Safety and efficacy of directly‐acting antiviral therapy for chronic hepatitis C virus in elderly people

Abstract

Introduction In Italy, the prevalence of hepatitis C virus (HCV) infection is higher in the elderly, although the efficacy and safety of treatment in this population has not been extensively studied. Moreover, little is known about how much pharmacological interaction affects eligibility to treatment and to what extent the treatment affects subsequent outcomes. Methods We retrospectively analyzed the efficacy and safety of directly acting antivirals (DAAs), drug‐to‐drug interactions, and post‐treatment outcomes in 138 patients with HCV aged 70 years or older, who were consecutively treated in our center between 2015 and 2020. Results The mean age was 77 years old (range = 70–95 years old). The Cumulative Illness Rating Scale of pretherapy severity was classified as moderate to severe in 65% of patients. Fifty‐five patients (40%) presented compensated cirrhosis, eight of which were complicated by hepatocellular carcinoma (HCC) and all were cured before treatment. One hundred two patients (74%) were taking two or more drugs (range = 0–5 concomitant drugs registered) and in 29 patients (21%) we found potential drug‐to‐drug interaction. In 11 of those 29 patients (38%), we were forced to change the chronic therapy, when all therapeutic regimens were equal in terms of efficacy and interactions, to avoid potentially serious drug interactions. One serious adverse event occurred in our sample population (i.e., diverticular bleeding due to interaction with direct oral anticoagulants [DOACs]), whereas mild side effects occurred in 37% of patients. The undetectability of HCV RNA at the end of treatment was achieved in 97% of patients, whereas a sustained virological response (SVR) 12 and SVR 24 were obtained in 98% of patients. When comparing pretherapy with post‐therapy data, after a medium follow‐up of 15 months (median = 1 year, minimum = 2 months, and maximum = 4 years), we observed a reduction in the incidence of episodes of liver decompensation in patients with cirrhosis and a slight increase in the incidence of HCC (with 6 recurrent and 5 de novo HCC), diagnosed within 13 months from the end of therapy. In all patients, we found a significant improvement in all ultrasound variables and a significant reduction in the elastographic measurements. No significant differences in outcomes were observed dividing the population into patients aged ≥ 80 and < 80 years old. Conclusions Directly acting antiviral therapy was found to be safe and effective in elderly people, and, despite the large number of concomitant drugs, pharmacological interactions appeared to not affect the adherence to therapy or the incidence of adverse events. Side effects were mostly independent from the type of DAA used and from the burden of comorbidity. In long‐term follow‐up, the benefit of DAA therapy mainly concerned liver pathology and should be strongly advised in patients with cirrhosis. The therapy was found to not affect...

Glecaprevir/Pibrentasvir is safe and effective in Italian patients with chronic hepatitis C aged 75 years or older: A multicentre study

“…While this bias can be excluded only by a randomized trial design, we think that our cohort is reflective of the elderly HCV‐compensated population as 32% of the patients had more than two concomitant comorbidities, while 25% of our patients were taking at least five concomitant medications and lastly 24% had liver cirrhosis. These figures are similar to those reported by other Italian studies focusing on treatment with DAAs in elderlies, where SOF‐based regimens were the most commonly used DAAs 13,17,18 . We are also aware of the limitations stemming from the inclusion of patients managed in expert tertiary referral centres; however, this was not the consequence of a flawed study design but rather than treatment in Italy is still restricted to specialist care.…”

“…Similarly, De Santis and colleagues, 17 who evaluated the efficacy and safety of multiple DAA regimens in patients older than 70 years found that in this cohort of 138 patients, of whom 34 (24.6%) received G/P for 8 or 12 weeks, SVR12 was achieved in 98% of patients. Interestingly, the authors found a higher incidence of itching in patients treated with G/P than those treated with other regimens (17% vs 3%), with G/P confirmed to be a risk factor for itching (odds ratio 3.6, p = 0.03) by logistic regression analysis 17 …”

“…In a multicentre real‐life study from Italy aimed at evaluating the efficacy and safety of DAAs in patients aged 80 and over, 43/170 (25.3%) received G/P for 8 or 12 weeks with SVR12 rates of 100%, in the absence of SAEs or premature discontinuations 13 . Similarly, De Santis and colleagues, 17 who evaluated the efficacy and safety of multiple DAA regimens in patients older than 70 years found that in this cohort of 138 patients, of whom 34 (24.6%) received G/P for 8 or 12 weeks, SVR12 was achieved in 98% of patients. Interestingly, the authors found a higher incidence of itching in patients treated with G/P than those treated with other regimens (17% vs 3%), with G/P confirmed to be a risk factor for itching (odds ratio 3.6, p = 0.03) by logistic regression analysis 17 …”

“…These figures are similar to those reported by other Italian studies focusing on treatment with DAAs in elderlies, where SOF-based regimens were the most commonly used DAAs. 13,17,18 We are also aware of the limitations stemming from the inclusion of patients managed in expert tertiary referral centres; however, this was not the consequence of a flawed study design but rather than treatment in Italy is still restricted to specialist care. Another limitation is the absence of patients infected with unusual HCV genotypes such as 1l, 4r, 3b, 3g, 6u and 6v, which have been shown to be prevalent in some regions of Asia and Africa and among migrants from these areas that, however, are extremely rare in Italy.…”

“…Interestingly, the authors found a higher incidence of itching in patients treated with G/P than those treated with other regimens (17% vs 3%), with G/P confirmed to be a risk factor for itching (odds ratio 3.6, p = 0.03) by logistic regression analysis. 17 Taken altogether all the literature is unanimous in emphasizing the efficacy and safety of G/P for the treatment of chronic HCV infection in elderly patients. We are, however, aware that most studies, ours included, might be influenced by a selection bias caused by the perception that SOF-based regimens might be safer in fragile HCV patients.…”