Dirks et al. 1 's recent study provides greater insight into the neu-ropsychiatric symptoms experienced by HCV-infected patients and questions how these symptoms are associated with HCV clearance. The authors show that in HCV-infected patients with mild liver disease , none of the following outcomes depend on HCV clearance: cognitive function, mood alteration, health-related quality of life (HRQL) and fatigue (FIS scores). However, these results may not be generalizable to HIV-HCV co-infected patients and cirrhotic patients , who were excluded from the study and who are generally more concerned by fatigue and neuropsychiatric symptoms. This restriction avoids possible interferences of specific clinical conditions with neuropsychiatric symptoms but reduces external validity. The HIV-HCV co-infected population includes a non-negligible proportion of individuals with a history of injection of opioids. Exposure to opioids tends to amplify neuropsychiatric and painful symptoms. Cirrhotic patients also have more numerous and more acute symptoms related to their disease, treatment experience and poor quality of life. The results from two studies we conducted in these specific patient subpopulations 2,3 were similar to those of Dirks et al. 1 The first of these studies was based on data collected on HIV-HCV-co-infected patients in the French cohort ANRS CO13-HEPAVIH. In that study, changes in FIS scores before/ after pegylated interferon (PegIFN)-based treatment were not significantly associated with HCV clearance. 2 Moreover, functional fatigue-related limitations persisted two years in median after the end of treatment. It is interesting to note that the characteristics of the 107 patients analysed in that study were quite different from those in Dirks et al's study. More specifically, time since HCV diagnosis was shorter in the former (10 years in median vs 26 years) and the percentage of HCV-cleared patients higher (53% vs 23%). Our second study analysed HRQL in 47 HCV-infected patients with compensated cirrhosis who switched from PegIFN-based to PegIFN-free therapy. Results showed no major improvement in physical HRQL after the end of therapy, despite HCV clearance and improved physical and mental HRQL being observed during PegIFN-free treatment. 3 However, just as for Dirks et al.'s study, 1 our results were obtained in patients treated with PegIFN-based therapies and may not be repeatable in the era of direct-acting antivirals (DAA). Data from DAA clinical trials show major improvements in patient-reported outcomes (including better HRQL, less fatigue and fewer symptoms) for HCV-treated patients. 4 However, real-world, long-term, post-HCV clearance changes in patient-reported outcomes of DAA-treated patients still require further evaluation. 5 ORCID F. Marcellin http://orcid.org/0000-0001-8853-3829 D. Salmon-Ceron http://orcid.org/0000-0002-6817-8951 M. P. Carrieri