Missing RNA Tests Skew Hepatitis C Cure Rates, Study Finds

Among insured US adults with hepatitis C virus (HCV) infection, laboratory-confirmed viral clearance was achieved by 40% of patients with initial infection, 36% initiated direct-acting antiviral (DAA) treatment, and 26% had documented viral clearance following treatment initiation, according to a nationwide retrospective cohort study published in JAMA Network Open. The findings show that care cascade outcomes vary substantially depending on whether health systems use laboratory data, pharmacy claims, or both to assess treatment progress.

Using the HealthVerity database, which links longitudinal laboratory results, pharmacy claims, and insurance enrollment information, investigators included US adults who underwent HCV testing between January 30, 2019, and June 30, 2022. Eligible patients had evidence of HCV infection, continuous insurance enrollment from 60 days prior to through 360 days following the index date, and no evidence of DAA treatment during the 60 days prior to the index date. Among 4,515,568 adults with at least one HCV test, 91,491 had evidence of ever having HCV infection. Most individuals in this group, 90.1%, underwent at least one HCV RNA test; nearly two thirds, 62.0%, had initial HCV infection, corresponding to 51,068 patients.

The investigators assessed three care cascade outcomes: laboratory-confirmed viral clearance, DAA treatment initiation, and viral clearance following treatment initiation, which served as a proxy for sustained virologic response. Among patients with initial infection, 39.9% had viral clearance, 35.7% initiated DAA treatment within 360 days, and 26.1% had viral clearance after treatment initiation. Similar care outcome patterns were seen across age groups and payer types, although the magnitude of each measure differed.

Among the 18,246 patients who initiated treatment, 73.2% subsequently had a negative HCV RNA result, 3.7% had a positive RNA result, and 23.2% had no documented follow-up RNA testing. Among those without follow-up testing, 90.8% had received at least 56 days of DAA therapy, suggesting many may have achieved treatment-induced viral clearance despite lacking confirmatory laboratory evidence. Conversely, among patients without documented treatment initiation, 21.3% subsequently had a negative RNA result, suggesting spontaneous viral clearance or treatment that was not captured in the pharmacy claims data.

The investigators noted that laboratory-based measures may underestimate viral clearance because many patients do not undergo follow-up RNA testing after treatment, and 38.3% of those with initial infection did not have a subsequent RNA test to assess clearance. Of these, 78.4% had no evidence of treatment initiation. Conversely, pharmacy-based measures may overestimate cure because treatment initiation does not confirm drug adherence. Viral clearance following treatment initiation most closely aligned with the definition of sustained virologic response, although it may also underestimate cure when follow-up testing is incomplete.

The study's limitations included potential unmeasured treatments received outside insurance claims, evolving screening recommendations that may have influenced testing patterns, the requirement for continuous insurance enrollment that may have excluded patients with unstable coverage, and reliance on available laboratory data that may have resulted in misclassification of infection status or care outcomes. Overall, the findings suggested that integrating laboratory and pharmacy data may provide the most complete assessment of HCV care outcomes, although viral clearance or treatment initiation alone may serve as reasonable surrogate measures when only one data source is available.

"Our findings suggest that improving follow-up RNA testing and integrating laboratory and pharmacy data will enhance accuracy and bridge gaps in [HCV] testing and treatment," the lead study author and colleagues wrote.