الفهرس 
HEPATOCELLULAR CARCINOMAOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is one of the
most common malignancies worldwide and it is one of
the major causes of death, because of its high
frequency and poor prognosis. It’s the cause of about
one million deaths annually allover the world. HCC is
now a rather common malignancy in Egypt which
usually develops on top of liver cirrhosis secondary to
viral infection either hepatitis B or C viruses which
are considered as definite risk factors for HCC.
Because of the high prevalence rate of HCV in
cirrhotic Egyptian patients, it accounts for most HCC
cases in Egypt.
When far advanced, HCC generally presents
with symptoms and physical signs and diagnosis is
easy, but before this late stage is reached, clinical
diagnosis is often difficult.
Conventional tests of hepatic function don’t
distinguish HCC from other hepatic masses or from
cirrhosis. Accordingly, they contribute little to the
diagnosis of the tumor. Diagnosis of HCC depends
mainly on the detection of tumor markers in the sera of the HCC patients in addition to other diagnostic
modalities such as ultrasound, spiral CT and liver
histopathology by biopsy.
Tumor markers are substances synthesized and
secreted by the malignant cells. They are not normally
present in serum and if present they are not
biologically active. Few tumor markers are produced in
a sufficient large proportion, so they can be used as
serum markers of tumors and they become helpful in
screening, diagnosis and follow up of cases. Serum AFP
concentrations have been shown to be the most useful
tumor marker with regards to HCC but it may be
normal in up to 40% of patients (lack of sensitivity). It
may be increased in hepatitis and cirrhotic patients
(lack of specificity). The availability of a more sensitive
serological marker that distinguishes between HCC
and benign hepatic lesions would therefore, be very
useful for early and specific diagnosis.
Chromogranin-A (Cg-A) is a 49-KDa acid
glycoprotein originally described in catecholamine
storage vesicles of the adrenal medulla. It has a wide
distribution in secretory vesicles of the endocrine,
neuroendocrine and nervous systems, where it is costored
and co-secreted with hormones and neurotransmitters. It is present in low concentration
in the serum of healthy individuals and in high
concentration in patients with renal failure and heart
failure.
Clusters of cells containing Cg-A have been
demonstrated within HCC tissues. Previous studies
reported high serum Cg-A values in patients with
HCC suggesting that Cg-A might represent a useful
marker for HCC and a complementary diagnostic tool,
unless kidney or heart failure is present.
The aim of this study was to investigate the
diagnostic utility of plasma Cg-A in patient with liver
cirrhosis and HCC in comparison to the conventional
markers, namely serum albumin, PT and INR in
cirrhotic patients and AFP in HCC. Our study was
conducted on 60 patients who presented to the Tropical
Department of Ain Shams University Hospitals and
National Liver Institute in Monofyia University. The
patients’ group included: group 1 (30 patients with
primary HCC) and group 2 (30 patients with liver
cirrhosis). In addition, 20 age- and sex-matched
healthy subjects were included as control group.All subjects included in this study were subjected to full history taking, clinical
examination, radiological investigations including CT scan and abdominal ultrasound for patients,
laboratory investigations including CBC, prothrombin concentration, INR, renal function (urea and
creatinine), liver function (ALT, AST, albumen, ALP and bilirubin), hepatitis markers (HBs Ag and
HCV Abs), AFP and Cg-A.
Regarding AFP and Cg-A, both were significantly higher in HCC patients compared to cirrhotic
patients and control group, respectively. However, a non significant difference was observed
between cirrhotic patients and control group regarding both markers.
Our correlation study between AFP and other studied parameters in all groups revealed a non
significant correlation with the exception of ALP which correlated positively with AFP in HCC
group. The correlation analysis between Cg-A and other studied parameters in all groups also
revealed a non
significant correlation.Regarding the diagnostic performance of AFP for
discriminating HCC patients versus cirrhosis and
control, the best cut-off value was 22.8ng/mL. This
had a diagnostic sensitivity of 87%, specificity 100%,
positive predictive value 100%, negative predictive
value 93% and a diagnostic efficiency 95%.
On the other hand, the best cut-off value of Cg-A
for discriminating HCC patients versus cirrhosis and
control was 53ng/mL. This had a diagnostic sensitivity
of 87%, specificity 86%, positive predictive value 79%,
negative predictive value 92% and a diagnostic
efficiency 86%.
The combined use of the two markers, AFP and
Cg-A, led to increase the sensitivity to 97% and
increase the specificity to 100%. This showed that
simultaneous measurements of serum AFP and Cg-A
are of value in detecting HCC.
In conclusion, Cg-A was proved to be
significantly higher in HCC patients compared to
cirrhotic patients and control group. Therefore, it can
be used as a potential serologic marker for HCC and a
complementary diagnostic tool in monitoring cirrhotic
patients for detection of HCC. An observation worth further investigation is that the combined use of AFP
and Cg-A increase the diagnostic performance for
detection of HCC which suggested that the inclusion
of Cg-A to the current standard tests for detection of
HCC may improve the ability to identify patients who
might be missed by current diagnostic strategies and
thus might provide a better therapeutic outcome .