Running head: CLINICAL INVESTIGATION OF HEPATITIS C AND VIRUS 1

Clinical Investigation of Hepatitis C and Virus

Christina (Ngu) W. Phoo

Molloy College
CLINICAL INVESTIGATION OF HEPATITIS C AND VIRUS 2

Clinical Investigation of Hepatitis C and Virus

Hepatitis C is a blood borne infection in which a person becomes infected after the initial

exposure or to come in contact with the blood of an infected person who has hepatitis C virus. It

can cause serious effects to the liver; indeed, it leads to a chronic liver disease, cirrhosis or

scarring of the liver, hepatocellular carcinoma, and liver cancer in which eventually follows

death in several years (Chen & Morgan, 2006). There are about 170 million people worldwide

affected by Hepatitis C virus (p. 47). It is a condition in which a person started with the acute

hepatitis with non-specific symptoms, and perhaps, it may resolve or may becomes chronic

resulting in major health consequences. Finally, it is essential to understand the concept of

etiology, pathogenesis, the clinical manifestations to pathophysiology, and the progression of the

HCV in a human host cell.

Hepatitis C is a RNA positive strand virus that belongs to the family of flavivirus and the

only member of genus hepacivirus. It replicates in the cytoplasm of hepatocytes. The HCV is

made of six genotypes and within these genotypes have the additional fifty-two subtypes (Joyce

& Tyrrell, 2010). There is a great variation among these subtypes which causes higher in

mutation rate of the virus; thus, its error prone RNA polymerase and other RNA viruses (Joyce

& Tyrrell, 2010). Despite the complexity of its structure, the virus has full mutation and

replication potential which makes it hard to search for the HCV vaccine; in addition, the prolong

treatment is necessary in severe and chronic conditions (Chen & Morgan, 2006).

Hepatitis C virus is found to be a non cytopathic for the infected host cell; therefore,

researchers concluded the fact that the host immune response must have played a major role in

the progression and spread of the virus (Cerny & Chisari, 1999). Humans are the only known
CLINICAL INVESTIGATION OF HEPATITIS C AND VIRUS 3

host; in fact, the disease pathogenesis depends upon the play of CD4+ and CD8+ T-cell response

in the lymphocyte, and specifically in elimination of the virus (Pawlotsky, 2004). According to

Pawlotsky (2004), “persistent infection appears to be due to weak CD4+ and CD8+ T-cell

responses during acute infection, which fail to control viral replication” (p. 96).

Hepatitis C is a blood borne infection of the liver; and yet, the mechanisms that cause the

tissue injury in both acute and chronic HCV infections are not yet identified (Cerny & Chisari,

1999). The transmission is from the contact of infected persons’ blood or secretions; indeed,

there are greater risks for the individual with high-risk sexual activity, intravenous drug use,

solid organ transplantation from an infected donor, hemodialysis, intranasal cocaine use, and

birth to an infected mother (Chen & Morgan, 2006).

When the person is first infected with HCV, most of the time it is unknown due to lack of

symptoms or being asymptomatic in this first phase of acute hepatitis C infection (Chen &

Morgan, 2006). The clinical symptoms are almost to become evident in three to twelve weeks; in

addition, the persistence of the infection for at least six months or more can be marked as a

chronic hepatitis C infection (Chen & Morgan, 2006). The early clinical manifestations are

malaise, weakness, anorexia, and jaundice; however, this may progresses onto extrahepatic

manifestations that can be involved with multiple organ systems (Chen & Morgan, 2006).

As mentioned earlier with immunological features, “the immune response to viral

antigens is thought to be responsible for viral clearance and disease pathogenesis during hepatitis

C virus (HCV) infection” (Cerny & Chisari, 1999, p. 595). The response of CD4+ helper T-cell

is associated with the viral clearance; nevertheless, “the dominant cause of viral persistence

during HCV infection may be the development of a weak antiviral immune response to the viral
CLINICAL INVESTIGATION OF HEPATITS C AND VIRUS 4

antigens, with corresponding inability to eradicate infected cells” (Cerny & Chisari, 1999, p.

595). Pawlotsky (2004) states the hepatitis C virus lifecycle is not fully understood due to “the

lack of a productive cell culture system” (p. 96).

According to Pawlotsky (2004), “the envelope glycoprotein complex is expressed on the

surface of the HCV particle;” indeed, “it is the obvious candidate ligand for cellular receptors”

(p. 96). He believed that the “early virion interaction with host-cell surface molecules, such as

glycosaminoglycans, might play a role in cell recognition and cellular tropism” (p. 96). In

addition, “the LDL receptor has been shown to mediate HCV internalization by binding to

virion-associated LDL particles;” however, this interactions have not demonstrated in the

experimental data (p. 97). As per Pawlotsky (2004), these are some “possible receptor-mediated

endocytosis;” thus, several candidate receptors for HCV (p. 97).

In continuing viral replication, Pawlotsky (2004) presented the fact that “the viral

nucleocapsid is thought to be uncoated by unknown mechanisms after its release into the

cytoplasm;” and afterwards, “HCV RNA then serves as a template for viral replication and as

mRNA for HCV protein synthesis” (p. 97). He concluded the fact that “the mature form of the

core protein (C), in conjunction with the genomic RNA, forms the HCV nucleocapsid; in

addition, to its role in nucleocapsid formation, HCV core protein . . . play a role in the

pathogenesis of liver disease by modulating host-cell transcription . . . and host immune

responses” (p. 97).

Pawlotsky (2004) concluded that the nonstructural proteins may also generate the

formation of the replication complex; thus, it “appears to have various additional properties, such

as inhibition of the antiviral action of interferon (INF), transcription activation, and involvement
CLINICAL INVESTIGATION OF HEPATITIS C AND VIRUS 5

in the regulation of cell growth and cellular signaling pathways” (p. 98). He believed that these

properties could be the well-defined course for HCV infection pathogenesis and liver disease.

The rate of hepatitis C infection travels in different length time; indeed, it started with the

acute phase and then moves onto more severe conditions and likely to cause permanent liver

damage. Our immune response plays a major role; in addition, high risk factors and comorbid

conditions produce long term complications and to extrahepatic manifestations. Some factors for

advanced progression of liver fibrosis include alcohol consumption, coinfection with HIV or

HBV, and age and time of infection (Chen & Morgan, 2006).

The extrahepatic manifestations are more associated with chronic HCV infection. It

involves “multiple organ systems, including renal, dermatologic, hematologic, and

rheumatologic systems;” indeed, the most common condition is called mixed cryoglobulinemia

(Chen & Morgan, 2006, p. 50). Finally, “the clinical manifestations are thought to be caused by

immune complex deposition in various organs” for cryoglobulinemia (p. 50). Scientists are in

process for further research on HCV and the risk factors that are associated to certain liver

diseases; and yet, the mechanism that causes tissue damage in HCV is still not well-defined in

the experiment (p. 47).

CLINICAL INVESTIGATION OF HEPATITS C AND VIRUS 6

 References

Cerny, A., Chisari, F. (1999). Pathogenesis of chronic hepatitis c: Immunological features of

hepatic injury and viral persistence. Hepatology, 30(3), 595-601.

Chen, S., Morgan, T. (2006). The natural history of hepatitis c virus (HCV) infection.

International Journal of Medical Sciences, 3(2), 47-52.

Joyce, M. A., Tyrrell, D. L. J. (2010). The cell biology of hepatitis c virus. Microbes and

Infection, 12, 263-271.

Pawlotsky, J. (2004). Pathophysiology of hepatitis c virus infection and related liver disease.

Trends in Microbiology, 12(2), 96-102.

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