Hepatitis C Virus Clearance Cascade

United States, 2013-2022

Carolyn Wester, MD; Ademola Osinubi, MS; Harvey W. Kaufman, MD; Hasan Symum, PhD; William A. Meyer III, PhD; Xiaohua Huang, MS; William W. Thompson, PhD


Morbidity and Mortality Weekly Report. 2023;72(26):716-720. 

In This Article

Abstract and Introduction


Approximately 2.4 million adults were estimated to have hepatitis C virus (HCV) infection in the United States during 2013–2016.[1] Untreated, hepatitis C can lead to advanced liver disease, liver cancer, and death.[2] The Viral Hepatitis National Strategic Plan for the United States calls for ≥80% of persons with hepatitis C to achieve viral clearance by 2030.[3] Characterizing the steps that follow a person's progression from testing to viral clearance and subsequent infection (clearance cascade) is critical for monitoring progress toward national elimination goals. Following CDC guidance,[4] a simplified national laboratory results-based HCV five-step clearance cascade was developed using longitudinal data from a large national commercial laboratory throughout the decade since highly effective hepatitis C treatments became available. During January 1, 2013–December 31, 2021, a total of 1,719,493 persons were identified as ever having been infected with HCV. During January 1, 2013–December 31, 2022, 88% of those ever infected were classified as having received viral testing; among those who received viral testing, 69% were classified as having initial infection; among those with initial infection, 34% were classified as cured or cleared (treatment-induced or spontaneous); and among those persons, 7% were categorized as having persistent infection or reinfection. Among the 1.0 million persons with evidence of initial infection, approximately one third had evidence of viral clearance (cured or cleared). This simplified national HCV clearance cascade identifies substantial gaps in cure nearly a decade since highly effective direct-acting antiviral (DAA) agents became available and will facilitate the process of monitoring progress toward national elimination goals. It is essential that increased access to diagnosis, treatment, and prevention services for persons with hepatitis C be addressed to prevent progression of disease and ongoing transmission and achieve national hepatitis C elimination goals.

An 8–12 week short-course of well-tolerated, oral-only treatment with DAA agents is recommended for nearly all persons with HCV infection[5] and results in a cure in ≥95% of cases.[6] A national program to eliminate hepatitis C in the United States was proposed earlier this year[7] to provide an opportunity to accelerate national efforts toward eliminating hepatitis C. The Viral Hepatitis National Strategic Plan for the United States calls for ≥80% of persons with hepatitis C to achieve viral clearance by 2030.[1] Characterizing the HCV clearance cascade is critical for monitoring progress toward national elimination goals, identifying gaps in care and program effectiveness, and prioritizing public health resource allocations. Developing a comprehensive national hepatitis C care cascade is challenging, because no single data source sufficiently describes all steps of the cascade. Previous HCV care cascades have required using data from a variety of sources (e.g., household surveys, cohort studies, laboratory testing, and pharmacy claims) to inform distinct steps in the cascade.[8] In response to these challenges, CDC developed guidance for generating a simplified, laboratory results–based HCV clearance cascade.[4] Following this methodology and using data from a large national commercial laboratory, this report presents a national HCV clearance cascade during the DAA era (January 1, 2013–December 31, 2022).

Data were analyzed from patients living in all 50 states and the District of Columbia who received hepatitis C testing by Quest Diagnostics. Quest Diagnostics programming was applied to de-identify and de-duplicate data. Tests included HCV antibody (anti-HCV), HCV RNA nucleic acid (quantitative or qualitative), and HCV genotype. The HCV clearance cascade characterized persons according to five steps, 1) ever infected, defined as any receipt of a positive HCV test result (i.e., any reactive anti-HCV or detectable HCV RNA or genotype) during January 1, 2013–December 31, 2021 (index period); 2) viral testing, defined as evidence of ≥1 HCV RNA test performed during January 1, 2013–December 31, 2022 (the follow-up period) for a person characterized as having ever been infected; 3) initial infection, defined as evidence of a detectable HCV RNA during the follow-up period in any person with viral testing; 4) cured or cleared, defined (among persons with an initial infection) as evidence of subsequent undetectable HCV RNA during the follow-up period (approximately one third of persons with acute infection will self-clear initial HCV infection without treatment); and 5) persistent infection or reinfection, defined as evidence of subsequent detectable HCV RNA in any person categorized as cured or cleared, during the follow-up period.[4]

Frequencies of persons at each cascade step were calculated. Conditional proportions for each step were calculated using the number of persons identified who met the definition for being at a particular step divided by the number that met the definition from the previous step, following the methods in the CDC guidance document.[4]

Persons in each of the HCV clearance cascade steps were analyzed by age group, sex, and payor type. Age group was categorized as 0–19, 20–39, 40–59, and ≥60 years. Payor type was categorized as Medicare, Medicaid, commercial, other (client or self-pay), and unspecified (no payor type provided). This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.*

A total of 1,719,493 persons were identified as ever having been infected. (Figure 1). For subsequent steps, 1,520,592 (88%) of those ever infected were categorized as having had viral testing; 1,042,082 (69%) of those with viral testing were categorized as having an initial infection; 356,807 (34%) of those with initial infection as cured or cleared; and 23,518 (7%) of those categorized as cured or cleared as having persistent infection or reinfection.

Figure 1.

Hepatitis C virus clearance cascade using national commercial laboratory data — United States, 2013–2022
Source: Quest Diagnostics (January 1, 2013–December 31, 2022).

Among those ever infected, 29%, 43%, and 27% were persons aged 20–39 years, 40–59 years, and ≥60 years, respectively; 60% were male. Among the 1,719,493 persons ever infected, 862,905 (50%) were covered by commercial health insurance, followed by 386,755 (23%) by other payor, 186,464 (11%) by Medicaid, 151,217 (9%) by unspecified payor, and 132,152 (8%) by Medicare (Table).

The prevalence of viral testing ranged from 79% (unspecified payor) to 91% (commercial and Medicare payors). Initial infection was lowest among those aged 0–19 years (41%); payor type ranged from 63% for those with commercial insurance to 82% for those with unspecified payor type. The prevalence of being cured or cleared was lowest among persons aged 20–29 years (24%), and highest among those aged ≥60 years (42%). By payor type, cured or cleared prevalences ranged from 23% for other to 45% for Medicare.

Hepatitis C viral clearance increased with age when stratified by payor type among those with initial infection (Figure 2). The lowest proportion of cured or cleared, across all age groups, was among those with other payor (range = 16%–29%), followed by unspecified (20%–41%) and Medicaid (23%–38%), and then by commercial (29%–49%) and Medicare (33%–46%) payors. The highest proportion of cured or cleared among all age groups and payors was 49% for commercially insured persons aged ≥60 years. Persistent infection or reinfection was highest among persons aged 20–39 years (9%).

Figure 2.

Proportion* of hepatitis C virus–infected persons with evidence of viral clearance, by age group and payor type§ — United States, 2013–2022
Source: Quest Diagnostics (January 1, 2013–December 31, 2022).
*With 95% CIs indicated by error bars.
Persons aged 0–19 years were not included because of small sample sizes.
§Other payor includes client or self-pay, and unspecified includes persons with no payor type provided in the record.
Includes all persons with initial infection during January 1, 2013–December 31, 2022.

*45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.