Paired assessment of liver telomere lengths in hepatocellular cancer is a reliable predictor of disease persistence

Feng, Wendu; Yu, Decai; Li, Binghua; Luo, Ouyang; Xu, Tiancheng; Cao, Yongkuan; Ding, Yitao

doi:10.1042/bsr20160621

Cited by 7 publications

(6 citation statements)

References 15 publications

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“…Moreover, the change in the RTL of PBMCs could be extrapolated to the liver, as indicated by Feng et al [27]. In this work, they observed similar variations in RTL values of paired liver biopsy and PBMC samples from HCV-monoinfected and HBV/HCV-coinfected patients with hepatocellular carcinoma.…”

Section: Discussionsupporting

confidence: 80%

Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals

Molina-Carrión

Brochado-Kith

González-García

et al. 2020

JCM

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Introduction: Human immunodeficiency virus (HIV) infection and cirrhosis are associated with a senescent phenotype that decreases telomere length. We evaluated the impact of hepatitis C virus (HCV) elimination on telomere length in patients with advanced HCV-related cirrhosis after sustained virological response (SVR), with all-oral direct-acting antiviral agents (DAAs). Methods: Prospective study of 60 HIV/HCV-coinfected and 30 HCV-monoinfected patients with advanced HCV cirrhosis (liver decompensation or liver stiffness measurement (LSM) ≥ 25 kPa, hepatic liver pressure gradient (HVPG) ≥ 10 mmHg, or Child–Pugh–Turcotte (CPT) ≥ 7). The relative telomere length (RTL) was quantified by real-time multiplex PCR (MMqPCR) on peripheral blood mononuclear cells at baseline and 48 weeks after HCV treatment. Generalized linear models (GLMs) adjusted for the most relevant clinical and epidemiological variables and mixed GLMs were used. Results: In comparison with HCV-monoinfected patients, HIV/HCV-coinfected patients were younger (p < 0.001), had lower body mass index (BMI) (p = 0.002), and had been exposed less frequently to interferons (p = 0.011). In addition, they were more frequently men (p = 0.011), smokers (p = 0.005), prior intravenous drug users (IVDUs) (p < 0.001), and alcohol abusers (p = 0.005). RTL was significantly lower in HIV/HCV-coinfected patients than in HCV-monoinfected patients, both at baseline (p < 0.001), and at the end of follow-up (p = 0.032). A significant RTL increase over time was found only for HIV/HCV-coinfected patients (p < 0.001), especially in those patients with compensated cirrhosis (p < 0.001). Conclusion: HCV eradication with all-oral DAAs was associated with an increase in telomere length in HIV/HCV-coinfected patients with advanced cirrhosis, particularly in compensated patients. This finding suggests that HCV clearance may have implications in age-related conditions in this population group.

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Section: Discussionsupporting

confidence: 80%

Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals

Molina-Carrión

Brochado-Kith

González-García

et al. 2020

JCM

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“…Telomerase RNA levels were found to be lower in the peripheral blood lymphocytes (PBLs) of HBV- and HCV-infected individuals that may contribute to immunosuppression [ 77 ]. Telomere length assessments in HCC patients infected with HBV or HCV demonstrated shorter telomere lengths not only in liver biopsied tissue, but also in PBLs [ 78 ]. Telomere attrition was not seen in HBV/HCV-noninfectious HCC.…”

Section: Telomere Dynamics and T-cell Exhaustion During Chronic/prmentioning

confidence: 99%

Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection

Bellon

Nicot

2017

Viruses

110

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The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics. A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells. While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals. This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein–Barr virus (EBV), Hepatitis B/C/D virus (HBV/HCV/HDV), human herpesvirus 8 (HHV-8), human immunodeficiency virus (HIV), human T-cell leukemia virus type I (HTLV-I), human papillomavirus (HPV), herpes simplex virus-1/2 (HSV-1/2), and Varicella–Zoster virus (VZV). Current literature linking T-cell exhaustion with critical telomere lengths and immune senescence are discussed. The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.

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“…On the contrary, longer telomere length detected 10 years prior to diagnosis contributed to the risk of developing HCC ( 256 ). Finally, Feng et al ( 258 ) indicated that peripheral blood samples could be used to measure telomere length in HBV or HCV-infected patients, but not in non-infected ones. The viral genome may affect telomerase activity, thus affecting disease development and persistence ( 258 ).…”

Section: Digestive Systemmentioning

confidence: 99%

Role of telomere length in human carcinogenesis (Review)

et al. 2023

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Cancer is considered the most important clinical, social and economic issue regarding cause-specific disability-adjusted life years among all human pathologies. Exogenous, endogenous and individual factors, including genetic predisposition, participate in cancer triggering. Telomeres are specific DNA structures positioned at the end of chromosomes and consist of repetitive nucleotide sequences, which, together with shelterin proteins, facilitate the maintenance of chromosome stability, while protecting them from genomic erosion. Even though the connection between telomere status and carcinogenesis has been identified, the absence of a universal or even a cancer-specific trend renders consent even more complex. It is indicative that both short and long telomere lengths have been associated with a high risk of cancer incidence. When evaluating risk associations between cancer and telomere length, a disparity appears to emerge. Even though shorter telomeres have been adopted as a marker of poorer health status and an older biological age, longer telomeres due to increased cell growth potential are associated with the acquirement of cancer-initiating somatic mutations. Therefore, the present review aimed to comprehensively present the multifaceted pattern of telomere length and cancer incidence association.

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Paired assessment of liver telomere lengths in hepatocellular cancer is a reliable predictor of disease persistence

Cited by 7 publications

References 15 publications

Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals

Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals

Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection

Role of telomere length in human carcinogenesis (Review)

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