Effect of PNPLA3 polymorphism on diagnostic performance of various non-invasive markers for diagnosing and staging nonalcoholic fatty liver disease
Effect of PNPLA3 polymorphism on diagnostic performance of various non-invasive markers for diagnosing and staging nonalcoholic fatty liver disease
Background and Aim: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver disease (NAFLD), but whether PNPLA3-I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype. Methods: Fifty-eight healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict hepatic steatosis (fatty liver index and hepatic steatosis index), nonalcoholic steatohepatitis (cytokeratin-18 M30 and M65), and significant fibrosis (≥F2 fibrosis) (fibrosis-4 and BARD), stratifying by rs738409 genotypes (CC and CG + GG groups). Results: Fatty liver index and hepatic steatosis index showed good diagnostic performance for diagnosing steatosis only in the CG + GG group with AUROCs ranging from 0.819 to 0.832. Cytokeratin-18 M30 (AUROC = 0.688) and M65 (AUROC = 0.678) had suboptimal performance for diagnosing nonalcoholic steatohepatitis in the CG + GG group, whereas both had good performance (AUROC = 0.814 and 0.813, respectively) in the CC group. BARD score showed good performance in the CG + GG group compared with the CC group (AUROC = 0.805 and 0.532, respectively). Fibrosis-4 had suboptimal performance in the CG + GG group and good performance in the CC group (AUROC = 0.662 and 0.801, respectively). Conclusions: Diagnostic performance of noninvasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of noninvasive diagnostic tests for diagnosing NAFLD.
Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, Noninvasive marker, Patatin-like phospholipase domain-containing protein 3, Single-nucleotide polymorphisms
1057-1064
Liu, Wen-Yue
3bfe6802-9fb3-4204-b240-a618d44cc5a1
Pan, Xiao-Yan
167535fb-0078-4c08-86d8-26d47008e345
Zheng, Kenneth I.
f6b488c7-4e4e-45f3-9078-e9c811bc2e57
Ma, Hong-Lei
b2c788d8-96d8-441b-8ac8-2a2386e65cc3
Zhu, Pei-Wu
57b40107-2dbf-42f0-9817-3071de1a671f
Wu, Xi-Xi
6954d429-5d43-47ef-b54f-4cff79090fbe
Rios, Rafael S.
987842cd-1666-4376-bfd1-03e7856fcfdb
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Wang, Xiao-Dong
4386ccdb-1ceb-4f72-834c-b987b631799b
Chen, Yong-Ping
6793a503-ee8d-4fd1-bc2a-c4b68c8c9571
Zheng, Ming-Hua
81634bd0-0fdd-4c94-9714-fbafc8be0137
June 2020
Liu, Wen-Yue
3bfe6802-9fb3-4204-b240-a618d44cc5a1
Pan, Xiao-Yan
167535fb-0078-4c08-86d8-26d47008e345
Zheng, Kenneth I.
f6b488c7-4e4e-45f3-9078-e9c811bc2e57
Ma, Hong-Lei
b2c788d8-96d8-441b-8ac8-2a2386e65cc3
Zhu, Pei-Wu
57b40107-2dbf-42f0-9817-3071de1a671f
Wu, Xi-Xi
6954d429-5d43-47ef-b54f-4cff79090fbe
Rios, Rafael S.
987842cd-1666-4376-bfd1-03e7856fcfdb
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Wang, Xiao-Dong
4386ccdb-1ceb-4f72-834c-b987b631799b
Chen, Yong-Ping
6793a503-ee8d-4fd1-bc2a-c4b68c8c9571
Zheng, Ming-Hua
81634bd0-0fdd-4c94-9714-fbafc8be0137
Liu, Wen-Yue, Pan, Xiao-Yan, Zheng, Kenneth I., Ma, Hong-Lei, Zhu, Pei-Wu, Wu, Xi-Xi, Rios, Rafael S., Targher, Giovanni, Byrne, Christopher, Wang, Xiao-Dong, Chen, Yong-Ping and Zheng, Ming-Hua
(2020)
Effect of PNPLA3 polymorphism on diagnostic performance of various non-invasive markers for diagnosing and staging nonalcoholic fatty liver disease.
Journal of Gastroenterology and Hepatology, 35 (6), .
(doi:10.1111/jgh.14894).
Abstract
Background and Aim: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver disease (NAFLD), but whether PNPLA3-I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype. Methods: Fifty-eight healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict hepatic steatosis (fatty liver index and hepatic steatosis index), nonalcoholic steatohepatitis (cytokeratin-18 M30 and M65), and significant fibrosis (≥F2 fibrosis) (fibrosis-4 and BARD), stratifying by rs738409 genotypes (CC and CG + GG groups). Results: Fatty liver index and hepatic steatosis index showed good diagnostic performance for diagnosing steatosis only in the CG + GG group with AUROCs ranging from 0.819 to 0.832. Cytokeratin-18 M30 (AUROC = 0.688) and M65 (AUROC = 0.678) had suboptimal performance for diagnosing nonalcoholic steatohepatitis in the CG + GG group, whereas both had good performance (AUROC = 0.814 and 0.813, respectively) in the CC group. BARD score showed good performance in the CG + GG group compared with the CC group (AUROC = 0.805 and 0.532, respectively). Fibrosis-4 had suboptimal performance in the CG + GG group and good performance in the CC group (AUROC = 0.662 and 0.801, respectively). Conclusions: Diagnostic performance of noninvasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of noninvasive diagnostic tests for diagnosing NAFLD.
Text
Manuscript_revised
- Accepted Manuscript
Text
Table 1
- Accepted Manuscript
Text
Table 2
- Accepted Manuscript
Text
Table_3
- Accepted Manuscript
Restricted to Repository staff only
Request a copy
Text
Table 4
- Accepted Manuscript
Restricted to Repository staff only
Request a copy
Image
Figure 1
- Accepted Manuscript
Restricted to Repository staff only
Request a copy
Image
Figure 2
- Accepted Manuscript
Restricted to Repository staff only
Request a copy
Show all 7 downloads.
More information
Accepted/In Press date: 8 October 2019
e-pub ahead of print date: 1 November 2019
Published date: June 2020
Keywords:
Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, Noninvasive marker, Patatin-like phospholipase domain-containing protein 3, Single-nucleotide polymorphisms
Identifiers
Local EPrints ID: 434880
URI: http://eprints.soton.ac.uk/id/eprint/434880
ISSN: 0815-9319
PURE UUID: 66a15c6c-008d-481a-9cff-ebfd82895c92
Catalogue record
Date deposited: 15 Oct 2019 16:30
Last modified: 17 Mar 2024 02:49
Export record
Altmetrics
Contributors
Author:
Wen-Yue Liu
Author:
Xiao-Yan Pan
Author:
Kenneth I. Zheng
Author:
Hong-Lei Ma
Author:
Pei-Wu Zhu
Author:
Xi-Xi Wu
Author:
Rafael S. Rios
Author:
Giovanni Targher
Author:
Xiao-Dong Wang
Author:
Yong-Ping Chen
Author:
Ming-Hua Zheng
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
