studies

372A AASLD ABSTRACTS HEPATOLOGY, October, 2015
316
TNF-alpha is the Most Consistent Predictor of Impairment
of Mental Health-Related Patient-Reported Outcomes
(PROs) in Patients with Chronic Hepatitis C (CH-C)
Treated with Ledipasvir (LDV) and Sofosbuvir (SOF) with
or without Ribavirin (RBV)
Zobair M. Younossi 1,2 , Maria Stepanova 2 , James M. Estep 2 , Azza
Karrar 2 , Bibiana Oe 2 , Elzafir Elsheikh 2 , Siddharth Hariharan 2 ,
Kazi Ahmed 2 , Patricia Tran 2 , Fatema Nader 2 , Linda Henry 2 , Ali
A. Weinstein 2 , Naomi Lynn Gerber 1,2 ; 1 Center For Liver Disease,
Department of Medicine, Inova Fairfax Hospital, Falls Church,
VA; 2 Betty and Guy Beatty Center for Integrated Research, Inova
Health System, Falls Church, VA
Background and aim: HCV infection has been associated with
changes in brain metabolites that may result directly from the
virus or mediated by exposure to proinflammatory cytokines
in the central nervous system. Our aim was to evaluate the
association of cytokines and mental health PROs in HCV+
patients treated with LDV/SOF±RBV. Methods: We included
100 CH-C GT1 patients (age 53.1±9.6, 57% male, 86%
white, BMI of 28.5±5.6) treated with LDV/SOF (N=50) or
LDV/SOF+RBV (N=50). All patients completed several validated
PRO instruments. Mental health PROs were measured
by the Role Emotional (RE), Mental Health (MH) and Mental
Component Summary (MCS) of SF-36, Emotional Well-being
(EWB) of FACIT-F, and Emotional domain (EMM) of CLDQ-
HCV. Frozen serum was analyzed for interleukins (IL) 1, 1ra,
8, 10, tumor necrosis factor-α (TNF-α), interferon-γ, monocyte
chemotactic protein 1/chemokine ligand 2, granulocyte colony
stimulating factor, vaso-endothelial and platelet-derived
growth factors using Bio-Plex, ELISA, and enzymatic assays
baseline, treatment week 12 and 4 weeks post-treatment. Relationships
between fatigue and clinical and laboratory data
were assessed by multiple regression analyses. Results: Patients
treated with LDV/SOF+RBV had more significant anemia (10%
vs 0%; p=0.02), more psychiatric (26% vs 10%; p=0.04) and
skin (22% vs 6%, p=0.02) adverse events during treatment.
After adjustment for pre-treatment history of anxiety, the most
consistent independent biomarker predictor of lower mental
health PROs during treatment was the level of serum TNF-α
(p