Dataset Information

RAGE is a Potential Cause of Onset and Progression of Nonalcoholic Fatty Liver Disease.

ABSTRACT:

Objective

Fatty liver is a rising global health concern, significantly increasing the burden of health care cost. Nonalcoholic fatty liver disease (NAFLD) has a correlation with metabolic syndrome and its complications.

Method

We reviewed the literature regarding the mechanisms of developing NAFLD through AGE-RAGE signaling.

Results

NAFLD, metabolic syndrome, and production of advanced glycation end-products (AGEs) share many common risk factors and appear to be connected. AGE induces production of the receptor for AGE (RAGE). AGE-RAGE interaction contributes to fat accumulation in the liver leading to inflammation, fibrosis, insulin resistance, and other complications of the fatty liver disease. The immune system, especially macrophages, has an important defense mechanism against RAGE pathway activities.

Conclusion

Soluble form of RAGE (sRAGE) has the capability to reduce inflammation by blocking the interaction of AGE with RAGE. However, sRAGE has some limitations, and the best method of usage is probably autotransplantation of transfected stem cells or monocytes, as a precursor of macrophages and Kupffer cells, with a virus that carries sRAGE to alleviate the harmful effects of AGE-RAGE signaling in the settings of fatty liver disease.

SUBMITTER: Asadipooya K

PROVIDER: S-EPMC6766674 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

RAGE is a Potential Cause of Onset and Progression of Nonalcoholic Fatty Liver Disease.

Asadipooya Kamyar K Lankarani Kamran B KB Raj Rishi R Kalantarhormozi Mohammadreza M

International journal of endocrinology 20190918

<h4>Objective</h4>Fatty liver is a rising global health concern, significantly increasing the burden of health care cost. Nonalcoholic fatty liver disease (NAFLD) has a correlation with metabolic syndrome and its complications.<h4>Method</h4>We reviewed the literature regarding the mechanisms of developing NAFLD through AGE-RAGE signaling.<h4>Results</h4>NAFLD, metabolic syndrome, and production of advanced glycation end-products (AGEs) share many common risk factors and appear to be connected. ...[more]

PMID: 31641351

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Project description:ImportanceThe onset age of nonalcoholic fatty liver disease (NAFLD) is decreasing, and whether earlier ages of NAFLD onset are associated with increased cancer risk is currently unclear.ObjectiveTo explore the association between NAFLD new-onset age and cancer risk.Design, setting, and participantsThis cohort study was conducted among 179 328 participants included in the Kailuan Cohort Study between 2006 and 2021. In total, 46 100 incident NAFLD cases were identified. For each case, a participant matched by age (older or younger by 1 year) and sex was randomly selected to create a new matched study cohort. Data were analyzed from December 2022 through April 2023.ExposureOnset of NAFLD.Main outcomes and measuresThe association between the onset age of NAFLD and the risk of different cancer types was evaluated using weighted Cox regression models. Population-attributable fractions (PAFs) were used to quantify the association of NAFLD with cancer risk at different ages.ResultsAmong 63 696 participants (mean [SD] age, 51.37 [12.43] years; ‭10 932 females [17.2%] and ‭52 764 males [82.8%]), 31 848 individuals had NAFLD and 31 848 individuals were in the control group. During a median (IQR) follow-up of 10.16 (7.89-11.67) years, 2415 patients were diagnosed with cancer. Compared with the matched group, patients aged less than 45 years at NAFLD onset exhibited a higher risk of cancer (average hazard ratio [AHR], 1.52; 95% CI, 1.09-2.12), and as the onset age of NAFLD increased, the cancer risk decreased (ages 45-54 years: AHR, 1.50; 95% CI, 1.15-1.97; ages 55-64 years: AHR, 1.13; 95% CI, 0.97-1.33; ages >65 years: AHR, 0.75; 95% CI, 0.45-1.27; P for interaction < .001). Among patients aged less than 45 years at NAFLD onset, cancers were mainly digestive system and lung cancers, with AHR values of 2.00 (95% CI, 1.08-3.47) and 2.14 (95% CI, 1.05-4.36), respectively. PAFs also showed that in patients aged less than 45 years at NAFLD onset, 17.83% (95% CI, 4.92%-29.86%) of cancer risk was attributable to NAFLD.‬‬‬‬.Conclusions and relevanceThis study found that NAFLD was associated with increased cancer risk and there was an interaction with onset age, such that the younger the onset age of NAFLD, the greater the cancer risk.

Project description:Importance:The histologic evolution of the full spectrum of nonalcoholic fatty liver disease (NAFLD) and factors associated with progression or regression remain to be definitively established. Objective:To evaluate the histologic evolution of NAFLD and the factors associated with changes in disease severity over time. Design, Setting, and Participants:A prospective cohort substudy from the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database study, a noninterventional registry, was performed at 8 university medical research centers. Masked assessment of liver histologic specimens was performed, using a prespecified protocol to score individual biopsies. Participants included 446 adults with NAFLD enrolled in the NASH CRN Database studies between October 27, 2004, and September 13, 2013, who underwent 2 liver biopsies 1 or more year apart. Data analysis was performed from October 2016 to October 2018. Main Outcomes and Measures:Progression and regression of fibrosis stage, using clinical, laboratory, and histologic findings, including the NAFLD activity score (NAS) (sum of scores for steatosis, lobular inflammation, and ballooning; range, 0-8, with 8 indicating more severe disease). Results:A total of 446 adults (mean [SD] age, 47 [11] years; 294 [65.9%] women) with NAFLD (NAFL, 86 [19.3%]), borderline NASH (84 [18.8%]), and definite NASH (276 [61.9%]) were studied. Over a mean (SD) interval of 4.9 (2.8) years between biopsies, NAFL resolved in 11 patients (12.8%) and progressed to steatohepatitis in 36 patients (41.9%). Steatohepatitis resolved in 24 (28.6%) of the patients with borderline NASH and 61 (22.1%) of those with definite NASH. Fibrosis progression or regression by at least 1 stage occurred in 132 (30%) and 151 [34%] participants, respectively. Metabolic syndrome (20 [95%] vs 108 [72%]; P = .03), baseline NAS (mean [SD], 5.0 [1.4] vs 4.3 [1.6]; P = .005), and smaller reduction in NAS (-0.2 [2] vs -0.9 [2]; P < .001) were associated with progression to advanced (stage 3-4) fibrosis vs those without progression to stage 3 to 4 fibrosis. Fibrosis regression was associated with lower baseline insulin level (20 vs 33 μU/mL; P = .02) and decrease in all NAS components (steatosis grade -0.8 [0.1] vs -0.3 [0.9]; P < .001; lobular inflammation -0.5 [0.8] vs -0.2 [0.9]; P < .001; ballooning -0.7 [1.1] vs -0.1 [0.9]; P < .001). Only baseline aspartate aminotransferase (AST) levels were associated with fibrosis regression vs no change and progression vs no change on multivariable regression: baseline AST (regression: conditional odds ratio [cOR], 0.6 per 10 U/L AST; 95% CI, 0.4-0.7; P < .001; progression: cOR, 1.3; 95% CI, 1.1-1.5; P = .002). Changes in the AST level, alanine aminotransferase (ALT) level, and NAS were also associated with fibrosis regression and progression (ΔAST level: regression, cOR, 0.9; 95% CI, 0.6-1.2; P = .47; progression, cOR, 1.3; 95% CI, 1.0-1.6; P = .02; ΔALT level: regression, cOR, 0.7 per 10 U/L AST; 95% CI, 0.5-0.9; P = .002; progression, cOR, 1.0 per 10 U/L AST; 95% CI, 0.9-1.2; P = .93; ΔNAS: regression, cOR, 0.7; 95% CI, 0.6-0.9; P = .001; progression, cOR, 1.3; 95% CI, 1.1-1.5; P = .01). Conclusions and Relevance:Improvement or worsening of disease activity may be associated with fibrosis regression or progression, respectively, in NAFLD.

Dataset Information

RAGE is a Potential Cause of Onset and Progression of Nonalcoholic Fatty Liver Disease.

Objective

Method

Results

Conclusion

Publications

RAGE is a Potential Cause of Onset and Progression of Nonalcoholic Fatty Liver Disease.

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