Direct-acting antivirals restore systemic redox homeostasis in chronic HCV patients

Villani, Rosanna; Bellanti, Francesco; Cavallone, Francesco; Bello, Giorgia di; Tamborra, Rosanna; Bukke, Vidyasagar Naik; Moola, Archana; Serviddio, Gaetano

doi:10.1016/j.freeradbiomed.2020.06.007

Cited by 7 publications

(7 citation statements)

References 28 publications

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“…It is well known that HCV can now be rapidly and sustainably cleared from chronically infected patients with this antiviral therapy (30), but the consequences of viral elimination on immune system remain elusive, especially in the HIV/HCV co-infection context. Our results agree with previous studies showing an increase of the enzymatic activity of several antioxidant enzymes in chronic HCV mono-infected patients after reaching SVR at the end of treatment with DAAs, such as GSH and GSH peroxidase (GPx) activity (31,32), as well as a decreasing effect for GSSG, among others (32). In some works, the beneficial effect was independent of HCV genotype and antiviral regimen used (31), which contrasts with another work which associated higher oxidative stress levels with genotype 1b (33).…”

Section: Discussionsupporting

confidence: 93%

“…Our results agree with previous studies showing an increase of the enzymatic activity of several antioxidant enzymes in chronic HCV mono-infected patients after reaching SVR at the end of treatment with DAAs, such as GSH and GSH peroxidase (GPx) activity (31,32), as well as a decreasing effect for GSSG, among others (32). In some works, the beneficial effect was independent of HCV genotype and antiviral regimen used (31), which contrasts with another work which associated higher oxidative stress levels with genotype 1b (33).…”

Section: Discussionsupporting

confidence: 93%

“…This is consistent with the reduction of AST, ALT and GGT parameters in CHC group during the follow-up. However, other important cytokines within the SASP remained stable, such as IL-8 which showed no significant changes compared to baseline, consistent with Villani and colleagues, who followed an HCV mono-infected cohort for 12 weeks after antiviral treatment with DAAs (31). On the other hand, they showed similar levels to the HIV group at the end of follow-up after completion of DAAs therapy, with a slight reduction in IL-6, the most prominent interleukin within the SASP (25) and which is known to induce ROS damage (37).…”

Section: Discussionsupporting

confidence: 83%

“…We did not observed changes in MDA levels during and at the end of follow-up, but it has been described that the reduction of some markers such as lipid peroxidation begins later than the recovery of glutathione activity after the end of DAAs therapy in HCV mono-infected patients (31). Recent research has reported a reduction in MDA in HCV+ patients after 8 weeks of DAAs treatment (32).…”

Section: Discussioncontrasting

confidence: 53%

“…Recent research has reported a reduction in MDA in HCV+ patients after 8 weeks of DAAs treatment (32). However, they did not indicate the fibrosis stage of their population, which it is an important factor due to that mono-infected HCV patients with fibrosis stage F0/F1 patients have been previously demonstrated reduced efficacy of DAAs therapy on circulating redox balance compared to F3/F4 patients (31). This could partially explain why we only observed a slight recovery of oxidative stress biomarkers, given that high fibrosis stages were considered exclusion criteria in our cohort.…”

Section: Discussionmentioning

confidence: 94%

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Dynamics of cellular senescence markers after HCV elimination in people living with HIV

Lara-Aguilar

Valle-Millares

Crespo-Bermejo

et al. 2023

Preprint

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Background: Previously, we identified that different HCV infection, either acute or chronic infection in people living with HIV (PLWHIV) drives dissimilar cellular senescence profile. However, variations in these profiles after HCV clearance, spontaneously or with direct-acting antivirals (DAAs), remains unclear. Methods: Longitudinal observational study (48 weeks of follow-up) in 70 PLWHIV with different HCV status: 23 PLWHIV with active HCV-chronic infection (CHC) before and after HCV eradication with DAAs, 12 PLWHIV who spontaneously clarify the HCV (SC), and 35 PLWHIV controls (HIV), all of them aviremic. Plasma oxidative stress biomarkers were quantified at DNA, lipid, protein, and nitrate levels, as well as the total antioxidant capacity and glutathione reductase enzyme. The replicative senescence was evaluated by relative telomere length (RTL) measurement by Monochromatic Multiplex Real-Time Quantitative PCR (MMqPCR). Finally, twenty-six factors associated to Senescence-Associated Secretory Phenotype (SASP) were characterized by Multiplex Immunoassay (Luminex xMAP technology). Differences in senescence markers was evaluated by generalized linear mixed model (GLMMs) for longitudinal series or generalized linear model (GLMs) for non-paired comparisons. Results: During follow-up, the SC group achieved a reduction of oxidative stress levels at glutathione enzyme and lipid peroxidation level. The secretion of SASP markers increased, being still lower than HIV group. elimination of chronic HCV infection by DAAs allowed an overall improvement of oxidative stress levels and SASP markers to levels like those of the HIV group. No significant differences were observed in telomere shorting between groups after follow-up. Conclusions: As the time since spontaneous resolution of HCV infection increased, patients had an improved senescence profile compared to the HIV control group, with a reduction in oxidative stress and SASP markers. Elimination of chronic HCV infection by DAAs led to a partial improvement of the senescence profile by restoring oxidative stress levels. However, although some SASP markers reached levels like those of the HIV group, others remained altered.

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