Page 306 - ebook HCC

GENEVA, SWITZERLANDA, SWITZERLAND
PROGRAMME
EASL
304 PROGRAMME AND ABSTRACTSAND ABSTRACTS GENEV EASL HCC SUMMITHCC SUMMIT 305
304
305
FEBRUAR
FEBRUARY 13 - 16, 2014Y 13 - 16, 2014
Poster Board Number C70 Poster Board Number C71
ASSOCIATION OF TNF-ALPHA CHARACTER OF NBNC-HCC

Naota Taura, Tatsuki Ichicawa , Kazuhiko Nakao
1
1
Dalia Shaalan , Amal K. Selim , Raghda E.-S. Farag , Basem El-deek 1 2 3
1
1
1 2
1 Medical Biochemistry Department., Tropical Medicine Department., Community 1 and Nagasaki Association Study of Liver Disease (NASLD) group
3
2
Medicine , Mansoura Faculty of Medicine, Mansoura University, Egypt, Mansoura, Egypt Department of Gastroenterology and Hepatology,, Graduate School of Biomedical
Sciences Nagasaki University, Nagasaki, Japan
Corresponding author’s e-mail: raghda.farag@yahoo.com Corresponding author’s e-mail: ntaura-gi@umin.ac.jp
Introduction: TNF-α plays a pivotal role in the host immune response to hepatitis C virus Introduction: HCC often develops in patients with liver cirrhosis caused by hepatitis B
infection as a well characterized inflammatory mediator and may be implicated in the virus (HBV), hepatitis C virus (HCV), excessive alcohol consumption, or nonalcoholic
development of hepatocellular carcinoma (HCC). fatty liver disease. Of the hepatitis viruses which cause HCC, HCV is predominant in
Japan.However, It has been reported that the number and ratio of both HBsAg and HCVab
Aims: The aim of the present study was to investigate the frequency of TNF-α 308 negative HCC (HCC-nonBC) steadily increases in Japan.
promoter genotype and its association with the risk of developing hepatocellular carcinoma
in Egyptians. Aims: The aim of this study was to determine the frequencies and utilities of elevated
α-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels as biomarkers in
Methodology: One hundred twelve of gender-matched and age-matched patients with cryptogenic HCC.
HCC and unrelated ninety six healthy controls were genotyped for TNF308 with polymerase
chain reaction and direct sequencing. DNA was extracted from peripheral blood of all Methodology: A total of 2,368 patients with HCC diagnosed between 1999 and 2010 in
cases and controls. DNA analysis was carried out by polymerase chain reaction (PCR), Nagasaki Association Study of Liver (NASLD), were recruited for this study. The etiology
then restriction digestion of the PCR products (RFLP) for TNF-α 308 gene. of HCC was categorized to four groups; HCC-B: HBsAg positive and HCVAb negative,
HCC-C: HCVAb positive and HBsAg negative, HCC-BC: both of HBsAg and HCVAb
positive, HCC-nonBC: both of HBsAg and HCVAb negative. The significance of factor
Results: Among HCC patients carriers of A alleles were significantly more frequent with were examined for HCC-nonBC using logistic regression analysis.
7.02 –fold higher risk of developing HCC among HCC /HBV group than control (OR=4.02,
95% CI=3.41-14.63, Corrected p value by using benferroni correction is <0 .001). That Results: Multivariate analysis identified age (≥70 years, hazard ratio [HR] 1.63), sex
risk increases to 14.05 fold in HCC/HCV when compared to control (OR= 14.04, 95% (female, HR 1.73), BMI (≥25, HR 2.12), alcohol consumption (excessive, HR 14.73),
CI 7.02-28.51, p<0 .001). On the other hand, the carriers of G alleles were significantly platelet count (<116,000 /μL, HR 1.88), AST (<56 IU/L, HR 1.47), ALT (<46 IU/L, HR
CLINICAL POSTER ABSTRACTS Patients with HCC with HBV or HCV had a lower frequency of TNF308.GG genotype independent and significant risk factors for HCC-nonBC. According to TNM stage, the CLINICAL POSTER ABSTRACTS
more frequent among control when compared to either HCC/HBV or HCC/HCV groups
2.48), AFP (20-199 ng/mL, HR 0.60; ≥200 ng/mL, HR 0.63), DCP (20-199 mAU/mL, HR
(OR=0.14, 95% CI = 0.07-0.29, and OR= 0.07, 95% CI =0.04-0.14 respectively, p<0 .001).
1.64; ≥200 mAU/mL, HR 2.08), and TNM stage (II, HR1.67; III, HR1.88; IV, HR 2.40), as
(38.5 % and 21.6%% vs 82% in control; OR=0.11, 0.05; with 95%CI (0.04-0.25) and (0.02-
median AFP levels in HCC-nonBC with TNM stages I, II, and III were significantly lower
0.12), p value is <0 .001). The frequency of TNF-α-308 GA genotypes was higher in HCC
than in either HCC-B or HCC-C. In TNM stage IV, the median AFP level in HCC-nonBC
patients with HBV or HCV than control (52% and 51.7% % vs 14.6%; OR= 6.33, 6.23
was significantly lower than in either HCC-B or HCC-BC. The median DCP levels in HCC-
nonBC with TNM stages I and II were significantly higher than those in either HCC-B or
with 95% CI (2.7-15.03) and (2.75-14.43) ; P<0 .001). When comparing the frequency
of TNF308.AA genotype among the studied groups, it was significantly more frequent in
than that in HCC-C. However, there were no significant differences in median DCP level
HCC patients versus control ( OR=3.04 , 3018 ; with 95% CI (2.14-3.85) and (2.49-4.06)
among HCC patients at TNM stage IV. The survival rate of patients in the high DCP group
, p=0.007, p<0 .001). HCC-C. In TNM stage III, the median DCP level in HCC-nonBC was significantly higher
(≥200 mAU/mL) was significantly lower than that of patients classified as having low DCP
Conclusion: This study concluded that, individuals carrying the A allele of TNFα -308 (40-199 mAU/mL) or being DCP negative (<40 mAU/mL) in the HCC-B, HCC-C, and HCC-
polymorphism may be more susceptible to hepatocellular carcinoma either in homozygous nonBC groups (p ≤ 0.001; log-rank test).
or heterozygous state.
Conclusion: DCP was more sensitive than AFP for the diagnosis of early stage cryptogenic
HCC. DCP should be used as the main serum test for cryptogenic HCC detection.