Circulating IL-13 Is Associated with De Novo Development of HCC in HCV-Infected Patients Responding to Direct-Acting Antivirals

Jílková, Zuzana Macek; Seigneurin, Arnaud; Coppard, Céline; Ouaguia, Laurissa; Aspord, Caroline; Marche, Patrice N.; Leroy, Vincent; Decaens, Thomas

doi:10.3390/cancers12123820

Cited by 9 publications

(14 citation statements)

References 21 publications

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“…Patients who developed de novo HCC following DAA treatment were compared to matched control patients that were selected based on DAA treatment, sex, age, fibrosis status, and platelet counts. As significant differences in IL-13 and IL-4 were observed, before DAA treatment, this study validates the existence of a specific immune-related profile in patients who develop de novo HCC after DAA-induced virus eradication [57].…”

Section: Immunological Biomarkerssupporting

confidence: 80%

Predictive Factors for Hepatocellular Carcinoma Development after Direct-Acting Antiviral Treatment of HCV

Jilkova

Saleem

Afzal

et al. 2021

Livers

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Chronic hepatitis C virus infection is still one of the major risk factors for the development of hepatocellular carcinoma (HCC), the most frequent type of primary liver cancer. Direct-acting antivirals have substantially improved the cure rate of the virus, but the risk of hepatitis C virus-related HCC remains high, mainly in patients with advanced liver fibrosis and cirrhosis. HCC is often asymptomatic and, therefore, remains undetected until the late tumor stage, which is associated with poor survival rates. Therefore, to improve the surveillance programs following HCV eradication, there is a need to summarize predictive factors or potential biomarkers, to specifically identify patients likely to develop HCC after direct-acting antiviral treatment. This review outlines the most recent data about different predictive factors for HCC development after direct-acting antiviral treatment of hepatitis C virus-infected patients, to improve the clinical management of patients with chronic hepatitis C virus.

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Section: Immunological Biomarkerssupporting

confidence: 80%

Predictive Factors for Hepatocellular Carcinoma Development after Direct-Acting Antiviral Treatment of HCV

Jilkova

Saleem

Afzal

et al. 2021

Livers

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“…The association of type 2 inflammation with tumorigenesis in humans is not limited to autoimmune disorders but also plays roles in a variety of conditions including infection and autoinflammatory conditions. A recent cohort study found that patients who developed hepatocellular carcinoma despite maintaining a sustained virological response against hepatitis C virus were linked to increased circulating levels of IL13 ( Macek Jilkova et al, 2020 ). These patients were matched to controls who did not develop hepatocellular carcinoma, and IL13 was found to be the only strong factor associated with its development.…”

Section: Type 2 Inflammation May Be a Shared Process Of Tumorigenesis Driven By Autoimmunity And Other Chronic Inflammatory Conditionsmentioning

confidence: 99%

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Chen

2021

Front. Cell Dev. Biol.

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Recent epidemiological studies have found an alarming trend of increased cancer incidence in adults younger than 50 years of age and projected a substantial rise in cancer incidence over the next 10 years in this age group. This trend was exemplified in the incidence of non-cardia gastric cancer and its disproportionate impact on non-Hispanic white females under the age of 50. The trend is concurrent with the increasing incidence of autoimmune diseases in industrialized countries, suggesting a causal link between the two. While autoimmunity has been suspected to be a risk factor for some cancers, the exact mechanisms underlying the connection between autoimmunity and cancer remain unclear and are often controversial. The link has been attributed to several mediators such as immune suppression, infection, diet, environment, or, perhaps most plausibly, chronic inflammation because of its well-recognized role in tumorigenesis. In that regard, autoimmune conditions are common causes of chronic inflammation and may trigger repetitive cycles of antigen-specific cell damage, tissue regeneration, and wound healing. Illustrating the connection between autoimmune diseases and cancer are patients who have an increased risk of cancer development associated with genetically predisposed insufficiency of cytotoxic T lymphocyte-associated protein 4 (CTLA4), a prototypical immune checkpoint against autoimmunity and one of the main targets of cancer immune therapy. The tumorigenic process triggered by CTLA4 insufficiency has been shown in a mouse model to be dependent on the type 2 cytokines interleukin-4 (IL4) and interleukin-13 (IL13). In this type 2 inflammatory milieu, crosstalk with type 2 immune cells may initiate epigenetic reprogramming of epithelial cells, leading to a metaplastic differentiation and eventually malignant transformation even in the absence of classical oncogenic mutations. Those findings complement a large body of evidence for type 1, type 3, or other inflammatory mediators in inflammatory tumorigenesis. This review addresses the potential of autoimmunity as a causal factor for tumorigenesis, the underlying inflammatory mechanisms that may vary depending on host-environment variations, and implications to cancer prevention and immunotherapy.

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“…A recent study showed that patients with the development of hepatocellular carcinoma (HCC) after DAA therapy have lower sCD137 compared to patients who do not develop HCC [37]. During the follow‐up of 3 months, six patients developed HCC in our cohort.…”

Section: Resultsmentioning

confidence: 93%

“…Activation of CD137 promotes tumoricidal effects in monocytes and T cells [7,64]. Unexpectedly, serum sCD137 levels were low in HCV-infected patients who developed HCC within 4 years after DAA therapy [37]. This difference in sCD137 levels was, however, no longer apparent at 3 months after viral eradication [37].…”

Section: Discussionmentioning

confidence: 99%

Soluble CD137 is a novel serum marker of liver cirrhosis in patients with hepatitis C and alcohol‐associated disease etiology

et al. 2021

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Defective T-cell functions play a role in the persistence of HCV infection. Activated T cells express CD137, which costimulates antivirus T-cell responses, and this activity is antagonized by soluble CD137 (sCD137). Here, we show that in sera of 81 patients with chronic HCV, sCD137 levels did not correlate with measures of viral infection, and did not decline after virus eradication using direct-acting antivirals. Thus, serum sCD137 was similar in patients infected with HCV and in uninfected controls. Of note, in HCV patients with liver cirrhosis and patients with mostly alcohol-associated liver cirrhosis, sCD137 was increased. A negative association of sCD137 and albumin existed in both cohorts. sCD137 concentrations were similar in hepatic and portal vein blood excluding the liver as the origin of higher levels. Recombinant sCD137 reduced Th1 and Th2 but not Th17 cell polarization in vitro, and accordingly lowered IFN-γ, TNF, and IL-13 in cell media. Serum sCD137 is associated with inflammatory states, and positively correlated with serum TNF in cirrhotic HCV patients following virus eradication. Our study argues against a role of sCD137 in HCV infection and suggests a function of sCD137 in liver cirrhosis, which yet has to be defined.

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Circulating IL-13 Is Associated with De Novo Development of HCC in HCV-Infected Patients Responding to Direct-Acting Antivirals

Cited by 9 publications

References 21 publications

Predictive Factors for Hepatocellular Carcinoma Development after Direct-Acting Antiviral Treatment of HCV

Predictive Factors for Hepatocellular Carcinoma Development after Direct-Acting Antiviral Treatment of HCV

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Soluble CD137 is a novel serum marker of liver cirrhosis in patients with hepatitis C and alcohol‐associated disease etiology

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