Transcript Prevalence of metabolic abnormalities in HBV related

Prevalence of metabolic abnormalities in
HBV-related HCC: clinical study
Jin-Yan Zhao
Department of Laboratory Medicine,
Eastern Hepatobiliary Hospital,
Second Military Medical University, Shanghai, China
Introduction
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Hepatocellular carcinoma (HCC) is the fifth most
common cancer and the third cause of cancerrelated death worldwide.
Hepatitis B virus (HBV) infection and hepatitis C
virus (HCV) infection played the most role in
western and Asia-Pacific region.
Introduction
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The relationship between metabolic factors and
chronic liver disease including liver cirrhosis (LC)
and HCC has become a hot topic.
Metabolic syndrome (MS) has been recognized
as a major public health problem worldwide,
aroused more and more attention.
Hypertension
ANS↑
HCV infection
Adiponectin↓
Leptin↑
Obesity
RAS↑
Mitochondrial dysfunction
ROS↑
Hepatic
steatosis
Activation of
macrophages
IR
HCC
TNF-α↑
Steatohepatitis
LC
IFN
resistance
Liver diseases and metabolic syndrome. J Gastroenterology 2008; 43:509–518
Object
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Previous studies suggested the role of metabolic factors
is a newly identified risk factor in HBV-related HCC. The
association between metabolic factors and HCC has not
been clarified up to now.
This case-control study was conducted to investigate the
prevalence of metabolic abnormalities in HCC and to
probe the association between metabolic parameters
and liver function so as to evaluate the role of metabolic
abnormalities in the pathogenesis of HBV-related HCC.
Materials and methods
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Totally 179 cases of HBV-related HCC, who were
surgically treated and pathologically confirmed were
enrolled in this study.
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The 150 cases of healthy controls were recruited from
routine physical examination.
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All the metabolic-related parameters and liver function
tests were determined with routine biochemical or
immunological analytic methods.
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Body mass index (BMI) was obtained from medical
documentation.
MDA and TAOC were adapted by chemical analytic
methods.
A stratified analysis was conducted according to BMI, GA,
FFA and the relationship between the metabolic-related
parameters and liver functions were analyzed in both
HCC and control subjects.
Statistical analysis
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The statistical analysis was conducted using SPSS
version 11.5 statistical software.
Comparisons on HCC and controls using Mann-Whitney
U test.
Categorical variables were compared using Wilcoxon
rank sum test and t test.
For Analysis of the correlation between two indicators
(liver functions and metabolic parameters): using
spearman correlation analysis.
Results
Table1 Baseline characteristic of HCC and normal subjects
Index
HCC
Median（range）
Normal
Median（range）
p
AGE
53（45～58.5）
49.5（43~53）
＜0.001
Gender
M/F（155/24）
M/F（118/32）
0.057
TBIL
14.60（11.30~17.50）
11.25（9.10~15.70）
＜0.001
TP
71.30（67.2~74.5）
78.20（75.50~79.50）
＜0.001
ALB
41.10（38.9~43.6）
46.95（45.50~50.00）
＜0.001
ALT
38.70（26.8~56.0）
18.35（15.50~27.90）
＜0.001
AFP
31.10（5.10~1210）
3.25（1.90~3.80）
＜0.001
There are statistically significant differences in TBIL, TP, ALB, ALT, AFP
between the two groups (p<0.05).
Table2 Metabolic parameters in HCC and normal control
indexes
Normal（median)
HCC (median)
p
GA
13.0（13~14）
15.0（14~16）
≤0.001
GLU
5.1（4.71~5.69）
4.9（4.57~5.33）
≤0.001
TC
4.5（4.11~4.89）
4.0（3.36~4.47）
≤0.001
TG
1.0（0.89~2.26）
0.90(0.68~1.16)
≤0.001
LDL
2.85（2.39~3.11）
2.40（1.94~2.83）
≤0.001
MDA
9.77（5.37~13.58）
10.68（7.38~15.47）
0.005
T-AOC
17.73（14.25~23.66）
14.43（10.90~17.63）
≤0.001
HCC group showed significantly higher levels of GA and MDA (p < 0.01) than
controls, While HCC group showed significantly lower levels of TC, TG, LDL and
TAOC (p < 0.01).
Table 3 Changes of metabolic parameters and liver functions
in HCC subjects with different BMI
BMI
parameters
≤23.9
(N=104)Median (range)
＞23.9
(N=69)Median (range)
P
INS
7.46（3.79~7.47）
7.77（5.15~10.18）
<0.001
IR
1.53（0.8~1.62）
1.9（1.11.~2.54）
<0.001
QUICKI
0.36（0.35~0.39）
0.35（0.33~0.37）
<0.001
TG
0.79（0.61~1.02）
1.2（0.83~1.31）
<0.001
LDL
2.24（1.92~2.64）
2.77（2.2~3.04）
0.003
HDL
1.31（1.14~1.59）
1.38（1.09~1.48）
0.036
The higher BMI, the higher levels of HOMA-IR（homeostasis model assessment for
insulin resistance), Insulin, FFA, TG, LDL (P<0.01) and lower level of QUICKI
(Quantitative insulin sensitivity check index ) (p<0.05).
Table 4 Changes of metabolic parameters and liver functions
in HCC subjects with different GA
GA
parameters
≤ 16
(N=144)Median (range)
＞16
(N=35)Median (range)
p
GLU
4.86(4.54~5.10)
6.43（5.06~6.59）
0.000
HDL
1.32(1.08~1.48)
1.35（1.22~1.63）
0.028
TAOC
12.46(10.47~17.04)
16.84(11.63~18.53)
0.048
ALB
41.60(39.04~43.7)
39.2(37.2~42.11)
0.018
ALP
84(67~110.25）
112(82~144)
0.006
PT
11.5(11.3~12.3）
11.80(11.75~12.75)
0.002
GLU were significantly higher than normal group
ALB was lower than control in HCC. (p<0.05).
Table 5 Changes of metabolic parameters and liver functions
in HCC subjects with different FFA
FFA
parameters
≤0.6
(N=91)Median (range)
＞0.6
(N=34)Median (range)
p
C peptide
1.18(1.00~1.56)
1.24(1.16~2.00)
0.044
MDA
9.75(6.38~15.06)
14.38(8.88~16.43)
0.032
GGT
62(35.5~99)
144 (81~215.5)
0.001
According to different levels of FFA, MDA and GGT were significantly
higher in abnormal groups than control (p<0.05)
Table 6 Associated study among liver function,
tumor marker and metabolic parameters in HCC
r
p
r
p
BMI
-0.034
0.663
0.018
0.813
IR
0.02
0.8
0.186
0.015
QU
-0.02
0.8
-0.186
0.015
GA
0.092
0.222
-0.248
0.001
GLU
0.018
0.816
-0.019
0.8
INS
0.019
0.806
0.196
0.01
C
peptide
0.043
0.573
0.08
0.296
ALT
r
p
-0.03
0.694
-0.013
0.863
0.013
0.863
0.08
0.289
0.102
0.175
-0.057
0.459
0.056
0.467
0.103
0.252
-0.024
0.753
0.064
0.403
-0.057
0.449
0.018
0.814
AST
r
p
-0.183
0.017
-0.217
0.004
0.217
0.004
0.188
0.013
-0.02
0.79
-0.241
0.002
-0.079
0.305
0.161
0.073
0.051
0.502
-0.073
0.339
-0.007
0.931
0.141
0.062
ALP
r
p
-0.204
0.008
-0.25
0.001
0.25
0.001
0.272
0
0.043
0.571
-0.302
0
-0.156
0.042
0.125
0.166
-0.054
0.476
-0.012
0.879
-0.125
0.098
0.111
0.143
GGT
r
p
-0.099
0.248
-0.102
0.232
0.102
0.232
0.063
0.452
-0.036
0.665
-0.136
0.11
0.033
0.699
0.311
0.002
0.1
0.235
0.063
0.459
0.035
0.675
0.174
0.037
AFP
r
-0.071
-0.091
0.091
-0.054
-0.131
-0.065
-0.108
0.069
-0.007
-0.115
-0.005
0.002
p
0.35
0.232
0.232
0.475
0.08
0.393
0.159
0.443
0.924
0.13
0.949
0.974
TBIL
ALB
FFA
0.188
0.036
-0.08
0.377
TC
0.091
0.23
0.165
0.029
TG
-0.228
0.002
-0.016
0.838
LDL
0.032
0.0675
0.189
0.012
HDL
0.236
0.002
-0.009
0.902
The parameters reflecting liver functions have obvious correlation
with metabolic indicators.
Table 7
Associated study between metabolic parameters in HCC
BMI
IR
GA
GLU
INS
FFA
TC
TG
LDL
HDL
MDA
TAOC
BMI
1
.
0.358
0
0.046
0.546
0.341
0
0.031
0.687
0.092
0.316
0.117
0.127
0.276
0
0.212
0.005
-0.238
0.002
-0.062
0.421
0.107
0.171
IR
0.358
0
1
.
0.55
0
0.795
0
-0.079
0.3
0.051
0.576
0.028
0.71
0.148
0.05
0.038
0.616
-0.051
0.499
-0.043
0.575
0.022
0.781
QU
0.364
0
0.708
0
0.213
0.005
0.958
0
0.208
0.006
0.018
0.844
0.041
0.591
0.112
0.144
0.071
0.352
-0.084
0.272
-0.051
0.506
0.072
0.356
GA
0.046
0.546
0.55
0
1
.
0.486
0
0.045
0.559
0.143
0.112
0.013
0.865
0.169
0.025
-0.007
0.927
0.005
0.944
0.021
0.786
0.03
0.696
GLU
0.341
0
0.795
0
0.486
0
1
.
0.199
0.009
0.068
0.462
0.04
0.603
0.148
0.053
0.062
0.421
-0.075
0.326
-0.041
0.593
0.075
0.336
INS
0.031
0.687
-0.079
0.3
0.045
0.559
0.199
0.009
1
.
0
0.998
-0.113
0.139
-0.079
0.303
-0.109
0.155
-0.041
0.595
0.004
0.957
0.014
0.854
FFA
0.092
0.316
0.051
0.576
0.143
0.112
0.068
0.462
0
0.998
1
.
0.006
0.943
0.062
0.497
-0.046
0.614
0.103
0.253
0.213
0.019
0.083
0.377
TC
0.117
0.127
0.028
0.71
0.013
0.865
0.04
0.603
-0.113
0.139
0.006
0.943
1
.
0.271
0
0.94
0
0.551
0
-0.13
0.086
0.172
0.025
TG
0.276
0
0.148
0.05
0.169
0.025
0.148
0.053
-0.079
0.303
0.062
0.497
0.271
0
1
.
0.263
0
-0.126
0.096
-0.035
0.648
0.224
0.003
LDL
0.212
0.005
0.038
0.616
-0.007
0.927
0.062
0.421
-0.109
0.155
-0.046
0.614
0.94
0
0.263
0
1
.
0.247
0.001
-0.081
0.287
0.112
0.146
HDL
-0.238
0.002
-0.051
0.499
0.005
0.944
-0.075
0.326
-0.041
0.595
0.103
0.253
0.551
0
-0.126
0.096
0.247
0.001
1
.
-0.168
0.026
0.155
0.043
BMI is positive associated with IR, GLU, TG, LDL and negative with HDL.
MDA is respectively associated with FFA and HDL.
TAOC is correlated with TC, TG, HDL (p<0.05)
Conclusion
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Metabolic abnormalities were associated with occurrence of HBV-related HCC.
HCC patients with overweight have insulin resistance,
reduced insulin sensitivity and higher plasma insulin
level.
Elevated MDA and reduced TAOC may lead to liver injury.
Acknowledgement
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Co-authors
Yun-Peng Zhao
Xing Gu
Jun Ji
Chun-Fang Gao*
Supported foundation
NSFC No.30971345 ,
Shanghai Science and Technology program
09XD1405800 40.
Thank you
r your attention!