Abstract
Background:
Chronic hepatitis C (CHC) is associated with significant economic burden. This study evaluated the healthcare cost alleviation associated with treatment of CHC.
Methods:
Health insurance claims from 60 self-insured US companies were analyzed (01/2001–03/2012). Adult patients with ≥1 CHC diagnosis (ICD-9-CM: 070.44, 070.54), initiating interferon, and with ≥2 dispensings and with ≥48 weeks of follow-up were selected. Patients diagnosed with HIV or who completed only 24 weeks of interferon therapy (a surrogate for CHC genotypes 2 and 3) were excluded from the study. Interferon users were categorized into complete and discontinued therapy cohorts. During the post–48-week treatment period, cohorts were compared for healthcare resource utilization using rate ratios (RRs), as well as healthcare costs using per-patient per-year (PPPY) cost differences.
Results:
A total of 1017 patients who completed and 953 patients who discontinued interferon therapy were identified. Relative to the discontinued therapy cohort, the completed therapy cohort had significantly fewer hospitalizations (RR [95% CI] = 0.74 [0.68, 0.81], p < 0.001), outpatient visits (RR [95% CI] = 0.92 [0.91, 0.93], p < 0.001), and ER visits (RR [95% CI] = 0.93 [0.87, 1.00], p = 0.039), which translated into significantly lower total healthcare costs PPPY (cost difference [95% CI] = $4540 [1570, 7680], p = 0.004) and hospitalization costs (cost difference [95% CI] = $3039 [1140, 5248], p = 0.002). Non–CHC-related costs accounted for 55% and CHC-related costs for 45% of the all-cause cost difference between cohorts.
Limitations:
Claims data may have contained inaccuracies, and genotypes of patients with CHC could not be confirmed. The study consisted of privately insured individuals and may not be generalizable to the entire CHC population.
Conclusion:
Compared to discontinued therapy patients, CHC patients who completed interferon therapy and presumably had a higher rate of achieving SVR were found to have lower levels of healthcare resource utilization and costs post-therapy. The reduction was primarily in costs associated with non–HCV-related comorbidities.
Introduction
The hepatitis C virus (HCV) is associated with significant economic burden, and several studies have documented the significant healthcare burden associated with the diseaseCitation1–8. Moreover, the total healthcare cost related to HCV in the US was estimated at $6.5 billion and is expected to rise to $9.1 billion by 2024Citation8. The most recent analysis of the NHANES (National Health and Nutrition Examination Survey) database estimated that 2.7 million US residents in the NHANES population have chronic hepatitis C (CHC)Citation9. Among patients chronically infected with hepatitis C in the US, 75% are infected with genotype 1, 25% have genotypes 2 and 3, and less than 1% are infected with genotypes 4, 5, and 6Citation10.
HCV treatment algorithms are evolving rapidly. Prior to 2011, the standard of care was 48-week therapy with pegylated interferon (PegIFN) and ribavirin (RBV) for HCV genotypes 1, 4, 5, and 6, and 24-week therapy for HCV genotypes 2 and 3Citation11–15. In 2011, two direct-acting antivirals (telaprevir and boceprevir) were approved for use in combination with PegIFN and RBV to treat genotype 1 CHC infection and quickly became the new standard of careCitation11–15. Studies have shown that a sustained virological response (SVR) is obtained for 40–50% of patients treated with PegIFN and RBV for genotypes 1, 4, 5, and 6, and for 70–80% of patients treated for genotypes 2 and 3Citation11,Citation12,Citation16. SVR rates from the telaprevir and boceprevir registrational studies increased to 65–80% in genotype 1 CHC patientsCitation17–20. Most recently, simeprevir and sofosbuvir were approved by the FDA in late 2013Citation21,Citation22 and have quickly replaced telaprevir and boceprevir as the new standard of care for the treatment of CHCCitation23.
A recent study reported that achieving an undetectable viral load was associated with decreased hepatic morbidity and mortalityCitation24. Moreover, a recent study found that healthcare utilization and costs after treatment with PegIFN and RBV were significantly lower for patients who achieved SVR than for those without SVRCitation25. These studies suggest that completing a CHC therapy may increase chances of achieving an SVR and potentially result in reduced clinical and healthcare cost burden.
As HCV therapies continue to evolve and new direct-acting antivirals are developed both with and without interferon, the ability to treat more patients and achieve high rates of SVR will exist in the next few years. While these new therapies may be associated with significant cost, they have the potential to reduce healthcare resource utilization (HRU) post-therapyCitation26. Therefore, we conducted a retrospective analysis to evaluate the HRU and cost alleviation associated with completing a 36–48-week HCV therapy using all of the currently available data from a large national healthcare claims database. This analysis could be used to design future retrospective and prospective clinical trials that incorporate the impact of HCV treatment on post-therapy HRU in addition to clinical outcomes like SVR.
Methods
Data source
Claims dated from January 2001 through March 2012 were analyzed from the OptumHealth Reporting and Insights Database. The database includes medical and pharmacy claims of more than 13 million privately insured individuals covered by 60 self-insured Fortune 500 companies with locations in all census areas of the US. The database was deidentified and was in compliance with the Health Insurance Portability and Accountability Act of 1996 to preserve patient anonymity and confidentiality. Data elements used in the present analysis included information on patient demographics (e.g. age, gender, insurance type), monthly enrollment history, and medical and pharmacy claims including actual payment amounts.
Study design
A retrospective cohort design was used to compare resource utilization and healthcare costs between CHC patients with a complete 36–48 weeks of interferon therapy and patients who discontinued interferon therapy prior to week 36. Patients included in the analysis were ≥18 years of age, with at least one diagnosis claim of CHC (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 070.44, 070.54), with ≥2 dispensings of interferon (i.e. peginterferon alfa-2a or alfa-2b, interferon alfa-2a or alfa-2b, or interferon alfacon-1), and continuously enrolled for 6 months prior to the first interferon dispensing. Interferon users were categorized into complete and discontinued therapy cohorts according to their adherence to therapy (i.e. no gap of 30 days or more between two refills) during the first 36 weeks of treatment. Patients diagnosed with HIV (ICD-9-CM: 042.xx, 043.xx, 044.xx, 079.53, and V08.xx) or patients who completed 20–28 weeks of interferon therapy (a surrogate of genotypes 2 and 3) were excluded, but patients with <20 weeks of therapy were not excluded and were included in the discontinued therapy cohort. Patients in the discontinued therapy cohort who had <48 weeks of follow-up were also excluded.
The first interferon dispensing was termed as the index date. The observation period spanned from 48 weeks after the index date to the earliest date between the end of insurance coverage or the end of data availability (March 2012). The baseline characteristics were evaluated within the 180-day period prior to the index date.
Study endpoints
Cohorts of complete therapy and discontinued therapy were compared in terms of healthcare resource use and healthcare costs. Healthcare resource use included medical visits stratified into three mutually exclusive components: (a) hospitalizations, (b) emergency room (ER) visits, and (c) outpatient visits. Healthcare costs included pharmacy costs and medical costs, which were stratified into costs attributable to hospitalizations, ER visits, and outpatient visits.
Finally, both all-cause and CHC-related healthcare costs were assessed. CHC-related costs included claims with a diagnosis of CHC or HCV therapy (i.e. peginterferon alfa-2a or alfa-2b, interferon alfa-2a or alfa-2b, or interferon alfacon-1, RBV, telaprevir, and boceprevir). All costs were adjusted to the 2012 US dollar value.
Statistical analysis
Descriptive statistics were generated to summarize the patient baseline characteristics and treatment patterns of the study population. Means and standard deviations were used for continuous variables, and frequencies and percentages were reported for categorical variables. Continuous and categorical variables were compared using Student’s t-tests and Pearson Chi-square tests, respectively.
To evaluate the impact of a completed interferon therapy on the rate of healthcare resource use, frequency rates of event were calculated as the number of events divided by patient-years of observation. Rate ratios (RRs) were used to compare HRU between cohorts, and adjusted RRs were calculated using negative binomial regression models, adjusting for baseline characteristics (i.e. age, gender, type of beneficiary, geographical region, payer type, year of index date, Quan-Charlson comorbidity indexCitation27, and total all-cause healthcare costs).
Cost differences between study cohorts were assessed based on incremental annualized costs. To avoid over-estimating costs by annualizing data for patients observed for less than 1 year, we calculated costs per-patient per-year (PPPY) by weighting each patient’s cost outcomes by the length of follow-up. For the multivariate analysis, adjusted cost differences were calculated using an ordinary least-squares regression model, adjusting for baseline characteristics. Confidence intervals and p-values were obtained using a non-parametric bootstrap with 999 replications.
As a sensitivity analysis, the total all-cause and CHC-related healthcare costs of the excluded HCV patients who completed 20–28 weeks of interferon therapy were compared to those of the complete and the discontinued therapy cohorts.
Results
A total of 1427 patients who had completed 36–48 weeks of therapy and 1939 patients who had discontinued the therapy prior to week 36 were identified (). After exclusion, 1017 patients from the complete therapy cohort and 953 patients from the discontinued therapy cohort were selected to form the study population. presents the baseline characteristics of both cohorts. Mean age of the complete therapy cohort was 49.6 years and 38.1% were female, compared to 50.4 years and 38.4% for the discontinued therapy cohort.
Figure 1. Patient’s disposition.
Table 1. Demographic and clinical characteristics of the complete and discontinued HCV therapy cohorts.
At baseline, the Quan-Charlson comorbidity index was 1.36 and 1.47 (p-value = 0.027) in the complete and discontinued therapy cohorts, respectively. Overall, for both the complete and discontinued therapy cohorts, the most common comorbidities were diabetes, psychiatric disease, depression, anemia, and substance abuse. Diabetes and anemia were less common in the complete therapy cohort compared with the discontinued therapy cohort (diabetes: 10.6% and 14.1%, p-value = 0.020; anemia: 5.8% and 8.9%, p-value = 0.008). Psychiatric disease (9.0% and 9.5%, p-value = 0.701), depression (8.4% and 9.8%, p-value = 0.279), and substance abuse (4.8% and 5.5%, p-value = 0.521) were equally common in both cohorts. The following extra-hepatic manifestations of HCV each occurred in <2% of HCV patients: lichen planus, porphyria cutanea tarda, vasculitis, psoriasis, and non-Hodgkin’s lymphoma.
presents the treatment characteristics of both cohorts. The mean post-therapy observation period for the complete therapy cohort and the discontinued therapy cohorts was 1731 and 1593 days, respectively, and patients had 353 and 108 days of persistent therapy in the complete and discontinued therapy cohorts, respectively.
Table 2. Treatment patterns of the complete and discontinued HCV therapy cohorts.
Impact of interferon therapy completion on healthcare resource use
Frequency rates of all-cause resource use for the complete and discontinued therapy cohorts are presented in . After the 48-week therapy period, the complete therapy cohort had significantly fewer hospitalizations (RR [95% CI] = 0.74 [0.68, 0.81]; p-value < 0.001), less frequent ER visits (RR [95% CI] = 0.93 [0.87, 1.00]; p-value = 0.039), and fewer outpatient visits (RR [95% CI] = 0.92 [0.91, 0.93]; p-value < 0.001) relative to the discontinued therapy cohort. As shown in , after multivariate adjustment, the same patterns were observed (hospitalization RR [95% CI] = 0.74 [0.68, 0.81], p-value < 0.001; ER visits RR [95% CI] = 0.96 [0.90, 1.03], p-value = 0.224; and outpatient visits RR [95% CI] = 0.95 [0.94, 0.97], p-value < 0.001).
Figure 2. Comparison of adjusted HRU between the complete (36–48 weeks) vs discontinued HCV therapy cohorts. HRU, healthcare resource utilization; HCV, hepatitis C virus; IP, inpatient; ER, emergency room; OP, outpatient; CHC, chronic hepatitis C. Rate ratios and confidence intervals were calculated using negative binomial regression models, adjusting for baseline characteristics including age, gender, type of beneficiary, geographic region, payer type, year of index date, Quan-Charlson comorbidity index, and total healthcare costs.
Table 3. Comparison of HRU among all beneficiaries in the complete (36–48 weeks) vs incomplete HCV therapy cohorts.
In both analyses, patients who completed 36–48 weeks of therapy had significantly fewer CHC-related hospitalizations than patients who discontinued their interferon therapy, although the reduction in hospitalizations was mainly driven by the non–CHC-related events.
Impact of interferon therapy completion on healthcare costs
summarizes the healthcare cost alleviation associated with the completion of interferon therapy. Total all-cause healthcare costs were ∼$3700 PPPY lower in the complete therapy cohort vs the discontinued therapy cohort (mean PPPY: $13,294 vs $17,834; adjusted cost difference [95% CI] = $3687 [822, 6503]; p-value = 0.008). Costs related to hospitalizations contributed the most to this cost difference (adjusted cost difference [95% CI] = $2726 [821, 4734]), followed by outpatient visits (adjusted cost difference [95% CI] = $535 [−603, 1537]), and pharmacy costs (adjusted cost difference [95% CI] = $371 [−366, 1099]).
Table 4. Comparison of PPPY healthcare cost between all beneficiaries in the complete vs discontinued HCV therapy cohorts.
Among the patients who completed their therapy, 27% ($3535/$13,294) of the total healthcare costs were directly linked to CHC; and this proportion was 30% ($5286/$17,834) among the patients who discontinued their therapy. Consequently, the CHC-related adjusted cost difference accounted for less than half (45%) of the adjusted all-cause incremental costs incurred by CHC patients. The large majority of healthcare resources are going towards managing non–CHC-related medical comorbidities that are an important part of the all-cause cost alleviation caused by interferon therapy completion.
The sensitivity analysis showed that patients who completed 20–28 weeks of interferon therapy had the greatest reduction in costs of all the studied groups. Patients who completed 20–28 weeks of therapy had lower total all-cause healthcare costs compared to both patients who completed 36–48 weeks of therapy (mean adjusted cost difference [95% CI] = $1299 [−1081, 4293]; p-value = 0.1942) and patients who discontinued therapy (mean adjusted cost difference [95% CI] = $5604 [2161, 8642]; p-value = 0.002) with the difference compared with the discontinued group achieving statistical significance. The CHC-related cost differences were significant for both compared with patients who completed 36–48 weeks of therapy (mean adjusted cost difference [95% CI] = $2028 [1205, 2887]; p-value < 0.001) and for patients who discontinued therapy (mean adjusted cost difference [95% CI] = $3644 [2189, 5157]; p-value < 0.001).
Discussion
Based on real-world data, this large retrospective study reported the treatment patterns of CHC patients who completed 36–48 weeks of interferon therapy vs CHC patients who discontinued their therapy prior to week 36 and compared their resource utilization and healthcare costs for the period after their HCV therapy. More specifically, using claims database information from January 2001 to March 2012, a total of 1017 patients who completed their interferon therapy and 953 patients who discontinued were compared. Both resource utilization and healthcare cost analyses indicated that the cohort of completed therapy patients was associated with a lower level of healthcare consumption compared to the cohort of discontinued therapy patients. After adjustments for baseline characteristics, the patients in the complete therapy cohort were associated with a statistically significant cost alleviation of $3687 and $1644 of all-cause and CHC-related healthcare costs, respectively, relative to patients in the discontinued therapy cohort.
CHC patients who completed interferon therapy and presumably had a higher probability of achieving SVR were expected to have lower costs post-therapy compared to patients that discontinued. Previous clinical trials reported that a SVR is achieved in 40–50% of patients treated with interferon therapy for a 48-week periodCitation11,Citation12. Our study used a period of 36–48 weeks of persistent therapy as a proxy of a cured patient. We expect the SVR rates to be lower in the real-world than that of clinical trials so the proportion of the patients in the complete therapy cohort failing to achieve SVR is likely higher than 60%. If we were able to identify which patients among the completed therapy cohort achieved SVR, the incremental cost difference among patients achieving SVR could be even higher than the one estimated in the current study. In addition, in a future with more effective therapies and higher SVR rates, the incremental cost difference could also be higher than the one estimated.
In our analysis, non–CHC-related medical conditions were the largest contributing factors to the alleviation of healthcare costs (representing more than half of the all-cause cost difference between the complete therapy cohort and the discontinued therapy cohort). Our findings suggest that, after baseline adjustment, the cohort of CHC patients who completed their therapy consumed significantly lower CHC-related healthcare resources and also non–CHC-related healthcare resources than a cohort of patients who discontinued their therapy. Future attempts to project post-HCV therapy cost implications should include reductions in both non–CHC-related and CHC-related costs, primarily driven by lower hospitalizations. Further, strategies to control both the CHC-related expenses and non–CHC-related costs, potentially through CHC eradication via antiviral therapy as well as closer management of non–CHC-related medical conditions, have to be weighed against the cost of therapyCitation28. Future analyses could attempt to identify sub-groups among the treated and cured population that have the greatest reduction in HRU post-therapy.
Recently conducted studies have reported the resource utilization and healthcare costs of HCVCitation3,Citation6,Citation7. In these studies, the yearly cost of HCV varies from $12,000–$20,000, including a previous study that used the same database and reported a PPPY cost of $16,721 among CHC patients. Our estimated yearly costs are comparable to those previously reported.
An analysis of the impact of drug therapy duration in patients with hepatitis C was conducted by McCombs et al.Citation29, using de-identified paid claims data of patients from 2003–2010. Patients classified by length of persistent interferon therapy were observed for costs and resource utilization for 1 year after a 1-year treatment period. They reported that the persistence to ≥48 weeks reduced the likelihood of a hospital admission by 58% (p < 0.001) and produced a cost reduction of $8130 (p < 0.01) relative to treated patients who were persistent for <24 weeks. The greater cost reduction post-therapy observed by McCombs et al. could be explained by the shorter length of the observation period of 1 year vs ∼3.5 years in our study or the slightly different definition of discontinued therapy, less than 24 weeks vs a gap of 30 days or more during the first 36 weeks of therapy in our study. In addition to the previous study, Manos et al.Citation25 conducted a retrospective study of patients receiving treatment with PegIFN and RBV in the Kaiser Permanente Medical Care Program of Northern California from 2002–2007 to quantify the short-term cost and utilization impact of achieving SVR. Post-treatment all-cause costs PPPY were $6301 and $10,149 for the SVR and non-SVR groups, respectively, and the adjusted difference in yearly total mean costs reported was $2648 (95% CI: 737, 4560). The SVR groups also incurred a lower level of resource utilization in any year post-treatment compared to the non-SVR group. While these studies are not directly comparable to ours, collectively, they add to the growing body of literature demonstrating that the achievement of a completed interferon therapy and/or the attainment of SVR leads to an alleviation of the all-cause healthcare costs.
Compared to the recent literature that has studied the impact of therapy completion among CHC patientsCitation29, our study has the advantage of relying on a long follow-up period, and, therefore, observing the cost alleviation of a completed interferon therapy in the long-term. The current standard of care for genotypes 2 and 3 HCV infection is a treatment with PegIFN and RBV for a total of 24 weeksCitation15. Since the genotype information was not available in the database, in an attempt to study HCV patients with genotype 1 who either completed or discontinued 48-week therapy, we excluded from the analysis patients who completed 20–28 weeks of therapy. These excluded patients represented 25% of the overall population of treated HCV patients, which is in a similar range as the proportion of HCV patients with genotypes 2 and 3 in the US that has been estimated at 22%Citation10. These patients experienced the greatest reduction in healthcare costs compared to both the completed and the discontinued therapy cohorts, which suggests that we correctly identified the genotype 2 and 3 patients who had the highest chance of achieving SVR which could have contributed to their reduction in HRU post-therapy. It is not clear from our analysis why the reduction in post-therapy HRU was mostly attributed to CHC-related costs in this sensitivity analysis of genotypes 2 and 3, whereas it was more due to non–CHC-related costs in our primary analysis (55% vs 45% for non-CHC and CHC related, respectively).
This study is subject to limitations. As it is the case with claims databases, the OptumHealth Reporting and Insights database may have contained inaccuracies or omissions in procedures, diagnoses, or costs; and no information was provided as to whether or not medication was taken as prescribed. Furthermore, even though the proportion of patients who completed 20–28 weeks of interferon therapy and the low healthcare costs of this group suggest that we have excluded HCV patients with genotypes 2 and 3, the genotypes of these patients, as well as those included in the study populations, cannot be confirmed. Moreover, the observational design was susceptible to various biases, such as information or classification bias (e.g. identification of false-positive CHC events). Nevertheless, it is probable that these limitations impacted both study cohorts similarly, thus preserving the validity of the findings. Lastly, our study population consisted of privately insured individuals, and, therefore, our results might not be generalizable to the entire HCV population, of which an important proportion is uninsured or publicly insuredCitation30. Of note, the evaluation of CHC healthcare cost alleviation in the current study was for the most part prior to triple therapy (peginterferon, RBV, and the direct antiviral agents boceprevir or telaprevir) usage since boceprevir and telaprevir were approved by the FDA in 2011. Despite all these limitations, well-designed observational studies, with appropriate statistical techniques adjusting for potential confounding factors through multivariate analyses, provide valuable information with real-life scenarios.
Conclusion
In a private-insurance setting, patients with CHC who completed 36–48 weeks of interferon therapy and presumably had a higher rate of achieving SVR were found to be significantly associated with lower levels of HRU. Consequently, CHC patients who completed their interferon therapy incurred significantly lower healthcare costs relative to those who discontinued their therapy. The majority of healthcare costs were attributed to non–CHC-related medical conditions, suggesting that the benefits of HCV therapy in terms of reduced healthcare burden apply equally or more to non–CHC-related conditions than to CHC-related healthcare use. Future analyses will attempt to quantify non–CHC-related and CHC-related HRU and identify comorbid conditions that could be driving the greatest incremental cost and warrant the most attention clinically both before and after HCV therapy.
Transparency
Declaration of funding
This research was funded by Janssen Scientific Affairs, LLC, Titusville, NJ.
Declaration of financial/other relationship
FL, DP, PL, and GG are employees of Analysis Group Inc., a consulting company that has received research grants from Janssen Scientific Affairs. NT and AP are employees of Janssen Scientific Affairs. LAB has received research grants from Janssen Scientific Affairs. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgments
Partial results were presented as posters at the 19th International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Annual International Meeting, Montreal, Canada, May 31–June 4, 2014 and at the 2013 HEP DART frontiers in drug development for viral hepatitis, Hawaii, December 8–12, 2013.
References
- Rosenberg DM, Cook SF, Lanza LL. Health care, treatment patterns and cost of services for patients infected with chronic hepatitis C virus in a large insured New England population. J Viral Hepat 2000;7:361-7
- Poret AW, Ozminkowski RJ, Goetzel R, et al. Cost burden of illness for hepatitis C patients with employer-sponsored health insurance. Dis Manag 2002;5:95-107
- Su J, Brook RA, Kleinman NL, et al. The impact of hepatitis C virus infection on work absence, productivity, and healthcare benefit costs. Hepatology (Baltimore, MD) 2010;52:436-42
- Davis KL, Mitra D, Medjedovic J, et al. Direct economic burden of chronic hepatitis C virus in a United States managed care population. J Clin Gastroenterol 2011;45:e17-24
- McCombs JS, Yuan Y, Shin J, et al. Economic burden associated with patients diagnosed with hepatitis C. Clin Therapeut 2011;33:1268-80
- 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. JMCP 2011;17:531-46
- Tandon N, Reddy KR, Lefebvre P, et al. Direct and indirect cost burden of chronic hepatitis c infection in privately-insured patients, stratified by liver disease severity. Value Health 2013;16:A6
- Razavi H, Elkhoury AC, Elbasha E, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology (Baltimore, MD) 2013;57:2164-70
- 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
- Blatt LM, Mutchnick MG, Tong MJ, et al. Assessment of hepatitis C virus RNA and genotype from 6807 patients with chronic hepatitis C in the United States. J Viral Hepat 2000;7:196-202
- Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-65
- Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975-82
- Hadziyannis SJ, Sette H, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140:346-55
- Akiyama MJ, Piotrowski JI, Roytman MM, et al. New triple therapy for chronic hepatitis C: real life clinical experience in a community setting. Hawaii J Med Public Health 2013;72(9 Suppl 4):6-13
- Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology (Baltimore, MD) 2009;49:1335-74
- Zeuzem S, Berg T, Moeller B, et al. Expert opinion on the treatment of patients with chronic hepatitis C. J Viral Hepat 2009;16:75-90
- Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011;364:2405-16
- Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011;364:2417-28
- Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011;364:1207-17
- Poordad F, McCone J, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011;364:1195-206
- U.S. Food and Drug Administration. Olysio (simeprevir) for the treatment of chronic hepatitis C in combination antiviral treatment. http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/ucm377234.htm. Accessed July 2014
- U.S. Food and Drug Administration. Approval of Sovaldi (sofosbuvir) tablets for the treatment of chronic hepatitis C. http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/ucm377234.htm. Accessed July 2014
- AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating Hepatitis C. http://www.hcvguidelines.org/full-report-view. Accessed July 2014
- McCombs J, Matsuda T, Tonnu-Mihara I, et al. The risk of long-term morbidity and mortality in patients with chronic hepatitis C: results from an analysis of data from a Department of Veterans Affairs Clinical Registry. JAMA Intern Med 2013;90007:1-8
- Manos MM, Darbinian J, Rubin J, et al. The effect of hepatitis C treatment response on medical costs: a longitudinal analysis in an integrated care setting. JMCP 2013;19:438-47
- Hoofnagle JH, Sherker AH. Therapy for hepatitis C–the costs of success. N Engl J Med 2014;370:1552-3
- Quan H, Sundararajan V, Halfon P, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 2005;43:1130-9
- Center for Disease Control and Prevention. Surveillance for Viral Hepatitis – United States. http://www.cdc.gov/hepatitis/Statistics/2011Surveillance/Commentary.htm. Accessed October 2013
- McCombs JS, Shin J, Hines P, et al. Impact of drug therapy duration in patients with hepatitis C. Am J Pharm Benefits 2012;4:19-27
- Ong JP, Collantes R, Pitts A, et al. High rates of uninsured among HCV-positive individuals. J Clin Gastroenterol 2005;39:826-30