Hepatitis C Virus Clearance in Older Adults

Antonio Massimo Ippolito, MD; Angelo Iacobellis, MD; Michele Milella, MD; Fabio Conti, MD; Vincenzo Messina, MD; Maria Rosa Valvano, PhD; Grazia Anna Niro, MD; Filomena Morisco, MD; Michele Barone, MD; Antonio Patrizio Termite, MD; Giuseppina Brancaccio, MD; Angelo Andriulli, MD


J Am Geriatr Soc. 2018;66(1):85-91. 

In This Article

Abstract and Introduction


Objectives To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct-acting antiviral therapy.

Participants Individuals aged 80 and older with chronic HCV infection (N = 253; n = 213 with cirrhosis, n = 40 with advanced fibrosis).

Measurements We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs). Participants with cirrhosis were staged according to Child-Pugh-Turcotte class, Model for End-Stage Liver Disease score, and the D'Amico staging system. The type and number of comorbidities at baseline and hepatic and nonhepatic events during follow-up were registered.

Results Ninety-five percent of participants with cirrhosis and 95% of those with advanced fibrosis attained SVR. The rate was independent of sex, HCV genotype, and treatment schedule. During a mean follow-up of 14 ± 4 months (range 5–23 months), 34 events occurred in 27 participants: 10 hepatocellular carcinomas, 12 hepatic decompensations, 9 nonhepatic events, 3 deaths. Multivariate analysis of risk factors for experiencing adverse events during follow up showed that participants in D'Amico Stages 4 and 5, with a baseline serum albumin level of 3.5 mg/dL or less, and 3 or more comorbidities were the most at risk.

Conclusion In a real-world setting, DAAs are safe and effective in older adults with HCV-related advanced fibrosis or cirrhosis. Individuals with preserved albumin synthesis and fewer than 3 comorbidities at baseline have the most to gain from long-term DAA therapy.


New epidemiological data indicate that the prevalence of hepatitis C virus (HCV) infection is almost null in young and middle-aged individuals and is peaking in older adults (≥70).[1] In a recent Italian survey, HCV prevalence was 0.2% in subjects younger than 30 and 6.0% in those aged 70 and older.[2] The current prevalence places particular argument in decision-making when prescribing antiviral treatment to elderly adults because it is unknown whether it can improve their natural history. Elderly adults with chronic hepatitis C infection are more likely than younger individuals to have progressed to the cirrhotic stage and to be at risk of liver-related complications.[3,4] HCV clearance is essential to improve the natural history of the disease in the general population,[5,6] but data on likelihood of reducing liver-related complications and increasing life expectancy after sustained viral response (SVR) in elderly adults are limited.[7–10] The combination of advanced liver disease and older age makes an individual vulnerable, and people with this combination are likely to have extrahepatic comorbidities (e.g., cardiac and renal disease);[11] these individuals may achieve a substantial increase in life expectancy despite an expected high rate of SVR.[12,13] Although they have a good safety profile, new interferon-free direct antiviral agent (DAA) regimens are expensive, and the treatment of elderly adults should be assessed according to an individualized cost-effectiveness approach to overall health.[12] The approach suggested for antiviral HCV treatment with DAAs in individuals aged 70 and older is to limit it to those with no major comorbidities, an estimated Metavir liver fibrosis score of F2 to F4, and a life expectancy of longer than 1 year.[7]

What constitutes an elderly population needs to be defined, varying from 60 and older to 80 and older.[4,7–12] Age itself is not a predictor of a negative response to the new DAAs. Even if real-world observational studies have increased the number of elderly adults treated with the new DAAs,[7–12] few individuals aged 80 and older have been enrolled in Phase III registration trials.[11,12] Even in these experiences, scanty information on whether successful viral treatment in old-old adults with HCV decreases mortality is available. Long-term follow-up studies have indicated that definitive HCV clearance can regress the extent of hepatic fibrosis and reduce the risk of cirrhosis-related complications, including hepatocellular carcinoma (HCC).[12,13] In addition, after viral clearance, favorable outcomes for extrahepatic events such as end-stage renal failure and cardiovascular events have been also documented.[14] These studies had individuals younger than 70 as their target population, which limits the generalizability of their conclusions to older adults. In very old adults, multiple comorbidities, multidrug consumption, and drug-drug interactions makes questionable the beneficial effect of HCV clearance. The evaluation of life expectancy based on liver disease with respect to that based on comorbidities can be considered useful criteria to identify suitable candidates for the highly effective oral antiviral drugs. With aging, the progression of liver fibrosis, and the presence of non-liver-related morbidities could make HCV clearance useless .[7,15] The aim of this study was to determine whether HCV clearance with new DAAs in individuals aged 80 and older, despite liver disease and multiple comorbidities, would reduce hepatic and extrahepatic events or mortality.