Efficacy and Safety of Direct-acting Antiviral Therapy for Hepatitis C Virus in Elderly Patients (≥65 Years old)

A Systematic Review and Meta-analysis

Jieun Lee; Sang Bong Ahn; Sun Young Yim; Jihyun An; Dae Won Jun; Min Jung Ko; Dong Ah Park; Jeong-Ju Yoo


J Viral Hepat. 2022;29(7):496-517. 

In This Article

Abstract and Introduction


Direct-acting agents (DAAs) have launched a new era of hepatitis C virus (HCV) treatment. As aged individuals comprise a large percentage of HCV-infected patients, the effectiveness and safety of DAAs in the elderly have come under scrutiny. This meta-analysis aimed to evaluate the efficacy and safety of DAAs in elderly patients. After a systematic search in PubMed (MEDLINE), Embase, OVID MEDLINE, the Cochrane Library and other databases, two investigators reviewed relevant abstracts and selected manuscripts for examination. The sustained virologic response (SVR) and adverse event (AE) rates were calculated with a random-effects model. Ninety studies evaluating SVR rates of elderly patients (≥65 years old) receiving DAAs were selected. DAAs in elderly patients exhibited a notable SVR rate of 96% (95% confidence interval [CI]: 95%–97%), accompanied by comparable rates in subgroup analyses. The comparison of SVR rates in elderly and non-elderly patients indicated no significant discrepancy (odds ratio [OR] 1.01, 95% CI: 1.00–1.01). The overall event rate of AEs was 45% (95% CI: 31%–60%), though AE rates varied by subgroups. Furthermore, AEs were comparatively more frequent (OR 1.15, 95% CI: 1.04–1.28) in the elderly than non-elderly, especially in subgroups such as SAE (OR 1.89, 95% CI: 1.52–2.36) and dose reduction in ribavirin (OR 1.90, 95% CI: 1.53–2.36). However, in the ribavirin (RBV)-free regimen, there was no significant difference in the incidence of AEs between the elderly and non-elderly groups. DAAs have high efficacy in elderly patients. Considering the possibility of AE, the RBV-free regimen should be given prior consideration for the treatment of elderly patients with HCV.


Hepatitis C virus infection is a prevailing medical issue with 100 million individuals exposed worldwide.[1] Due to the progressive nature of HCV infection developing into chronic hepatitis and complications such as cirrhosis and hepatocellular carcinoma,[2] the World Health Organization (WHO) aims to treat 80% of eligible patients with chronic HCV infection and reduce 65% of hepatitis-related mortalities by 2030.[3]

To efficiently manage chronic HCV infections, it is essential to target one of the most afflicted age groups, that is elderly patients. According to the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002, the peak prevalence of an HCV-infected age group in the United States was 4.3% in individuals aged 40–49 years, due to exposure to contaminated blood products in the 1970s and 80s.[4] It is speculated that such peak prevalence, having moved two decades forward, has contributed to the increase in HCV prevalence in the elderly.[5] A similar trend is also evident in countries with a skewed age distribution. South Korea, a country with individuals aged 65 and older accounting for 15.7% of the total population,[6] reports a peak prevalence rate of 0.39% in individuals aged 60–69.[7] Such a figure shows a striking contrast to the lower rates of 0.04% and 0.08% in the age groups of 20–29 and 30–39, respectively. Compared with the HCV prevalence rate of 0.18% in the general population, the HCV prevalence in the elderly is substantially higher.

Elderly patients with HCV have also become the spotlight of the medical community, due to their well-known vulnerability to liver-related complications. According to Poynard,[8] age and the duration of HCV infection were the key variables of the progression of liver fibrosis, as proven by the proportion of patients without cirrhosis in those with 20 years (91%; 95% CI: 90–92%) versus those over 40 years of infection (56%; 95% CI: 48–64%). Such noteworthy increase in liver diseases has been attributed to the physiologic characteristics of the elderly, which include increased oxidative stress, decreased mitochondrial capacity, inadequate immune system, reduced hepatic flow and increased carcinogenicity in DNA repair.[9] Thus, finding an effective HCV therapy for aged individuals has been an inevitable quest for numerous physicians.

Previously, various side effects of interferon (IFN)-based antiviral therapy, including fatigue, flu-like symptoms and haematologic disorders, have limited the availability of chronic HCV treatment for the susceptible elderly.[10] After the 2011 FDA approval, DAA therapy has become an efficient and relatively safe alternative with a high SVR rate of over 95% and low adverse event rate of less than 10% for the general population.[11,12]

Despite such revolutionary findings, various aspects of DAA therapy in elderly patients remain in question. Previous studies have reported significantly increased risk of AEs in elderly patients in use of DAAs.[13] Moreover, the concomitant use of ribavirin has been suspected to factor in the increase of adverse events: after a series of reports on anaemia in elderly patients treated with ribavirin-inclusive regimen,[14] ribavirin-free regimen has been the newly recommended treatment for the last 2 years.[15] The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of DAAs, assessed by SVR and AE rates, respectively, in both elderly and non-elderly patients.