Outcomes Using Direct-acting Antiviral Hepatitis-C Treatment in Older Versus Younger Veterans

Carmelo J. Blanquicett MD, PhD; Tapasya Raavi MD, MPH; Anna Mirk MD; Theodore M. Johnson II MD, MPH; Michael Jaglal MD; Emily J. Cartwright MD


J Am Geriatr Soc. 2021;69(12):3602-3607. 

In This Article

Abstract and Introduction


Background: Historically, older adults have been excluded from trials evaluating hepatitis C virus (HCV) treatment, in part, due to the adverse effects associated with previous regimens. Veterans are at high risk of HCV infection. Ledipasvir/sofosbuvir (LED/SOF) is a once daily antiviral regimen with demonstrated efficacy and tolerability among the younger population. We examined the tolerability and effectiveness of LED/SOF in Veterans age ≥65 years versus those <65 years who were treated at the Atlanta VA Health Care System (AVAHCS).

Methods: Using the VA Clinical Case Registry, all persons who filled a LED/SOF prescription at the AVAHCS from January 1, 2015, through March 31, 2016, were identified. The electronic medical records were reviewed to identify basic demographic information: comorbidities; polypharmacy; and outcomes. Sustained virologic response (SVR) was defined as an undetectable HCV RNA, at least 12 weeks after completing treatment. Descriptive statistics were employed using SAS v9.2.

Results: We identified 345 Veterans who filled LED/SOF during the study period; 94 were excluded due to exposure to ribavirin and IFN containing regimens; 97 (38.6%) were ≥65 years. Veterans were predominantly black (57%) and male (97%). Cancer was more prevalent among older Veterans (p = 0.047) as was polypharmacy (p = 0.001). Treatment completion rates between older and younger Veterans were not significantly different (99 vs. 95%, respectively; p = 0.16), but significantly more older Veterans achieved SVR (98 vs. 91%; p = 0.03).

Conclusions: LED/SOF was a well-tolerated and effective regimen in an older Veteran population despite their multiple comorbidities and polypharmacy presence.


One hundred and seventy million people globally (3% of the world population) are infected with the Hepatitis C virus[1] with a prevalence of about 2.4 million in the United States alone.[2] Veterans, in particular, are at higher risk for Hepatitis C virus (HCV) infection, and the prevalence of HCV among Veterans at the Atlanta Veterans Affairs Health Care System (AVAHCS) has been shown to be 15% for those born between 1945 and 1965, and 4% for those born before 1945.[3]

Historically, older adults have been excluded from trials evaluating treatment regimens for HCV, with few exceptions including Afdhal et al., who studied the treatment of HCV genotype 1 infection among all adult age groups.[4] Previous Interferon (IFN)-based treatments have been shown to be toxic, and those of advanced age (65 years and older) are presumed to have less tolerability,[5] higher discontinuity rates, more comorbidities with more drug–drug interaction potential as compared to their younger cohorts. The advent of IFN-free, direct-acting antivirals (DAAs) that have come on the market since 2014 has revolutionized the treatment of HCV. Ledipasvir/Sofosbuvir, (LED/SOF) is one such an example. LED/SOF is a one-pill, daily regimen with very few drug interactions that is expected to be well-tolerated, including among older patients with several comorbidities and medications. If tolerated (and successful), the treatment of older, HCV-infected individuals could confer a positive health impact overall and in the quality of life of older persons.[6]

HCV infected individuals have potential for inferior quality of life (QOL) due to symptoms associated with HCV infection that may range from psychological distress and fatigue before the progression of cirrhosis, liver failure, or hepatocellular carcinoma (HCC) that can result from the Hepatitis C virus.[7] Vespansiani-Gentilucci and others maintain that the progression of HCV-related liver disease is accelerated with aging and that extrahepatic manifestations of HCV infection are greater in the elderly.[8–10] Additionally, SVR after treatment among HCV-infected persons at any stage of fibrosis is associated with reduced HCC.[11]

In this study, we identified and compared Veterans age 65 and older to those under the age of 65 who were treated with the IFN-free regimen, Ledipasvir/Sofosbuvir (LED/SOF). Given the tolerability, reported effectiveness and convenience of LED/SOF, we hypothesized that younger and older (65 and older) Veterans could experience similar treatment-related outcomes, specifically, in terms of cure, tolerability, and relapse rates.