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Development and validation of a novel non‐invasive test for diagnosing fibrotic non‐alcoholic steatohepatitis in patients with biopsy‐proven non‐alcoholic fatty liver disease

Development and validation of a novel non‐invasive test for diagnosing fibrotic non‐alcoholic steatohepatitis in patients with biopsy‐proven non‐alcoholic fatty liver disease
Development and validation of a novel non‐invasive test for diagnosing fibrotic non‐alcoholic steatohepatitis in patients with biopsy‐proven non‐alcoholic fatty liver disease
Background and Aim

There is an immediate need for non‐invasive accurate tests for diagnosing liver fibrosis in patients with non‐alcoholic steatohepatitis (NASH). Previously, it has been suggested that MACK‐3 (a formula that combines homeostasis model assessment‐insulin resistance with serum serum aspartate aminotransferase and cytokeratin [CK]18‐M30 levels) accurately identifies patients with fibrotic NASH. Our aim was to assess the performance of MACK‐3 and develop a novel, non‐invasive algorithm for diagnosing fibrotic NASH.

Methods

Six hundred and thirty‐six adults with biopsy‐proven non‐alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration‐controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.

Results

Metabolic syndrome (MetS), platelet count and MACK‐3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75–0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74–0.87) than that of MACK‐3 (AUROC: 0.75, 95%CI 0.68–0.82; P < 0.05) with a NPV of 93.2%. The sequential combination of this nomogram with LSM data avoided the need for liver biopsy in 56.9% of patients.

Conclusions

Our novel nomogram (combining MACK‐3, platelet count and MetS) shows promising utility for diagnosing fibrotic NASH. The sequential combination of this nomogram and vibration‐controlled transient elastography limits indeterminate results and reduces the number of unnecessary liver biopsies.

NAFLD, clinical, NASH, diagnostic tests, liver biopsy, liver fibrosis
0815-9319
1804-1812
Gao, Feng
0ecdc8db-c742-4261-a650-4f23be840b86
Huang, Jiao-Feng
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Zheng, Kenneth I.
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Pan, Xiao-Yan
9e596b30-2bb2-4bde-a72e-f7b843a238d9
Ma, Hong-Lei
ef5f55b5-5389-447d-b171-db79f1549edc
Liu, Wen-Yue
6c778681-36ff-4f19-a3de-16c3b115d64d
Byrne, Christopher
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Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Li, Yang-Yang
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Chen, Yong-Ping
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Chan, Wah-Kheong
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Zheng, Ming-Hua
3ffa12d0-d9fb-42de-bb82-687de1b63e16
Gao, Feng
0ecdc8db-c742-4261-a650-4f23be840b86
Huang, Jiao-Feng
babc991a-6bde-4a81-bec6-db39ed94b653
Zheng, Kenneth I.
0451445c-c5a0-4cf2-9716-7d6367890a6a
Pan, Xiao-Yan
9e596b30-2bb2-4bde-a72e-f7b843a238d9
Ma, Hong-Lei
ef5f55b5-5389-447d-b171-db79f1549edc
Liu, Wen-Yue
6c778681-36ff-4f19-a3de-16c3b115d64d
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Li, Yang-Yang
1d2aec87-fb0c-4e9c-a061-06a728781380
Chen, Yong-Ping
b641f5c8-1ea7-41c4-ba70-e144ff2ed0e1
Chan, Wah-Kheong
2c95b017-659e-4671-a5a6-c95a334684f0
Zheng, Ming-Hua
3ffa12d0-d9fb-42de-bb82-687de1b63e16

Gao, Feng, Huang, Jiao-Feng, Zheng, Kenneth I., Pan, Xiao-Yan, Ma, Hong-Lei, Liu, Wen-Yue, Byrne, Christopher, Targher, Giovanni, Li, Yang-Yang, Chen, Yong-Ping, Chan, Wah-Kheong and Zheng, Ming-Hua (2020) Development and validation of a novel non‐invasive test for diagnosing fibrotic non‐alcoholic steatohepatitis in patients with biopsy‐proven non‐alcoholic fatty liver disease. Journal of Gastroenterology and Hepatology, 35 (10), 1804-1812. (doi:10.1111/jgh.15055).

Record type: Article

Abstract

Background and Aim

There is an immediate need for non‐invasive accurate tests for diagnosing liver fibrosis in patients with non‐alcoholic steatohepatitis (NASH). Previously, it has been suggested that MACK‐3 (a formula that combines homeostasis model assessment‐insulin resistance with serum serum aspartate aminotransferase and cytokeratin [CK]18‐M30 levels) accurately identifies patients with fibrotic NASH. Our aim was to assess the performance of MACK‐3 and develop a novel, non‐invasive algorithm for diagnosing fibrotic NASH.

Methods

Six hundred and thirty‐six adults with biopsy‐proven non‐alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration‐controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.

Results

Metabolic syndrome (MetS), platelet count and MACK‐3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75–0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74–0.87) than that of MACK‐3 (AUROC: 0.75, 95%CI 0.68–0.82; P < 0.05) with a NPV of 93.2%. The sequential combination of this nomogram with LSM data avoided the need for liver biopsy in 56.9% of patients.

Conclusions

Our novel nomogram (combining MACK‐3, platelet count and MetS) shows promising utility for diagnosing fibrotic NASH. The sequential combination of this nomogram and vibration‐controlled transient elastography limits indeterminate results and reduces the number of unnecessary liver biopsies.

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More information

Accepted/In Press date: 24 March 2020
e-pub ahead of print date: 4 April 2020
Published date: 1 October 2020
Keywords: NAFLD, clinical, NASH, diagnostic tests, liver biopsy, liver fibrosis

Identifiers

Local EPrints ID: 439054
URI: http://eprints.soton.ac.uk/id/eprint/439054
ISSN: 0815-9319
PURE UUID: 9d77335c-7bd2-444b-8e14-5019687521a6
ORCID for Christopher Byrne: ORCID iD orcid.org/0000-0001-6322-7753

Catalogue record

Date deposited: 02 Apr 2020 16:31
Last modified: 28 Apr 2022 04:53

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Contributors

Author: Feng Gao
Author: Jiao-Feng Huang
Author: Kenneth I. Zheng
Author: Xiao-Yan Pan
Author: Hong-Lei Ma
Author: Wen-Yue Liu
Author: Giovanni Targher
Author: Yang-Yang Li
Author: Yong-Ping Chen
Author: Wah-Kheong Chan
Author: Ming-Hua Zheng

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