studies

816A AASLD ABSTRACTS HEPATOLOGY, October, 2015
The following authors have nothing to disclose: Mark Pedersen, David W. Backstedt,
Bobby Kakati, Myunghan Choi
The following authors have nothing to disclose: Craig Haifer, Lijia Yu, Julie Pavlovic,
Paul Gow, Kumar Visvanathan, Adam Testro
1225
Quantiferon-CMV testing after cessation of antiviral
therapy predicts late CMV reactivation after Liver Transplantation
Siddharth Sood 2,1 , Craig Haifer 1 , Lijia Yu 3 , Julie Pavlovic 1 , Paul
Gow 1 , Robert M. Jones 1 , Kumar Visvanathan 3 , Peter W. Angus 1 ,
Adam Testro 1 ; 1 Department of Gastroenterology and Liver Transplant
Unit, Austin Health, Heidelberg, VIC, Australia; 2 Department
of Gastroenterology & Hepatology, Royal Melbourne Hospital,
Melbourne, VIC, Australia; 3 Innate Immunity Laboratory, University
of Melbourne, Melbourne, VIC, Australia
Introduction CMV is the most common infection to reactivate
following liver transplantation (OLT). Although antivirals are
effective in preventing reactivation, some patients develop late
CMV after prophylaxis or treatment has ceased. Quantiferon–
CMV (QFN-CMV, Qiagen, USA) measures immune response
towards CMV. We have previously shown that early non-reactive
(n.r.) QFN-CMV (suggesting insufficient immunity) at 2
weeks post-OLT predicts early CMV reactivation, usually within
the first 2 months post-OLT. This study investigates whether
n.r. QFN-CMV at 6 months (M6) is associated with late CMV
after antiviral cessation. Methods 75 OLT recipients were
monitored as part of a prospective blinded study. Absolute
QFN-CMV1000 copies/mL). Treatment
or prophylaxis was continued until M6. After M6, patients
were monitored with CMV PCR monthly and treated for late
CMV if they developed recurrent DNAemia. Fisher’s exact test
was used. No organs were donated from prisoners. Results
Fifty-six OLT recipients (D+ and/or R+) were monitored to 12
months post-OLT. 47/56(84%) had a reactive QFN-CMV by
M6. 24/56(43%) received prophylaxis or treatment before M6
(either high-risk or developed early CMV DNAemia). 18/24
had developed a reactive QFN-CMV by M6, of whom 78%
had already developed a reactive QFN-CMV by 4 months.
3/56(5%) of patients developed late CMV (median 251 days
post-OLT). 1 asymptomatic patient commenced treatment with
viral load 1100 copies/mL, while two developed CMV disease
with very high viral loads (79,970 and 276,380 copies/mL).
All 3 had a n.r. M6 QFN-CMV, suggesting they were high risk
of late CMV following cessation of therapy. A M6 n.r. QFN-
CMV was significantly associated with late CMV p=0.003,
with an OR of 51.2 (sens 1.00, spec 0.89, PPV = 0.33, NPV =
1.00). Conclusion Only 5% of recipients developed late CMV,
but 2 of 3 suffered CMV disease. A n.r. M6 QFN-CMV is significantly
associated with risk of late CMV, and QFN-CMV-ve
patients likely require either extension of antiviral treatment
or more regular monitoring. Conversely, M6 QFN-CMV has
a high NPV, suggesting patients with robust ex-vivo immune
response towards CMV at M6 can cease further monitoring.
We also show that 78% of patients on antivirals may have
protective immunity towards CMV before 4 months post-OLT,
and antiviral prophylaxis could be discontinued early in this
group with potential to reduce both drug side-effects and costs.
Disclosures:
Siddharth Sood - Grant/Research Support: Cellestis Ltd
Robert M. Jones - Speaking and Teaching: Novartis, Astellas, Roche, Novartis,
Astellas, Roche, Novartis, Astellas, Roche, Novartis, Astellas, Roche
Peter W. Angus - Advisory Committees or Review Panels: Gilead Sciences, BMS;
Grant/Research Support: Gilead sciences
1226
Everolimus is Associated with Lower Weight Gain Two
Years Following Liver Transplantation – Results of a
Randomized Multicenter Study
Michael R. Charlton 1 , Mary E. Rinella 2 , Julie Heimbach 3 ; 1 Intermountain
Medical Center, Salt Lake City, UT; 2 Northwestern University,
Chicago, IL; 3 Mayo Clinic, Rochester, MN
Background: The prevalence and severity of obesity increase
following liver transplantation. Complications of obesity, including
posttransplant metabolic syndrome, are an important cause
of post-transplant morbidity and mortality. mTOR inhibitors have
been shown to lead to lower body mass when compared to
calcineurin inhibitors in animal studies. In contrast, calcineurin
inhibitor-based immunosuppression is associated with steady
weight gain in liver transplant recipients. Aims: To determine
the comparative impact of mTOR inhibition on the course of
post-transplant weight gain in humans following liver transplantation
in the context of a randomized, controlled trial. Methods:
Per protocol data on change in weight from baseline during
a 24-month period were analyzed from a prospective, randomized,
multicenter, open-label study, in which de novo liver
transplant patients were randomized at 30 days to one of three
immunosuppression protocols: 1) everolimus (EVR) + reduced
tacrolimus (TAC; n = 245), or 2) TAC control (n = 243) or 3)
TAC elimination (n = 231). Results: The treatment groups were
well balanced in terms of age, gender, baseline weight, BMI,
pre-transplant HCV infection and the incidence of diabetes.
Randomization to TAC elimination was stopped prematurely
due to a significantly higher rate of treated biopsy-proven acute
rejection (tBPAR). Among patients who remained on treatment,
mean increase in weight was significantly greater at month 12
and 24 months from baseline in the TAC control arm than in the
EVR + reduced TAC and the TAC elimination group (p=0.037-
0.001, see table). Study medication was discontinued due to
adverse events in 28.6% of EVR + reduced TAC and 18.2%
of TAC control patients. Average daily prednisone doses were
similar between treatment arms. The frequency of cardiovascular
events and new onset diabetes mellitus was similar between
treatment arms. Hyperlipidemia was more frequent in the EVR
containing arms (p