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J-shaped relationship between serum zinc levels and the severity of hepatic necro-inflammation in patients with MAFLD

J-shaped relationship between serum zinc levels and the severity of hepatic necro-inflammation in patients with MAFLD
J-shaped relationship between serum zinc levels and the severity of hepatic necro-inflammation in patients with MAFLD
Background and Aims Zinc is an essential trace element that plays an important role in maintaining health, and affecting gene expression, signal transduction and regulation of apoptosis. It is uncertain whether serum zinc levels are altered in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). We aimed to investigate the association between serum zinc levels and the severity of hepatic necro-inflammation (HN) in patients with MAFLD. Methods and Results Liver disease severity was graded histologically using the NAFLD activity score. HN was defined as the sum of ballooning and lobular inflammation. We used a smooth function regression model to analyze the relationship between serum zinc levels and HN. A total of 561 (76.5% men) patients with biopsy-confirmed MAFLD were enrolled. They had a mean age of 41.3 years, and a mean serum zinc level of 17.0 ± 4.1 μmol/L. Compared to those with mild hepatic necro-inflammation (MHN, grades 0-2; n=286), patients with severe hepatic necro-inflammation (SHN, grades 3-5; n=275) had lower serum zinc concentrations (16.3±4.2 vs. 17.6±4.0 μmol/L; p<0.001). However, a threshold saturation effect analysis showed that there was an inflection in serum zinc levels at 24 μmol/L. After adjustment for potential confounders, serum zinc levels <24 μmol/L were inversely associated with SHN (adjusted-odds ratio 0.88, 95%CI 0.83-0.93; p<0.001), whereas serum zinc levels >24 μmol/L were positively associated with SHN (adjusted-odds ratio 1.42, 95%CI: 1.03-1.97; p=0.035). Conclusions There is a J-shaped relationship between serum zinc levels and the severity of hepatic necro-inflammation in patients with biopsy-proven MAFLD.
Hepatic necro-inflammation, Liver biopsy, MAFLD, Serum zinc
0939-4753
1259-1265
Chen, Sui-Dan
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Zhang, Huai
93fa39bb-fc56-4fb1-80d7-01bc21cdbc6a
Rios, Rafael S.
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Li, Yang-Yang
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Zhu, Pei-Wu
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Jin, Yi
ec34985c-e69a-49bd-8689-f061f43fd8b8
Ma, Hong-Lei
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Tang, Liang-Jie
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Li, Gang
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Huang, Ou-Yang
b421237b-a428-41df-9eaf-f2c32ac029f4
Zheng, Kenneth I.
f503059d-6a92-4dc3-bbf0-d944d757d449
Byrne, Christopher
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Targher, Giovanni
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Zheng, Ming-Hua
3ef6b7f2-3a66-42d5-af48-1e0323f1f741
Chen, Sui-Dan
7a23d53e-2419-43cd-956c-f1ced0488292
Zhang, Huai
93fa39bb-fc56-4fb1-80d7-01bc21cdbc6a
Rios, Rafael S.
f96fb804-6a7e-4867-b9c3-ce523c6ef38a
Li, Yang-Yang
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Zhu, Pei-Wu
c2c848a3-a10f-46e8-8f03-81136bc1d05b
Jin, Yi
ec34985c-e69a-49bd-8689-f061f43fd8b8
Ma, Hong-Lei
45f2d300-ad0a-41d4-bc1b-6ba36fd1d748
Tang, Liang-Jie
301c5801-9235-444b-be29-3955c50d3e9c
Li, Gang
b251f35e-cd58-4e2b-a71a-fd1b38851774
Huang, Ou-Yang
b421237b-a428-41df-9eaf-f2c32ac029f4
Zheng, Kenneth I.
f503059d-6a92-4dc3-bbf0-d944d757d449
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Targher, Giovanni
fb906185-aa1c-4154-9b4c-b0cd0ece8e01
Zheng, Ming-Hua
3ef6b7f2-3a66-42d5-af48-1e0323f1f741

Chen, Sui-Dan, Zhang, Huai, Rios, Rafael S., Li, Yang-Yang, Zhu, Pei-Wu, Jin, Yi, Ma, Hong-Lei, Tang, Liang-Jie, Li, Gang, Huang, Ou-Yang, Zheng, Kenneth I., Byrne, Christopher, Targher, Giovanni and Zheng, Ming-Hua (2022) J-shaped relationship between serum zinc levels and the severity of hepatic necro-inflammation in patients with MAFLD. Nutrition, Metabolism & Cardiovascular Diseases, 32 (5), 1259-1265. (doi:10.1016/j.numecd.2022.01.035).

Record type: Article

Abstract

Background and Aims Zinc is an essential trace element that plays an important role in maintaining health, and affecting gene expression, signal transduction and regulation of apoptosis. It is uncertain whether serum zinc levels are altered in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). We aimed to investigate the association between serum zinc levels and the severity of hepatic necro-inflammation (HN) in patients with MAFLD. Methods and Results Liver disease severity was graded histologically using the NAFLD activity score. HN was defined as the sum of ballooning and lobular inflammation. We used a smooth function regression model to analyze the relationship between serum zinc levels and HN. A total of 561 (76.5% men) patients with biopsy-confirmed MAFLD were enrolled. They had a mean age of 41.3 years, and a mean serum zinc level of 17.0 ± 4.1 μmol/L. Compared to those with mild hepatic necro-inflammation (MHN, grades 0-2; n=286), patients with severe hepatic necro-inflammation (SHN, grades 3-5; n=275) had lower serum zinc concentrations (16.3±4.2 vs. 17.6±4.0 μmol/L; p<0.001). However, a threshold saturation effect analysis showed that there was an inflection in serum zinc levels at 24 μmol/L. After adjustment for potential confounders, serum zinc levels <24 μmol/L were inversely associated with SHN (adjusted-odds ratio 0.88, 95%CI 0.83-0.93; p<0.001), whereas serum zinc levels >24 μmol/L were positively associated with SHN (adjusted-odds ratio 1.42, 95%CI: 1.03-1.97; p=0.035). Conclusions There is a J-shaped relationship between serum zinc levels and the severity of hepatic necro-inflammation in patients with biopsy-proven MAFLD.

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Accepted/In Press date: 1 February 2022
e-pub ahead of print date: 8 February 2022
Published date: 1 May 2022
Additional Information: Funding sources This work is supported by grants from the National Natural Science Foundation of China (82070588), High-Level Creative Talents from the Department of Public Health in Zhejiang Province (S2032102600032), Project of New Century 551 Talent Nurturing in Wenzhou. GT is supported in part by grants from the University School of Medicine of Verona, Verona, Italy. CDB is supported in part by the Southampton NIHR Biomedical Research Centre (IS-BRC-20004), UK.
Keywords: Hepatic necro-inflammation, Liver biopsy, MAFLD, Serum zinc

Identifiers

Local EPrints ID: 454758
URI: http://eprints.soton.ac.uk/id/eprint/454758
ISSN: 0939-4753
PURE UUID: 545db806-ad10-45c8-890a-e4b5d8a1f38e
ORCID for Christopher Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 22 Feb 2022 17:42
Last modified: 01 Feb 2023 05:01

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Contributors

Author: Sui-Dan Chen
Author: Huai Zhang
Author: Rafael S. Rios
Author: Yang-Yang Li
Author: Pei-Wu Zhu
Author: Yi Jin
Author: Hong-Lei Ma
Author: Liang-Jie Tang
Author: Gang Li
Author: Ou-Yang Huang
Author: Kenneth I. Zheng
Author: Giovanni Targher
Author: Ming-Hua Zheng

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