| Serum copper and ceruloplasmin levels as biomarkers reflecting liver fibrosis in children with autoimmune hepatitis |
Salma Abdel Megeed Nagi1,2 
, Mai Ibrahim Elashmawy3
, Amany E. Elashkar3
, Mohamed Zaeim Hafez4
, Ashraf A.E. Emara5, Osama Mohammad Abdelhay5, Albayoumi A.B. Fouda5, Mohamed AbdelAziz Doma6, Ahmad Mohamed Awad6, Ahmed Mohammed Saba6, Hesham Abdelrahman Ahmed7, Ahmed Mohamed Gad Allah8, Fatma Mahmoud Abdelraheem9, Mohamed A. Gad10, Mohamad A. Soliman11, Tamer I. Abdalrhman11, Khaled Hassaan Awad12, Ismael A.K.M. El-lebedy12, Mostafa M. Abdelnaser13, Mohammed Z. Abdel Kareem13, Marwa Fekry Hassan14
, Shymaa Sobhy Menshawy Khalifa15
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1Faculty of Medicine, King Salman International University, South Sinai, Egypt
2Pediatric Hepatology, Gastroenterology, and Nutrition Department, National Liver Institute, Menoufia University, Shebin ElKom, Egypt
3Clinical Pathology Department, National Liver Institute, Menoufia University, Shebin ElKom, Egypt
4Medical Physiology Department, Faculty of Medicine, Al-Azhar University (Assiut), Assiut, Egypt
5Medical Physiology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
6Medical Biochemistry Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
7Medical Biochemistry Department, Faculty of Medicine, Al-Azhar University (Assiut), Assiut, Egypt
8Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Al-Azhar University (Assiut), Assiut, Egypt
9Histology and Cell Biology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
10Medical Biochemistry Department, Faculty of Medicine, Al-Azhar University, Damietta, Egypt
11Medical Histology and Cell Biology Department, Faculty of Medicine, Al-Azhar University (Assiut), Assiut, Egypt
12Pediatric Department, Faculty of Medicine, Al-Azhar University (Assiut), Assiut, Egypt
13Medical Microbiology and Immunology Departments, Faculty of Medicine, Al-Azhar University (Assiut), Assiut, Egypt
14Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia, Egypt;
15Pediatrics Department, Faculty of Medicine, Menoufia University, Shebin ElKom, Egypt |
Correspondence:
Salma Abdel Megeed Nagi, Email: salmanage@liver.menofia.edu.eg
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Received: 4 May 2025 • Revised: 11 June 2025 • Accepted: 11 June 2025 |
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| Abstract |
Background
Clinical, biochemical, histological, and immunological indicators are frequently used to diagnose autoimmune hepatitis (AIH), a chronic inflammatory liver disease affecting children. Wilson disease, which resembles AIH, is mainly evaluated using serum ceruloplasmin and copper levels. However, changes in these biomarkers have also been observed in AIH, raising the question of whether they could be useful for evaluating children with AIH.
Purpose
When selecting a treatment plan and estimating the long-term prognosis of patients with AIH, assessing the liver fibrosis stage is crucial. It is also crucial to identify noninvasive indicators of liver fibrosis, for which ceruloplasmin has been suggested as a biomarker in several liver diseases. Therefore, this study aimed to investigate the potential significance of serum ceruloplasmin and copper levels for identifying liver fibrosis in children with AIH.
Methods
One hundred children with AIH treated at Menoufia University’s National Liver Institute Pediatric Hepatology, Gastroenterology, and Nutrition Department were enrolled. The duration of the study was 5 years (February 2020 to February 2025). The patients' histopathological, radiographic, laboratory, and clinical data were collected. We used the revised score to diagnose AIH. A Beckman Coulter AU480 chemistry analyzer was used to measure serum copper, while an enzyme-linked immunosorbent assay was used to measure serum ceruloplasmin.
Results
Serum ceruloplasmin levels were considerably lower in patients with advanced fibrosis (F3–4) than in those without advanced fibrosis (F0–2) (P<0.001). However, in patients with extensive fibrosis, the serum copper levels were considerably elevated (P<0.001). Compared to serum copper level, which had an area under a curve of 0.939 (95% confidence interval [CI], 0.887–0.991; P<0.001) and a cutoff of >24.7 mg/dL (90.8% sensitivity, 66.9% specificity), ceruloplasmin level had an area under a curve of 0.945 (95% CI, 0.889–1.00; P<0.001), suggesting that it could be a useful tool for the detection of advanced liver fibrosis in children.
Conclusion
To estimate the long-term prognosis of patients with AIH, it is crucial to assess liver fibrosis stage. It is crucial to identify noninvasive indicators of liver fibrosis, for which ceruloplasmin has been suggested as a biomarker. Therefore, serum copper and ceruloplasmin levels may provide important information for the identification of advanced liver fibrosis in children with AIH. |
| Key Words:
Autoimmune hepatitis, Ceruloplasmin, Liver fibrosis, Serum copper, Wilson disease |
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