Features of liver injury in 138 Chinese patients with NICCD

MinYan Jiang; MinZhi Peng; ZhiKun Lu; YongXian Shao; ZongCai Liu; XiuZhen Li; YunTing Lin; Li Liu; Wen Zhang; YanNa Cai

doi:10.1515/jpem-2023-0026

Article

Features of liver injury in 138 Chinese patients with NICCD

MinYan Jiang , MinZhi Peng , ZhiKun Lu , YongXian Shao , ZongCai Liu , XiuZhen Li , YunTing Lin , Li Liu , Wen Zhang and YanNa Cai

Published/Copyright: November 10, 2023

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 36 Issue 12

Abstract

Objectives

To find biochemical and molecular markers can assist in identifying serious liver damage of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) patients.

Methods

138 patients under 13 days to 1.1 year old diagnosed of NICCD in our center from 2004 to 2020. Base on the abnormal liver laboratory tests, we divided 138 patients into three groups: acute liver failure (ALF), liver dysfunction, and non-liver dysfunction groups, then compared their clinical, biochemical and, molecular data.

Results

96 % of 138 patients had high levels of citrulline and high ratio of threonine to serine, which is the distinctive feature of plasma amino acid profile for NICCD. A total of 18.1 % of 138 patients had evidence of ALF who presented the most severity hepatic damage, 51.5 % had liver dysfunction, and the remaining 30.4 % presented mild clinical symptoms (non-liver dysfunction). In ALF group, the levels of citrulline, tyrosine, TBIL, ALP, and γ-GT was significantly elevated, and the level of ALB and Fisher ratio was pronounced low. Homozygous mutations of 1,638_1660dup, IVS6+5G.A, or IVS16ins3kb in SLC25A13 gene were only found in ALF and liver dysfunction groups. Supportive treatment including medium-chain triglyceride supplemented diet and fresh frozen plasma could be life-saving and might reverse ALF.

Conclusions

High level of citrulline, tyrosine, TBIL, ALP, γ-GT, and ammonia, low level of albumin, and low Fisher ratio were predictors to suggest severe liver damage in NICCD patients who may go on to develop fatal metabolic disorder. Early identification and proper therapy is particularly important for these patients.

Keywords: amino acids; citrin deficiency; NICCD; SLC25A13

Corresponding authors: Wen Zhang and YanNa Cai, Department of Genetics and Endocrinology, Guangzhou Women and Children’s Medical Center, 9 Jinsui Road, Guangzhou 510623, P.R. China, Phone/Fax: +86 020 38076074, E-mail: zhw2001zhw@126.com (W. Zhang), anniecai95@126.com (Y. Cai)

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: 81800789

Award Identifier / Grant number: 81802125

Research ethics: The study protocol conforms to ethical guidelines of the Declaration of Helsinki in 2000, and the Ethics Committee on human research of the Guangzhou Women and Children’s Medical Center.
Informed consent: Informed consent was obtained from all individuals included in this study.
Author contributions: MinYan Jiang designed and wrote the manuscript. MinZhi Peng cellected data and revised the manuscipt. YongXian Shao and ZhiKun Lu were responsible for SLC25A13 gene detection. ZongCai Liu and YunTing Lin were responsible for data statiscal analysis. XiuZhen Li and Wen Zhang diagnosed and followed up the NICCD patients. YanNa Cai designed and revised the manuscript.
Competing interests: Authors state no conflict of interest.
Research funding: This work was supported by the National Natural Science Foundation of China (grant number 81800789 and 81802125).
Data availability: Original dataset was available from the corresponding author upon reasonable request.

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Received: 2023-01-17

Accepted: 2023-10-16

Published Online: 2023-11-10

Published in Print: 2023-12-15

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Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0026

Keywords for this article

amino acids; citrin deficiency; NICCD; SLC25A13