studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1093A
for (1) appropriate resource allocation to meet the needs of
the affected patients and (2) strategic deployment of antiviral
therapy to mitigate the current and future burden of HCV.
Disclosures:
W. Ray Kim - Advisory Committees or Review Panels: Bristol Myers Squibb,
Gilead Sciences, Abbvie, Merck
Nancy Reau - Advisory Committees or Review Panels: Jannsen, Merck, AbbVie,
Intercept, Salix, BMS, Jannsen; Grant/Research Support: Merck, Gilead, BMS,
AbbVie, Jannsen, BI
Mitchell L. Shiffman - Advisory Committees or Review Panels: Merck, Gilead,
Boehringer-Ingelheim, Bristol-Myers-Squibb, Abbvie, Janssen, Acchillion; Consulting:
Roche/Genentech; Grant/Research Support: Merck, Gilead, Boehringer-Ingelheim,
Bristol-Myers-Squibb, Abbvie, Beckman-Coulter, Achillion, Lumena,
Intercept, Novartis, Gen-Probe; Speaking and Teaching: Roche/Genentech,
Merck, Gilead, Abbvie, Janssen, Bayer
Tarek I. Hassanein - Advisory Committees or Review Panels: AbbVie, Bristol-Myers
Squibb; Grant/Research Support: AbbVie Pharmaceuticals, Obalon, Bristol-Myers
Squibb, Eiasi Pharmaceuticals, Gilead Sciences, Janssen R&D, Idenix
Pharmaceuticals, Ikaria Therapeutics, Merck Sharp & Dohme, NGM BioPharmaceuticals,
Ocera Therapeutics, Salix Pharmaceuticals, Sundise, TaiGen Biotechnology,
Takeda Pharmaceuticals, Vital Therapies, Tobria; Speaking and
Teaching: Baxter, Bristol-Myers Squibb, Gilead, Salix, AbbVie
The following authors have nothing to disclose: Henri Cournand
1814
Patients with Hepatitis C (HCV) Advanced Cirrhosis and
the rs738409 GC/GG Genotype of Platatin-Like Phosphatase
Domain Containing (PNPLA-3) are at Risk for
Further Decompensation Despite Direct-Acting Antiviral
(DAA) Treatment
Winston Dunn 1 , Anusha Vittal 1 , Melissa Whitener 1 , Jie Zhao 1 ,
Brian Bridges 1 , Shweta Chakraborty 1 , K. James Kallail 2 , Prashant
K. Pandya 3 , Chuanghong Wu 4,1 , Ryan Taylor 1 , Jody C. Olson 1 ,
Richard Gilroy 1 , Mojtaba S. Olyaee 1 , Timothy Schmitt 1 , Steven
A. Weinman 1 ; 1 The University of Kansas Medical Center, Kansas
City, KS; 2 Office of Research, The University of Kansas School of
Medicine-Wichita, Wichita, KS; 3 Kansas City VA Medical Center,
Kansas City, MO; 4 Shekou People’s hospital, Shenzhen, China
HCV patients with compensated cirrhosis generally do well
after successful virological cure, but approximately 1/3 of
patients with decompensated cirrhosis experience further
decompensation or develop hepatocellular carcinoma (HCC).
The PNPLA3 genotype is correlated with fibrosis progression
from HCV. We tested the hypothesis that the PNPLA3 genotype
can predict recovery versus further decompensation in
advanced cirrhosis after HCV is cured. We studied 27 patients
with advanced HCV cirrhosis who were treated with an interferon-free
DAA-based treatment regimen. We excluded patients
with HCC, previous transplantation, and censored patients
upon transplantation. Nine patients had bilirubin ≥2 mg/dl or
INR ≥2 before DAA treatment. All remaining patients had clinical
decompensation. Eight were listed for transplantation. The
median follow-up was 166 days. The primary outcome was
a change in Model for End Stage Liver Disease (MELD) from
before DAA treatment. Figure 1 shows a comparison of before
DAA treatment to the end of follow-up. Two patients, both with
the GC genotype, died of sepsis and variceal bleeding, and
one patient each with GC and CC genotypes underwent liver
transplantation. Using a random coefficient model that considers
repeated measurement of MELD and adjusting for baseline
MELD and duration since treatment, patients with the CC allele
dropped an average of 2.5 (95% confidence interval, 1.4 -
3.6) MELD points compared to patients with the GC/GG allele
(p = 0.0001). The effect remained significant after adjusting
for age, gender, diabetes, and BMI (p = 0.02).This prospective
cohort study showed a statistically significant and clinically
meaningful difference in which patients with HCV advanced
cirrhosis and an unfavorable PNPLA3 genotype are at risk
for further decompensation despite virological cure. PNPLA3
genotyping may be clinically useful to better target patients for
liver transplant evaluation.
Disclosures:
Prashant K. Pandya - Grant/Research Support: Gilead, Merck; Speaking and
Teaching: Genentech, AbbVie, Vertex
Jody C. Olson - Advisory Committees or Review Panels: Baxter
Richard Gilroy - Speaking and Teaching: Salix, NPS, Gilead, AbbVie, Novartis
Steven A. Weinman - Consulting: Cardax, Inc.
The following authors have nothing to disclose: Winston Dunn, Anusha Vittal,
Melissa Whitener, Jie Zhao, Brian Bridges, Shweta Chakraborty, K. James
Kallail, Chuanghong Wu, Ryan Taylor, Mojtaba S. Olyaee, Timothy Schmitt
1815
Natural History of Decompensated Cirrhosis after
Direct-Acting Antivirals (DAA) Treatment of Hepatitis C
(HCV)
Winston Dunn 1 , Melissa Whitener 1 , Shweta Chakraborty 1 , Anusha
Vittal 1 , Prashant K. Pandya 2 , K. James Kallail 3 , Brian Bridges 1 ,
Chuanghong Wu 4 , Ryan Taylor 1 , Jody C. Olson 1 , Richard Gilroy 1 ,
Timothy Schmitt 1 , Mojtaba S. Olyaee 1 , Steven A. Weinman 1 ; 1 The
University of Kansas Medical Center, Kansas City, KS; 2 Kansas
City VA Medical Center, Kansas City, MO; 3 Office of Research,
The University of Kansas School of Medicine-Wichita, Wichita, KS;
4 Shekou People’s hospital, Shekou, China
With the recent approval of newer DAA, more than 95% of
patients with HCV infections can achieve a Sustained Virological
Response (SVR). Although patients with compensated
cirrhosis generally do well after viral clearance, the outcome
for decompensated cirrhosis after SVR is not well defined. This
study reports the outcomes of a cohort of decompensated HCV
cirrhosis patients undergoing interferon free DAA-treatment in
an academic transplant center. We included 96 patients in
total all of whom had one or more indications of advanced disease
such as hepatocellular carcinoma (HCC, n=21), clinical
decompensation defined as hepatic encephalopathy, ascites,
or variceal bleeding (n=81) or biochemical decompensation
(bilirubin ≥2 mg/dl or INR ≥1.7, n=47). The median follow-up
was 181 days. Six patients received liver transplantation and
3 died. Three patients had to discontinue treatment due to
adverse events. SVR occurred in 33/45 eligible (adequate