studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 585A
serelaxin was well tolerated. These results support further evaluation
of the effect of serelaxin on HVPG in patients with PHT.
Percent reductions in PPG and PVP from baseline during serelaxin
infusion
All values are median values. TGT – Thromboplastin generation
time done using patients adsorbed plasma with control serum and
control platelets. K – kinetic time, R – Reaction time.
Disclosures:
The following authors have nothing to disclose: Vaibhav S. Somani, Apurva
Shah, Deepak N. Amarapurkar
753
Serelaxin reduced portal pressure gradient and portal
vein pressure in patients with cirrhosis and portal
hypertension
Neil J. Lachlan 1 , Neil Masson 2 , Hamish Ireland 2 , Graeme Weir 2 ,
Christopher Hay 2 , Thomas Severin 3 , Neelesh Dongre 3 , Rajnish
Saini 4 , Judy Pak 4 , David Carr 3 , Denise Yates 5 , John P. Iredale 6 ,
Peter C. Hayes 1 , Jonathan A. Fallowfield 1,6 ; 1 Liver Unit, Royal
Infirmary of Edinburgh, Edinburgh, United Kingdom; 2 Department
of Radiology, Royal Infirmary of Edinburgh, Edinburgh, United
Kingdom; 3 Novartis Pharma AG, Basel, Switzerland; 4 Novartis
Pharmaceuticals Corporation, East Hanover, NJ; 5 Novartis Institutes
for Biomedical Research, Cambridge, MA; 6 MRC Centre for
Inflammation Research, University of Edinburgh, Edinburgh, United
Kingdom
Background: Portal hypertension (PHT) accounts for the most
serious complications of cirrhosis. A reduction in the hepatic
venous pressure gradient (HVPG) to 20% has
been reported to improve clinical outcomes, but current drug
therapy is ineffective in a significant proportion of patients and
adverse effects (AEs) are common. We have recently shown
that serelaxin, a recombinant form of the human peptide hormone
relaxin-2, has anti-fibrotic and portal hypotensive effects
in cirrhotic rats. Direct measurement of portal hemodynamics
in response to vasoactive drugs can be performed in patients
with a transjugular intrahepatic portosystemic shunt (TIPSS) at
the time of portography assessment. In a two-part exploratory
open-label study, Part B examined the safety, tolerability, and
effects of serelaxin on portal and systemic hemodynamics in
patients with cirrhosis, PHT and a TIPSS. Methods: Patients
with alcohol-related cirrhosis, a functioning TIPSS confirmed by
portography, and a portal pressure gradient (PPG = portal vein
pressure (PVP) - inferior vena cava pressure (IVCP)) >5mmHg
were treated with serelaxin (i.v. for 60 minutes at 80ug/kg/
day then at least 60 minutes at 30ug/kg/day). PPG was measured
at baseline and post infusion. PVP and blood pressure
(BP) were measured every 15 and 10 minutes, respectively.
Safety, including AEs, was assessed. Results: 3 male and 3
female patients entered the study (mean age 42.8±7.7 years).
The mean baseline PPG was 8.2mmHg (95% CI 6.1, 11.1).
Following at least 120 minutes of serelaxin infusion there was
a 31.3% (95% CI -66.5, 71.6) reduction in the PPG compared
to baseline. During the infusion there was a progressive reduction
in the PVP reaching a decrease of 25.2% (95% CI -12.7,
50.3) from baseline at the 120 minute time point (Table). The
reduction in PVP started at 30 minutes and continued through
to the 135 minute time point. With serelaxin infusion, there
were no newly occurring liver enzyme abnormalities, no clinically
significant changes in BP, and no discontinuations due
to AEs. Conclusions: In this small exploratory study serelaxin
induced a rapid and potentially clinically significant reduction
in portal pressure. Despite advanced cirrhosis in these patients,
Disclosures:
Thomas Severin - Employment: Novartis Pharma AG; Stock Shareholder: Novartis
Pharma AG
Neelesh Dongre - Employment: Novartis Pharma AG; Stock Shareholder: Novartis
Pharma AG
Rajnish Saini - Employment: Novartis Pharmaceutical Corporation
Judy Pak - Employment: Novartis Pharmaceuticals
Denise Yates - Employment: Novartis
Peter C. Hayes - Advisory Committees or Review Panels: Roche, MSD, Jannsen,
Gilead, ?ONO, Norgine; Grant/Research Support: Novartis; Speaking and
Teaching: Roche, MSD, Pfiser, Gore, Falk, Ferring
The following authors have nothing to disclose: Neil J. Lachlan, Neil Masson,
Hamish Ireland, Graeme Weir, Christopher Hay, David Carr, John P. Iredale,
Jonathan A. Fallowfield
754
Transjugular intrahepatic portosystemic shunt for portal
vein thrombosis with variceal bleeding in liver cirrhosis:
Outcomes and predictors in a prospective cohort study
Xingshun Qi, Chuangye He, Wengang Guo, Zhanxin Yin, Jianhong
Wang, Zhengyu Wang, Jing Niu, Ming Bai, Zhiping Yang,
Daiming Fan, Guohong Han; Xijing Hospital of Digestive Diseases,
Xijing Hospital, Fourth Military Medical University, Xi’an, China
This prospective cohort study aimed to assess the risk factors
associated with transjugular intrahepatic portosystemic shunt
(TIPS) technical success, outcome, and prognosis in cirrhotic
patients with portal vein thrombosis (PVT) and a history of variceal
bleeding. Between May 2009 and April 2011, 51 cirrhotic
patients with PVT who attempted TIPS procedures for the
prevention of variceal rebleeding were enrolled. TIPS success
rate was 84% (43/51). An increased degree of thrombosis
within the portal trunk and portal vein branches was inversely
associated with TIPS success. Median follow-up time was 40.07
months (range: 0.02-56.87). The cumulative risk of rebleeding
was significantly different between TIPS success and failure
group (p=0.002). The univariate analysis also demonstrated
that TIPS failure was the only significant predictor associated
with rebleeding (hazard ratio [HR]=4.174, 95% confidence
interval [CI]: 1.558-11.186). In TIPS success group, the cumulative
rates free of shunt dysfunction at the 6th and 12th month
were 79% and 76%, respectively. Absence of total superior
mesenteric vein (SMV) thrombosis was the only independent
predictor (HR=0.189, 95%CI: 0.047-0.755). In TIPS success
group, the 1- and 3-year cumulative survival rates were 77%
and 62%, respectively. Albumin level was the only independent
predictor (HR=0.877, 95% CI: 0.779-0.986). Successful
TIPS insertions could effectively prevent from rebleeding in
cirrhotic patients with PVT and variceal bleeding. Degree of
PVT and SMV thrombosis was associated with TIPS failure and
shunt dysfunction, respectively.
Disclosures:
The following authors have nothing to disclose: Xingshun Qi, Chuangye He,
Wengang Guo, Zhanxin Yin, Jianhong Wang, Zhengyu Wang, Jing Niu, Ming
Bai, Zhiping Yang, Daiming Fan, Guohong Han