Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

Llorens-Revull, Meritxell; Costafreda, María Isabel; Rico, Angie; Guerrero-Murillo, Mercedes; Soria, María Eugenia; Píriz-Ruzo, Sofía; Vargas-Accarino, Elena; Gabriel-Medina, Pablo; Rodríguez‐Frías, Francisco; Riveiro‐Barciela, Mar; Perales, Celia; Quer, Josep; Sauleda, Sílvia; Esteban, Juan Ignacio; Bes, Marta

doi:10.1371/journal.pone.0254243

Cited by 12 publications

(9 citation statements)

References 58 publications

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“…DAA-mediated HCV clearance was associated with the preferential maintenance of memory-like cells [ 85 ]. This is consistent with the fact that DAA treatment results in only partial reversal of T cell exhaustion, whereby proliferative responses are restored but the capacity to produce cytokines or cytotoxicity are not [ 85 , 87 , 88 ].…”

Section: Systems Biology Studies Of the Immune Response During Acute And Chronic Hcv Infectionsupporting

confidence: 80%

Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV

Shoukry

2021

Viruses

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Over the past decade, tremendous progress has been made in systems biology-based approaches to studying immunity to viral infections and responses to vaccines. These approaches that integrate multiple facets of the immune response, including transcriptomics, serology and immune functions, are now being applied to understand correlates of protective immunity against hepatitis C virus (HCV) infection and to inform vaccine development. This review focuses on recent progress in understanding immunity to HCV using systems biology, specifically transcriptomic and epigenetic studies. It also examines proposed strategies moving forward towards an integrated systems immunology approach for predicting and evaluating the efficacy of the next generation of HCV vaccines.

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Section: Systems Biology Studies Of the Immune Response During Acute And Chronic Hcv Infectionsupporting

confidence: 80%

Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV

Shoukry

2021

Viruses

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“…In large population-based cohorts treated with DAA and associated with SVR, HCV-related mortality was significantly reduced [ 18 ], though restoration of immune response is only partial [ 19 ] and circulating CD-8 + T cells remain still dysfunctional, especially in advanced chronic liver disease [ 20 ]. After 5 years from SVR, the risk of relapse/reinfection is small, mainly in high-risk patients (HIV associated).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C and hepatitis B virus infection in hemodialysis patients after nationwide direct antiviral agents therapy—experience of 10 Romanian HD centers

et al. 2023

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Purpose End-stage kidney disease patients (ESKD) receiving hemodialysis (HD) are at a greater risk of hepatitis virus (HV) infections due to the invasive nature of the procedures, frequent hospital stays and surgeries, as well as the immune deficiency status of ESKD. The aim This study was to reassess the hepatitis virus infections prevalence in the HD population in Romania after 5 years of oral DAAs therapy and assess the impact on HD patients’ outcomes in two cohorts (2015 and 2019). Methods We compared ESKD patients treated with HD in 10 HD centers from the historical regions of Romania in 2015 (n = 1401, Mean age 59.7 ± 12.92 years) with patients treated in the same centers in 2019 (n = 1698, mean age 61 ± 12.93 years). All patients went through HD therapy for more than 90 days. Results The patients from the 2019 cohort were significantly older (p = 0.005), had a longer duration of HD therapy (p < 0.0001), and had more vascular calcifications (p = 0.015); the crude one-year mortality rate did not differ from the 2015 cohort (9.9 vs. 10.7%, p = 0.46). The prevalence of HBV infection did not differ between the cohorts (4.7% vs. 4.8, p = 0.604) but the prevalence of HCV significantly decreased from 2015 to 2019 (16.9 vs. 10.5%, p < 0.0001). Conclusion After 15 years of a nationwide infection prevention program for HV infections and 5 years of DAAs treatment in Romania, the prevalence of HBV did not change but HCV infections decreased significantly, however, it still remained high.

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“…Biologically, IFN family members, especially class I IFN (IFN-α, IFN-β), have important anti-HCC effects[ 32 ]. However, some investigators have suggested that the sudden decrease in viral load caused by DAA treatment causes immune distortion, thus deregulating the antitumor response and releasing precancerous foci from immune surveillance[ 34 , 35 ]. Although it can be explained theoretically, there is little clinical evidence regarding the difference in the HCC risk for patients with DAA-SVR and IBT-SVR.…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study

Choi¹,

Jang²,

Kim³

et al. 2022

WJG

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BACKGROUND Prospective studies of the long-term outcomes of patients with hepatitis C virus (HCV) infection after treatment with interferon-based therapy (IBT) or direct-acting antivirals (DAA) are limited in many Asian countries. AIM To elucidate the incidences of hepatocellular carcinoma (HCC) and death/transplantation based on treatment with IBT or DAA, to compare the outcomes of the sustained virologic response (SVR) to IBT and DAA, and to investigate outcome-determining factors after SVR. METHODS This cohort included 2054 viremic patients (mean age, 57 years; 46.5% male; 27.4% with cirrhosis) prospectively enrolled at seven hospitals between 2007 and 2019. They were classified as the untreated group ( n = 619), IBT group ( n = 578), and DAA group ( n = 857). Outcomes included the incidences of HCC and death/transplantation. The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution. A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation, followed by propensity score matching to confirm the results. RESULTS During a median of 4.1 years of follow-up, HCC and death/transplantation occurred in 113 and 206 patients, respectively, in the entire cohort. Compared with the untreated group, the incidences of HCC and death/transplantation were significantly lower in the IBT group [adjusted hazard ratio (aHR) 0.47, 95%CI: 0.28-0.80 and aHR 0.28, 95%CI: 0.18-0.43, respectively] and the DAA group (aHR 0.58, 95%CI: 0.35-0.96, and aHR 0.19, 95%CI: 0.20-0.68, respectively). Among 1268 patients who attained SVR with IBT ( n = 451) or DAA ( n = 816), the multivariable-adjusted analysis showed no differences in the risks of HCC (HR 2.03; 95%CI: 0.76-5.43) and death/transplantation (HR 1.38; 95%CI: 0.55-3.49) between the two groups. This was confirmed by a propensity score-matching analysis. Independent factors for HCC after SVR were age, genotype 1, and the presence of cirrhosis. CONCLUSION Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection. The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.

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Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

Cited by 12 publications

References 58 publications

Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV

Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV

Hepatitis C and hepatitis B virus infection in hemodialysis patients after nationwide direct antiviral agents therapy—experience of 10 Romanian HD centers

Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study

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