A novel noninvasive diagnostic method for nonalcoholic steatohepatitis using two glycobiomarkers
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 reli...
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| Published in | Hepatology (Baltimore, Md.) Vol. 62; no. 5; pp. 1433 - 1443 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Wolters Kluwer Health, Inc
01.11.2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0270-9139 1527-3350 1527-3350 |
| DOI | 10.1002/hep.28002 |
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| Abstract | 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. (Hepatology 2015;62:1433–1443) |
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| AbstractList | 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. (Hepatology 2015;62:1433–1443) 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.UNLABELLEDNonalcoholic 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.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.CONCLUSIONThe 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. 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. (H epatology 2015;62:1433–1443) 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. (Hepatology 2015;62:1433-1443) 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. 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. 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. (Hepatology 2015; 62:1433-1443) |
| Author | Kamada, Yoshihiro Sumida, Yoshio Ono, Masafumi Yoshida, Yuichi Mori, Kojiroh Akita, Maaya Takamatsu, Shinji Miyoshi, Eiji Yamamoto, Akiko Fujii, Hironobu Hyogo, Hideyuki Tanaka, Saiyu Kawada, Norifumi Yamada, Makoto Saibara, Toshiji Chayama, Kazuaki Fujii, Hideki Itoh, Yoshito Mizutani, Kayo Takehara, Tetsuo |
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| Notes | Potential conflict of interest: Nothing to report. Supported as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P‐Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan, and by Grants‐in‐Aid for Scientific Research (C, 24590972; B, 15H04810) from the Japan Society for the Promotion of Science, Kurozumi Medical Foundation, Shimadzu Science Foundation, Kondou kinen Medical Foundation, and Japanese Society of Laboratory Medicine Fund for the Promotion of Scientific Research. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
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| PublicationCentury | 2000 |
| PublicationDate | November 2015 |
| PublicationDateYYYYMMDD | 2015-11-01 |
| PublicationDate_xml | – month: 11 year: 2015 text: November 2015 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Hoboken |
| PublicationTitle | Hepatology (Baltimore, Md.) |
| PublicationTitleAlternate | Hepatology |
| PublicationYear | 2015 |
| Publisher | Wolters Kluwer Health, Inc |
| Publisher_xml | – name: Wolters Kluwer Health, Inc |
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| Title | A novel noninvasive diagnostic method for nonalcoholic steatohepatitis using two glycobiomarkers |
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