Clinical and Experimental Hepatology
eISSN: 2449-8238
ISSN: 2392-1099
Clinical and Experimental Hepatology
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1/2025
vol. 11
 
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abstract:
Original paper

NADK as a molecular marker to distinguish between alcohol- and non-alcohol-associated liver cirrhosis: A pilot study

Ki-Hoon Park
1, 2
,
Seok-Hyung Kim
3
,
So-Woon Kim
4
,
Kiyong Na
4
,
Sunyoung Kim
5
,
Young-Il Choi
6
,
Hyung-Joo Chung
1
,
Junyang Jung
2, 7, 8
,
Na Young Jeong
9

  1. Department of Anesthesiology and Pain Medicine, College of Medicine, Kosin University, South Korea
  2. Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, South Korea
  3. Sarcopenia Total Solution Center, Wonkwang University, South Korea
  4. Department of Pathology, College of Medicine, Kyung Hee University Medical Center, Kyung Hee University, South Korea
  5. Department of Family Medicine, College of Medicine, Kyung Hee University Medical Center, Kyung Hee University, South Korea
  6. Department of Surgery, College of Medicine, Kosin University, South Korea
  7. Department of Biomedical Science, Graduate School, Kyung Hee University, South Korea
  8. Department of Precision Medicine, College of Medicine, Kyung Hee University, South Korea
  9. Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, South Korea
Clin Exp HEPATOL 2025; 11, 1: 71-80
DOI: https://doi.org/10.5114/ceh.2025.146956
Online publish date: 2025/03/07
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Aim of the study:
We investigated whether nicotinamide adenine dinucleotide kinase (NADK) expression is selectively diminished in alcohol-associated liver cirrhosis (AC), and evaluated its potential as a biomarker for this condition.

Material and methods:
Human liver samples were obtained during liver transplantation or resection procedures at Kosin University Gospel Hospital and classified into two groups: AC and non-AC (NAC). NAD+ and NADP+ levels were measured using liquid chromatography-mass spectrometry (LC-MS). RNA-seq data from the NCBI Gene Expression Omnibus were utilized to identify AC-specific differentially expressed genes (DEGs). Multi-level expression analyses and immunohistochemistry were performed to assess NADK expression in liver tissues.

Results:
LC-MS analysis indicated a significant reduction in NAD+ and NADP+ levels in AC patients compared to both normal and NAC groups, with a corresponding increase in the NAD+/NADP+ ratio (AC = 3.93, NAC = 2.75, normal = 2.64). We identified 881 AC-specific DEGs, including 27 kinase-encoding genes. Multi-level expression analyses confirmed a significant decrease in NADK gene expression in AC patients. Immunohistochemistry showed a marked reduction in NADK protein expression in AC patients, underscoring its involvement in altered metabolic processes.

Conclusions:
This study revealed a distinct decrease in NADK expression in AC, suggesting its utility as a molecular marker for diagnosing and understanding metabolic dysregulation in these patients. These findings provide a foundation for developing targeted therapeutic strategies for alcohol-associated liver cirrhosis.

keywords:

nicotinamide-adenine dinucleotide (NAD), NAD kinase (NADK), alcoholic liver cirrhosis, meta-analysis, biomarker
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