studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 935A
1485
Development of a Novel Clinician Reported Outcome
Tool for Assessment of Hepatic Encephalopathy
Jasmohan S. Bajaj 1,2 , Nathan M. Bass 3 , R Todd Frederick 4 ,
Karin Coyne 5 , Mary Kay Margolis 5,6 , Dion F. Coakley 7 , Masoud
Mokhtarani 7 , Marzena Jurek 7 , Bruce F. Scharschmidt 7 ; 1 Virginia
Commonwealth University, Richmond, VA; 2 McGuire VA Hospital,
Richmond, VA; 3 University of California, San Francisco, CA;
4 California Pacific Medical Center, San Francisco, CA; 5 Evidera,
Bethesda, MD; 6 Patient-Centered Outcomes Research Institute
(PCORI), Washington, DC; 7 Horizon Therapeutics (formerly Hyperion
Therapeutics, Inc.), Brisbane, CA
The West Haven scale (WH), used for decades in clinical practice,
was neither developed as an outcome assessment tool
using methodology acceptable to regulatory authorities, nor
is it consistently applied. Although recent ISHEN and EASL/
AASLD Guidelines have clarified HE nomenclature and treatment,
there is no standardized tool for assessing overt HE
(OHE). A standardized clinician reported outcome (ClinRO)
tool to diagnose and grade OHE was developed, in compliance
with methodologies accepted by regulatory authorities,
for use in clinical trials as well as daily clinical practice. Study
Design: A two part iterative Delphi method was employed
using a 3-member steering committee and a panel of 40
practicing hepatologists in the US, Canada, Europe, South
America, and Australia to develop a new ClinRO instrument
(HE Grading Instrument, HEGI) for OHE identification and
grading. Part 1 involved open-ended concept elicitation from
the panel regarding clinical findings they use in their daily
practice to diagnose and rate OHE severity. Part 2 included
testing the HEGI for clarity, usability, and inter- and intra-rater
reproducibility. To assess inter-rater reproducibility, 34 panelists
viewed 5 videos depicting HE episodes of differing severity
and determined the presence/absence of OHE, as well as its
severity. Intra-rater reproducibility was assessed among a subset
of the panelists who viewed the video vignettes a second
time, in random order, and rated each episode again. Results:
Of the 40 panelists, 97.5% had participated in clinical trials,
52.5% saw > 10 HE patients/week, and 32% were from outside
the US. Major OHE criteria recommended in Part 1 for
inclusion in the HEGI included disorientation to time (90%),
place (72.5%), and person (70.0%), asterixis (97.5%), lethargy
(92.5%), and coma (100%). Assuming exclusion of other
causes, consensus was reached that any of the following constituted
a minimum requirement for diagnosis of OHE: (1) any
disorientation, (2) presence of both lethargy and asterixis, or
(3) coma. The overall adjudicated concordance in Part 2 for
discriminating between presence/absence of OHE using HEGI
was 97.1%; the overall concordance for rating episode severity
was 87.1%; and the overall concordance for reproducibility
was 98%. Conclusions: The HEGI, a ClinRO tool for diagnosis
and grading of OHE episodes, was developed using the principles
contained in the FDA Guidance for Development of Patient
Reported Outcomes for instrument validity and reproducibility.
It is anticipated to aid in the identification of OHE in clinical
practice and enhance the reliability of endpoint assessment in
clinical trials for OHE.
Disclosures:
Jasmohan S. Bajaj - Advisory Committees or Review Panels: Salix, Merz, otsuka,
ocera, grifols, american college of gastroenterology; Grant/Research Support:
salix, otsuka, grifols
Nathan M. Bass - Advisory Committees or Review Panels: Quest Diagnostics
R Todd Frederick - Advisory Committees or Review Panels: Gilead, Bristol Myers
Squibb, Salix, Vital Therapies, Hyperion, AbbVie
Karin Coyne - Consulting: Evidera
Dion F. Coakley - Employment: Horizon Therapeutics
Masoud Mokhtarani - Employment: Hyperion; Stock Shareholder: Hyperion
Marzena Jurek - Employment: Horizon Therapeutics, Inc.
The following authors have nothing to disclose: Mary Kay Margolis, Bruce F.
Scharschmidt
1486
Usefulness of Balloon-Occluded Retrograde Obliteration
(B-RTO) as a Consolidation Procedure after Anticoagulation
Therapy in Cirrhotic Patients with Portal Vein
Thrombosis
Mie Inao, Kazuki Hirahara, Kayoko Sugawara, Nobuaki
Nakayama, Yukinori Imai, Satoshi Mochida; Department of Gastroenterology
& Hepatology, Saitama Medical University, Moroyama-Machi,
Japan
Aim: Although anticoagulation therapies with Xa inhibitors and
antithrombin concentrates were shown to be effective for attenuation
of portal vein thrombosis in cirrhotic patients, aggravation
or recurrence of the lesions may occur following the
therapies leading to derangement of liver function. Decrease
of blood flow in the portal vein as a consequence of porto-systemic
shunts may responsible for thrombosis development.
Thus, the usefulness of B-RTO as a consolidation procedure
after anticoagulation therapies was evaluated. Methods: The
subjects were 43 patients (23 men and 20 women, aged from
40 to 76 years old) with liver cirrhosis complicating portal vein
thrombosis. Both danaparoid Na (2,500 units/day) and antithrombin
concentrates (1,500 units/day) were intravenously
administrated for 3 days followed by danaparoid Na injections
for further 11 days. Patients seen in April 2013 and later
received B-RTO procedures after anticoagulation therapies,
when porto-systemic shunts were observed on CT and/or MRI
imaging. A balloon catheter was inserted into the shunts followed
by injection of 5% ethanolamine oleate through the catheter
under balloon inflation. The balloon was kept inflation for
6 to 48 hours depending on sizes of the shunts. Results: Immediately
after anticoagulation therapies, portal vein thrombosis
was completely disappeared in 11 patients (25%) and the
sizes of thrombosis were attenuated in 15 patients (35%), while
the lesions did not change in 17 patients (40%). B-RTO was
additionally done in 4 patients; 2 patients showing complete
thrombosis disappearance and 2 patients failing to achieve
thrombosis attenuation. Following B-RTO procedures, thrombosis
did not recur in both of the former patients and the lesions
disappeared in both of the latter patients despite that anticoagulation
therapies were ineffective. In contrast, in 39 patients
without additional B-RTO procedures, thrombosis recurred in
4 among 9 patients after thrombosis disappearance and was
aggravated in 6 among 15 patients achieving thrombosis
attenuation. Conclusion: B-RTO was effective as a consolidation
procedure after anticoagulation therapies for patients with
portal vein thrombosis even in those failing to achieve attenuation
of the lesions when porto-systemic shunts responsible for
decrease of blood flows in the portal vein were observed.
Disclosures:
Satoshi Mochida - Grant/Research Support: Chugai, MSD, Tioray Medical,
BMS; Speaking and Teaching: MSD, Toray Medical, BMS, Tanabe Mitsubishi
The following authors have nothing to disclose: Mie Inao, Kazuki Hirahara,
Kayoko Sugawara, Nobuaki Nakayama, Yukinori Imai