Innate immunity and nonalcoholic fatty liver disease

Kountouras, Jannis; Kazakos, Evangelos; Kyrailidi, Foteini; Polyzos, Stergios A.; Zavos, Christos; Arapoglou, Stergios; Boziki, Marina; Μουρατίδου, Μαρία; Tzitiridou‐Chatzopoulou, Maria; Chatzopoulos, Dimitrios; Doulberis, Michael; Papaefthymiou, Apostolis; Vardaka, Elisabeth

doi:10.20524/aog.2023.0793

Cited by 10 publications

(5 citation statements)

References 101 publications

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“…Thus, ICIs should be cautiously selected as the first-line therapeutic option for NAFLD-associated HCC, until future studies provide a clearer understanding of the efficacy of ICIs in NAFLD-associated HCC. Notably, it becomes more and more apparent that the dysmetabolic and inflammatory microenvironment in NAFLD and NAFLD-associated HCC may impact the functionality of the immune system [86][87][88]; therefore, the development of combination therapies that target both immune responses and metabolic or inflammatory factors (such as adiponectin or TNF-α or both) may hold a promise as a potential therapeutic approach for treating HCC in the context of NAFLD (Figure 2). In this regard, combination treatment of NAFLD, i.e., targeting more than one of its pathogenic contributors (e.g., metabolic, inflammatory, fibrogenic, and possibly tumorigenic) in an individual basis was long ago proposed by our group [89,90].…”

Section: Treatment Considerations For Nafld-associated Hccmentioning

confidence: 99%

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

Vachliotis,

Valsamidis,

Polyzos

2023

Cancers

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Nonalcoholic fatty liver disease (NAFLD) is emerging as an important risk factor for hepatocellular carcinoma (HCC), whose prevalence is rising. Although the mechanisms of progression from NAFLD to HCC are not fully elucidated, tumor necrosis factor-α (TNF-α) and adiponectin, as well as their interplay, which seems to be antagonistic, may contribute to the pathophysiology of NAFLD-associated HCC. TNF-α initially aims to protect against hepatocarcinogenesis, but during the progression of NAFLD, TNF-α is increased, thus probably inducing hepatocarcinogenesis in the long-term, when NAFLD is not resolved. On the other hand, adiponectin, which is expected to exert anti-tumorigenic effects, is decreased during the progression of the disease, a trend that may favor hepatocarcinogenesis, but is paradoxically increased at end stage disease, i.e., cirrhosis and HCC. These observations render TNF-α and adiponectin as potentially diagnostic biomarkers and appealing therapeutic targets in the setting of NAFLD-associated HCC, possibly in combination with systematic therapy. In this regard, combination strategy, including immune checkpoint inhibitors (ICIs) with anti-TNF biologics and/or adiponectin analogs or medications that increase endogenous adiponectin, may warrant investigation against NAFLD-associated HCC. This review aims to summarize evidence on the association between TNF-α and adiponectin with NAFLD-associated HCC, based on experimental and clinical studies, and to discuss relevant potential therapeutic considerations.

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Section: Treatment Considerations For Nafld-associated Hccmentioning

confidence: 99%

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

Vachliotis,

Valsamidis,

Polyzos

2023

Cancers

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“…For example, certain immune cells that are prevalent in MAFLD, such as regulatory T cells, have previously been reported to suppress liver inflammation. This could potentially mitigate the inflammatory cascades that drive carcinogenesis in patients with CHB infection ( 40 ). A liver with MAFLD undergoes a high rate of hepatocyte turnover due to recurrent minor injury and repair.…”

Section: Discussionmentioning

confidence: 99%

Effect of metabolic dysfunction‑associated fatty liver disease on the risk of hepatocellular carcinoma in patients with chronic hepatitis B: A systematic review and meta‑analysis

Shen,

Pan

2024

Exp Ther Med

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Hepatocellular carcinoma (HCC) remains an important complication in patients with chronic hepatitis B (CHB). An association between the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) and an increased HCC risk in patients with CHB may exist; however, the exact nature of this possible association remains unclear. The present study conducted a comprehensive meta-analysis by pooling data from 18 studies encompassing 23,927 participants. The odds ratios (ORs) were calculated using a random-effects inverse-variance model, and heterogeneity was assessed using Cochran's Q test and the I² statistic. In addition, subgroup analyses were performed on the basis of geographical region, study design and follow-up length. Publication bias and meta-regression were also assessed. The overall pooled OR for the association between MAFLD and HCC risk in patients with CHB was 1.053 (95% CI, 0.704-1.576), which suggested a lack of association. Heterogeneity was observed across studies. Subgroup analyses demonstrated a potentially protective effect for MAFLD on the risk of HCC in patients in Asian countries (OR, 0.783; 95% CI, 0.568-1.080) and the opposite effect in other regions (OR, 4.380; 95% CI, 2.440-7.864). Analysis of the prospective cohort studies suggested a significant protective effect for MAFLD (OR, 0.479; 95% CI, 0.365-0.629), while analysis of retrospective cohorts did not. The publication bias assessment was inconclusive and the meta-regression failed to identify heterogeneity sources. The association between MAFLD and HCC risk in patients with CHB appeared to be multifactorial and may vary on the basis of geographical region and study design. While the exact mechanisms remain elusive, the potential protective effect demonstrated in certain subgroups warrants further investigation.

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“…The prevalence of NASH has risen rapidly worldwide. In the last three decades, these rates have increased from 25% to 38%, and NASH is likely to become the main indication for liver transplantation in the near future [23][24][25][26]. On the other hand, CHC is an infectious disease, caused by HCV infection.…”

Section: Discussionmentioning

confidence: 99%

IL-23/IL-17 Axis in Chronic Hepatitis C and Non-Alcoholic Steatohepatitis—New Insight into Immunohepatotoxicity of Different Chronic Liver Diseases

Vujovic,

Isakovic,

Misirlic-Dencic

et al. 2023

IJMS

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Considering the relevance of the research of pathogenesis of different liver diseases, we investigated the possible activity of the IL-23/IL-17 axis on the immunohepatotoxicity of two etiologically different chronic liver diseases. A total of 36 chronic hepatitis C (CHC) patients, 16 with (CHC-SF) and 20 without significant fibrosis (CHC-NSF), 19 patients with non-alcoholic steatohepatitis (NASH), and 20 healthy controls (CG) were recruited. Anthropometric, biochemical, and immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed in accordance with standard procedure. Our analysis revealed that a higher concentration of plasma IL-23 was associated with NASH (p = 0.005), and a higher concentration of plasma IL-17A but a lower concentration of plasma IL-10 was associated with CHC in comparison with CG. A lower concentration of plasma IL-10 was specific for CHC-NSF, while a higher concentration of plasma IL-17A was specific for CHC-SF in comparison with CG. CHC-NSF and CHC-SF groups were distinguished from NASH according to a lower concentration of plasma IL-17A. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in comparison with NASH, regardless of the same stage of the liver fibrosis, whereas only IL-17A tissue levels showed a difference between the CHC-NSF and CHC-SF groups, namely, a lower concentration in CHC-NSF in comparison with CHC-SF. In CHC-SF and NASH liver tissue, IL17-A and IL-23 were significantly higher in comparison with plasma. Diagnostic accuracy analysis showed significance only in the concentration of plasma cytokines. Plasma IL-6, IL-17A and IL-23 could be possible markers that could differentiate CHC patients from controls. Plasma IL-23 could be considered a possible biomarker of CHC-NSF patients in comparison with controls, while plasma IL-6 and IL-17-A could be biomarkers of CHC-SF patients in comparison with controls. The most sophisticated difference was between the CHC-SF and CHC-NSF groups in the plasma levels of IL-10, which could make this cytokine a useful biomarker of liver fibrosis.

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Innate immunity and nonalcoholic fatty liver disease

Cited by 10 publications

References 101 publications

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

Effect of metabolic dysfunction‑associated fatty liver disease on the risk of hepatocellular carcinoma in patients with chronic hepatitis B: A systematic review and meta‑analysis

IL-23/IL-17 Axis in Chronic Hepatitis C and Non-Alcoholic Steatohepatitis—New Insight into Immunohepatotoxicity of Different Chronic Liver Diseases

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