What are the results of the Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) test?

From the Guidelines

HCV RNA testing is a crucial diagnostic tool for detecting and monitoring hepatitis C virus infection, and it should be performed after a positive HCV antibody screening test to confirm current infection, as antibodies remain positive even after cleared infections. This test directly measures the amount of viral genetic material in the blood, confirming active infection and quantifying viral load. For diagnosis, HCV RNA testing is essential to distinguish between current and past infections, as antibodies can persist indefinitely in chronic hepatitis C patients and after recovery 1. During treatment, HCV RNA levels are monitored to assess response, with testing typically done before treatment, at 4 weeks to evaluate early response, at the end of treatment to confirm viral suppression, and 12 weeks after completing therapy to determine sustained virologic response (SVR) 1.

The test uses polymerase chain reaction (PCR) or other nucleic acid amplification techniques to detect even small amounts of viral RNA. A negative HCV RNA result after treatment indicates cure, while persistent detection suggests treatment failure or reinfection. The sensitivity of modern HCV RNA assays allows detection of viral loads as low as 10-15 IU/mL, making them highly reliable for both diagnosis and monitoring treatment outcomes 1.

Key points to consider when using HCV RNA testing include:

• The test should be performed using a sensitive assay with a lower limit of detection of ≤15 IU/ml 1.
• HCV genotype and genotype 1 subtype (1a or 1b) must be assessed prior to treatment initiation to determine the choice of therapy 1.
• Systematic testing for HCV resistance prior to treatment is not recommended, but physicians with access to a reliable test assessing HCV resistance to NS5A inhibitors can use these results to guide their decisions 1.

Overall, HCV RNA testing is a vital tool in the diagnosis and management of hepatitis C virus infection, and its use should be guided by the most recent and highest-quality evidence 1.

From the FDA Drug Label

Plasma HCV RNA values were measured during the clinical trials using the COBAS TaqMan HCV test (version 2. 0), for use with the High Pure System. The assay had a lower limit of quantification (LLOQ) of 25 IU per mL. Sustained virologic response (SVR12) was the primary endpoint which was defined as HCV RNA less than LLOQ at 12 weeks after the end of treatment.

The HCV RNA levels were measured using the COBAS TaqMan HCV test with a lower limit of quantification of 25 IU per mL. The primary endpoint, SVR12, was defined as HCV RNA less than LLOQ at 12 weeks after the end of treatment 2.

• Key points:
  • HCV RNA measurement: COBAS TaqMan HCV test (version 2.0)
  • Lower limit of quantification (LLOQ): 25 IU per mL
  • SVR12 definition: HCV RNA less than LLOQ at 12 weeks after the end of treatment

From the Research

HCV RNA Treatment Outcomes

• The treatment outcomes for HCV RNA have been studied in various research papers, with a focus on the effectiveness and safety of different direct-acting antiviral (DAA) regimens 3, 4, 5, 6, 7.
• One study found that sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved a sustained virological response (SVR) rate of 95% in patients with chronic hepatitis C who had previously failed DAA treatment 3.
• Another study reported that sofosbuvir-velpatasvir (SOF/VEL) had excellent activity against all 6 major HCV genotypes, with SVR rates ranging from 95% to 100% in various patient populations 4.
• Real-world data from Taiwan showed that SOF/VEL was highly effective and well-tolerated in patients with HCV genotype 1,2,3,4, and 6, with an overall SVR rate of 99.4% 6.
• A study on chronic hepatitis C patients with genotype-2 infection found that DAA regimens, including SOF-based and non-SOF-based treatments, achieved high SVR rates, ranging from 95.6% to 100% 7.

Factors Affecting Treatment Outcomes

• Cirrhosis and hepatocellular carcinoma were found to be predictors of treatment failure in some studies 3, 5.
• Genotype 3 infection was also associated with lower SVR rates in some studies 3, 6.
• Treatment adherence, high viral load, and genotype 3 were found to be factors associated with failure to achieve SVR in one study 6.
• Baseline resistance-associated substitutions did not impact SVR rates in some studies 3, 5.

Safety and Tolerability

• SOF/VEL/VOX and SOF/VEL were found to be well-tolerated in clinical trials, with mild and non-specific adverse effects reported 3, 4, 5, 6.
• The most common adverse events reported in one study included fatigue, headache, nausea, and nasopharyngitis 4.
• Treatment discontinuation due to adverse events was rare, ranging from 0.3% to 0.6% in some studies 6, 7.