Efficacy and Safety of Direct-acting Antivirals for Hepatitis C in the Elderly

A Systematic Review and Meta-analysis

Marcus M. Mücke; Eva Herrmann; Victoria T. Mücke; Christiana Graf; Stefan Zeuzem; Johannes Vermehren


Liver International. 2019;39(9):1652-1660. 

In This Article

Abstract and Introduction


Background&Aims: Since the introduction of direct-acting antivirals (DAAs) several studies have reported high efficacy and safety in Hepatitis C infected patients, even in those earlier considered difficult-to-treat. We aimed to assess the efficacy and safety of DAA therapy in elderly patients.

Methods: The PubMed MEDLINE, Embase and Cochrane databases were searched through July 2018. Two independent researchers extracted data and assessed the quality and risk of bias. Risk ratios (RRs) were pooled using random effects models. The primary outcome was efficacy of DAA therapy assessed by the RR for non-sustained virologic response (SVR) among patients aged <65 vs ≥65 years.

Results: Overall, we identified 63 studies including 34 082 patients treated with different DAAs. Risk for non-SVR was comparable in patients <65 and ≥65 years of age (RR 1.00, 95% CI 0.86-1.15; P = 0.979) and even lower in a subgroup analysis of cirrhotic patients ≥65 years of age (RR 0.59, 95% CI 0.35-0.99, P = 0.044). Risk for non-SVR was similar between age groups in all other subgroup analyses. Elderly patients had a significantly increased risk of adverse events (AEs) (RR 1.30, 95% CI 1.11-1.52, P = 0.001), but not for serious adverse events (P = 0.43) or treatment discontinuation (P = 0.15). Risk for anaemia if treated with additional ribavirin was 2.84 (95% CI 1.73-4.66, P < 0.001) in elderly patients compared to patients <65 years.

Conclusion: Our results show that DAAs are highly effective and safe in elderly patients. Ribavirin should be avoided in the elderly as more AEs and particularly anaemia is observed. Further cost-effectiveness analyses are needed to evaluate the socio-economic benefit of treating elderly people without advanced liver disease.


With approximately 70 million infected individuals worldwide, chronic hepatitis C virus (HCV) infection remains a major global health problem resulting in significant morbidity and mortality.[1,2] The ultimate goal of therapy is to achieve sustained HCV eradication which is associated with reduced liver inflammation, fibrosis progression, increased quality of life and overall survival.[3–5] Elderly patients are disproportionally affected by HCV and are more likely to suffer from advanced liver disease and its complications compared to younger patients.[6]

Hepatitis C virus treatment has been revolutionized with the introduction of direct-acting antivirals (DAAs). High sustained virologic response (SVR) rates can now be achieved in virtually all patient populations, even in those earlier considered difficult-to-treat.[7,8]

Historically, age has been a major limitation of interferon (IFN)-based antiviral therapy because of poor tolerability, reduced efficacy and an increasing number of comorbidities.[9] Following the introduction of DAAs, a number of studies have been published that specifically looked at the safety and efficacy in elderly patients, while others have reported subgroup efficacy analyses of elderly study populations.

The aim of this systematic review and meta-analysis was to assess and compare the efficacy and safety of DAA therapy among the elderly (≥65 or ≥75 years) and younger (<65 or <75 years) patients with chronic HCV infection.