Missing RNA Tests Skew Hepatitis C Cure Rates, Nationwide U.S. Cohort Study Finds
核心洞察
Among 91,491 U.S. adults with evidence of HCV infection, 38.3% of those with initial infection lacked follow-up RNA testing to confirm viral clearance, and 23.2% of treated patients had no post-treatment RNA test.
Viral clearance after treatment initiation, requiring both laboratory and pharmacy data, was identified as the most rigorous outcome measure but likely underestimates cure due to incomplete follow-up testing.
When only one data source is available, laboratory-confirmed viral clearance or pharmacy-recorded treatment initiation can serve as reasonable surrogate measures for tracking progress toward hepatitis C (搜索) elimination.
A nationwide cohort study of insured U.S. adults reveals that hepatitis C (搜索) care cascade outcomes can vary substantially depending on whether health systems rely on laboratory data, pharmacy claims, or both to assess treatment progress. The findings, published in JAMA Network Open, underscore how missing follow-up RNA testing may significantly skew estimates of cure rates in real-world settings.
The analysis, led by Symum and colleagues, drew from the HealthVerity (搜索) database and included adults aged 18 years and older who underwent hepatitis C (搜索) virus (HCV) antibody, RNA, or genotype testing between January 30, 2019, and June 30, 2022. Investigators used longitudinal laboratory results, pharmacy claims, and insurance enrollment information to compare outcome measures across the hepatitis C care cascade.
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.
Viral Clearance and Treatment Initiation
Among people with initial infection, 39.9% had viral clearance, 35.7% initiated direct-acting antiviral (DAA) treatment within 360 days, and 26.1% had viral clearance after treatment initiation, which the authors used as a proxy for sustained virologic response (SVR). Similar care outcome patterns were observed across age groups and payer types, although the magnitude of each measure differed.
The findings highlight a major challenge in hepatitis C (搜索) care cascade measurement: laboratory-based viral clearance can be limited by missing follow-up RNA testing. Among people with initial infection, 38.3% did not have a subsequent RNA test to assess viral clearance. Of these, 78.4% had no evidence of treatment initiation.
Data Gaps Affect Cure Estimates
Among 18,246 individuals who initiated treatment, 73.2% had a subsequent HCV RNA-negative result, 3.7% had an RNA-positive result, and 23.2% had no evidence of subsequent testing. Most of those without follow-up testing, 90.8%, received at least 56 days of DAA treatment, suggesting many may have achieved treatment-induced viral clearance despite lacking confirmatory laboratory evidence.
The study also found that 21.3% of individuals without recorded treatment initiation later had an RNA-negative result, suggesting spontaneous clearance or treatment not captured in the claims data. Conversely, 32.1% remained RNA positive and 46.7% had no follow-up testing.
Integrated Data Offers Most Rigorous Assessment
The authors noted that viral clearance after treatment initiation, which requires both laboratory and pharmacy data, is the most rigorous measure and most closely aligns with sustained virologic response. However, this approach may underestimate cure when patients do not return for follow-up RNA testing.
"Laboratory-based measures of viral clearance may underestimate cure because many patients who complete treatment do not return for follow-up RNA testing," the researchers noted. They added that laboratory-confirmed viral clearance did not necessarily indicate treatment success because some patients may have cleared HCV spontaneously or received treatment not captured in the database.
The study had several limitations, including the possibility that treatments outside insurance claims were not captured, changes in HCV testing recommendations during the study period, the exclusion of people without continuous insurance coverage, and potential misclassification arising from incomplete laboratory data.
Overall, the findings suggest that better integration of laboratory and pharmacy data, alongside improved follow-up RNA testing, could strengthen monitoring of hepatitis C (搜索) testing and treatment outcomes. When only one data source is available, viral clearance or treatment initiation may still provide a reasonable substitute for tracking progress toward hepatitis C elimination.
Direct-acting antivirals (搜索) cure more than 95% of infections, with SVR defined as undetectable HCV RNA at least 12 weeks after treatment completion considered evidence of cure. Hepatitis C (搜索), if left untreated, can lead to advanced liver disease, liver cancer, and death.