studies

814A AASLD ABSTRACTS HEPATOLOGY, October, 2015
1221
Renal Recovery Outcomes after Liver Transplantation
in Patients Requiring Pre-operative Renal Replacement
Therapy
Rex Cheng 1 , Kimberly Muczynski 2 , Lena Sibulesky 3 , Renuka Bhattacharya
1 ; 1 Gastroenterology/Hepatology, University of Washington,
Seattle, WA; 2 Nephrology, University of Washington, Seattle,
WA; 3 Transplant Surgery, University of Washington, Seattle, WA
Background: The purpose of this study is to characterize the
long-term outcomes of renal recovery in liver transplant (OLT)
recipients who required preoperative renal replacement therapy
(RRT). Methods: A single center retrospective review was
performed for OLT recipients who were transplanted from January
2009 to April 2015 and required RRT at least one day
prior to transplant. Patients were excluded if they received a
combined liver-kidney transplant or required a repeat transplant.
Patient demographics, clinical data, pre- and post-transplant
laboratory data, number of days on RRT, time to RRT
cessation were extracted from an electronic medical record.
Outcomes measured include early renal recovery (cessation
of RRT within 30 days after OLT), delayed renal recovery (cessation
of RRT more than 30 days after OLT) or development
of end-stage renal disease, as well as residual renal function,
characterized by serum creatinine at 30 and 90 days after
cessation of RRT. Results: Excluding combined liver-kidney
transplants (n=17) and patients requiring repeat transplant (n
= 14), 454 patients underwent liver transplantation during this
time period. Sixty patients (mean age 51.9 ± 9.7 years, 55.0%
male, 62% with acute tubular necrosis, mean Model of End-
Stage Liver Disease score 36.7 ± 4.7 at transplant) received
RRT prior to OLT. 34 (57%) achieved early renal recovery, 15
(25%) achieved delayed renal recovery over a mean of 57.6
days and 11 (18%) were deemed to have end-stage renal
disease with RRT dependence. Patients who achieved early
renal recovery had a shorter duration of pre-transplant RRT
than those who did not, 17 days, [95% confidence interval
(CI), 12-21 days] versus 26 days [(95% CI, 19-33 days), p =
0.044]. At 30 days after cessation of RRT (n= 48), 70.5% of
patients with early renal recovery vs 40.0% of patients with
delayed renal recovery attained a serum creatinine < 2 (p =
0.046). At 90 days after cessation of RRT (n=44), 93.3% of
patients with early renal recovery vs 78.5% of patients with
delayed renal recovery attained a serum creatinine < 2 (p =
0.148). Conclusion: Over three-quarters of patients requiring
pre-transplant RRT achieve renal recovery. Shorter duration
of RRT is associated with earlier renal recovery. Early renal
recovery is associated with more rapid improvement in residual
renal function. The majority of patients who achieve renal
recovery have improved residual renal function at 90 days
after RRT cessation.
Disclosures:
The following authors have nothing to disclose: Rex Cheng, Kimberly Muczynski,
Lena Sibulesky, Renuka Bhattacharya
1222
Coffee consumption promotes survival and protects
against hepatocellular carcinoma recurrence following
liver transplantation: putative mechanisms involve modulation
of adenosinergic signalling
Georg Wiltberger 1 , Ruoyu Miao 2 , Undine G. Lange 1 , Rudi
Ascherl 1 , Hans-Michael Hau 1 , Felix Krenzien 1 , Georgi Atanasov 1 ,
Christian Benzing 1 , Elliot B. Tapper 2 , Linda Feldbrügge 2 , Johannes
Broschewitz 1 , Michael Bartels 1 , Sven Jonas 3 , Johann Pratschke 4 ,
Yan Wu 2 , Simon C. Robson 2 , Moritz Schmelzle 4 ; 1 Department of
Visceral, Transplant, Thoracic and Vascular Surgery, University
Hospital Leipzig, Leipzig, Germany, Leipzig, Germany; 2 Department
of Medicine, Beth Israel Deaconess Medical Center, Harvard
Medical School, Liver Center and The Transplant Institute, Div. of
Gastroenterology, Boston, MA; 3 Department of Hepato-, Pancreato-
and Biliary Surgery, 310Klinik, Nürnberg, Nürnberg, Germany;
4 Department of General, Visceral, and Transplant Surgery,
Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum,
Berlin, Germany
Background: Increasing evidence suggests that coffee consumption
might decrease liver cirrhosis death risk and reduce
the risk for hepatocellular carcinoma (HCC). Caffeine is a natural
antagonist to adenosine-mediated receptor signaling and
has tumoricidal activity in experimental settings. Aim: To determine
whether coffee consumption decreases HCC recurrence
and promotes survival following orthotopic liver transplantation
(OLT) and to examine putative mechanisms of action.
Methods: Patients who underwent OLT for HCC from January
2002 to December 2012 were interviewed on the numbers
of consumed cups of coffee per day before and after OLT.
Coffee consumption was correlated with patients’ data with
regard to HCC recurrence and patient survival. For in vitro
mechanistic assays, human HepG2 HCC cells were analyzed
for expression of adenosine receptors and ectoenzymes. Cells
were also treated with adenosine, in the presence or absence
of 8-(3-Chlorostyryl)-caffeine (CSC) or alloxazine, followed by
analyses of proliferation, metastasis and alterations in key adenosine-mediated
cancer pathways inclusive of MAPK (ERK and
JNK) and NF-kappa B. Results: 90 patients with a median
age of 60 years (range 73 – 37) and a median BMI of 26.95
(range 18.3 – 39.4) underwent OLT for histologically confirmed
HCC. 16 (17.8 %) patients experienced HCC-recurrence after
median time of 11.5 months (range 1 - 40.5) post-transplant.
In patients with a high preoperative or postoperative coffee
intake HCC recurrence was observed less frequently than
in those with low coffee intake (p=0.018). In a multivariate
Cox’ proportional hazard model for recurrence-free survival
only postoperative coffee intake ≥3 cups daily showed a significant
relevance. HepG2 cells express abundant levels of
A2A and A2B as well as several key ectoenzymes (including
ENTPD3, ENTPD5, ENTPD8, CD73, and adenosine deaminase
1 (ADA1)). These cells show intrinsic capacity to generate
extracellular adenosine. Exogenous adenosine promotes HCC
cell growth and metastasis in vitro, which is blocked by CSC,
but not by alloxazine. Moreover, adenosine induces activation
of MAPK (ERK and JNK) and NF-kappaB pathways, which can
be prevented by antagonism of A2A and A2B receptors. Conclusions:
Coffee consumption is associated with a decreased
risk of HCC recurrence and increased survival following OLT.
Experimental data suggest that these results might be, at least
in part, associated with the antagonist activity of caffeine on
adenosine-A2AR mediated growth-promoting effects in HCC
cells. If validated further, our findings have implications for
future recommendations for HCC patients after OLT.