Predicting Fibrosis Worsening in Obese Patients With NASH Through Parenchymal Fibronectin, HOMA-IR, and Hypertension

Sorrentino, Paolo; Terracciano, Luigi; D’Angelo, Salvatore; Ferbo, Umberto; Bracigliano, Alessandra; Vecchione, R

doi:10.1038/ajg.2009.587

Cited by 70 publications

(42 citation statements)

References 24 publications

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“…Cell surface delivery of integrins, which are fibronectin-binding receptors, is also reduced in AnxA6 overexpressing cells, thereby impairing cell migration [12]. Fibronectin is a component of the extracellular matrix and a sensitive marker of liver fibrogenesis in NAFLD [13]. The proinflammatory cytokine TNF is involved in various aspects of NAFLD pathophysiology and its neutralization ameliorates murine NASH [14].…”

Section: Introductionmentioning

confidence: 99%

Annexin A6 protein is downregulated in human hepatocellular carcinoma

et al. 2016

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Annexin A6 (AnxA6) is a lipid-binding protein highly expressed in the liver, regulating cholesterol homeostasis and signaling pathways with a role in liver physiology. Here, we analyzed whether hepatic AnxA6 levels are affected by pathological conditions that are associated with liver dysfunction and liver injury. AnxA6 levels in the fatty liver of mice fed a high-fat diet, in ob/ob and db/db animals and in human fatty liver are comparable to controls. Similarly, AnxA6 levels appear unaffected in murine nonalcoholic steatohepatitis and human liver fibrosis. Accordingly, adiponectin, lysophosphatidylcholine, palmitate, and TGFbeta, all of which have a role in liver injury, do not affect AnxA6 expression in human hepatocytes. Likewise, adiponectin and IL8 do not alter AnxA6 levels in primary human hepatic stellate cells. However, in hepatic tumors of 18 patients, AnxA6 protein levels are substantially reduced compared to nontumorous tissues. AnxA6 mRNA is even increased in the tumors suggesting that posttranscriptional mechanisms are involved herein. Lipidomic analysis shows trends toward elevated cholesteryl ester and sphingomyelin in the tumor samples, yet the ratio of tumor to nontumorous AnxA6 does not correlate with these lipids. The current study shows that AnxA6 is specifically reduced in human hepatocellular carcinoma suggesting a role of this protein in hepatocarcinogenesis.

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Section: Introductionmentioning

confidence: 99%

Annexin A6 protein is downregulated in human hepatocellular carcinoma

et al. 2016

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“…Obesity and insulin resistance are thought to play an important role in the pathogenesis of NAFLD (12,23,87,120,152). An elegant study identified ER stress as a molecular link between obesity and deterioration of insulin action in liver and adipose tissue (117).…”

mentioning

confidence: 99%

Endoplasmic Reticulum Stress and the Unfolded Protein Response in Nonalcoholic Fatty Liver Disease

Gentile

Frye

Pagliassotti

2011

Antioxidants & Redox Signaling

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The underlying causes of nonalcoholic fatty liver disease (NAFLD) are unclear, although recent evidence has implicated the endoplasmic reticulum (ER) in both the development of steatosis and progression to nonalcoholic steatohepatitis. Disruption of ER homeostasis, often termed ''ER stress,'' has been observed in liver and adipose tissue of humans with NAFLD and/or obesity. Importantly, the signaling pathway activated by disruption of ER homeostasis, the unfolded protein response, has been linked to lipid biosynthesis, insulin action, inflammation, and apoptosis. Therefore, understanding the mechanisms that disrupt ER homeostasis in NAFLD and the role of ER-mediated signaling have become topics of intense investigation. The present review will examine the ER and the unfolded protein response in the context of NAFLD. Antioxid. Redox Signal. 15, 505-521.

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“…Although an association between hypertension and the development of HCC in NAFLD has not been directly demonstrated, an indirect association has been previously reported [25]. Hypertension is known to be one of the features of metabolic syndrome.…”

Section: Discussionmentioning

confidence: 95%

“…Hypertension is known to be one of the features of metabolic syndrome. Previous studies have shown that hypertension promotes liver fibrosis in patients with NAFLD [25], and that liver fibrosis is a predominant risk factor for the development of HCC [18].…”

Section: Discussionmentioning

confidence: 99%

Diabetic Retinopathy as a Risk Factor Associated with the Development of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

Azuma

Asahina

Kakinuma

et al. 2019

Dig Dis

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Background: The risk factors associated with the development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD) are still unclear. The aim of the present study was to identify such risk factors in NAFLD patients who developed HCC. Methods: Between April 2000 and December 2016, a total of 182 patients with NAFLD were enrolled in this study; of these, only 22 patients had HCC. To identify risk factors, univariate and multivariate analyses were performed. To identify risk factors other than the degree of fibrosis, propensity matched analysis adjusted by the NAFLD fibrosis score (NFS) was carried out on 44 patients. Multivariate and survival analyses were also performed in HCC patients. Results: In 182 patients, multivariate analysis highlighted the NFS (OR 2.275; p < 0.001) and hypertension (OR 5.868; p = 0.037) as independent factors that were significantly associated with the development of HCC. After adjustment for the NFS, multivariate analysis identified diabetic retinopathy (OR 8.654; p = 0.017) as an independent factor that was significantly associated with the development of HCC. For predicting the development of HCC, the area under the receiver operating characteristic curve of diabetic retinopathy was significantly higher than that of diabetes (0.731 vs. 0.615; p < 0.001). In patients with HCC, multivariate analysis indicated that the NFS were significantly associated with diabetic retinopathy. Conclusions: Diabetic retinopathy as well as liver fibrosis is a risk factor that associates with the development of HCC in NAFLD patients. Therefore, NAFLD patients with diabetic retinopathy should undergo careful screening for HCC.

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Predicting Fibrosis Worsening in Obese Patients With NASH Through Parenchymal Fibronectin, HOMA-IR, and Hypertension

Cited by 70 publications

References 24 publications

Annexin A6 protein is downregulated in human hepatocellular carcinoma

Annexin A6 protein is downregulated in human hepatocellular carcinoma

Endoplasmic Reticulum Stress and the Unfolded Protein Response in Nonalcoholic Fatty Liver Disease

Diabetic Retinopathy as a Risk Factor Associated with the Development of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

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