Hepatitis C management options in the US

Hepatitis C management in the United States stands at a critical inflection point. Direct-acting antiviral (DAA) therapies can now cure more than 95% of patients who complete treatment, yet national data consistently show that only approximately one-third of Americans living with the virus actually receive those curative regimens. 1 Understanding the full continuum of care, from initial screening through post-treatment monitoring, is essential for patients, clinicians, and public health stakeholders navigating the HCV landscape.

What Hepatitis C Is and Why Chronic Infection Matters

Hepatitis C is a viral infection caused by the hepatitis C virus (HCV) that triggers liver inflammation and, over time, progressive tissue damage. 2 The infection can present in two distinct clinical phases. Acute hepatitis C is a short-term infection that resolves on its own in roughly 25% of cases. Chronic hepatitis C, however, develops in more than half of acutely infected individuals when the virus persists in the body without clearance. 3 Left unmanaged, chronic infection carries a 15 to 30% risk of cirrhosis after approximately 20 years, and significantly elevates the likelihood of hepatocellular carcinoma, diabetes, and chronic kidney disease. 4

Because HCV is typically asymptomatic for years or even decades, a person can carry an active infection without any clinical signals. The CDC reported 69,000 acute HCV infections and 101,525 newly reported chronic HCV cases in the United States in 2023 alone. 5 An estimated 2.5 to 4 million Americans remain chronically infected, underscoring the scale of an under-recognized public health burden. 1

Screening Protocols and Diagnostic Pathways

Current US guidelines from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) call for near-universal screening, recommending that every adult aged 18 to 79 receive at least one lifetime HCV antibody test. 6 Women should be screened during each pregnancy, and individuals engaged in ongoing high-risk behaviors such as injection drug use require regular repeat testing. The standard diagnostic workflow begins with an HCV antibody test that automatically reflexes to a quantitative or qualitative HCV RNA (PCR) test if the antibody result is positive; a positive RNA result confirms active viremic infection. 7

A significant advancement in the diagnostic pipeline is the approval of a point-of-care HCV RNA test, specifically the Xpert HCV test developed by Cepheid. This fingerstick test delivers an on-site RNA-confirmed diagnosis within 60 minutes, enabling clinicians to apply a test-and-treat model where diagnosis and treatment initiation occur during the same clinical encounter. 8 Research published in JAMA Network Open found that point-of-care HCV RNA-first testing was the dominant strategy across all high-prevalence care settings evaluated, projecting substantial improvements in diagnosis rates, linkage to care, treatment initiation, and reductions in chronic HCV incidence compared with the standard laboratory-based algorithm. 9

First-Line Direct-Acting Antiviral Regimens

DAAs have replaced interferon-based regimens as the standard of care in the United States since their initial approval in 2013, with pan-genotypic agents introduced in 2016 further simplifying treatment selection. 10 The two most widely prescribed regimens are sofosbuvir/velpatasvir (Epclusa) and glecaprevir/pibrentasvir (Mavyret), both of which cover all six HCV genotypes. Treatment duration typically ranges from 8 to 12 weeks of once-daily oral dosing for most patients without cirrhosis.

Among patients with a prior cured HCV infection who develop acute reinfection, an 8-week course of glecaprevir/pibrentasvir has demonstrated high sustained virologic response rates comparable to those in first-time treatment, supporting its use in recurrent infection scenarios. 11 Baseline evaluation before initiating any DAA regimen should include HCV RNA quantification, genotype analysis where clinically relevant, and noninvasive liver fibrosis staging using tools such as transient elastography or serum-based markers to guide regimen selection and duration. 6

Insurance Coverage, Cost Realities, and Access Barriers

The list prices of DAA regimens are substantial, but actual patient out-of-pocket costs are frequently far lower due to negotiated insurer rebates, discounted Medicaid rates, and manufacturer patient assistance programs available to qualifying uninsured individuals. Analysis of national prescription data from 2013 to 2025 found that the majority of DAA prescriptions were covered by commercial insurance (44.7%) or Medicare (36.8%), with Medicaid accounting for 48.7% of covered courses by 2025. 12 Many state Medicaid programs have removed prior authorization restrictions that historically blocked access to HCV treatment, following legal and advocacy pressure.

Despite improved coverage infrastructure, treatment access remains uneven. The annual volume of DAA courses dispensed nationwide peaked at 185,677 in 2015 and fell to just 68,523 in 2025, a decline of nearly 66%. 13 Researchers note that the US is currently treating approximately the same number of people each year as there are new infections, a dynamic that represents holding steady rather than progress toward elimination. The World Health Organization has set a 2030 elimination target requiring diagnosis of at least 90% of infected individuals and treatment of at least 80%, thresholds the United States is not currently on track to meet. 14

Treatment Gaps and the Care Cascade Challenge

Multiple national analyses have documented persistent gaps across the hepatitis C care cascade. A study combining CDC and Quest Diagnostics data found that less than half of diagnosed patients were advised to undergo follow-up confirmatory testing, and more than three in four patients showed no evidence of initiating treatment. 5 A separate analysis of LabCorp and Quest Diagnostics data covering 46.6 million adults who tested for HCV antibody between 2014 and 2021 found that 4.8% tested positive, but only approximately 34.5% of those with confirmed HCV received treatment, while 96% of those who were treated achieved cure. 15

Management of HCV is progressively shifting toward primary care settings, with family physicians increasingly positioned to prescribe DAAs. However, research from the American Board of Family Medicine indicates that treatment rates among early-career family physicians remain low, reflecting a broader need for expanded provider training and system-level changes. 16 Specialist prescribing, which peaked in 2015, has declined steadily, while the age profile of treated patients has shifted toward younger individuals and those covered by Medicaid. 12

Post-Treatment Monitoring and Long-Term Considerations

Achieving a sustained virologic response (SVR), defined as undetectable HCV RNA measured 12 weeks after completing DAA therapy, is considered a virologic cure. Patients who achieve SVR are not considered capable of transmitting HCV to others and face substantially reduced risks of liver-related complications. 5 However, post-treatment management does not end at cure. Individuals with advanced fibrosis or cirrhosis at the time of treatment require ongoing liver cancer surveillance with periodic imaging even after achieving SVR, given that residual risk of hepatocellular carcinoma persists in those with pre-existing structural liver damage. 4

Reinfection is a documented risk for individuals with continued behavioral exposure, such as ongoing injection drug use. There is no vaccine against HCV, making behavioral risk reduction and harm reduction services important components of long-term management. 2 Microsimulation modeling published in Nature Communications projected that a national HCV elimination initiative, if fully implemented from 2025 to 2034, could reduce the number of persons living with HCV to approximately 100,000 compared with 1.3 million under the status quo, avert 20,000 cases of hepatocellular carcinoma, and save an estimated $17.7 billion in healthcare spending over a decade. 17 These projections reinforce that the clinical tools for HCV elimination already exist; the primary challenges are systemic, logistical, and financial.

Sources

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2. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) - Hepatitis C (niddk.nih.gov)
3. American Academy of Family Physicians (AAFP) FP Essentials - Viral Hepatitis (aafp.org)
4. Medscape Reference - Chronic HCV Infection: WHO 2022 Guideline Summary (reference.medscape.com)
5. Hep Magazine - Troubling Gaps in Treatment and Testing Among People With Hepatitis C (hepmag.com)
6. Healio Gastroenterology - Physicians must proactively look for hepatitis C to identify, treat patients (healio.com)
7. AASLD/IDSA HCV Guidance - Evaluate and Treat (hcvguidelines.org)
8. Gastroenterology and Hepatology - Examining the Recent AASLD/IDSA Guidance Test-and-Treat Algorithm Using Point-of-Care HCV RNA Testing (gastroenterologyandhepatology.net)
9. JAMA Network Open - Cost-Effectiveness of Point-of-Care Hepatitis C Virus RNA Testing in the US (jamanetwork.com)
10. Exploration of Drug Science - Direct-acting antivirals and management of hepatitis C: updates on treatment guidelines (explorationpub.com)
11. Gastroenterology Advisor - Glecaprevir/Pibrentasvir Effective for Acute HCV Following Prior Cure (gastroenterologyadvisor.com)
12. Healio Gastroenterology - Antiviral prescriptions for HCV drop by nearly 66% since 2015 (healio.com)
13. Brightsurf - Dramatic reduction in prescribing of hepatitis C antivirals may leave many curable patients untreated (brightsurf.com)
14. Cancer Health - Hepatitis C Treatment Rates Lag Behind Elimination Goals (cancerhealth.com)
15. Gastroenterology Advisor - Only a Third of US Adults With Hepatitis C Virus Are Treated (gastroenterologyadvisor.com)
16. American Board of Family Medicine - Hepatitis C Treatment by Early-Career US Family Physicians (theabfm.org)
17. Nature Communications - Projected health benefits and cost offsets from the United States National Hepatitis C Elimination Initiative (nature.com)