Senescence mirrors the extent of liver fibrosis in chronic hepatitis C virus infection

Wandrer, Franziska; Han, Byungjoo; Liebig, Stephanie; Schlué, Jérôme; Manns, Michael P.; Schulze‐Osthoff, Klaus; Bantel, Heike

doi:10.1111/apt.14802

Cited by 29 publications

(29 citation statements)

References 54 publications

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“…The association between liver fibrosis and IFN‐λ3 levels shown in our results supports the possibility that IFN‐λ3 is induced during a fibrosis‐related immune response. In addition, there could be other causes of liver inflammation, such as liver steatosis or cellular senescence, as previously reported, although the association with liver fat or senescence‐associated secretory phenotypes was not evaluated in this study. Thus, it is possible that IFN‐λ3 might be induced by such chronic inflammation, which possibly promotes NHHN and HCC development after HCV clearance.…”

Section: Discussionmentioning

confidence: 83%

Association of serum interferon‐λ3 levels with hepatocarcinogenesis in chronic hepatitis C patients treated with direct‐acting antiviral agents

Inoue-Shinomiya

Murakawa

Asahina

et al. 2019

Hepatology Research

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Aim Although the efficacy of hepatitis C virus (HCV) treatment is improved dramatically by direct‐acting antiviral agents (DAAs), the assessment of hepatocellular carcinoma (HCC) remains important. Interferon lambda 3 (IFN‐λ3) is associated with liver fibrosis and inflammation in chronic hepatitis C (CHC) patients, but its impact on carcinogenesis remains controversial and little is known about its effects after viral clearance. To determine the contribution of IFN‐λ3 to hepatocarcinogenesis after HCV clearance, we analyzed IFNL3 genotypes and serial serum IFN‐λ3 levels in CHC patients who achieved sustained virologic responses (SVR). Methods This study comprised 201 CHC patients treated with DAAs. Serum samples were collected sequentially and IFN‐λ3 levels were quantified by chemiluminescence enzyme immunoassay. The IFNL3 polymorphism (rs8099917) was genotyped in 195 patients. Results One hundred and twenty‐five patients were rs8099917 T/T and 70 were non‐T/T. Serum IFN‐λ3 levels did not differ significantly with IFNL3 genotype, dropped markedly by 1 week and remained low up to 24 weeks after the end of treatment. Interferon‐λ3 levels were significantly higher after viral clearance in patients who developed HCC and were associated with a higher potential for hepatocarcinogenesis, such as a higher frequency of non‐hypervascular hypointensive nodules (P = 0.046), higher stages of liver fibrosis (P < 0.001), and higher post‐treatment levels of Wisteria floribunda agglutinin positive Mac‐2 binding protein (P < 0.001) and alanine aminotransferase (P < 0.001). Conclusions Serum IFN‐λ3 levels after HCV clearance are associated with the potential for HCC development. Interferon‐λ3 could be helpful for elucidating the relationships among immunologic status, liver fibrosis, liver inflammation, and hepatocarcinogenesis, after achieving SVR.

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Section: Discussionmentioning

confidence: 83%

Association of serum interferon‐λ3 levels with hepatocarcinogenesis in chronic hepatitis C patients treated with direct‐acting antiviral agents

Inoue-Shinomiya

Murakawa

Asahina

et al. 2019

Hepatology Research

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“…142 However, Wandrer et al proposed that immune CD3þ T cells, rather than hepatocytes, are the predominant senescent population in HCV during fibrosis progression. 149 This finding opens new avenues for the selective targeting of different liver populations by inducing host senescence to avoid viral replication or inhibiting immune senescence to contain the infection.…”

Section: Hepatocytes and Cellular Senescencementioning

confidence: 99%

“…Senescence in lymphocytes has been described in chronic viral hepatitis (CD4 þ , 182 CD3 þ , 149,183,184 and CD8 þ 185 T cells), cirrhosis, 136 and liver transplant recipients. 186 This phenotype has been associated with increased fibrogenesis, immune exhaustion, and viral persistence.…”

Section: Other Liver Populations and Cellular Senescencementioning

confidence: 99%

“…103 Either as a triggering factor or a consequence of the pathology, senescence has proven to be a relevant factor in liver disease. As so, several groups propose to use senescence markers to help establish diagnosis and severity of chronic conditions (such as p21 in CR, 95 chitotriosidase in HCV, 149 or SMP30 in NAFLD 166 ). However, the necessity of finding several factors and lack of superficial noninvasive markers complicate the use of senescence as a diagnostic tool.…”

Section: Targeting Cellular Senescence: the Future Of Therapeutics Inmentioning

confidence: 99%

“…For example, manipulation of host senescence could block hepatitis virus infection, 142 while inhibiting immune senescence could prevent the spread of hepatitis viruses. 149 Induction of senescence in HSCs could reduce fibrosis, 19 while blocking hepatocellular senescence might be advantageous to reverse cirrhosis 133,138 and treat NAFLD. 137 Blocking of SASP factors could prevent the detri-mental effects of cholangiocyte senescence in PBC 103 and promote liver regeneration in the setting of acute liver damage.…”

Section: Targeting Cellular Senescence: the Future Of Therapeutics Inmentioning

confidence: 99%

See 2 more Smart Citations

Cellular Senescence in Liver Disease and Regeneration

et al. 2021

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Cellular senescence is an irreversible cell cycle arrest implemented by the cell as a result of stressful insults. Characterized by phenotypic alterations, including secretome changes and genomic instability, senescence is capable of exerting both detrimental and beneficial processes. Accumulating evidence has shown that cellular senescence plays a relevant role in the occurrence and development of liver disease, as a mechanism to contain damage and promote regeneration, but also characterizing the onset and correlating with the extent of damage. The evidence of senescent mechanisms acting on the cell populations of the liver will be described including the role of markers to detect cellular senescence. Overall, this review intends to summarize the role of senescence in liver homeostasis, injury, disease, and regeneration.

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HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART

Lara-Aguilar

Crespo-Bermejo

Llamas-Adán

et al. 2023

Journal of Medical Virology

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Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as

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Senescence mirrors the extent of liver fibrosis in chronic hepatitis C virus infection

Abstract: Senescence of hepatic T-cells is enhanced in chronic viral hepatitis and increases with fibrosis progression. Serological detection of senescence-associated chitotriosidase might allow for the non-invasive detection of relevant fibrosis stages.

Cited by 29 publications

References 54 publications

Association of serum interferon‐λ3 levels with hepatocarcinogenesis in chronic hepatitis C patients treated with direct‐acting antiviral agents

Association of serum interferon‐λ3 levels with hepatocarcinogenesis in chronic hepatitis C patients treated with direct‐acting antiviral agents

Cellular Senescence in Liver Disease and Regeneration

HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART

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