الفهرس 
HEPATOCELLULAR CARCINOMA
Medical Risk FactorsOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is the sixth most common
neoplasm worldwide and the third most frequent cause of cancerrelated
death. The major risk factor associated with HCC is liver
cirrhosis, which is predominantly caused by chronic HBV and/or
HCV infections, aflatoxin B1 exposure, and alcoholic liver
disease. It is estimated that HBV and HCV account for
approximately 75%-80% of HCC cases worldwide.
The diagnosis of HCC is mainly based on a combination of
abdominal ultrasound and serum alpha-fetoprotein level. However,
tumors that are too small will be missed by abdominal ultrasound,
and serum alpha fetoprotein level has a low sensitivity particularly
in early-stage disease. Clearly, the available screening methods are
inadequate for early detection and follow up of HCC. So there is
a need for a higher sensitivity aiming at early diagnosis of HCC as
well as a better specificity aiming at differentiation between HCC
and benign lesions.
Telomerase is a specialized ribonucleoprotein
polymerase, composed of RNA subunit (human telomerase
RNA, hTR) and a catalytic protein (human telomerase reverse
transcriptase, hTERT) which can elongate telomeric DNA using
its own RNA subunit as a template. TERT activity is generally
found in stem cells, hematopoietic progenitor cells, activated
lymphocytes and fetal cells. TERT activity was found to be absent in most normal human somatic cells but present in
cancerous cells where progressive telomere shortening is halted
and thus, the cells become immortal.
In this regard, our study aimed to evaluate the clinical
utility of TERT mRNA in the diagnosis and prognosis of HCC
and to correlate its levels with AFP, the routinely used
serological marker, for diagnosis of the disease nowadays.
This study was conducted at the Tropical Medicine and
Clinical Pathology Departments of Ain Shams University
Hospitals on 50 hepatic patients in addition to 20 apparently
healthy age-matched controls. Patients were divided into two
groups according to their diagnosis. group Ia included 30 HCC
patients who were further subdivided into three subgroups
based on the stage of the disease, as determined by the BCLC
Staging System (10 patients in stage A, 10 patients in stage B,
10 patients in stage D). group Ib included 20 patients with liver
cirrhosis.
All patients in the study were subjected to full history
taking, thorough clinical examination, radiological investigations
including abdominal U/S and CT scan, routine laboratory
investigations (ALT, AST, serum albumin, total bilirubin,
conjugated bilirubin and INR) in addition to serum AFP and
TERT mRNA assay by real-time polymerase chain reaction
technique Both AFP and TERT mRNA are significantly higher in
HCC patients group compared to CLD patients and control
groups.
The correlation analysis between AFP and other studied
parameters in HCC patients revealed a highly significant
positive correlation between AFP and TERT mRNA.
The correlation analysis between TERT mRNA and
different studied parameters in HCC patients revealed a
significant positive correlation between TERT mRNA,
conjugated bilirubin, INR and AFP and a significant negative
correlation between TERT mRNA and albumin. However, a non
significant correlation is observed between TERT mRNA and
all other studied parameters.
Regarding the comparison between Barcelona A and
Barcelona B, TERT mRNA is significantly lower in Barcelona
A compared to Barcelona B subgroup. Regarding the
comparison between Barcelona A and Barcelona D, AFP and
TERT mRNA are significantly higher in Barcelona D compared
to Barcelona A subgroup. Regarding the comparison between
Barcelona B and Barcelona D, TERT mRNA are significantly
higher in Barcelona D compared to Barcelona B subgroup.
Regarding the comparison between Child A versus Child
B, INR and TERT mRNA are significantly higher in B compared to A and albumin is significantly lower in Child B
versus Child A. Regarding the comparison between Child A and
Child C, INR and TERT mRNA is significantly higher in Child
C compared to Child A, while albumin is significantly lower in
Child C compared to Child A. Regarding the comparison
between Child B and Child C, TERT mRNA is significantly
higher in Child C compared to Child B and AFP is significantly
lower in Child C compared to Child B.
Regarding the diagnostic performance of serum AFP for
discrimination between HCC and CLD patients, the best cut-off
was 14 IU/mL. This has a diagnostic sensitivity 70%, specificity
60%, PPV 72.4%, NPV 57.1% and efficacy 66%.
On the other hand, the best cut-off value of TERT mRNA
for discrimination of HCC from CLD patients was 18(2-ΔΔCT).
This has a diagnostic sensitivity 100%, specificity 100%, PPV
100%, NPV 100% and diagnostic efficacy 100%. This proved
the superiority of TERT mRNA estimation over AFP in
discriminating HCC from CLD.
Regarding the diagnostic performance of AFP for
discrimination between HCC and control group, the best cut-off
value was 10 IU/mL. This had a diagnostic sensitivity 70%,
specificity 80%, PPV 84%, NPV 64% and a diagOn the other hand, the best cut-off value of TERT mRNA
for discrimination between HCC and control group was 2 (2-ΔΔCT).
This had a diagnostic sensitivity 100%, specificity 100%, PPV
100%, NPV 100% and a diagnostic efficacy 100%.