Clinical Summary

About 75% of all individuals infected with hepatitis C virus (HCV) will develop chronic hepatitis C with ongoing viral replication in the liver and detectable HCV RNA in serum or plasma, eventually resulting in cirrhosis. The remaining 25% of the infected individuals recover from the infection without evidence of viral replication or presence of detectable HCV RNA in serum or plasma. Chronic HCV infection can be cured at variable success rates with either combined interferon-alpha and ribavirin therapy or interferon-free combination of direct-acting antiviral (DAA) agents.

The antiviral response rates correlate with pretreatment serum or plasma HCV RNA levels (viral load) and the HCV genotype found in the infected individuals. The optimal duration of combined interferon and ribavirin therapy can be determined from the patient's pretreatment viral load and HCV genotype. Clinical trial studies indicated that a decrease in HCV RNA levels of more than 2 log IU/mL at 4 weeks or 12 weeks of therapy is predictive of an increased chance of achieving a sustained virologic response (defined as undetectable HCV RNA levels in serum 6 months after completing antiviral therapy). Despite receiving longer duration of antiviral therapy (48 weeks versus 24 weeks), patients with chronic infection due to HCV genotypes 1 and 4 generally have less favorable sustained virologic response rates (40%-50%) than those infected with genotypes 2 and 3 (>80%). Due to the necessary prolonged duration (typically 24- to 48-week duration) and low cure rates of such antiviral therapy, interferon-based therapy has been supplanted with potent interferon-free DAA combination therapy.

Cure rates, as defined by sustained virologic response, of over 90% are observed among patients infected with HCV and treated with interferon-free DAA combinations that are of shorter treatment duration (eg, 8 or 12 weeks) than those of interferon-based therapy. Current guidelines for antiviral therapy of chronic hepatitis C recommend quantitative testing for HCV RNA in serum or plasma before initiating antiviral therapy, at 4 weeks of therapy, and 12 weeks after completion of therapy. A HCV RNA level below 25 IU/mL in serum or plasma 12 weeks after ending therapy is the therapeutic goal and indicates an SVR is achieved. Quantitative HCV RNA testing can be considered at the end of therapy and at 24 weeks or later after completion of antiviral therapy.

CAUTIONS 

Except for immunocompromised patients or patients with suspected acute hepatitis, laboratory evaluation of hepatitis C virus (HCV) infection status should begin with HCV serologic testing, including testing for the presence of HCV antibodies (see Hepatitis C: Testing Algorithm for Screening and Diagnosis). A diagnosis of chronic HCV infection should not be based solely on the presence of detectable or quantifiable HCV RNA in a single serum specimen.

An "Undetected" HCV RNA test result with a "Reactive" HCV antibody screen result may be due to:

1. A false-reactive HCV antibody screen result

2. Resolved or past HCV infection

3. Transient low viremia (ie, episodic viral replication) of active HCV infection

To distinguish between the first 2 conditions, another HCV antibody test (eg, HCCAD / Hepatitis C Virus Antibody Screen for Cadaveric or Hemolyzed Specimens, Serum) can be requested. To distinguish between the latter 2 conditions, patients should be retested for HCV RNA in 1 to 2 months, as clinically indicated.