Virological and Clinical Outcome of DAA Containing Regimens in a Cohort of Patients in Calabria Region (Southern Italy)

Abstract

Background and objectives: In Italy, Hepatitis C Virus (HCV) infections are most prevalent in people older than 50 years of age, who often experience multi-morbidities, take co-medications, and have a long history of liver disease. These characteristics could potentially affect tolerability of HCV treatments and adherence in this subgroup. After achievement of sustained virological response (SVR), retention into care is very important both to detect the onset of possible complications and prevent further infections. In this study, SVR rates and retention into care of patients treated with directly acting antivirals (DAAs) of a single-center cohort in Southern Italy were evaluated. Materials and Methods: Patients treated with directly acting antivirals from 2014 to 2018 were included. Patients were stratified by age (i.e., <65 vs. ≥65 years) and by cirrhosis presence (i.e., liver stiffness >14.6 KPa or clinical/ultrasound cirrhosis vs. absence of these criteria). Primary outcome was availability of SVR at Weeks 12-24 after the end of treatment. Inter-and intra-group comparisons were performed along the follow-up for significant laboratory parameters. Results: In total, 212 patients were treated; 184 (87%) obtained SVR after the first treatment course and 4 patients after retreatment. Twenty-two (10.4%) patients were lost to follow-up before assessment of SVR, and two patients died before the end of treatment for liver decompensation. Considering only the first treatment episode, per protocol analysis (i.e., excluding patients lost to follow-up) showed the following rates of SVR: 97% (overall), 97% (older age group), 96% (age group <65 years), 94% (cirrhotics), and 100% (non-cirrhotics). By contrast, at the intention to treat analysis (i.e., patients lost were computed as failures), SVR percentages were significantly lower for patients <65 years of age (80%) and for non-cirrhotics (85%). Conclusions: High rates of SVR were obtained. However, younger patients and those without cirrhosis displayed an apparent high risk of being lost to follow-up. This may have important implications: since those who are lost may transmit HCV in case SVR is not achieved, these subpopulations should receive appropriate counselling during treatment.

Socio‐economic factors associated with loss to follow‐up among individuals with HCV: A Dutch nationwide cross‐sectional study

“…Although many studies have quantified the number of individuals with HCV who are lost from each step in the cascade of HCV care, few have explored the reasons for which these individuals become LTFU. The most commonly observed risk factor across studies has been age, with some suggesting that younger individuals are more likely to become LTFU 7,13–16 . In contrast, we did not find a significant association between age and LTFU in our study.…”

Effect of directly acting antivirals for hepatitis C virus infection on proprotein convertase subtilisin/kexin type 9 level

“…22 SVR, corresponding to HCV eradication, is obtained in more than 95% of the treated patients for most DAA-containing regimens in clinical trials, 23 which has also been confirmed in real-life studies including our cohort from which patients were selected for the present analysis based on availability of serum samples taken before and after DAA therapy. 24 However, some major clinical adverse events, such as arrhythmia, impairment of cardiac function, or increased prevalence of dyslipidemia have been reported. [25][26][27] In contrast, several studies have shown the clinical benefit of SVR induced by DAA treatment with respect to "hard" clinical endpoints such as CVD-related mortality.…”

“…Furthermore, the control group was proportionally homogeneous with respect to gender, but not regarding age, which is because of the prevalence of the HCV infection in aged people in Italy. 24 Finally, the Note: P-values are from the interaction "covariate by time" calculated using repeated measures analysis of variance (ANOVA) to investigate the presence of different patterns from pretherapy baseline to SVR between the classes of the covariates.…”

“…Our results show large standard deviations in PCSK9 levels in the cases and the control group; the considerable variation in the levels of this molecule in the samples studied may be explained by the complex relationships between several variables, which are actually not completely understood and not well investigated owing to the small size of our sample. Furthermore, the control group was proportionally homogeneous with respect to gender, but not regarding age, which is because of the prevalence of the HCV infection in aged people in Italy 24 . Finally, the efficacy of different DAA regimens targeting related virus molecules (ie, first and second‐generation protease inhibitors and nucleoside or nonnucleoside inhibitors of viral polymerase) or the significance of using ribavirin as part of the therapeutic regimen were not explored due to the limited sample size.…”

Phylogenetic and Molecular Analyses of More Prevalent HCV1b Subtype in the Calabria Region, Southern Italy

“…However, the 97% of treated patients with DAAs achieved sustained virological response (SVR). According to our experience about a single-center cohort in Southern Italy, the SVR rate was 97% for the older age group, 96% for people under 65 years old, finally 94% and 100% for cirrhotic and non-cirrhotic patients, respectively [ 38 ].…”