The Oncogenic Hepatitis C Virus and Direct-Acting Antivirals: Economic Implications for Hepatocellular Carcinoma in Medicaid Beneficiaries With Cirrhosis

The oncogenic effects of the hepatitis C virus can impact patient outcomes for hepatocellular carcinoma (HCC) and have economic implications for medical spending. This study underscores the importance of treating patients early in the disease process for savings associated with reducing the risks of HCC.
Published Online: April 20, 2017
S. Mantravadi, PhD, MS, MPH

Background: The hepatitis C virus (HCV) is an oncogenic virus that is the primary risk factor for hepatocellular carcinoma (HCC), illustrating the relative importance of tertiary prevention of liver cancer.1,2 Health disparities in HCV indicate its disproportionate prevalence among low-income populations. Due to low efficacy rates, predominant treatment regimens do not significantly prevent disease progression toward HCC among all populations—although the risk of HCV is higher in the Medicaid population. Direct-acting antivirals (DAAs) result in improved efficacy and ease of administration compared with current hepatitis treatment options.

Methods: Published literature and the Medicaid National Average Drug Acquisition Cost were used to estimate treatment costs, and averted medical HCC costs were modeled for DAAs and prevailing treatment options for HCV.

Results: Approximately $14,473 in medical expenses related to HCC treatment per person can be avoided over the next 10 years with the sofosbuvir-ledipasvir combination treatment for cirrhotic Medicaid beneficiaries infected with HCV genotype 1a. The DAAs result in lower HCC-related medical spending costs than peginterferon-ribavirin and watch-and-wait regimens.

Conclusions: The oncogenic effects of HCV can impact patient outcomes for HCC and have economic implications for medical spending. The study provides evidence that underscores the importance of treating patients early in the disease process to reap savings related to reduced risks of HCC.
The hepatitis C virus (HCV) is an oncogenic virus that can lead to variable degrees of liver fibrosis and damage (cirrhosis). HCV and associated cirrhosis are the leading causes of hepatocellular carcinoma (HCC).1,3 Most cases of HCC are HCV related; treatment of HCV can reduce the risk of HCC by 50%.1 The risk of HCC increases by 2-6% annually.4 The lag time between acute phase and the development of chronic HCV infection can be 20 to 30 years,5 thus creating a silent epidemic of patients infected with HCV who are at risk for HCC.6

Several groups are at an increased risk for HCV. Disease prevalence is higher in the population under age 55, and it disproportionally affects the poor.7,8 This places the Medicaid population at greater risk and makes the treatment of HCV a priority for Medicaid. The number of Medicaid beneficiaries with oncogenic HCV is high and is only rising.9,10

Reaching sustained virologic response (SVR) has been shown to reduce the imminent risk of HCC; however, the predominant treatment regimen for HCV has only had modest efficacy. Although treatment has been noted to delay development of HCV-related HCC,2 the lack of ease of administration and the associated adverse effects result in high percentages of treatment discontinuation, thereby reducing the absolute effect of peginterferon-ribavirin treatment. A new form of treatment, direct-acting antivirals (DAAs), has emerged to overcome the notable limitations of interferon-based regimens. These medications are expensive, with treatment costs averaging $80,000 for a 12-week regimen, but they do have a much greater success rate over the established interferon-ribavirin regimen, especially for patients with cirrhosis and they reduce the potential risks for HCC. Due to the high prevalence of HCV in the under 55-years group and low-income populations, Medicaid programs are facing the economic burden of efficacious, yet expensive, DAA treatments for HCV.11-15 The cost:benefit ratio of DAAs is being considered, particularly in the context of greater efficacy, reduced risk of HCC, averted HCC treatment–related expenses, and unnecessary future healthcare utilization.

Patients with HCV and cirrhosis face several complications with liver and nonliver-related cancers therapies.3 The prognosis and treatment decisions for HCC depend on the extent of fibrosis in the liver,3 illustrating the importance of efficacious HCV treatments. The increased SVR rate/ “cure” associated with interferon-free DAA treatments lowers the need for HCV-related HCC treatments.3 However, specific data on the number of cases and associated reduction in HCC costs with the use of DAAs have not been fully researched.

To evaluate changes and economic implications for HCC savings, this study modeled HCV-infected genotype 1a Medicaid beneficiaries with cirrhosis undergoing current FDA-approved and American Association for the Study of Liver Diseases (AASLD) and Infectious Disease Society of America (IDSA)–recommended treatments compared with the prevailing options of interferon-ribavirin regimen and watch-and-wait (no treatment for oncogenic disease) over a 10-year time span.


This study modeled a cohort of Medicaid enrollees, including beneficiaries across all states, over a period of 10 years. Published data and reports were used to define the size of the population of patients with Medicaid and HCV genotype 1a infection.16,17 The 10-year time frame is ideal to determine both the short-term and long-term impact of these treatments. To qualify for Medicare, individuals must be 65 years; thus, the modeled cohort was limited to Medicaid beneficiaries 55 years and younger.17 The model considered 28,765 patients with HCV with cirrhosis on Medicaid, as per public literature estimates, age/genotype distributes, and the chronic HCV cohort study.10 This study was exempt from evaluation by an Institutional Review Board as only published literature and existing data were used.

Probabilities of disease progression, obtained from published literature, were included. In the first year, patients with HCV with cirrhosis received a specific treatment regimen (12-to-48 weeks, depending on the regimen) and patients who had not discontinued treatment could reach SVR/“cure” after their HCV treatment ends. The cohort of Medicaid beneficiaries was modeled year-by-year, beginning in the second year, to evaluate changes in the number of patients who would progress to HCC, as well as HCC-related costs. The successive disease progression stages that were modeled were F4-compensated cirrhosis/fibrosis, decompensated cirrhosis (DCC), liver cancer, and liver transplantation.18 During each successive year that the cohort was modeled, the patient progressed toward the endpoint along the disease stages, as per expected probabilities, unless a treatment-related “cure” was documented. At baseline, all patients were assumed to have compensated cirrhosis. If an individual failed to reach SVR/ “cure”, he or she had a 1-time, 50% chance of retreatment with the same regimen (year 2). Each year, an individual might remain in the same disease stage or have disease progression (F4 compensated to DCC or liver cancer, DCC to liver cancer or transplant, liver cancer to transplant).18

For our study, we evaluated elbasvir-grazoprevir, sofosbuvir-ledipasvir, sofosbuvir-velpatasvir, and ribavirin-peginterferon, which are FDA-approved and AASLD-IDSA–recommended treatment regimens for treatment-naïve patients infected with HCV genotype 1a who have cirrhosis.17 These medications were evaluated in the context of a watch-and-wait scenario.

For the treatment regimens considered, efficacy rates from published clinical trial data (NEUTRINO, ION-1, OPTIMIST-2, ALLY, and ASTRAL trials), treatment discontinuation rates from observational studies and meta analyses, and treatment costs from the Medicaid National Average Drug Acquisition Cost and published literature were used.19-23 All-cause healthcare costs for HCV disease progression (F4, DCC, HCC, and liver transplantation) were extracted from published literature.24 Table 1 illustrates the variable inputs used in the model.

The number of patients who progressed to HCC from F4 cirrhosis, as well as their related costs, were tabulated annually. For each treatment, all-cause healthcare/medical costs for HCC that were averted by treatment and medical costs encountered for no treatment/watch-and-wait were accumulated over 10 years. In addition, the number of patients with HCV who progressed to HCC was determined.

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