, Italy.
Francesco
F
Procaccio
Italian National Transplant Center (CNT), Italian National Institute of Health (ISS), Rome, Italy.
Andrea
A
Ricci
'Lazzaro Spallanzani' National Institute for Infectious Diseases IRCCS, Rome, Italy.
Maria R
MR
Capobianchi
University of California San Francisco, San Francisco, CA, USA.
Norah A
NA
Terrault
'Lazzaro Spallanzani' National Institute for Infectious Diseases IRCCS, Rome, Italy.
Giuseppe
G
Ippolito
D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D058625:End Stage Liver Disease / Q000175:diagnosis / Q000401:mortality / Q000601:surgery* / Q000821:virology; D005260:Female; D006292:Health Priorities; D016174:Hepacivirus / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D007558:Italy; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D015999:Multivariate Analysis; D018579:Patient Selection; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D014775:Virus Activation
D000998:Antiviral Agents; D015415:Biomarkers; D018937:Hepatitis C Antibodies
Donor-recipient age difference; MELD score; donor-recipient sex matching; liver graft failure; multicentre study