Yoshihiro Kamada1,2, Masafumi Ono3, Hideyuki Hyogo4, Hideki Fujii5,6, Yoshio Sumida7, Kojiroh Mori8, Saiyu Tanaka8, Makoto Yamada9, Maaya Akita1, Kayo Mizutani1, Hironobu Fujii1, Akiko Yamamoto1, Shinji Takamatsu1, Yuichi Yoshida2, Yoshito Itoh7, Norifumi Kawada5, Kazuaki Chayama4, Toshiji Saibara3, Tetsuo Takehara2, Eiji Miyoshi1. 1. Department of Molecular Biochemistry and Clinical Investigation, Osaka University, Graduate School of Medicine, Osaka, Japan. 2. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan. 3. Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan. 4. Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan. 5. Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan. 6. Department of Gastroenterology, Osaka City Juso Hospital, Osaka, Japan. 7. Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 8. Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan. 9. aMs New Otani Clinic, Osaka, Japan.
Abstract
UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem; thus, discriminating nonalcoholic steatohepatitis (NASH) from NAFLD is of great clinical significance. For the diagnosis of NASH, liver biopsy-proven histological examination is the current gold standard, and noninvasive and reliable biomarkers are greatly needed. Recently, we found that two glycobiomarkers, fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac2bp), are useful independently for NASH diagnosis. In this study, we confirmed that serum Fuc-Hpt is suitable for the prediction of ballooning hepatocytes and that serum Mac2bp is suitable for the prediction of liver fibrosis severity in 124 biopsy-proven NAFLD patients (training cohort). In addition, we found that the combination of serum Fuc-Hpt and Mac2bp levels was an excellent tool for NASH diagnosis. Using receiver operating characteristic analyses, the area under the receiver operating characteristic curve, sensitivity, and specificity of the combination of these two glycobiomarkers were 0.854, 81.1%, and 79.3%, respectively. We established a prediction model for NASH diagnosis using logistic regression analysis: logit (p)=-2.700+0.00242×Fuc-Hpt+1.225×Mac2bp. To validate the prediction model, another 382 biopsy-proven NAFLD patients were enrolled (validation cohort). In the validation cohort, the area under the receiver operating characteristic curve of this model for NASH diagnosis was 0.844, with 71.4% and 82.3% sensitivity and specificity, respectively. In addition, we investigated the significance of our developed NASH diagnosis model in ultrasound-diagnosed NAFLD subjects who received medical health checkups (n = 803). Our model also could predict NAFLD disease severity in this larger population. CONCLUSION: The combination of serum Fuc-Hpt and Mac2bp can distinguish NASH from NAFLD patients. Our noninvasive model using two serum glycobiomarkers contributes to a novel NASH diagnostic methodology that could replace liver biopsy.
UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem; thus, discriminating nonalcoholic steatohepatitis (NASH) from NAFLD is of great clinical significance. For the diagnosis of NASH, liver biopsy-proven histological examination is the current gold standard, and noninvasive and reliable biomarkers are greatly needed. Recently, we found that two glycobiomarkers, fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac2bp), are useful independently for NASH diagnosis. In this study, we confirmed that serum Fuc-Hpt is suitable for the prediction of ballooning hepatocytes and that serum Mac2bp is suitable for the prediction of liver fibrosis severity in 124 biopsy-proven NAFLD patients (training cohort). In addition, we found that the combination of serum Fuc-Hpt and Mac2bp levels was an excellent tool for NASH diagnosis. Using receiver operating characteristic analyses, the area under the receiver operating characteristic curve, sensitivity, and specificity of the combination of these two glycobiomarkers were 0.854, 81.1%, and 79.3%, respectively. We established a prediction model for NASH diagnosis using logistic regression analysis: logit (p)=-2.700+0.00242×Fuc-Hpt+1.225×Mac2bp. To validate the prediction model, another 382 biopsy-proven NAFLD patients were enrolled (validation cohort). In the validation cohort, the area under the receiver operating characteristic curve of this model for NASH diagnosis was 0.844, with 71.4% and 82.3% sensitivity and specificity, respectively. In addition, we investigated the significance of our developed NASH diagnosis model in ultrasound-diagnosed NAFLD subjects who received medical health checkups (n = 803). Our model also could predict NAFLD disease severity in this larger population. CONCLUSION: The combination of serum Fuc-Hpt and Mac2bp can distinguish NASH from NAFLD patients. Our noninvasive model using two serum glycobiomarkers contributes to a novel NASH diagnostic methodology that could replace liver biopsy.
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Authors: Michael M Mendelson; Riccardo E Marioni; Roby Joehanes; Chunyu Liu; Åsa K Hedman; Stella Aslibekyan; Ellen W Demerath; Weihua Guan; Degui Zhi; Chen Yao; Tianxiao Huan; Christine Willinger; Brian Chen; Paul Courchesne; Michael Multhaup; Marguerite R Irvin; Ariella Cohain; Eric E Schadt; Megan L Grove; Jan Bressler; Kari North; Johan Sundström; Stefan Gustafsson; Sonia Shah; Allan F McRae; Sarah E Harris; Jude Gibson; Paul Redmond; Janie Corley; Lee Murphy; John M Starr; Erica Kleinbrink; Leonard Lipovich; Peter M Visscher; Naomi R Wray; Ronald M Krauss; Daniele Fallin; Andrew Feinberg; Devin M Absher; Myriam Fornage; James S Pankow; Lars Lind; Caroline Fox; Erik Ingelsson; Donna K Arnett; Eric Boerwinkle; Liming Liang; Daniel Levy; Ian J Deary Journal: PLoS Med Date: 2017-01-17 Impact factor: 11.069