The implementation of direct-acting antivirals for the treatment of Hepatitis C Virus (HCV), beginning with their Food and Drug Administration approval in 2011 (1), was a major clinical breakthrough that resulted in a reduction in the burden of disease among those infected with HCV (2). These new treatments have significantly increased the number of patients successfully cured, and shorter regimens have been shown to reduce the overall cost of treatment while achieving comparable rates of sustained virologic response (SVR) to the 12-week course (2, 3). Current guidelines recommend an eight or 12-week pan-genotypic treatment for HCV treatment-naïve patients with and without cirrhosis (4, 5). Beginning with the approval of ledipasvir/sofosbuvir (LDV/SOF) in 2014, some HCV treatment-naïve patients became eligible for this shortened 8-week treatment duration (3, 6, 7). Approval of the pan-genotypic HCV regimen glecaprevir/pibrentasvir (G/P) in 2017 (8) expanded patient eligibility for these shortened 8-week treatments (2, 5–7).

Previous studies have measured the healthcare costs associated with length of treatment, including expenses related to HCV treatment in those dually infected with Human Immunodeficiency Virus (HIV) (9–11). Shorter treatment times may critically reduce the financial impact on vulnerable patients and allow savings to both payors and hospital systems. Despite these treatment innovations, data on the real-world implementation of the shorter 8-week treatment regimen assessing the clinical and economic benefits are limited. To our knowledge, no study has reviewed the differential impact of varying treatment durations on healthcare utilization, and there are few data on these differences analyzed by type of healthcare encounter. To address this gap, our study aimed to measure healthcare resource utilization, by encounter type, in a retrospective cohort study of HCV-infected, non-cirrhotic, HIV-uninfected, and treatment naïve patients completing either eight or 12-weeks of therapy.

Our findings indicate a moderate reduction in healthcare utilization among patients receiving a shorter treatment regimen for HCV infection. While the number of in-person clinical visits and other ancillary support visits were similar for both treatment duration groups, the 8-week treatment regimen resulted in significantly less laboratory testing following HCV treatment initiation.

Additionally, we found that patients receiving an 8-week treatment regimen had decreased testing before HCV treatment initiation, including testing for the severity of disease and liver cirrhosis, compared to the 12-week treatment group. Notably, patients undergoing the 12-week regimen had liver biopsies more frequently than those on the 8-week regimen. While this may suggest a differential clinical presentation between these two groups, our data revealed that both groups were otherwise clinically comparable treatment-naïve, non-cirrhotic HCV patients (16). It is possible, however, that other non-clinical factors – such as a patient’s degree of insurance coverage or their ability to access hospital resources – affected a provider’s prescription of one treatment duration or another. These possible factors may have similarly influenced a patient’s access to liver biopsy resources. It is also worth noting that this study outcome was based on the number of encounters and not on individual tests. Our data imply that increased healthcare utilization for 12-week treatments includes additional care before and during treatment. In addition, a previous study suggests that less than half of patients eligible for 8-week treatment received it – this may further contribute to increased resource utilization (17). This disparity may be partly driven by a combination of provider preference or practice and health insurance requirements favoring a 12-week regimen. System-level changes such as expanded insurance authorization for 8-week regimens may be crucial in developing uptake and reducing the utilization of healthcare resources (18–20).

Though similar across treatment groups, office visits and communications were the most utilized encounters. In addition, we found that encounters entailing notes and orders related to patient management were more frequent among those in the longer treatment group. This supports our findings on laboratory testing data, suggesting that longer treatment durations may require more follow-up. As a result, those in the longer duration groups require more provider clinical notes regarding treatment status or orders for additional lab work, tests, or procedures to monitor patient clinical status. Hospital admission and emergency room visits were a priori excluded in our analysis due to the ambiguity surrounding the connection between HCV treatment and those encounter types.

With the expansion of the Centers for Disease Control and Prevention screening recommendations in 2020 to include at least one HCV screening test for all adults, the United States can expect to see an increase in the identification of cases (21). The application of shorter treatment durations can save substantial time and resources as the number of treated cases increases. One ongoing study monitors the efficacy of minimal monitoring in the administration of HCV treatment. These promising results show comparable SVR-12 outcomes to current, more involved treatment practices while minimizing the number of resources required for treatment monitoring (22). Conclusions such as these go hand in hand with our results, supporting the elimination of HCV by implementing both patient and provider interventions and system-level changes that will promote more efficient HCV treatment plans, reduce healthcare utilization, and ultimately improve capacity to increase HCV treatment.

The findings of this study should be interpreted considering some limitations. Our results are based on data collected from electronic health records. As a result, any encounter information such as case management interactions between staff that were not included in the electronic health record would not have been captured as part of this analysis. Our data likely underestimate the actual frequency of healthcare utilization; however, we anticipate that this potential bias is non-differential by treatment duration. Even though our study used a 3-year time frame to include eligible patients, the approval of 8-week G/P by the U.S. Food and Drug Administration occurred at the start of our study period, likely contributing to fewer patients in the 8-week treatment groups. While time trends by year of treatment initiation did not reveal a differential between the two groups (data not shown), the smaller sample size limited statistical power. This precluded us from conducting analyses beyond the descriptive statistics provided as part of this manuscript. Finally, our data are based on patients receiving care as part of an extensive, well-resourced healthcare system and may not be generalizable to other settings. Nonetheless, this study provides novel information about resource utilization and the potential for expanded treatment capacity resulting from shorter duration treatments for HCV infection.

While other studies have examined the outcome of healthcare resource utilization in terms of financial costs to HCV-infected patients (23) and the health system (24–26), our study is one of the first to explore differences in healthcare utilization by treatment duration. Our findings suggest that the use of shorter regimens among non-cirrhotic HCV patients, when clinically indicated, may decrease healthcare resource utilization. These reductions would chiefly impact those with inadequate engagement with healthcare or with challenges related to transportation and access to laboratory services.

The datasets presented in this article are not readily available as they were utilized under license for the current study. Requests to access the datasets should be directed to Katia Valdez, at katia.valdez@northwestern.edu.

KV, KK and JD abstracted the data for analysis. KV analyzed the data, wrote the main manuscript text, and constructed Tables 1 – 3 . KV and RA constructed Figure 1 , and SM, AK, and DD constructed Figure 2 . MJ and JK created the experimental design and significantly contributed to the analysis of data, writing of the manuscript, and creation of Figure 1 and Tables 1 – 3 throughout the study. All authors contributed to the study design, interpretation of data, and review of the final manuscript. All authors have read and approved the manuscript.

We would like to thank Arash Shamsian and the UCLA ISS Care Connect team for their continued support throughout this project.

SM, AK, and DD are employees of AbbVie and may hold stock/share options.

The authors declare that this study was funded by a contract provided by AbbVie (Project ID: H18.VirologyHCV.07-SR1808). AbbVie sponsored the study, contributed to its design, and participated in collecting, analyzing, interpreting the data, writing, reviewing, and approving the manuscript.

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