Usefulness of a Combined Evaluation of the Serum Adiponectin Level, HOMA-IR, and Serum Type IV Collagen 7S Level to Predict the Early Stage of Nonalcoholic Steatohepatitis

Shimada, Masahiko; Kawahara, Hiromu; Ozaki, Kazuaki; Fukura, Masayuki; Yano, Hirokazu; Tsuchishima, Mutsumi; Tsutsumi, Mikihiro; Takase, Shujiro

doi:10.1111/j.1572-0241.2007.01322.x

Cited by 131 publications

(82 citation statements)

References 37 publications

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“…Specifically, adiponectin signalling alleviated or prevented NASH in mice, 33,34 and associations of hypoadiponectinaemia with fatty liver and/or NASH have been reported in humans. 35,36 Furthermore, genetic studies revealed associations of ADIPOR1/2 with IR and liver fat content, 37,38 and overexpression of ADIPOR1/2 has been shown to potentiate subeffective doses of adiponectin. 39 We therefore suggest that the increased ADIPOR1/2 mRNA expression in obese, insulin-resistant subjects represents a mechanism that may partially compensate for reduced plasma adiponectin.…”

Section: Discussionmentioning

confidence: 99%

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

et al. 2010

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Objective: Adiponectin signalling attenuates insulin resistance (IR) and steatosis hepatis in animal models. As adiponectin receptor (ADIPOR)1 and ADIPOR2 are critical components in the adiponectin signalling cascade, we studied hepatic ADIPOR1/2 mRNA levels in humans and their relation to IR. Design: We determined metabolic risk factors and levels of hepatic mRNA transcribed from ADIPOR1, ADIPOR2 and FOXO1, a putative up-stream regulator, in 43 and 34 obese subjects with low and high homeostasis model assessment-IR, respectively. Results: Plasma adiponectin and metabolic risk factors showed associations with IR as expected. Both hepatic ADIPOR1 and ADIPOR2 mRNA expression levels were higher in insulin-resistant subjects (Po0.0035). ADIPOR1 mRNA correlated with FOXO1 mRNA in obese insulin resistant (P ¼ 0.0034), but not insulin-sensitive subjects, while no correlations of ADIPOR2 with FOXO1 mRNA were noted. FOXO1 enhanced transcription from the ADIPOR1, but not the ADIPOR2 promoter in HepG2 cells. Conclusion: Increased hepatic ADIPOR1 and ADIPOR2 mRNA in insulin-resistant obese subjects may, at least in part, reflect a compensatory mechanism for reduced plasma adiponectin. FOXO1 may contribute to enhanced ADIPOR1, but not ADIPOR2 transcription in IR.

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Section: Discussionmentioning

confidence: 99%

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

et al. 2010

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“…In our study, 36.2% of nonobese patients with NAFLD were diagnosed as having NASH. Also, several studies have shown that BMI is not a useful independent factor for differentiating NAFL from NASH in Japanese patients with NAFLD [6,19,20]. Based on these perspectives, an accurate tool for differentiating NAFL from NASH would be needed even in nonobese patients with NAFLD.…”

Section: Discussionmentioning

confidence: 99%

A Caution in the use of the NAFIC Scoring System as a Diagnostic Screening Tool for Nonalcoholic Steatohepatitis

Nakamura¹,

Yoneda²,

Sumida³

et al. 2014

J Gastroint Dig Syst

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Objective: We reinvestigated the clinical usefulness of the NAFIC and modified NAFIC scoring systems in Japanese patients with nonalcoholic fatty liver disease (NAFLD) according to the presence/absence of obesity.Methods: A total of 141 Japanese patients with liver-biopsy-confirmed NAFLD were enrolled. All patients were classified as having nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH) on the basis of Matteoni's classification. Obesity was defined as a body mass index of ≥25. To evaluate the overall accuracy of the NAFIC and modified NAFIC scoring systems, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of these scoring systems for the diagnosis of NASH were calculated. Results:In the obese group, the sensitivity, specificity, PPV and NPV of the NAFIC scoring system for the diagnosis of NASH were 67.3%, 76.2%, 77.8% and 65.3%, respectively, while the corresponding values for the modified NAFIC scoring systems were 78.8%, 69.0%, 75.9% and 72.5%. On the other hand, in the nonobese group, the sensitivity, specificity, PPV and NPV of the NAFIC scoring system were 47.1%, 86.7%, 66.7% and 74.3%, respectively, while those of the modified NAFIC scoring system were 58.8%, 83.3%, 66.7% and 78.1%, respectively. When the patients were divided by sex, the sensitivity of the NAFIC and modified NAFIC scoring systems in the female nonobese group were 53.8% and 69.2%, respectively. However, surprisingly, in the male nonobese group, the sensitivity of both the scoring systems was only 25.0%. Conclusion:The sensitivity of both the NAFIC and modified NAFIC scoring systems for the diagnosis of NASH was lower in the male nonobese group than in all the other groups. These findings suggest that caution should be exercised in the use of the NAFIC scoring system as a diagnostic screening tool for NASH in Japanese patients with NAFLD, especially male nonobese patients.

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“…CK-18 is an intracellular protein mainly produced by necrosis and apoptosis of cells of epithelial origin including hepatocytes, and is a useful serum biomarker that reflects cell death [26]. Recently, serum CK-18M65 released in NAFLD patients in the process of the cellular death has been proposed as a possible serum biomarker of NASH [27,28]. The increased serum levels of CK-18 fragments, in some clinical cohorts of obese patients or those with insulin resistance, are associated with hepatocyte injury, inflammation and fibrosis [29.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Cytokeratin-18M65 in Diagnosing Non-Alcoholic Steatohepatitis in Japanese Population

Kim¹,

Hatori

Ohta

et al. 2015

Dig Dis

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Objective: The aim of this study was to evaluate cytokeratin-18M65 (CK-18M65) for distinguishing between simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) against healthy individuals (HIs) in Japanese population. Methods: The serum from 24 HIs, 21 patients with SS and 20 patients with NASH were examined. Serum CK-18M65 was measured by enzyme-linked immunosorbent assay. Results: Aspartate aminotransferase was significantly different between NASH patients and HIs with p < 0.0001 (SS patients and HIs: p < 0.0001), as was alanine aminotransferase between NASH patients and HIs with p < 0.0001 (SS patients and HIs: p < 0.0001). Serum CK-18M65 increased in a stepwise fashion in HIs and also in SS and NASH patients. Multivariate logistic regression analysis revealed that NASH could be diagnosed with the use of CK-18M65 alone (p = 0.0285, OR 1.0038, 95% CI 1.0004-1.0073). At the optimal cut-off level of 548 U/l, CK-18M65 had an AUC value of 0.7369, 60.00% sensitivity and 85.70% specificity. In patients with NASH, no significant difference was observed between low fibrosis (Stage 0-1, 794.30 ± 454.41, n = 10) and high fibrosis (Stage 2-3, 809.70 ± 641.43, n = 10; p = 0.5967) and between slight steatosis (<33%, 512.89 ± 229.65, n = 9) and moderate steatosis (≥33%, 655.13 ± 480.78, n = 32) in patients with non-alcoholic fatty liver disease (NAFLD; p = 0.7647) with the use of CK-18M65. Conclusion: Serum CK-18M65 distinguished NASH from SS, but could not assess the severity of steatosis in NAFLD patients or the grade of fibrosis in NASH patients in Japanese population.

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Usefulness of a Combined Evaluation of the Serum Adiponectin Level, HOMA-IR, and Serum Type IV Collagen 7S Level to Predict the Early Stage of Nonalcoholic Steatohepatitis

Abstract: Approximately 90% of the patients with early-stage NASH can be predicted by a combined evaluation of the serum adiponectin level, HOMA-IR, and serum type IV collagen 7S level.

Cited by 131 publications

References 37 publications

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

A Caution in the use of the NAFIC Scoring System as a Diagnostic Screening Tool for Nonalcoholic Steatohepatitis

Usefulness of Cytokeratin-18M65 in Diagnosing Non-Alcoholic Steatohepatitis in Japanese Population

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