studies

312A AASLD ABSTRACTS HEPATOLOGY, October, 2015
203
Long-term complete prophylaxis withdrawal in liver-transplanted
patients for HBV-related cirrhosis is safe
and frequently associated with spontaneous ANTI-Hbs
seroconversion
Ilaria Lenci 1,3 , Daniele Di Paolo 1 , Martina Milana 1 , Francesco
Santopaolo 1 , Leonardo Baiocchi 1 , Valentina Svicher 2 , Laura Tariciotti
3 , Giuseppe Tisone 3 , Carlo Federico Perno 2 , Mario Angelico 1 ;
1 Liver Unit, Tor Vergata University, Rome, Italy; 2 Virology Unit, Tor
Vergata University, Rome, Italy; 3 Liver Transplant Unit, Tor Vergata
University, Rome, Italy
Background and aims. Long-term use of hepatitis-B-virus (HBV)
specific immunoglobulins (HBIg) and/or nucleoside analogs
(NA) is recommended to prevent HBV reinfection in HBsAg
positive liver transplant (LT) recipients. Searching for a more
rational and tailored approach, we showed (J. Hepatol. 2011;
55:587-593) that weaning of HBV prophylaxis was feasible
and safe in a selected group of LT recipients considered at
“low risk” of HBV recurrence (undetectable HBV-DNA at LT
and undetectable intra-hepatic total HBV-DNA and ccc-DNA
5 years after LT), with small percentage of HBV recurrence, in
the absence of clinically relevant events during the first 2 years
after HBIg and NA withdrawal. We report here the extended
follow-up of this selected group of LT recipients, up to 6 years
(median months 78) after complete prophylaxis withdrawal.
Methods. The study included 30 LT recipients, all HBeAg negative,
with HBV genotype D, including 6 with HCV and 7 with
HDV coinfections, who initially received HBIg and NA (mostly
lamivudine) for at least 5 years following LT. Sequential HBIg
and NA withdrawal was performed in two six-month periods
under strict monitoring of HBV virology, based on monthly
blood tests and liver biopsies every 6 months for the first two
years. All patients were then followed with clinical and virological
test at 3-6 months intervals. Results. Only two patients
(6.7%) underwent sustained HBV recurrence, with HBsAg and
HBV-DNA reappearance after 45 and 78 months of prophylaxis
withdrawal. Both received tenofovir therapy and promptly
returned HBV-DNA negative and did not experience any clinical
event. Four patients showed a transient HBsAg positivity (2,
4, 6 and 45 months after HBIg and NA withdrawal, respectively),
in one case with transient HBV-DNA detectable, followed
by later anti-HBs seroconversion. Additional 14 patients
mounted a measurable anti-HBs titer during the long-term follow
up, without showing transient HBsAg/HBV-DNA detectability.
Thus, 28 (93.3%) patients were HBsAg and HBV-DNA negative
and 18 (60%) were anti-HBs positive at completion of the
extended follow up. The average lastly detected anti-HBs titer
was 276 IU/L), with 2 patients showing titers >1000 IU/L.
Anti-HBs seroconversion occurred after a median of 70 months
(range: 32-70) after complete prophylaxis withdrawal and was
unrelated to HCV or HDV coinfections. Conclusion. Complete
prophylaxis withdrawal is safe in patients liver-transplanted
for HBV-related disease at low risk of recurrence and in the
majority of cases is followed by spontaneous anti-HBs seroconversion.
Disclosures:
Mario Angelico - Advisory Committees or Review Panels: Gilead, Janssen;
Grant/Research Support: Roche; Speaking and Teaching: GSK, Roche, Gilead,
Novartis, BMS, Bayer
The following authors have nothing to disclose: Ilaria Lenci, Daniele Di Paolo,
Martina Milana, Francesco Santopaolo, Leonardo Baiocchi, Valentina Svicher,
Laura Tariciotti, Giuseppe Tisone, Carlo Federico Perno
204
Impact of Sofosbuvir-Based Regimens on Renal Function
in Liver Transplant Recipients: Results of a Multicenter
Study
Nabiha Faisal 1 , Eberhard L. Renner 1 , Marc Bilodeau 2 , Bandar
Aljudaibi 3 , Geri Hirsch 4 , Eric M. Yoshida 5 , Tarana Hussaini 5 ,
Peter Ghali 6 , Stephen E. Congly 7 , Mang M. Ma 8 , Jennifer Leonard
10 , Curtis Cooper 9 , Kevork M. Peltekian 4 , Nazia Selzner 1 , Les
Lilly 1 ; 1 Multi organ Transplant, Toronto General Hospital, Toronto,
ON, Canada; 2 University of Montreal, Montreal, QC, Canada;
3 London Health Sciences, University of Western Ontario, London,
ON, Canada; 4 Dalhousie University, Halifax, NF, Canada; 5 University
of British Columbia, Vancouver, BC, Canada; 6 University of
McGill, Montreal, QC, Canada; 7 University of Calgary, Calgary,
AB, Canada; 8 University of Alberta, Edmonton, AB, Canada; 9 University
of Ottawa, Ottawa, QC, Canada; 10 Memorial University,
St. John’s, NF, Canada
BACKGROUND & AIMS: The first nucleotide NS5B polymerase
inhibitor, sofosbuvir (SOF), is not recommended for patients
with severe renal impairment due to pharmacokinetic studies
demonstrating higher serum drug and metabolite levels in such
patients. However, renal function in cirrhotic and non-cirrhotic
patients treated with SOF-based regimens is often compromised
yet poorly assessed. This analysis aims to assess the
impact of SOF-based regimens on renal function in liver transplant
(LT) recipients with recurrent HCV, and to assess the role
of renal function on the efficacy and safety of these regimens.
METHODS: 165 LT recipients across Canada with HCV recurrence
were treated with SOF-based regimens from January
2014 to May 2015. Mean patient age was 58±6.85 years;
the majority were male, GT1, Caucasian and treatment-experienced.
One third had aggressive HCV in the graft; 50% had
F3/4 fibrosis. The majority were on tacrolimus based immunosuppression.
Median time from LT to treatment was 27 (1-309)
months. Baseline eGFR was calculated by Modification of Diet
in Renal Disease formula (MDRD) and patients were stratified
into 3 groups: eGFR60 ml/min. The primary
outcome was post treatment changes in renal function from
baseline. Secondary outcomes included sustained virological
response at 12 weeks after treatment end (SVR12), anemia
related adverse events (AEs), need for blood transfusions or
growth factors, serious AEs, treatment discontinuation due to
AE, or death. RESULTS: An improvement in post treatment renal
function was seen in the majority (58%) of patients, mostly in
the SVR12 group (81% vs. 19%). A decline in renal function
seen in 22%; more marked in poorest renal function (eGFR