studies

936A AASLD ABSTRACTS HEPATOLOGY, October, 2015
1487
Osteopontin is a new prognostic marker of liver cirrhosis
Radan Bruha 1 , Marie Jachymova 2 , Jaromir Petrtyl 1 , Karel Dvorak 1 ,
Martin Lenicek 2 , Petr Urbanek 3 , Libor Vitek 2 ; 1 4th Intenal Clinic,
Charles University in Prague, 1st Faculty of Medicine, Prague,
Czech Republic; 2 Institute of Clinical Biochemistry and Laboratory
Diagnostics, Charles University in Prague, 1st Faculty of medicine,
Prague, Czech Republic; 3 Internal Clinic, Central Military Hospital,
Prague, Czech Republic
Background and Aims: Portal hypertension leads to major
complications of cirrhosis. Invasively measured hepatic venous
pressure gradient (HVPG) is a strong prognostic indicator in
patients with cirrhosis and portal hypertension. Recently, osteopontin
has emerged as a new marker with a possible relation
to fibrosis and cirrhosis and close correlation to portal hypertension.
Our aim was to evaluate the relationship of osteopontin
plasma concentrations to the prognosis of patients with
cirrhosis. Methods: A cohort of 154 patients with liver cirrhosis
(112 ethylic, 108 men, age 34-72 years) were enrolled. The
HVPG was measured by standard catheterization using the
balloon wedge technique. The mean follow-up of the patients
was 3.7±2.6 years (maximal length 7 years). Osteopontin was
measured by ELISA method. Results: The mean value of HVPG
was 16.18±5.6 mmHg. Patients with osteopontin values above
80 ng/ml had a significantly lower cumulative survival rate
compared to those with osteopontin ≤80 ng/ml (37% vs. 56%,
p=0.00035; OR 2.23, 95% CI 1.06-4.68; Fig 1). Similarly,
the HVPG cut-off value of 10 mm Hg divided patients into 2
groups with significantly different probabilities of cumulative
survival (39% for those with HVPG>10 mm Hg compared to
65% for those with HVPG≤10 mm Hg; p=0.0086, OR 2.92,
95% CI 1.09-7.76). Mortality in patients with at least one risk
factor (HVPG above 10 mm Hg or plasma OPN above 80
ng/l) was more than twice as high compared to patients without
any risk factors (OR=2.34); in those with both risk factors,
mortality was more than five times as high (OR=5.1) compared
to patients without any risk factors. Conclusions: Osteopontin is
a strong prognostic factor for overall survival in patients with
cirrhosis. Supported by SVV 260 156/2015.
Figure 1: Cumulative proportion of surviving patients with plasma
OPN levels below and above 80 ng/ml using the Kaplan-Meier
method.
1488
Liver Injury Independently Predicts Incident Cardiovascular
Disease (CVD) Risk
Kaku So-Armah 1 , Janet Tate 3,2 , Joseph K. Lim 2 , Vincent Lo Re 14 ,
Vincent Marconi 4 , Jeffrey Samet 1 , Cynthia Gibert 8 , David Leaf 9,10 ,
Adeel Butt 6,7 , Matthew B. Goetz 9,10 , David Rimland 4,11 , Maria C.
Rodriguez-Barradas 12,13 , Matthew Budoff 5 , Chung-Chou Chang 15 ,
Amy Justice 2,3 , Matthew Freiberg 16 ; 1 Boston University School of
Medicine, Boston, MA; 2 Yale University School of Medicine, New
Haven, CT; 3 VA Connecticut Healthcare System, West Haven,
CT; 4 Emory University School of Medicine, Atlanta, GA; 5 LA
Biomed Research Institute, Torrance, CA; 6 VA Pittsburgh Healthcare
System, Pittsburgh, PA; 7 Hamad Healthcare Quality Institute
and Hamad Medical Corporation, Doha, Qatar; 8 Washington DC
VA Medical Center, Washington, DC; 9 David Geffen School of
Medicine at UCLA, Los Angeles, CA; 10 VA Greater Los Angeles
Healthcare System, Los Angeles, CA; 11 Atlanta VA Medical Center,
Atlanta, GA; 12 Michael E. DeBakey VA Medical Center, Houston,
TX; 13 Baylor College of Medicine, Houston, TX; 14 University of
Pennsylvania School of Medicine, Philadelphia, PA; 15 University of
Pittsburgh Medical Center, Pittsburgh, PA; 16 Vanderbilt University
School of Medicine, Nashville, TN
Background: Multiple etiologies of liver injury are associated
with cardiovascular disease (CVD) e.g., hepatitis C or B (HCV,
HBV) and HIV co-infection, alcohol, and obesity. We hypothesize
that liver injury is a mechanism of increased CVD risk.
We assessed whether liver fibrosis index 4 (FIB4) predicted
incident CVD. Liver-related comorbidities may have extra-hepatic
contribution to CVD risk. Thus, we performed sensitivity
analyses excluding people with HCV, HBV, HIV, alcohol use
disorder, and obesity. Methods: Participants from the Veterans
Aging Cohort Study Virtual Cohort (VACS VC), without CVD
at baseline (first clinical visit after 4/1/2003) were included.
Liver injury was categorized using baseline FIB4 (calculated
using age, liver transaminases and platelets) and ICD-9 codes
for cirrhosis and hepatic decompensation. Total non-fatal and
fatal CVD was assessed using VA, VA Fee For Service and
Medicare ICD-9 and procedure codes for myocardial infarction,
heart failure, coronary heart disease and stroke, and
National Death Index cause of death data. Follow-up ended
after a CVD event, or death, or on 9/30/2012. Cox regression
analyses were used to estimate CVD risk adjusting for
confounders including renal disease. Results: After excluding
21488 people with prevalent CVD, 104731 people remained.
Mean (SD) age was 49.6 (9.5) years in this largely male (90%)
cohort followed for a median (IQR) of 7 (3, 9) years. LDL cholesterol
and body mass index decreased with increasing FIB4.
African American race, HIV, HCV, HBV, current smoking, type
2 diabetes, alcohol use disorder, cocaine use, and anemia
were more common among those with FIB4>1.45 than those
with FIB43.25 or a clinical diagnosis of cirrhosis or
hepatic decompensation had significantly elevated CVD risk
despite also having higher mortality rates (see Table below).
This association persisted among those without heart failure or
without HCV, HBV, HIV, alcohol abuse/dependence diagnosis
and BMI>30 kg/m 2 . Conclusions: FIB4 and severe liver injury
independently predict risk of CVD in VACS VC. Future studies
should assess if treatment of liver injury reduces CVD risk.
Disclosures:
The following authors have nothing to disclose: Radan Bruha, Marie Jachymova,
Jaromir Petrtyl, Karel Dvorak, Martin Lenicek, Petr Urbanek, Libor Vitek