Determining hepatitis C virus genotype (1 to 5) to guide antiviral therapy in patients with chronic hepatitis C.
Differentiating between hepatitis C virus subtypes 1a and 1b
Caution: This assay should not be used as a screening test for hepatitis C virus (HCV) infection. It should be performed only on specimens obtained from patients confirmed to have HCV RNA levels in serum of 500 IU/mL or higher.
Serum specimens previously submitted to other laboratories for non-microbiology tests are NOT acceptable for add-on test requests, due to the possible sample-to-sample carryover from the automation used for those tests.
An "Undetected" or "Indeterminate" hepatitis C virus (HCV) genotype result does not rule-out active HCV infection. Test results should be correlated with routine serologic and molecular-based testing, as well as clinical presentation. Specimens with indeterminate results will be automatically evaluated with the subsequent test HCVGR / Hepatitis C Virus Genotype Resolution, Serum.
Known cross-reactivity between the assay probes and various HCV genotypes limits the ability of this assay to identify multiple HCV genotypes present in a given specimen. Such cross-reactivity or the actual presence of multiple HCV genotypes in the same specimen may result in an "Indeterminate" or multiple/mixed genotype result.
Unique nucleotide sequences of certain regions (eg, 5'-noncoding, core, NS5b) of the hepatitis C virus (HCV) genome allow classification of HCV into 6 major genotypes or clades (1-6), based on the most recently proposed HCV genotype nomenclature. In the United States, the most commonly encountered HCV genotypes are 1a and 1b, followed by genotypes 2 and 3. Worldwide geographic distribution, disease outcome, and response to antiviral therapy differ among the genotypes. Therefore, reliable methods for genotype determination are important for proper selection of antiviral therapy and optimal patient management. Infections with HCV genotypes 2 and 3 have better therapeutic response rates (80%-90%) than genotypes 1 and 4 (40%-50%) to previous standard combination therapy (ribavirin plus pegylated interferon alpha-2a or alpha-2b). Duration of such combination therapy is 24 weeks for chronic HCV genotype 2 and 3 infections in patients who show early virologic response (>2 log or 100-fold decrease in HCV RNA or no detectable HCV RNA at week 12 of therapy), while patients with chronic HCV genotype 1 and 4 infections receive a minimum of 48 weeks of such combination therapy if early virologic response is achieved (undetectable HCV RNA at week 4 of therapy).
Therapeutic response rates for HCV genotype 1 infection are improved significantly (80%-90%) when oral direct acting antiviral agents (eg, daclatasvir, sofosbuvir, ledispasvir + sofosbuvir, velpatasvir + sofosbuvir, glecaprevir + pibrentasvir, elbasvir + grazoprevir, velpatasvir + voxilaprevir + sofosbuvir) are added or used in lieu of interferon-based combination therapy.
An "Undetected" result indicates the absence of detectable hepatitis C virus (HCV) RNA in the specimen.
An "Indeterminate" result may be due to 1 or more of the following causes: 1) low HCV RNA level (ie,<500 IU/mL), 2) HCV genotype 6, 3) probe reactivity with multiple HCV genotypes, or 4) variation in patient's HCV target sequences with mismatches to PCR primers and/or probes. Specimens generating indeterminate results with this assay will be automatically evaluated with the subsequent test HCVGR / Hepatitis C Virus Genotype Resolution, Serum.
An HCV genotype result of "1" without a subtype result may be due to 1 or more of the following causes: 1) low HCV RNA level (ie, <500 IU/mL), 2) probe reactivity with multiple genotype 1 subtypes, 3) variation in HCV genotype 1 target sequence, or 4) misclassification of some true genotype 6 strains. This assay is able to differentiate between HCV subtypes 1a and 1b. However, subtypes are not reported for HCV genotypes 2 to 5 due to limitations of the current genotyping assay in accurately differentiating the various subtypes of these genotypes.
Results with multiple or mixed HCV genotypes (eg, 1, 5; 1a, 2; or 3, 5) may be due to mixed genotype infection or assay probe cross-reactivity. Only those specimens with multiple or mixed genotype results containing genotype 1 but no subtype will be automatically evaluated with the subsequent test HCVGR / Hepatitis C Virus Genotype Resolution, Serum.