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risk factors particularly the majority of hepatitis B and C the tissues. [29,30] Lipid peroxidation (LPO) is responsible for
[10]
viral infection and alcoholic liver disease. Chronic HBV formation of many toxic products, such as 4-hydroxynonenal
infection cause of HCC in different area, where the virus and malondialdehyde MDA which attack cellular targets,
is largely endemic and vertical transmission common. [11,12] thereby inducing carcinogenicity. [31-33] Many biochemical and
High alcohol consumption; smoking of cigarette; obesity; molecular changes leads to free radical metabolites causing
and diabetes have also been associated with an increased the chemical carcinogens induce oxidative stress leading to
risk of developing HCC. [13-15] Previous studies have tumor promotion. [34,35] The failure of antioxidant defense
reported a close correlation with obesity and diabetes mechanism and tissue damage were enhanced by increasing
and an increased risk of HCC progression. Also, there LPO. Glutathione (GSH) is present in high concentration of
[16]
are common environmental factor associated with HCC liver and widely distributed in cells. It has many properties
[36]
development such as aflatoxin, a product of the Aspergillus as, protects the cell against free radical, peroxides and other
fungus. Several physiological disorders of the liver have toxins, so after decreased of GSH level in tissue causing DNA
[17]
been implicated in the HCC development, including α-1 damage, protein oxidation and LPO of the cell membrane
[37]
antitrypsin deficiency; certain porphyrias; Olchi’s disease; biomolecules lead to hepatocyte damage. However, the
and hereditary hemachromatosis, each typically in the setting decrease of the antioxidant enzymes activity (superoxide
[18]
of cirrhosis. Additionally, an automimmune disorders have dismutase and catalase) caused the increase of hepatocytes
been implicated in HCC pathogenesis, including primary in the cirrhotic livers. The production of cytokines, ROS, and
[38]
biliary cirrhosis and autoimmune hepatitis. [19] inflammation-mediated events leads to tumor formation.
The inflammatory diseases of cell, is produced by many
PATHOPHYSIOLOGY OF HCC pro-inflammatory cytokine as TNF-α and structural cells
[39]
especially the pathogenesis of asthma. Liver cirrhosis
HCC majority occurs in the setting of liver cirrhosis. causes elevated in the pro-inflammatory cytokine TNF-α
The accumulations of genetic and epigenetic changes as a major marker for inflammatory state in the cirrhotic
related to hepatocarcinogenesis disease are well known. liver. HCC has an anti-apoptotic genes expression and
[40]
However, the regulating cell cycle and suppressing rapid cell proliferation, due to apoptosis resistance
[41]
apoptosis used for maintenance the survival of cancerous under conventional therapies and incomplete cell cycle
cells. Retinoblastoma and p53 genes responsible for arrest. HCC increased apoptosis by the down-regulation
[42]
the oncogenes activation and tumor suppressor genes of the Bcl2 level, the activation of caspase cascade, and the
are the good markers that understand the molecular, up-regulation of Bax and the p53 level. [43-45] Additionally,
physiological mechanisms and disorders in the cellular HCC contains various histological changes such as: (1)
signaling pathways of HCC incidence growing. When pseudoglandular pattern including gland-like dilatation
[20]
the liver gets injured, necrosis will appear in the liver of the canaliculi in tumor cells; and (2) trabecular pattern
accompanied by the subsequent hepatocyte proliferation, of growth. Cytologically; polygonal and displaying
[46]
after continuous cycles of destructive-regenerative of tumoral hepatocytes; smaller tumor cell; granular
process. The hyperplastic nodules will turn into dysplastic eosinophilic cytoplasm; vesicular nuclei; giant tumor cells;
nodules inducing a high risk of developing HCC. [21] and conspicuous nucleoli are associated with HCC. [46-48]
Furthermore HCC well associated with various metabolic MANAGEMENT AND PROGNOSIS OF HCC
changes including biochemical alterations. Alfa-fetoprotein
(AFP) is a glycoprotein in serum that was first recognized There is a wide heterogeneity in HCC pattern, patient
as a major marker for HCC. AFP elevation indicating to variations as candidates for recommended treatments, and
malignant after pathological diagnosis and endodermal increasingly complex available therapeutic options with
[49]
[22]
lining tumor of the stomach, pancreas, and biliary tree. diverse responses to these therapies in clinical practice.
Moreover, HCC development has also been associated with Also HCC is highly associated with variable biologic behavior
plasma lipid and lipoprotein alterations. This alterations and the frequent coexistence of chronic liver disease and
[23]
result in cellular dysfunction, reduction in the membrane cirrhosis. So, it is important to manage HCC patients
[50]
integrity, fluidity and regulation of cellular processes related by multidisciplinary HCC teams including hepatologists;
to growth and cell survival causing cancer development. [24,25] medical and surgical oncologists; transplantation surgeons;
The cirrhosis and HCC characterized by a decrease of total diagnostic and interventional radiologists; pathologists;
protein and impair hepatic function indicating by increasing nurses and nurse practitioners. The most commonly used
[51]
hepatic enzymes (aspartate aminotransferase, alanine treatment by the enhancement of latent antitumor immune
transaminase, alkaline phosphatase, and gamma glutamyl response through chemotherapy. Chemotherapy has
[52]
transferase) activity through the loss of functional integrity varying effects, and work is underway in the search for active
of the cell membrane in liver resulting liver damage. [26-28] chemotherapy and appropriate for chemo-embolization,
Furthermore, the development and progression of HCC an intensive localized chemotherapy method by using
are well associated with the oxidative stress status that improvement prognosis. However, chemotherapy still
[53]
[54]
produced by increasing level of reactive oxygen species (ROS) has severe side effects and low survival rates. As a recent
resulting distortion and decrease the antioxidant activity in reports, a large number of natural antioxidant extracts
Hepatoma Research | Volume 2 | August 5, 2016 217