Etiology
Hepatitis C virus (HCV) belongs to the Flavivirus family.[1] It is a single-stranded, enveloped RNA virus with a genome about 10,000 nucleotides in length.
The virus is transmitted by percutaneous blood exposure. Unsafe healthcare procedures (including unsafe injection practices) and injection drug use are the leading cause of new infections.[8] Less frequently it is spread through sexual activity, perinatally, intranasal drug use, or after accidental blood contact (e.g., hemodialysis). Blood and blood products not screened for HCV have also been sources of infection. About 10% of people with HCV infection have no recognized risk factor.[26]
The perinatal (vertical) transmission rate has been estimated to be 6%, while the horizontal transmission rate is <1%.[27][28]
Pathophysiology
Following acute infection, up to 45% of young, healthy patients may develop a vigorous antibody and cell-mediated immune response, which leads to the spontaneous eradication of the virus.[29] However, the majority of infected patients fail to clear the virus. This results in chronic infection and progressive liver damage.
Persistent viremia is accompanied by variable degrees of hepatic inflammation and fibrosis over time. Recent studies suggest that 50% or more of hepatocytes may be infected with hepatitis C virus (HCV).[30] Persistent infection appears to be due to weak CD4+ and CD8+ T-cell responses during acute infection, which fail to control viral replication.[30] Acute HCV infection is characterized by co-infection with multiple viral subtypes representing highly diverse intrapatient genetic variability.[31]
When chronic infection is established, HCV may not be cytopathic. Liver damage probably results from locally driven immune responses, which are mainly nonspecific. Local inflammation triggers fibrogenesis, in which hepatic stellate cells play a major role. Cirrhosis is facilitated by factors such as chronic alcohol consumption, metabolic dysfunction-associated steatohepatitis (nonalcoholic steatohepatitis), and coincidental viral infections.[30]
Classification
Hepatitis C virus genotypes
There are 8 major genotypes and more than 50 subtypes.[2][3][4]
In Japan, North America, and western Europe, the majority of infections are with genotypes 1, 2, and 3. Subtype 1a is the most predominant genotype in the US, while subtype 1b predominates in Asia and Europe.
Genotype 3 is the predominant genotype in India and southeast Asia.
Genotype 4 is more prevalent in the Middle East and in northern and central Africa.
Genotypes 5 and 6 have been identified in South Africa and southeast Asia, respectively.
Genotypes 7 and 8 have been identified in the Democratic Republic of Congo and India, respectively.
Genotype testing can be used to differentiate between genotypes and subtypes. Differences in subtype can result in subtle differences in response to antiviral therapies.
Use of this content is subject to our disclaimer