After serologic tests for HAV and HBV were developed, apparent viral hepatitis nonreactive to tests for HAV and HBV or to other viruses that affect the liver was called non-A, non-B (NANB) hepatitis virus. Eventually, hepatitis D virus was discovered and separated from the NANB group. It was also known that NANB represented both a short-incubation and a long-incubation component, so the short-incubation component was separated from NANB and called hepatitis E. The long-incubation component retained the designation NANB. When the first serologic test for viral antibody reactive with a single antigen from NANB infectious material became commercially available in 1991, the virus identified was named hepatitis C (HCV). A second-generation test for HCV antibody became commercially available in early 1993, using 3 antigens from the HCV infectious agent. A third generation test became available in 1994. Both the first and second generation tests detect only IgG antibody. A test for HCV antigen is not commercially available in 1994, although nucleic acid RNA probe methods for HCV antigen have been developed by some investigators. HCV appears to be a group of closely related viruses, at least some of which have subgroups. In addition, it is not proven that HCV is the only hepatitis virus that produces long-incubation NANB.

HBV e antigen and antibody

Fig. 17-6 HBV e antigen and antibody.

HCV antigen and antibody

Fig. 17-7 HCV antigen and antibody.

HCV is a small RNA virus that is currently being classified as a Flavivirus (although some have proposed reclassifying it as a Pestivirus). It has been shown to exist in at least 4 genotypes or strains; the frequency of each strain differs in various geographic locations. Average HCV incubation is 6–8 weeks. However, incubation of 2 weeks to 1 year has been reported. Most cases (80%, range 70%–90%) develop IgG antibody by 6 weeks (range, 5–30 weeks) after onset of symptoms (similar to HBV). Like HBV, HCV has been detected in serum, semen, and saliva. Transmission is thought to be similar to that of HBV (major risk groups are IV drug abusers and transfusions of blood and blood products), but some differences exist. Male homosexuals currently are much less likely to become infected by HCV (less than 5% of cases) than with HBV (40%-80% of cases). Also, HCV is less apt to be transmitted through heterosexual intercourse than HBV. Although sexual transmission can occur, it appears to be infrequent. There is some disagreement using current tests regarding frequency of HCV transmission from mother to infant. Most investigators report that fetal or neonatal infection is very uncommon. However, if the mother is coinfected with HIV, newborn HCV infection as well as HIV infection were frequent. Passive transfer of maternal anti-HCV antibody to the fetus is very common.

HCV hepatitis now accounts for about 80%-90% of posttranfusion hepatitis cases when blood comes from volunteer donors whose serologic test results for HBV are negative. HCV is also reported to cause 12%-25% of cases of sporadic hepatitis (hepatitis not related to parenteral inoculation or sexual transmission). Only about 25% of acute HCV cases develop jaundice. The clinical illness produced is similar to HBV but tends to be a little less severe. However, progression to chronic hepatitis is significantly more frequent than in HBV; occurring in about 60% (range, 20%-75%) of posttransfusion cases by 10 years. About 30% (range, 20%–50%) of HCV patients develop cirrhosis by 10 years. Apparently, HCV acquired by transfusion is more likely to become chronic and lead to cirrhosis than community-acquired HCV (in one study, liver biopsy within 5 years of HCV onset showed 40% of transfusion-related cases had chronic active hepatitis and 10%-20% had cirrhosis, whereas in community-acquired cases less than 20% had chronic active hepatitis and 3% had cirrhosis).

HCV has been proposed as a major etiology for hepatocellular carcinoma (hepatoma), similar to HBV. Antibodies to HCV have been reported in about 40%-60% of patients (range, 5%-94%) with hepatoma. The incidence varies considerably in different geographical areas, different regions within the same geographical area, and different population groups. In some areas HBV predominates; in others, HCV is more common and may even exceed HBV in frequency. HCV (or HBV) proteins can be detected in hepatoma cancer cells in varying number of cases.

HCV-Ag
Nucleic acid probe (without PCR)

Appearance: About 3-4 weeks after infection (about 1-2 weeks later than PCR-enhanced probe)
Becomes nondetectable: Near the end of active infection, beginning of convalescence

Nucleic acid probe with PCR

Appearance: As early as the second week after infection
Becomes nondetectable: End of active infection, beginning of convalescence

HCV-Ab (IgG)
2nd generation (gen) ELISA

Appearance: About 3-4 months after infection (about 2-4 weeks before first gen tests); 80% by 5–6 weeks after symptoms
Becomes nondetectable: 7% lose detectable antibody by 1.5 years; 7%-66% negative by 4 years (by 1st gen tests; more remain elevated and for longer time by 2nd gen tests)

Summary: Hepatitis C Antigen and Antibody
HCV-Ag by nucleic acid probe

Shows current infection by HCV (especially using PCR amplification)

HCV-Ab (IgG)

Current, convalescent, or old HCV infection (behaves more like IgM or “total” Ab than usual IgG Ab)