Spearman CW, Dusheiko GM, Hellard M, Sonderup M. Hepatitis C. Lancet. 2019;394(10207):1451–66.

Article  PubMed  Google Scholar 

Grebely J, Page K, Sacks-Davis R, van der Loeff MS, Rice TM, Bruneau J, Morris MD, Hajarizadeh B, Amin J, Cox AL, et al. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology. 2014;59(1):109–20.

Article  CAS  PubMed  Google Scholar 

Bulteel N, ParthaSarathy P, Forrest E, Stanley AJ, Innes H, Mills PR, Valerio H, Gunson RN, Aitken C, Morris J, et al. Factors associated with spontaneous clearance of chronic hepatitis C virus infection. J Hepatol. 2016;65(2):266–72.

Article  PubMed  Google Scholar 

Page K, Hahn JA, Evans J, Shiboski S, Lum P, Delwart E, Tobler L, Andrews W, Avanesyan L, Cooper S, et al. Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection. J Infect Dis. 2009;200(8):1216–26.

Article  PubMed  Google Scholar 

GhamarTalepoor A, Doroudchi M. Immunosenescence in atherosclerosis: a role for chronic viral infections. Front Immunol. 2022;13:945016.

Article  Google Scholar 

Wykes MN, Lewin SR. Immune checkpoint blockade in infectious diseases. Nat Rev Immunol. 2018;18(2):91–104.

Article  CAS  PubMed  Google Scholar 

Shoukry NH, Walker CM. T cell responses during HBV and HCV infections: similar but not quite the same? Curr Opin Virol. 2021;51:80–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang SJ, Dougan SK, Dougan M. Immune mechanisms of toxicity from checkpoint inhibitors. Trends Cancer. 2023;9(7):543–53.

Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M, Shabafrouz K, Ribi C, Cairoli A, Guex-Crosier Y, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;16(9):563–80.

Article  CAS  PubMed  Google Scholar 

Lian J, Yue Y, Yu W, Zhang Y. Immunosenescence: a key player in cancer development. J Hematol Oncol. 2020;13(1):151.

Article  PubMed  PubMed Central  Google Scholar 

Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence. Trends Cell Biol. 2018;28(6):436–53.

Article  CAS  PubMed  Google Scholar 

Santoro A, Bientinesi E, Monti D. Immunosenescence and inflammaging in the aging process: age-related diseases or longevity? Ageing Res Rev. 2021;71:101422.

Article  CAS  PubMed  Google Scholar 

Fulop T, Larbi A, Dupuis G, Le Page A, Frost EH, Cohen AA, Witkowski JM, Franceschi C. Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes? Front Immunol. 1960;2017:8.

Google Scholar 

de Paula HHS, Ferreira ACG, Caetano DG, Delatorre E, Teixeira SLM, Coelho LE, Joao EG, de Andrade MM, Cardoso SW, Grinsztejn B, et al. Reduction of inflammation and T cell activation after 6 months of cART initiation during acute, but not in early chronic HIV-1 infection. Retrovirology. 2018;15(1):76.

Article  PubMed  PubMed Central  Google Scholar 

Osuji FN, Onyenekwe CC, Ahaneku JE, Ukibe NR. The effects of highly active antiretroviral therapy on the serum levels of pro-inflammatory and anti-inflammatory cytokines in HIV infected subjects. J Biomed Sci. 2018;25(1):88.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chan YT, Cheong HC, Tang TF, Rajasuriar R, Cheng KK, Looi CY, Wong WF, Kamarulzaman A. Immune checkpoint molecules and glucose metabolism in hiv-induced T cell exhaustion. Biomedicines. 2022;10(11):0.

Osuch S, Metzner KJ, Caraballo Cortes K. Reversal of T cell exhaustion in chronic HCV infection. Viruses. 2020;12(8):799.

Oltmanns C, Liu Z, Mischke J, Tauwaldt J, Mekonnen YA, Urbanek-Quaing M, Debarry J, Maasoumy B, Wedemeyer H, Kraft ARM, et al. Reverse inflammaging: long-term effects of HCV cure on biological age. J Hepatol. 2023;78(1):90–8.

Article  CAS  PubMed  Google Scholar 

Hengst J, Falk CS, Schlaphoff V, Deterding K, Manns MP, Cornberg M, Wedemeyer H. Direct-acting antiviral-induced hepatitis C virus clearance does not completely restore the altered cytokine and chemokine milieu in patients with chronic hepatitis C. J Infect Dis. 2016;214(12):1965–74.

Article  CAS  PubMed  Google Scholar 

Khera T, Du Y, Todt D, Deterding K, Strunz B, Hardtke S, Aregay A, Port K, Hardtke-Wolenski M, Steinmann E, et al. Long-lasting imprint in the soluble inflammatory milieu despite early treatment of acute symptomatic hepatitis C. J Infect Dis. 2022;226(3):441–52.

Article  CAS  PubMed  Google Scholar 

Hakim MS, Rahmadika N, Jariah ROA. Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: implications for therapeutic monitoring and personalized therapy. Rev Med Virol. 2020;30(2):e2094.

Article  PubMed  Google Scholar 

Urbani S, Amadei B, Tola D, Massari M, Schivazappa S, Missale G, Ferrari C. PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J Virol. 2006;80(22):11398–403.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bowen DG, Shoukry NH, Grakoui A, Fuller MJ, Cawthon AG, Dong C, Hasselschwert DL, Brasky KM, Freeman GJ, Seth NP, et al. Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection. J Virol. 2008;82(10):5109–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ackermann C, Smits M, Woost R, Eberhard JM, Peine S, Kummer S, Marget M, Kuntzen T, Kwok WW, Lohse AW, et al. HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules. Sci Rep. 2019;9(1):10624.

Article  PubMed  PubMed Central  Google Scholar 

Zoldan K, Ehrlich S, Killmer S, Wild K, Smits M, Russ M, Globig AM, Hofmann M, Thimme R, Boettler T. Th1-biased hepatitis C virus-specific follicular T helper-like cells effectively support B cells after antiviral therapy. Front Immunol. 2021;12: 742061.

Article  CAS  PubMed  Google Scholar 

Smits M, Zoldan K, Ishaque N, Gu Z, Jechow K, Wieland D, Conrad C, Eils R, Fauvelle C, Baumert TF, et al. Follicular T helper cells shape the HCV-specific CD4+ T cell repertoire after virus elimination. J Clin Invest. 2020;130(2):998–1009.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Baz-Martinez M, Da Silva-Alvarez S, Rodriguez E, Guerra J, El Motiam A, Vidal A, Garcia-Caballero T, Gonzalez-Barcia M, Sanchez L, Munoz-Fontela C, et al. Cell senescence is an antiviral defense mechanism. Sci Rep. 2016;6:37007.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wandrer F, Han B, Liebig S, Schlue J, Manns MP, Schulze-Osthoff K, Bantel H. Senescence mirrors the extent of liver fibrosis in chronic hepatitis C virus infection. Aliment Pharmacol Ther. 2018;48(3):270–80.

Article  CAS  PubMed  Google Scholar 

Tacke F, Trautwein C, Yagmur E, Hellerbrand C, Wiest R, Brenner DA, Schnabl B. Up-regulated eotaxin plasma levels in chronic liver disease patients indicate hepatic inflammation, advanced fibrosis and adverse clinical course. J Gastroenterol Hepatol. 2007;22(8):1256–64.

Article  CAS  PubMed  Google Scholar 

Ferrari SM, Fallahi P, Ruffilli I, Elia G, Ragusa F, Paparo SR, Patrizio A, Mazzi V, Colaci M, Giuggioli D, et al. Immunomodulation of CXCL10 secretion by hepatitis C virus: could CXCL10 be a prognostic marker of chronic hepatitis C? J Immunol Res. 2019;2019:5878960.

Article  PubMed  PubMed Central  Google Scholar 

You CR, Park SH, Jeong SW, Woo HY, Bae SH, Choi JY, Sung YC, Yoon SK. Serum IP-10 levels correlate with the severity of liver histopathology in patients infected with Genotype-1 HCV. Gut Liver. 2011;5(4):506–12.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lopez Angel CJ, Pham EA, Du H, Vallania F, Fram BJ, Perez K, Nguyen T, Rosenberg-Hasson Y, Ahmed A, Dekker CL, et al. Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination. Proc Natl Acad Sci USA. 2021;118(14):e2022928118.

Baden R, Rockstroh JK, Buti M. Natural history and management of hepatitis C: does sex play a role? J Infect Dis. 2014;209(Suppl 3):S81-85.

Article  CAS  PubMed  Google Scholar 

Badeaux MD, Rolig AS, Agnello G, Enzler D, Kasiewicz MJ, Priddy L, Wiggins JF, Muir A, Sullivan MR, Van Cleef J, et al. Arginase therapy combines effectively with immune checkpoint blockade or agonist anti-OX40 immunotherapy to control tumor growth. Cancer Immunol Res. 2021;9(4):415–29.

Article  CAS  PubMed  Google Scholar 

Cao W, Sun B, Feitelson MA, Wu T, Tur-Kaspa R, Fan Q. Hepatitis C virus targets over-expression of arginase I in hepatocarcinogenesis. Int J Cancer. 2009;124(12):2886–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Antonelli A, Ferrari SM, Ruffilli I, Fallahi P. Cytokines and HCV-related autoimmune disorders. Immunol Res. 2014;60(2–3):311–9.

Article  CAS  PubMed  Google Scholar 

Giannakoulis VG, Dubovan P, Papoutsi E, Kataki A, Koskinas J. Senescence in HBV-, HCV- and NAFLD-mediated hepatocellular carcinoma and senotherapeutics: current evidence and future perspective. Cancers (Basel). 2021;13(18):4732.

Bouman A, Heineman MJ, Faas MM. Sex hormones and the immune response in humans. Hum Reprod Update. 2005;11(4):411–23.

Article  CAS  PubMed  Google Scholar 

Ng M, Hazrati LN. Evidence of sex differences in cellular senescence. Neurobiol Aging. 2022;120:88–104.

Article