Page 27 - JCTR-11-4

Journal of Clinical and
Translational Research Propranolol as a treatment for HCC

and E2), and a single capsid (C) protein. Like HBV, HCV proliferation. Key factors include genetic mutations
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is transmitted by blood and body fluids. Despite having (e.g., TP53 and CTNNB1), dysregulated signaling
2,11
no known DNA form during its life cycle or latent stage, pathways (e.g., Wnt/β-catenin and PI3K/AKT/mTOR),
HCV commonly causes recurrent liver infections. Unlike and epigenetic modifications that drive uncontrolled
HBV infections, the probability of developing a chronic hepatocyte proliferation. The tumor microenvironment,
HCV infection is between 55% and 85%, and it does comprising immune cells, fibroblasts, and extracellular
11
not change much with age. Worldwide, there are over matrix components, further promotes HCC by fostering
170 million HCV-infected people, and 20% of them will immune evasion, angiogenesis, and metastasis. Chronic
develop cirrhosis. Unlike patients with chronic hepatitis inflammation due to hepatitis B/C infection, metabolic
B, those with chronic hepatitis C nearly invariably disorders (e.g., non-alcoholic fatty liver disease), and
develop HCC in the context of cirrhosis. Annually, 1 oxidative stress also contribute to HCC pathogenesis by
– 4% of chronic hepatitis C patients with cirrhosis are sustaining pro-tumorigenic conditions. In addition, HCV
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prone to developing HCC, whereas 1 – 3% of patients proteins, notably core and NS5A, directly contribute to
with a chronic HCV infection will do so within 30 years. hepatocarcinogenesis by interfering with essential cellular
Similar to HBV, the association between HCV and HCC processes. NS5A enhances cell proliferation and inhibits
likely involves both the indirect effect of cirrhosis and apoptosis, whereas the core protein disrupts cell cycle
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HCV’s direct role in promoting hepatocarcinogenesis. regulation and promotes genomic instability. Moreover,
2
Because of the expression of the entry receptors needed HCV-induced oxidative stress and DNA damage play
for viral replication and host liver-enriched cellular essential roles in the progression of HCC. The virus
factors (miRNA-122), HCV infects mainly hepatocytes. induces the production of reactive oxygen species and
Extrahepatic manifestations were, however, observed in impairs antioxidant defense mechanisms, resulting in DNA
26
kidneys, peripheral nervous system, epithelial cells, and lesions and genomic modifications. These alterations can
mononuclear blood cells. 20 activate oncogenes and inactivate tumor suppressor genes,
The livers of HCV-infected individuals have higher further promoting hepatocarcinogenesis. Furthermore,
amounts of the hepatic low-density lipoprotein (LDL) persistent inflammation in the liver brought on by HCV
receptor, which is crucial for assessing blood cholesterol infection creates an environment that is favorable for
levels. This suggests that in HCV patients, viral infection tumor development and progression. Pro-inflammatory
directly causes decreased LDL levels. The combination cytokines and chemokines are released by the virus, drawing
6
of environmental, host, and viral variables is one of the immune cells that produce growth factors and encourage
angiogenesis. This sustained inflammatory response
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processes behind HCV-induced HCC. HCV does not also contributes to the activation of cell proliferation and
incorporate into the host genome such as HBV does. survival signaling pathways. In addition, HCV proteins
However, like HBV, HCV may cause chromosomal interact with host factors to dysregulate cellular
instability by directly affecting genes that control how signaling pathways, such as those associated with cell
centrosomal processes and mitotic spindles are arranged proliferation, apoptosis, and immune responses. These
during the cell cycle. 21
interactions disrupt normal cellular functions and foster
The attachment of HCV to cells marks the start of the growth of cancer. Individuals infected with HCV
its life cycle. HCV particle entrance into hepatocytes is develop hepatocarcinogenesis due to the complex effects
facilitated by a variety of cellular components, including of HCV on critical cellular processes, including oxidative
proteins, lipids, and glycans. HCV first binds to surface stress-induced DNA damage, chronic inflammation, and
proteoglycans, including the tetraspanin CD81 and the dysregulation of signaling pathways. Moreover, HCV
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scavenger receptor class B type I. Following their relocation infection affects hepatocytes and the microenvironment
to tight junctions, occluding proteins and claudin-1 surrounding the liver. Chronic inflammation triggered
become essential for HCV penetration. 22 by HCV recruits immune cells, such as macrophages
and lymphocytes, which release pro-inflammatory
3.2. Mechanisms of HCV-induced HCC cytokines and chemokines. This disruption permits
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The mechanisms of HCV-induced HCC involve a complex unrestrained cell proliferation and survival, thereby
interplay of numerous factors. Through its persistent fostering the development of HCC. Taken together,
infection, the virus causes chronic inflammation in the the complex interplay between chronic inflammation,
liver. This inflammatory response activates multiple oxidative stress-induced DNA damage, and dysregulated
signaling pathways, including the JAK/STAT and signaling pathways underlie the pathogenesis of HCV-
NF-κB pathways, which promote cell survival and associated hepatocarcinogenesis. Understanding these

Volume 11 Issue 4 (2025) 21 doi: 10.36922/JCTR025080010