studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 287A
category of 45-49 (4.21%, [3.14-5.28]), ESRD (966.31%,
[954.86-977.88]), disabled status (43.22%, [41.67-44.80]),
Charlson score (46.78%, [46.31-47.26]), and year study
(2.72%, (2.58-2.85]) were all independently associated with
an increase in total payments. Conclusions: Prevalence of HCV
is higher in Baby boomers Medicare recipients. For the entire
BB cohort, HCV positivity is independently associated with
higher mortality and resource utilization.
Disclosures:
Zobair M. Younossi - Advisory Committees or Review Panels: Salix, Janssen,
Vertex; Consulting: Gilead, Enterome, Coneatus
The following authors have nothing to disclose: Mehmet Sayiner, Mark Wymer,
Pegah Golabi, Joel S. Ford, Indie Srishord
154
Bariatric surgery for the treatment of nonalcoholic steatohepatitis:
Results of a Markov Model
Matthew Klebanoff 1,2 , Kathleen E. Corey 2,3 , Lee M. Kaplan 2,3 ,
Raymond T. Chung 2,3 , Chin Hur 2,3 ; 1 Institute for Technology
Assessment, Massachusetts General Hospital, Boston, MA; 2 Gastrointestinal
Unit, Massachusetts General Hospital, Boston, MA;
3 Harvard Medical School, Boston, MA
Obese individuals are at heightened risk of developing nonalcoholic
steatohepatitis (NASH), which can give rise to cirrhosis
and hepatocellular carcinoma. Current treatments for NASH
are poorly tolerated or have little long-term data to support their
use. A growing body of evidence suggests that bariatric surgery
not only leads to weight loss but may also improve NASH.
Using a Markov model, we determined the gain in life years
(LYs) and quality-adjusted life years (QALYs) following laparoscopic
Roux-en-Y gastric bypass (L-RYGB) for patients in various
weight classes with varying degrees of NASH fibrosis (F0-F3).
After surgery, a percentage of patients who benefit (69.7% in
base-case, from Mathurin et al., 2009) enter a ‘NASH remission’
state and stop progressing toward cirrhosis, although
they may later relapse (Fig. 1). The primary analysis does not
model surgery in F4 patients due to a lack of data in this group.
The model incorporated life year and quality-of-life decrements
associated with L-RYGB and complications. Extensive sensitivity
analyses examined the impact of model input uncertainty on
results. For all classes of obesity (mild, moderate and severe),
surgery led to a gain in LYs and QALYs. When we excluded
benefits of weight loss to explore the potential impact of surgery
on non-obese NASH patients, surgery reduced life expectancy
by 0.02 LYs for F0 patients, but increased LYs for F1-F3
patients. Surgery also decreased quality-adjusted survival for
F0 and F1 patients by 0.28 and 0.22 QALYs, respectively,
but increased QALYs for F2 and F3 patients. The number of
F3 patients needed to treat (NNT) to prevent one liver-related
death was seven; for F2 patients, the NNT was 17. Conclusions:
Bariatric surgery is effective as a treatment for patients
with NASH in all obesity classes. When we focused only on the
benefit due to NASH remission by eliminating any weight loss
benefit from the model, bariatric surgery improved life expectancy
for F1-F3 patients, but increased quality-adjusted survival
only for patients with more advanced fibrosis (F2 and F3), with
relatively favorable NNTs.
Disclosures:
Kathleen E. Corey - Advisory Committees or Review Panels: Gilead; Speaking
and Teaching: Synageva
Lee M. Kaplan - Consulting: Johnson and Johnson, GI Dynamics, Novo Nordisk;
Grant/Research Support: Ethicon
Raymond T. Chung - Grant/Research Support: Gilead, Mass Biologics, Abbvie,
Merck, BMS
The following authors have nothing to disclose: Matthew Klebanoff, Chin Hur
155
A Trial-based Model of Liver Transplant and Liver-related
Death in Patients with Primary Biliary Cirrhosis
(PBC)
Marco Carbone 1 , Richard Pencek 2 , Tracy J. Mayne 2 , Tonya Marmon
2 , George F. Mells 3 , David Shapiro 2 ; 1 Division of Gastroenterology
and Hepatology, Department of Medicine, Addenbrooke’s
Hospital, Cambridge, United Kingdom; 2 Intercept Pharmaceuticals,
Inc., San Diego, CA; 3 Division of Gastroenterology and
Hepatology, Department of Medicine, University of Cambridge,
Cambridge, United Kingdom
Background: The UK-PBC research group derived and validated
a predictive model for liver transplant or liver-related
death in PBC patients based on Cox proportional hazards
regression analysis of the UK-PBC cohort (n=4022). Predictors
included ALP, bilirubin, ALT, albumin and platelet count. Obeticholic
acid (OCA) is a selective FXR agonist in development for
the treatment of PBC. In a recent Phase 3 trial (POISE), OCA
treatment was associated with significant improvements in ALP,
bilirubin and transaminases compared to placebo +UDCA.
Objective: To apply the UK-PBC risk algorithm to the POISE
trial data to predict effect of OCA on liver transplant and liver-related
death. Methods: In POISE, 216 PBC patients with
inadequate response or intolerance to UDCA were randomly
assigned to: OCA 10 mg, OCA titration (starting at 5 mg and
adjusted to 10 mg at 6 months based on clinical response) or
placebo; pre-trial UDCA continued. Treatment effect on liver
biochemistry was assessed at 12 months. The UK-PBC algorithm
assessed risk for liver-transplant or liver-related death at
5, 10 and 15 years based on 12-month change from baseline.
Results: The demographics of the POISE cohort were: mean age
56 years, 91% female, 94% white, 93% on UDCA. At baseline,
the UK-PBC algorithm indicated that placebo patients were
at slightly higher risk for events compared to both OCA arms.
At 12 months, predicted risk had significantly improved with
OCA, primarily due to improved ALP and bilirubin. Risk worsened
in the placebo arm, primarily due to increased bilirubin.
Predicted risk at 5, 10 and 15 years is shown below. Based on
absolute risk reduction at 15 years, the number needed to treat
with OCA to avoid liver transplant or liver-related death was
13 (OCA 10 mg) and 11 (OCA titration). Conclusions: The
UKPBC risk model is a validated prognostic indicator of liver
transplant-free survival. When applied to patients in POISE,