Safety and Efficacy of Direct-Acting Antivirals for the Treatment of Chronic Hepatitis C in a Real-world Population Aged 65 Years and Older

F. Conti; S. Brillanti; F. Buonfiglioli; R. Vukotic; M. C. Morelli; C. Lalanne; M. Massari; F. G. Foschi; V. Bernabucci; I. Serio; G. M. Prati; E. Negri; L. Badia; P. Caraceni; P. Muratori; G. Vitale; A. Porro; M. Morotti; G. Mazzella; P. Andreone

Disclosures

J Viral Hepat. 2017;24(6):454-463. 

In This Article

Abstract and Introduction

Abstract

The availability of direct-acting antiviral agents (DAA) regimens has expanded the pool of patients eligible for treatment. However, data on the virologic response and tolerability of DAAs in elderly patients are lacking. We evaluated the efficacy and safety of DAAs in patients with advanced fibrosis/cirrhosis in real-life practice with the focus on those aged ≥65 years. Between January and December 2015, all consecutive patients with HCV-related advanced fibrosis/cirrhosis treated with DAA at eleven tertiary referral centres in Emilia Romagna (Italy) were enrolled. Regimen choice was based on viral genotype and stage of disease, according to guidelines. The primary end point was sustained virologic response 12 weeks after the end of treatment (SVR12). Overall, 282 of 556 (50.7%) patients evaluated were elderly, most of them with cirrhosis. Antiviral therapy was stopped prematurely in four (1.4%) patients. Two patients, both with cirrhosis, died during treatment due to worsening of liver/renal function. SVR12 was achieved by 94.7% and was comparable to that obtained in patients aged <65 (P = .074). Similar data were also reported in subgroup of patients aged ≥75 years. All patients with advanced fibrosis achieved virologic response. SVR12 was 80.8% in Child-Pugh-Turcotte (CTP)-B cirrhosis and 95.4% in CTP-A (P = .013). According to genotype, the SVR12 was achieved in 172 of 181 (95%) with genotype 1b cirrhosis and in 44 of 48 (91.7%) with genotype 2 cirrhosis. In conclusions, in a real-world setting, DAAs are safe and effective in elderly patients with HCV-related advanced fibrosis/cirrhosis, but SVR12 is lower with worsening CTP class.

Introduction

The mean age of hepatitis C virus (HCV)-infected population and the number of elderly patients with more advanced liver disease are gradually increasing.[1,2] Moreover, this cohort is expected to rise in the next 10 years[3] and will significantly contribute to higher patient mortality and resource utilization, heavily influencing public health and healthcare management worldwide. Although the eradication of HCV by antiviral therapy seems to reduce the risk of complications of liver disease,[4–7] elderly patients have been considered a difficult-to-treat subgroup, given the higher risk of adverse events, discontinuations and mortality.[8] In addition, advanced age has been reported as a predictor of nonresponse to interferon-based therapy.[9–11] The concomitant comorbidities, particularly metabolic and cardiovascular disease, along with renal, pulmonary and haematologic conditions, limited the use of pegylated interferon (IFN) and ribavirin (RBV) in these subjects. Now that scenario is rapidly changing, and interferon-free antiviral therapy regimens with direct-acting antivirals (DAA) have shown higher efficacy, shortened treatment duration and a better safety profile.[12–18] All these regimens are expected to expand and revolutionize treatment options for patients with HCV and may provide a solution to continually postponed demand of treating the "baby boomers" with chronic hepatitis C (CHC).[19] However, the high costs of these medications have resulted in controversy as to which patients should be offered therapy.[20,21]

Although in clinical trials there was no upper limit of age, the number of elderly patients, especially of those aged ≥75 years, was too small to determine whether they respond differently from younger patients.[12–18] Moreover, the proportion of elderly with advanced liver disease was too limited and data about the efficacy/safety in this group of patients are lacking. Thus, there is a need for further prospective trials to be conducted in elderly patients with advanced CHC, to better evaluate safety and efficacy of HCV treatment in this group. Many studies highlight the benefits of treating HCV beyond achieving sustained virologic response (SVR). Subjects who achieve SVR demonstrated improved quality of life, patient-related outcomes and work productivity, irrespective of the severity of liver disease.[22–24] Younossi et al.[25] recently showed that subjects over 65 years of age also obtain a significant benefit in patient-related outcomes after achieving SVR.

The aim of our multicentre study was to evaluate the efficacy and safety of the treatment with DAA-based regimens in a large cohort of HCV patients aged ≥65 years with advanced fibrosis/cirrhosis (including subgroup analysis of patients ≥75 years), in a real-life clinical setting.

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