Genetic variants in IL-6 and IL-10 genes and susceptibility to hepatocellular carcinoma in HCV infected patients

Sghaier, Ikram; Mouelhi, Leïla; Rabia, Noor A.; Alsaleh, Bano; Ghazoueni, Ezzedine; Almawi, Wassim Y.; Yacoubi-Loueslati, Besma

doi:10.1016/j.cyto.2016.10.004

Cited by 35 publications

(35 citation statements)

References 41 publications

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“…In addition, SVR was accompanied by a significant decrease in IL-6 levels (from 2.7 to 1.5 pg/ml; P = 0.029) at 4 weeks of treatment, remaining significantly lower in responder than in non-responder ( 26 ). In other studies, it was observed that certain polymorphisms in IL-6 or its promoter are associated with lower rate of spontaneous clearance ( 11 ), and increased risk of HCC in patients with CVH-related cirrhosis ( 10 , 37 ). Many other proinflammatory cytokines, including interleukin IL-1β, IL-18, and TNF-α have been associated with increased risk of progression to cirrhosis ( 38 – 40 ).…”

Section: An Overview Of General Inflammatory Biomarkers As Outcome Prmentioning

confidence: 99%

“…Therefore, these research together bring to light the importance of the interleukin-17 in pathogenesis and progression of CVH and can be one of the ways by which neutrophils, and other immune cell populations, exercise their pathogenic and predictive effect in CVH. Other Th17-related cytokines, such as IL-6 and IL-23, are involved in the evolution of CVH, regardless of stimulation of Th17 ( 11 , 37 , 69 ). The IL-23 and its receptor, in particular, have been found higher among HCV-infected patients than in control (mean 24.6 vs. 20.2 pg/mL; P = 0.005), with a positive correlation with ALT in HCV patients ( 69 ).…”

Section: The Th17/il-17 Axis and Outcome Prediction In Cvhmentioning

confidence: 99%

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Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced Chronic Hepatitis and Progression to Cirrhosis

Paquissi

2017

Front. Immunol.

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Cirrhosis is a common final pathway for most chronic liver diseases; representing an increasing burden worldwide and is associated with increased morbidity and mortality. Current evidence has shown that, after an initial injury, the immune response has a significant participation in the ongoing damage, and progression from chronic viral hepatitis (CVH) to cirrhosis, driving the activation and maintenance of main fibrogenic pathways. Among immune deregulations, those related to the subtype 17 of T helper lymphocytes (Th17)/interleukin-17 (IL-17) axis have been recognized as key immunopathological and prognostic elements in patients with CVH. The Th17/IL-17 axis has been found involved in several points of fibrogenesis chain from the activation of stellate cells, increased expression of profibrotic factors as TGF-β, promotion of the myofibroblastic or epithelial–mesenchymal transition, stimulation of the synthesis of collagen, and induction of imbalance between matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). It also promotes the recruitment of inflammatory cells and increases the expression of proinflammatory cytokines such as IL-6 and IL-23. So, the Th17/IL-17 axis is simultaneously the fuel and the flame of a sustained proinflammatory and profibrotic environment. This work aims to present the immunopathologic and prognostic role of the Th17/IL-17 axis and related pathways in fibrogenesis and progression to cirrhosis in patients with liver disease due to hepatitis B virus (HBV) and hepatitis C virus (HCV).

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Section: An Overview Of General Inflammatory Biomarkers As Outcome Prmentioning

confidence: 99%

Section: The Th17/il-17 Axis and Outcome Prediction In Cvhmentioning

confidence: 99%

Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced Chronic Hepatitis and Progression to Cirrhosis

Paquissi

2017

Front. Immunol.

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“…Chronic infection and inflammatory response are closely related to tumorigenesis. HCC is the result of chronic inflammatory response induced by hepatitis B/C [79] . IKK/NF-κB pathway plays an important role in hepatitis, liver fibrosis and HCC.…”

Section: Nf-κb Pathwaymentioning

confidence: 99%

Understanding the inflammation-cancer transformation in the development of primary liver cancer

Chen¹,

Hu²,

Xu³

et al. 2018

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Primary liver cancer is one of the leading causes of cancer-related deaths worldwide. China has more than 55% liver cancer cases globally. The development of hepatocellular carcinoma (HCC) was caused by a variety of risks factors, including chronic inflammation by virus, alcohol consumption and non-alcoholic steatohepatitis. Emerging evidence has notarized inflammation as a critical component of HCC progression. The development of HCC is a multistep process which may originate from liver chronic injury and inflammation to subsequent fibrosis and/or cirrhosis and finally HCC. A large number of studies indicate that chemokines and cytokines are candidates linking molecules between inflammation and liver cancer. Here, we will describe a few of the key cytokines and chemokines and signal pathways which are involved in the inflammation of HCC. Inhibitors of inflammation for the prevention and overcoming antitumor immunity for treatment of liver cancer are promising candidates for the future management of patients with HCC.

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“…Transformation of normal hepatocytes to cancer cells during hepatocarcinogenesis is accompanied by characteristic patterns of somatic mutations in, e.g., P53 , PIK3CA , and CTNNB1 , that promote genetic instability and uncontrolled proliferation [ 89 , 90 , 91 ]. Tumor cells have been found to differ from adjacent non-tumor tissue on the order of 50,000 single nucleotide variants that might affect any of nearly 1000 oncogenes and tumor suppressors [ 92 , 93 ].…”

Section: Molecular Mechanisms Of Hccmentioning

confidence: 99%

Molecular Mechanisms of Hepatocarcinogenesis Following Sustained Virological Response in Patients with Chronic Hepatitis C Virus Infection

Hayes

Zhang

et al. 2018

Viruses

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Despite the success of direct-acting antiviral (DAA) agents in treating chronic hepatitis C virus (HCV) infection, the number of cases of HCV-related hepatocellular carcinoma (HCC) is expected to increase over the next five years. HCC develops over the span of decades and is closely associated with fibrosis stage. HCV both directly and indirectly establishes a pro-inflammatory environment favorable for viral replication. Repeated cycles of cell death and regeneration lead to genomic instability and loss of cell cycle control. DAA therapy offers >90% sustained virological response (SVR) rates with fewer side effects and restrictions than interferon. While elimination of HCV helps to restore liver function and reverse mild fibrosis, post-SVR patients remain at elevated risk of HCC. A series of studies reporting higher than expected rates of HCC development among DAA-treated patients ignited debate over whether use of DAAs elevates HCC risk compared to interferon. However, recent prospective and retrospective studies based on larger patient cohorts have found no significant difference in risk between DAA and interferon therapy once other factors are taken into account. Although many mechanisms and pathways involved in hepatocarcinogenesis have been elucidated, our understanding of drivers specific to post-SVR hepatocarcinogenesis is still limited, and lack of suitable in vivo and in vitro experimental systems has hampered efforts to examine etiology-specific mechanisms that might serve to answer this question more thoroughly. Further research is needed to identify risk factors and biomarkers for post-SVR HCC and to develop targeted therapies based on more complete understanding of the molecules and pathways implicated in hepatocarcinogenesis.

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Genetic variants in IL-6 and IL-10 genes and susceptibility to hepatocellular carcinoma in HCV infected patients

Cited by 35 publications

References 41 publications

Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced Chronic Hepatitis and Progression to Cirrhosis

Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced Chronic Hepatitis and Progression to Cirrhosis

Understanding the inflammation-cancer transformation in the development of primary liver cancer

Molecular Mechanisms of Hepatocarcinogenesis Following Sustained Virological Response in Patients with Chronic Hepatitis C Virus Infection

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