Chronic hepatitis C virus (HCV) infection kills more people than any other infectious disease in the United States, and, as of 2013, mortality associated with this disease has been rising.1 In 2014, the estimated number of persons living with chronic HCV in the United States was 2.7 million, based on data from the 2003-2010 National Health and Nutrition Examination Survey (NHANES).2,3 This prevalence estimate was considered low, because certain high-risk populations (eg, institutionalized, incarcerated, and homeless persons) were excluded from this survey.2 Researchers estimate that after adjusting for populations excluded from the NHANES, the prevalence of chronic HCV is at least 3.5 million.3 This number does not include individuals who were infected with HCV and whose disease cleared spontaneously and did not become chronic.3 Recent studies demonstrated that healthcare costs for HCV-infected individuals are higher than for noninfected individuals, and that those costs increase as the disease progresses.4,5
According to the Centers for Disease Control and Prevention (CDC), the incidence rates for HCV peaked in the 1970s and 1980s.6,7 The majority of patients with newly diagnosed HCV today have chronic HCV and are thought to have been infected during the decades of peak HCV incidence rates.6,7 Targeted screening is an important strategy to identify asymptomatic patients and to engage them in the healthcare system to improve health outcomes.
In 1998, the CDC issued risk-based screening recommendations targeting individuals who currently or previously used injection drugs, received blood transfusions before July 1992, were receiving chronic hemodialysis, received clotting factors concentrates produced before 1987, were a healthcare or emergency medical services worker with recognized exposure to HCV, or were born to HCV-infected mothers.8-10 Risk-based HCV screening was expanded in 1999 to include persons infected with HIV.9 In 2012 and 2013, the CDC and the US Preventive Services Task Force (USPSTF), respectively, expanded their HCV screening guidelines to include all persons born between 1945 and 1965.8-10
Because HCV infection is often asymptomatic, many individuals are unaware of their status, do not seek care, and can continue to be a source of transmission.11,12 It is estimated that as many as half of infected individuals are unaware of their diagnosis.13 To our knowledge, the financial burden of undiagnosed patients has not yet been explored.
In late 2013, new interferon-free direct-acting antiviral drugs (eg, sofosbuvir) became available. Interferon-free direct-acting antiviral therapy, with its low rate of side effects and high cure rate, took away one obstacle to testing, namely, the adverse effects of earlier HCV therapy. Patients who were newly diagnosed with HCV before receiving interferon-free direct-acting antiviral therapy might have been more likely to have symptoms at the time of diagnosis than newly diagnosed patients in the years immediately after the introduction of interferon-free direct-acting antiviral drugs.
A review of medical costs is useful for comparing patients newly diagnosed and those previously diagnosed with HCV, because treatments for cirrhosis and liver failure have not changed materially since 2013. Given the societal impact of the medical cost of patients with advanced-stage HCV, we expect that insight on newly diagnosed patients and those not yet diagnosed will be of interest to healthcare providers, payers, and policymakers who are interested in what the future demand for HCV oversight and treatment may be.
We compared the previous years’ healthcare costs, demographics, and comorbidities for patients newly diagnosed with HCV in 2013 with those of patients who were previously diagnosed with HCV. Although patients with newly diagnosed HCV are different from undiagnosed patients, examining the experience of newly diagnosed patients before their diagnosis provides an opportunity to explore the undiagnosed population.
This retrospective study includes data from the Truven Health MarketScan Commercial database, a medical database that includes annual private-sector health data from approximately 100 US payers. The database contains more than 35 million commercially insured lives, which is approximately 1 of every 6 employees and dependents in the United States, and is geographically diverse. It represents the medical experience of insured subscribers and their dependents for active employees, early retirees, COBRA continuation beneficiaries, and Medicare-eligible retirees with employer-provided supplemental plans. We restricted our analysis to members whose employee status was indicated as active or unknown, plus their dependents, and we excluded those enrolled in capitated health plans.
Patients aged ≤64 years as of the end of 2013 were identified as diagnosed with HCV if they had at least 1 acute inpatient, observation, emergency department, or nonlaboratory/nonradiology physician claim with an HCV International Classification of Diseases, Ninth Edition (ICD-9) diagnosis code in any position incurred in 2013 (see Appendix Table 1). We included all patients diagnosed with HCV who were continuously enrolled from January 2010 through December 2013.
In 2013, we identified 9193 commercially insured patients with an HCV diagnosis and continuous enrollment from 2010 through 2013 (see Appendix Table 2). Among this population, 2428 (26%) patients met our criteria of being newly diagnosed with HCV, because they had no HCV-related diagnoses in the previous 36 months (2010-2012 claims). Of the approximately 2428 newly diagnosed patients, 12% (N = 299) had advanced-stage HCV. As expected, decreasing the look-back period increased the count of patients whose first diagnosis appeared in 2013. Specifically, 24-month and 12-month look-back periods yielded 31% and 41% of patients, respectively, as being newly diagnosed with HCV. It is possible that some patients identified as newly diagnosed with HCV with a 36-month look-back period had been diagnosed at some earlier time.
Disease Stage and Comorbidities
We used the 2014 Centers for Medicare & Medicaid Services US Department of Health and Human Services (HHS)-Hierarchical Condition Categories (HCC) risk-adjuster model to assign patients to their HCV disease stages. HHS-HCC is a concurrent model designed for the commercially insured population to predict a patient’s cost in the same year as the input data. The model has separate sets of factors for each of the different metallic levels for health insurance specified by the Affordable Care Act.14 The HHS-HCC classification includes 4 hierarchical stages of liver disease based on ICD-9 diagnosis codes, including chronic HCV (HCC037), cirrhosis of the liver (HCC036), end-stage liver disease (ESLD; HCC035), and liver transplant (HCC034).
Comorbidities, such as diabetes, were also identified by applying HHS-HCC criteria. We labeled HCV-infected status other than chronic HCV (HCC037) as “advanced HCV disease stages.” The risk scores for individuals were calculated using the HHS-HCC 2014 gold risk coefficients, which were chosen because the MarketScan Commercial database cost-sharing is, in aggregate, approximately gold level.15
The all-cause medical and pharmacy costs were summarized for this analysis. The amounts reported represent the negotiated terms between the insurers and the healthcare providers, and include insurance payments and patients’ out-of-pocket costs. The medical costs included inpatient admissions, outpatient and ambulatory surgical center facility bills, professional charges, services incurred by independent laboratory facilities, transportation, and other miscellaneous costs such as eye care, hearing aids, acupuncture, and dental services when covered under the medical benefits. The pharmacy costs were segmented into the 2 categories of antiviral drugs (including HCV treatments) and all other drugs. The costs were calculated for each calendar year separately for patients newly diagnosed with HCV and for previously diagnosed patients, regardless of the date of diagnosis, and were reported as per patient per month (PPPM).
To determine statistical significance when comparing newly diagnosed patients with HCV with previously diagnosed patients, we calculated P values using a t-test for 2 independent sample comparison of means tests with adjustments for unequal variance. Patients with newly diagnosed disease and those previously diagnosed with HCV were compared without adjustment for demographics or other variables, with the goal of developing descriptive statistics.
The average age of patients newly diagnosed with HCV was 49.5 years compared with 54.1 years for previously diagnosed patients. The cumulative percentage of patients aged ≤30 years was 11.5% for newly diagnosed patients compared with 2.9% reported by previously diagnosed patients. There was a higher proportion of females than males aged ≤30 years among the newly diagnosed patients. The age and sex distribution for both cohorts is provided in Table 1. Because the prevalence of HCV is heavily skewed toward older-aged patients, older newly diagnosed patients are more likely to emerge from patients who have been infected with HCV for many years, whereas younger patients are more likely to be newly infected.
The distribution of HCV disease stage in 2013 for newly and previously diagnosed patients is provided in Table 2. Patients with newly diagnosed HCV had a lower prevalence (12.3%) of advanced disease stage (cirrhosis, ESLD, and liver transplant) compared with 21.9% for previously diagnosed patients. Of patients with newly diagnosed disease, 4.6% had ESLD in 2013 compared with 7.7% of previously diagnosed patients.
Certain clinical conditions are known to frequently occur in people with HCV.16 Table 3 provides the details of 15 of the most common HCV-related comorbidities in the study population, including relativity ratios and P values. The number of these comorbidities was similar in both cohorts. Drug-induced psychosis was 8.1% in newly diagnosed patients versus 4.7% for previously diagnosed patients (P ≤.01). In addition, newly diagnosed patients had a 2.5% prevalence of acute liver failure versus 1.3% for previously diagnosed patients (P ≤.01). Conversely, newly diagnosed patients had a significantly lower prevalence (P ≤.01) for HIV (HCC001), diabetes (HCC019, HCC020, HCC21), and severe cancers (HCC009) than previously diagnosed patients. The prevalence of the 10 additional comorbidities examined was not statistically different between the 2 cohorts.
The average HHS-HCC risk score, which is based on age, sex, and diagnosis codes, was higher in the previously diagnosed patients (7.80) than in newly diagnosed patients (6.92; P ≤.01). The lower risk scores among newly diagnosed patients are consistent with the lower average age, which is an important component of the risk adjuster. The lower average age is also correlated with a lower number of diagnoses, which is the other component of the risk-adjustment model.
In 2013, the average allowed monthly medical cost per member for patients newly diagnosed with HCV was $1817, which is more than 5 times higher than the average cost of $330 PPPM across all commercially insured members in the MarketScan database. The average annual PPPM medical costs for both groups was approximately $2200 in 2013. This number reflects the full calendar year of costs for both groups. The newly diagnosed patients were diagnosed, on average, by midyear; an analysis of monthly costs may show additional relationships. The annual PPPM medical cost for newly diagnosed patients was $588 in 2010 (ie, 3 years before diagnosis), $626 in 2011, and $854 in 2012.
The medical PPPM costs (excluding prescription drugs) for newly diagnosed and previously diagnosed patients were $1817 and $1675, respectively, and were not significantly different. Patients with newly diagnosed HCV and more advanced disease stages had higher PPPM costs compared with the less advanced, noncirrhotic newly diagnosed patients. The PPPM cost comparisons shown in Table 4 represent the all-cause medical services only and do not include costs for prescription drug benefits.
The pharmacy PPPM costs in 2013 were significantly higher in previously diagnosed patients than in newly diagnosed patients for HCV antiviral prescriptions ($206 vs $131, respectively; P <.01) and for all other prescriptions ($310 vs $263; P = .046). Of note, the HCV antiviral PPPM costs in this study do not reflect the impact of interferon-free direct-acting antiviral drugs, which were launched after November 2013 and created a surge in prescription drug costs for patients with HCV. A comparison of the average medical and pharmacy PPPM costs in 2013 for newly diagnosed and previously diagnosed patients is shown in Table 5.
Despite a lower average age, 12.3% of newly diagnosed patients had advanced-stage HCV, which suggests that many patients’ disease is not identified early. Still, this portion is lower than the 21.9% of patients previously diagnosed with HCV who have advanced-stage disease.
Comorbidities are a marker of the course of HCV, as well as of mortality outcomes.17 Patients previously diagnosed with HCV had a higher prevalence of HIV, diabetes, and severe cancers. Acute liver failure and drug-induced psychosis were more prevalent in newly diagnosed than in previously diagnosed patients, suggesting that newly diagnosed patients could have been identified through the implementation of risk-based screening guidelines or through symptomatic screening. For the 10 additional HCV comorbidities examined, no significant differences in prevalence were observed between the 2 cohorts based on the t-test results. These results suggest that a broad range of extrahepatic complications can arise by the time of diagnosis and can persist thereafter.
The medical costs of newly diagnosed HCV in the years leading up to diagnosis were lower than in the year of diagnosis ($588 PPPM 3 years before diagnosis vs $1817 PPPM in the year of diagnosis). The PPPM costs of patients with newly diagnosed HCV were higher in the years before diagnosis for those who were diagnosed at later stages of the disease than in those diagnosed with early-stage HCV, but the costs were still lower than those in the year of diagnosis.
In the year of diagnosis, the cost of patients newly diagnosed with HCV was not significantly different from previously diagnosed patients ($1817 PPPM vs $1675 PPPM, respectively). However, the risk score of newly diagnosed patients was significantly lower (6.92) than that of previously diagnosed HCV (7.80). This observation (using concurrent risk scoring) is consistent with patients previously diagnosed with HCV being older and having more advanced disease states, as well as having a higher prevalence of certain comorbidities (eg, HIV, diabetes, and cancer).
The age and sex differences may partially account for the various prevalence rates for HIV, diabetes, and cancer. It is also possible that patients diagnosed with HIV, diabetes, or cancer are more likely to be screened for HCV and are thus diagnosed at an earlier date than they otherwise would have been.
This study has several limitations. The data come from a large commercially insured population, which implies the socioeconomic status represents a population with employer-sponsored insurance. Other populations with different characteristics or access to care could exhibit different outcomes.
In addition, the commercial population described in this study had continuous insurance coverage; therefore, its utilization, coverage, and access-to-care characteristics may differ from patients who are not continuously enrolled in a health plan. Consequently, the results of this study may not apply to other patient populations.
Furthermore, using 3 years of look-back to identify patients with newly diagnosed HCV could mean that some patients identified as being newly diagnosed might have been diagnosed earlier but were not actively treated during the look-back period.
Finally, curative treatment for HCV before the introduction of interferon-free direct-acting antiviral drugs in 2013 was not common at the time of this study, and we did not attempt to distinguish patients who received curative treatment. Therefore, the costs analyzed in this study do not reflect the recent surge in the use of all-oral interferon-free direct-acting antiviral drugs.
This study described the commercially insured US population who were newly diagnosed with HCV in 2013 and compared them with patients previously diagnosed with HCV, specifically examining demographics, comorbidities, and healthcare costs. The characteristics of patients newly diagnosed with HCV reflect the impacts from the expanded CDC/USPSTF screening guidelines (promulgated in 2012 and 2013), which include the 1945 to 1965 birth cohort screening in addition to the previous existing non–age-specific risk-based screening recommendations. In their year of diagnosis, newly diagnosed patients in 2013 had a medical costs burden similar to previously diagnosed patients.
To our knowledge, there is limited evidence on the economic burden of undiagnosed HCV. This analysis identifies and examines patients with newly diagnosed HCV to provide a window into the undiagnosed populations and to provide information on the characteristics of patients newly diagnosed with HCV.
Early detection and linkage to care for asymptomatic patients with chronic HCV are critical to improving HCV-associated morbidity and mortality, as recognized by the updated CDC recommendations for screening. Although this study demonstrates that the medical cost burden of HCV among newly diagnosed patients is comparable to that of previously diagnosed patients, the burden in the years before diagnosis is considerably lower. These findings can be used to inform further research into the characteristics of patients with newly diagnosed HCV.
The authors wish to thank Andrew Bochner and Motoharu Dei for their review of the data analytics and statistical process.
Source of Funding
Financial support for this study was provided by AbbVie.
Author Disclosure Statement
Mr Pyenson, Ms Dieguez, and Ms Ferro received research support from AbbVie, and are consultants to numerous organizations in healthcare through Milliman; Ms Mavinkurve reported no conflicts of interest; Dr Sanchez Gonzalez is an employee of and has stock options in AbbVie.
1. Ly KN, Hughes EM, Jiles RB, Holmberg SD. Rising mortality associated with hepatitis C virus in the United States, 2003–2013. Clin Infect Dis. 2016;62:1287-1288.
2. Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160:293-300.
3. Edlin BR, Eckhardt BJ, Shu MA, et al. Toward a more accurate estimate of the prevalence of hepatitis C in the United States. Hepatology. 2015;62:1353-1363.
4. Razavi H, Elkhoury AC, Elbasha E, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013;57:2164-2170.
5. McAdam-Marx C, McGarry LJ, Hane CA, et al. All-cause and incremental per patient per year cost associated with chronic hepatitis C virus and associated liver complications in the United States: a managed care perspective. J Manag Care Pharm. 2011;17:531-546.
6. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705-714.
7. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341:556-562.
8. Chou R, Cottrell EB, Wasson N, et al. Screening for hepatitis C virus infection in adults: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013;158:101-108.
9. Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR Recomm Rep. 2012;61:1-32. Erratum in: MMWR Recomm Rep. 2012;61:886.
10. Workowski KA, Bolan GA. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137. Erratum in: MMWR Recomm Rep. 2015;64:924.
11. Office of Population Affairs, Department of Health and Human Services. Hepatitis C. www.hhs.gov/opa/reproductive-health/sexually-transmitted-infections/hepatitis-c/index.html#. Accessed March 30, 2017.
12. Centers for Disease Control & Prevention. Hepatitis C: testing baby boomers saves lives. CDC Vital Signs. Updated May 7, 2013. www.cdc.gov/vitalsigns/hepatitisc/. Accessed March 30, 2017.
13. Denniston MM, Klevens RM, McQuillan GM, Jiles RB. Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Health and Nutrition Examination Survey 2001-2008. Hepatology. 2012;55:1652-1661.
14. Kautter J, Pope GC, Ingber M, et al. The HHS-HCC risk adjustment model for individual and small group markets under the Affordable Care Act. Medicare Medicaid Res Rev. 2014;4.
15. Centers for Medicare & Medicaid Services (CMS), HHS. Patient Protection and Affordable Care Act; HHS notice of benefit and payment parameters for 2014. Proposed rule. Fed Regist. 2012;77:73118-73218.
16. Nuño Solinís R, Arratibel Ugarte P, Rojo A, Sanchez Gonzalez Y. Value of treating all stages of chronic hepatitis C: a comprehensive review of clinical and economic evidence. Infect Dis Ther. 2016;5:491-508.
17. El-Zayadi AR. Hepatitis C comorbidities affecting the course and response to therapy. World J Gastroenterol. 2009;15:4993-4999.