Efficacy and Tolerability of Direct–Acting Antivirals for Hepatitis C in Older Adults

Chiara Mazzarelli, MD; Aisling Considine, MPharm; Kate Childs, MBBS, MPH; Ivana Carey, MD, PhD; Matteo Angelo Manini, MD; Abid Suddle, MBBS, MD; Geoffrey Dusheiko, MB, BCh; Kosh Agarwal, BMed Sci (Hons), MD; Mary D. Cannon, MB, BCh, PhD


J Am Geriatr Soc. 2018;66(7):1339-1345. 

In This Article

Abstract and Introduction


Objectives: To evaluate the efficacy and tolerability of direct–acting antiviral (DAA) therapy in individuals aged 65 and older.

Design: Retrospective review between June 2014 and January 2017.

Setting: Viral hepatitis outpatient clinic.

Participants: Individuals aged 65 and older treated with DAA therapy for hepatitis C virus (HCV) during the study period (N=113) divided into 2 cohorts: aged 65 to 74 (n=88) and aged 75 and older (n=25).

Measurements: Drug–drug interactions (DDIs), adverse events (AEs), and rates of sustained virologic response with DAA therapy were assessed.

Results: Sustained virologic response rate was 97.7% in individuals aged 65 to 74 and 95.8% in those aged 75 and older. Individuals aged 75 and older were more likely to be taking more than 2 medications per day for chronic conditions (84% vs 62%, p=.02) and more likely to have clinically significant DDIs necessitating cessation or adjustment of medications before commencement of DAA therapy (80% vs 36%, p=.001). Moreover, individuals aged 75 and older were more likely to experience an AE during therapy (50% vs 26%, p=.03) and were more susceptible to developing anemia secondary to ribavirin (60% vs 20%, p=.02).

Conclusion: DAA therapy is highly efficacious for the treatment of HCV in older adults, but those aged 75 and older are more likely to have clinically significant pretreatment DDIs and experience AEs, including ribavirin–induced anemia, during therapy.


Chronic hepatitis C virus (HCV) infection is a major public health problem, with almost 200 million people affected worldwide.[1] According to estimates from the National Health and Nutrition Examination Survey in the United States, the prevalence of HCV infection is disproportionally higher in older adults.[2,3] Older adults with HCV tend to have a greater risk of hepatocellular carcinoma (HCC) and experience more rapid disease progression than younger individuals.[4–6] In a large cohort study, a major acceleration in hepatic fibrosis was observed in individuals aged 50 and older.[7] Treatment of HCV and achievement of a sustained virologic response (SVR) has been shown to mitigate this risk and to lead to improvements in quality of life.[8,9] Historically, the poor tolerability, low efficacy, and high rate of adverse events (AEs) associated with interferon–based regimens limited access to treatment for older adults.[10,11]

The advent of direct–acting antiviral agents (DAAs) has created equity in access to treatment for everyone with HCV, allowing older adults with multiple comorbidities to achieve viral eradication. Despite the excellent tolerability of DAA therapy, the majority of the registration trials enrolled limited numbers of participants aged 65 and older and excluded those with significant comorbidities.[12–15] In a retrospective analysis of the safety and efficacy of sofosbuvir and ledipasvir in individuals aged 65 and older enrolled in Phase 3 clinical trials,[16] SVR and AE rates were comparable with those in younger individuals, but older individuals treated with ribavirin had a higher rate of AEs.

Older adults tend to have more chronic comorbidities and a greater likelihood of polypharmacy than younger individuals. Both of these factors may increase the risk of treatment–associated AEs. A previous study reported that, although individuals aged 65 and older had a greater risk of drug–drug interactions (DDIs), they did not have a higher rate of AEs than younger individuals.[17] In a large real–life cohort, it was confirmed that DAAs are extremely efficacious regardless of age, and comparable SVR rates across all age groups were reported after stratification according to genotype, treatment experience, treatment regimen, and stage of liver disease.[18] More recently, an SVR rate of 95% with DAAs was reported in a large cohort of individuals aged 80 and older, the majority of whom had cirrhosis.[19]

In this study, we retrospectively assessed the efficacy and tolerability of DAA therapy for HCV in a cohort of older adults who commenced DAA treatment at a single U.K. center.