Hepatitis C
Hepatitis C virus (HCV) affects 170 mil-lion people worldwide. Around 1.8 per-cent of the U.S. population is positive for HCV antibodies.
For some time, blood transfusion was the primary cause of HCV infection in developed countries. With the introduction of blood-screening measures in the early 1990s, transmission by blood transfusion has decreased considerably. However, new cases continue to emerge, primarily as a result of intravenous drug use and percutaneous or mucous membrane exposure. Nosocomial infection is also a cause of HCV as the rate of transmission is estimated to be 3 percent in needle-stick injuries.
HCV belongs to the family of flavivi-ruses. The structural components include the core and two envelope proteins. One of the envelope proteins, E2, contains the binding site for CD81, which is present on hepatocytes and B lymphocytes and is thought to function as a cellular recep-tor for the virus. The regulatory proteins include helicase, protease, and polymerase. HCV replicates by means of an RNA-dependent RNA polymerase that lacks a “proofreading” function. This process can result in the evolution of genomic varia-tions of the virus within an individual, making immune-mediated control of HCV difficult. In addition, six distinct genotypes and around 100 subtypes of HCV have been identified. Genotypes 1a and 1b are the most prevalent in the United States and western Europe, followed by genotypes 2 and 3. Genotype helps to predict effective-ness of antiviral therapy, with genotypes 2 and 3 demonstrating the best responses.
Study of acute HCV infection has been limited because these individuals are often asymptomatic. It is currently thought that the pathology, which results from HCV infection, is the result of both direct cytopathic effects of the virus and the immune response. The immune response to HCV, as with HBV, is still incompletely understood.
Due to the strict affinity of HCV for human cells, in the past only humans and higher primates such as monkeys could be infected with HCV. However, rodents make for a more appropriate and useful biological model in that their gestational periods are short, they are small, and cost less to maintain. Some models, which are currently being developed, include an immunotolerized rat and a Trimera mouse model. In the immunotolerized rat model, human hepatoma cells (Huh7) are introduced to fetal rats in utero and transplanted with the same cell line after birth. The rat is subsequently infected with HCV using HCV-positive human serum. In the Trimera model, mice are irradi-ated and reconstituted using SCID mouse bone marrow. HCV-infected liver fragments from patients with HCV or ex vivo infected HCV liver fragments are trans-planted into the ear pinna or under the kidney capsule. More research is needed, but these particular models could be help-ful in studying the effects of therapeutic regimens against HCV. In addition, several trans genic mouse models have been stud-ied that have allowed for the analysis of the direct cytopathic effects of HCV protein and its correlation with the pathogenesis of chronic hepatitis C.
In the rare instances in which clinical acute hepatitis has been identified, symp-toms have included jaundice, malaise, and nausea. Although infection becomes chronic in about 75–80 percent of affected individuals, it is often characterized by a prolonged asymptomatic period of any-where from twenty to thirty years. Patients may present with nonspecific symptoms of fatigue (90 percent). Severe complications
and death tend to occur primarily in individuals who progress to cirrhosis, which is around 15–20 percent of infected patients. Extra hepatic manifestations of HCV tend to be associated with autoimmune and lympho proliferative states. These
Hepatitis C virus (HCV) affects 170 mil-lion people worldwide. Around 1.8 per-cent of the U.S. population is positive for HCV antibodies.
For some time, blood transfusion was the primary cause of HCV infection in developed countries. With the introduction of blood-screening measures in the early 1990s, transmission by blood transfusion has decreased considerably. However, new cases continue to emerge, primarily as a result of intravenous drug use and percutaneous or mucous membrane exposure. Nosocomial infection is also a cause of HCV as the rate of transmission is estimated to be 3 percent in needle-stick injuries.
HCV belongs to the family of flavivi-ruses. The structural components include the core and two envelope proteins. One of the envelope proteins, E2, contains the binding site for CD81, which is present on hepatocytes and B lymphocytes and is thought to function as a cellular recep-tor for the virus. The regulatory proteins include helicase, protease, and polymerase. HCV replicates by means of an RNA-dependent RNA polymerase that lacks a “proofreading” function. This process can result in the evolution of genomic varia-tions of the virus within an individual, making immune-mediated control of HCV difficult. In addition, six distinct genotypes and around 100 subtypes of HCV have been identified. Genotypes 1a and 1b are the most prevalent in the United States and western Europe, followed by genotypes 2 and 3. Genotype helps to predict effective-ness of antiviral therapy, with genotypes 2 and 3 demonstrating the best responses.
Study of acute HCV infection has been limited because these individuals are often asymptomatic. It is currently thought that the pathology, which results from HCV infection, is the result of both direct cytopathic effects of the virus and the immune response. The immune response to HCV, as with HBV, is still incompletely understood.
Due to the strict affinity of HCV for human cells, in the past only humans and higher primates such as monkeys could be infected with HCV. However, rodents make for a more appropriate and useful biological model in that their gestational periods are short, they are small, and cost less to maintain. Some models, which are currently being developed, include an immunotolerized rat and a Trimera mouse model. In the immunotolerized rat model, human hepatoma cells (Huh7) are introduced to fetal rats in utero and transplanted with the same cell line after birth. The rat is subsequently infected with HCV using HCV-positive human serum. In the Trimera model, mice are irradi-ated and reconstituted using SCID mouse bone marrow. HCV-infected liver fragments from patients with HCV or ex vivo infected HCV liver fragments are trans-planted into the ear pinna or under the kidney capsule. More research is needed, but these particular models could be help-ful in studying the effects of therapeutic regimens against HCV. In addition, several trans genic mouse models have been stud-ied that have allowed for the analysis of the direct cytopathic effects of HCV protein and its correlation with the pathogenesis of chronic hepatitis C.
In the rare instances in which clinical acute hepatitis has been identified, symp-toms have included jaundice, malaise, and nausea. Although infection becomes chronic in about 75–80 percent of affected individuals, it is often characterized by a prolonged asymptomatic period of any-where from twenty to thirty years. Patients may present with nonspecific symptoms of fatigue (90 percent). Severe complications
and death tend to occur primarily in individuals who progress to cirrhosis, which is around 15–20 percent of infected patients. Extra hepatic manifestations of HCV tend to be associated with autoimmune and lympho proliferative states. These
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