Page 243 - ebook HCC

PROGRAMME
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240 PROGRAMME AND ABSTRACTSAND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 241
FEBRUARY 13 - 16, 2014

Poster Board Number C29

RS4374383 SINGLE NUCLEOTIDE NOTES
POLYMORPHISM OF MERTK GENE IS
ASSOCIATED WITH HEPATOCELLULAR
CARCINOMA (HCC) IN PATIENTS WITH HCV
CIRRHOSIS

Vincenza Calvaruso , Stefania Grimaudo , Maria Rosaria Pipitone ,
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Maria Grazia Bavetta , Giuseppe Cabibbo , Elisabetta Conte , Antonio Craxì , Vito Di Marco 1
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1 Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
Corresponding author’s e-mail: vincenza.calvaruso@unipa.it
Introduction: MERTK gene encode factors involved in phagocytosis of apoptotic cells by
macrophages. Genome-wide association (GWA) studies reported that rs4374383-SNP of
MERTK gene is associated with fibrosis in patients with HCV chronic infection.
Aims: We evaluated if rs4374383-SNP influenced the risk of liver events in patients with
HCV-cirrhosis.
Methodology: A prospective cohort of patients with compensated HCV cirrhosis treated
with Peg-IFN alfa-2b/Ribavirin were evaluated for rs4374383-SNP using the TaqMan
SNP-genotyping allelic discrimination method. All patients were screened for esophageal
varices (EV) and underwent to surveillance for HCC by ultrasound every six months.
Multivariate Cox regression analysis were used to determine factors associated with
development of liver decompensation (LD) and hepatocellular carcinoma (HCC).
Results: Among 404 patients enrolled (mean age:58.2±8.6 years, 63% men, 84%
genotype 1), 17.5%, 45.8% and 36.6% had AA, GA and GG MERTK gene respectively.
104 patients (25.7%) achieved a Sustained Virological Response (SVR). During the follow-
CLINICAL POSTER ABSTRACTS patients (22.3%) developed HCC. By multivariate analysis EV (HR:2.21; 95%CI:1.32-3.72; CLINICAL POSTER ABSTRACTS
up (median:81 months; range:12-144) LD was observed in 95 patients (23.5%) while 90
p=0.003), platelets (HR:0.98; 95%CI:0.97-0.99; p<0.001), albumin (HR:0.37; 95%CI:0.19-
0.71; p=0.003), and SVR (HR:0.20; 95%CI:0.08-0.49; p<0.001) were independently
associated to LD. The variables independently associated to HCC were age (HR:1.03;
95%CI:1.00-1.06; p=0.049), gender (HR:0.58; 95%CI:0.36-0.95; p=0.032), GGT (HR:1.21;
95%CI:1.08-1.36; p=0.001), SVR (HR:0.27; 95%CI:0.13-0.60; p=0.001) and rs4374383-
SNP (AA:HR:2.68; 95%CI:1.45-4.91; p=0.001–AG:HR:1.69; 95%CI:1.01-2.94; p=0.047).
The risk to developed HCC was of 0.98 per 100 persons/years in patients with SVR and of
2.42, 4.19 and 7.64 per 100 persons/years in no responder to therapy with genotype GG,
GA and AA of rs4374383 SNP, respectively
Conclusions: The AA MERTK allele is associated with high risk of HCC in HCV cirrhosis.
MERTK gene is involved in the regulation of inflammatory responses and may be involved
in the angiogenesis and growth of liver cancer.