Only about a third of Americans with hepatitis C receive direct-acting antiviral therapy, and treatment rates have declined since the drugs were first approved, according to a new report in JAMA. This leaves a majority of people with active hepatitis C virus (HCV) infection, which can lead to complications, such as cirrhosis and liver cancer.

“Hepatitis C is a curable disease, but current treatment levels are substantially below what’s needed to achieve national elimination targets,” lead study author Sanjay Kishore, MD, of the University of Virginia School of Medicine said in a news release. “Elimination will require system-level changes, not just better screening,” added senior author Benjamin Rome, MD, MPH, of Mass General Brigham.

More than 2 million people in the United States have chronic hepatitis C, estimates suggest. Direct-acting antiviral (DAA) therapy is highly effective. Widely used regimens, including Epclusa (sofosbuvir/velpatasvir) and Mavyret (glecaprevir/pibrentasvir), can cure more than 95% of treated patients in two or three months.

Although antivirals that can be used without interferon were first approved in the United States in 2013, treatment gaps persist more than a decade later. A 2023 study from the Centers for Disease Control and Prevention (CDC), using data from Quest Diagnostics, found that just a third of Americans with hepatitis C have been successfully treated. A more recent analysis of data from Quest and LabCorp likewise found that only about a third of people diagnosed with HCV received treatment, meaning the United States is not on track to meet hepatitis C elimination goals.

In the new analysis, Kishore, Rome and colleagues looked at changes in prescribing of DAA therapy from 2013 to 2025. This cross-sectional study analyzed data from the Symphony Health Metys database, which estimates U.S. prescription counts based on a large sample of retail, mail-order and specialty pharmacies.

The researchers found that an estimated 1.3 million courses of DAA therapy were dispensed during this period. The annual prescription count was highest (185,677 courses) in 2015, soon after the initial approval of DAAs, reflecting a large backlog of untreated patients. Treatment declined thereafter—with a steeper drop during the COVID-19 crisis—and stood at 68, 523 courses in 2025.

Medicare and commercial insurance covered most prescriptions in 2015 (37% and 45%, respectively), while Medicaid covered the largest share in 2025 (49%). When DAAs were first approved, many state Medicaid programs limited treatment to people with more advanced liver disease, those who had achieved sobriety from alcohol and drug use and those receiving care from liver specialists. Specialist prescribing fell from a peak of 66% in 2015 to 28% in 2025, as prescribing shifted to primary care providers.

Treatment also shifted over time from older to younger patients. In 2015, adults older than 61 years accounted for 42% of prescriptions, falling to 26% in 2025, while the share of people younger than 40 rose from 5% to 29%. Treatment rates were initially highest in cities but shifted to nonmetropolitan areas since 2018.

In more recent years, the annual number of DAA prescriptions was similar to the estimated number of new HCV infections in the United States but was substantially below the approximately 260,000 yearly treatment courses needed to achieve national hepatitis C elimination targets. “This may explain why HCV prevalence in the U.S. did not decrease in 2017 to 2020 compared with earlier periods and may have even increased according to estimates of national surveys adjusting for underrepresentation of people who inject drugs,” the study authors noted.

Many people remain unaware of their HCV status and do not know that effective and well-tolerated treatment is available. According to the CDC and the U.S. Preventive Services Task Force, all adults should be screened for HCV at least once, regardless of risk factors. After a positive HCV antibody screening test, an HCV RNA viral load test must be done to determine whether a person has active infection and is eligible for treatment. The CDC now recommends reflex testing, which tests for both HCV antibodies and RNA using a single blood sample, which can speed up treatment initiation after diagnosis.

“To increase HCV treatment and support eradication in the U.S., several changes are needed,” the researchers concluded. “Further efforts to accelerate progress include expanded point-of-care diagnostics to facilitate same-day treatment, implementing telehealth and mobile outreach and financing reforms such as the proposed national subscription model under the Cure Hepatitis C Act of 2025.”

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