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      Have serum vitamin D and ferritin a role in predicting the prognosis of autoimmune hepatitis treatment in children?

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          Abstract

          Aim of the study

          To investigate whether serum ferritin and vitamin D levels before starting autoimmune hepatitis (AIH) treatment have a role in disease prognosis regarding a therapeutic response.

          Material and methods

          The prospective study included 100 children diagnosed with AIH according to simplified criteria for diagnosis of AIH. They attended the Pediatric Hepatology Department, National Liver Institute, Menoufia University. The patients underwent measurement of liver transaminases before starting AIH treatment after 6 months from starting therapy. They underwent liver biopsy before starting treatment for proper diagnosis, grading, and staging; only 25 cases were compliant and underwent liver biopsy before treatment withdrawal.

          Results

          Serum ferritin and 25 hydroxy vitamin D levels were significantly higher among those with a complete response (1000-3100 ng/ml, 29-48 ng/ml) than a partial response (550-600 ng/ml, 23-28 ng/ml) and non-response (29.28-92.14, 2.16-8.72) ( p < 0.001).

          Conclusions

          Our study showed a relation between serum vitamin D before starting AIH treatment, the severity of AIH and response to therapy. This opens a new area of research on the potential use of vitamin D in patients with AIH. Also, hyperferritinemia at the diagnosis can predict the treatment response.

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          Most cited references30

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          Simplified criteria for the diagnosis of autoimmune hepatitis.

          Hans-Peter Dienes, Achiléa Bittencourt, Mark J. Czaja … (2008)
          Diagnosis of autoimmune hepatitis (AIH) may be challenging. However, early diagnosis is important because immunosuppression is life-saving. Diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) were complex and purely meant for scientific purposes. This study of the IAIHG aims to define simplified diagnostic criteria for routine clinical practice. Candidate criteria included sex, age, autoantibodies, immunoglobulins, absence of viral hepatitis, and histology. The training set included 250 AIH patients and 193 controls from 11 centers worldwide. Scores were built from variables showing predictive ability in univariate analysis. Diagnostic value of each score was assessed by the area under the receiver operating characteristic (ROC) curve. The best score was validated using data of an additional 109 AIH patients and 284 controls. This score included autoantibodies, immunoglobulin G, histology, and exclusion of viral hepatitis. The area under the curve for prediction of AIH was 0.946 in the training set and 0.91 in the validation set. Based on the ROC curves, two cutoff points were chosen. The score was found to have 88% sensitivity and 97% specificity (cutoff > or =6) and 81% sensitivity and 99% specificity (cutoff > or =7) in the validation set. A reliable diagnosis of AIH can be made using a very simple diagnostic score. We propose the diagnosis of probable AIH at a cutoff point greater than 6 points and definite AIH 7 points or higher.
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            Relapse is almost universal after withdrawal of immunosuppressive medication in patients with autoimmune hepatitis in remission.

            Nicole van Gerven, Bart J Verwer, Birgit I Witte … (2013)
            Current treatment strategies in autoimmune hepatitis (AIH) include long-term treatment with corticosteroids and/or azathioprine. Here we determined the risk of relapse after drug withdrawal in patients in long-term remission and factors associated with such a relapse.
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              Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation.

              Eliano Bonaccorsi-Riani, Alberto Sanchez-Fueyo, Juan José Lozano … (2011)
              Following organ transplantation, lifelong immunosuppressive therapy is required to prevent the host immune system from destroying the allograft. This can cause severe side effects and increased recipient morbidity and mortality. Complete cessation of immunosuppressive drugs has been successfully accomplished in selected transplant recipients, providing proof of principle that operational allograft tolerance is attainable in clinical transplantation. The intra-graft molecular pathways associated with successful drug withdrawal, however, are not well defined. In this study, we analyzed sequential blood and liver tissue samples collected from liver transplant recipients enrolled in a prospective multicenter immunosuppressive drug withdrawal clinical trial. Before initiation of drug withdrawal, operationally tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis. Furthermore, as compared with non-tolerant recipients, operationally tolerant patients exhibited higher serum levels of hepcidin and ferritin and increased hepatocyte iron deposition. Finally, liver tissue gene expression measurements accurately predicted the outcome of immunosuppressive withdrawal in an independent set of patients. These results point to a critical role for iron metabolism in the regulation of intra-graft alloimmune responses in humans and provide a set of biomarkers to conduct drug-weaning trials in liver transplantation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Exp Hepatol
                Journal ID (iso-abbrev): Clin Exp Hepatol
                Journal ID (publisher-id): CEH
                Title: Clinical and Experimental Hepatology
                Publisher: Termedia Publishing House
                ISSN (Print): 2392-1099
                ISSN (Electronic): 2449-8238
                Publication date (Electronic): 28 March 2024
                Publication date (Print): March 2024
                Volume: 10
                Issue: 1
                Pages: 53-61
                Affiliations
                [1 ]Pediatric Hepatology, Gastroenterology and Nutrition Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
                [2 ]Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
                [3 ]Laboratory Medicine Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
                [4 ]Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
                Author notes
                Address for correspondence: Salma Abdel Megeed Nagi, Pediatric Hepatology, Gastroenterology and Nutrition Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt. phone: +20 109 722 6684, fax: +20 048 205 3449. e-mail: salmanage@ 123456liver.menofia.edu.eg
                Article
                Publisher ID: 52701
                DOI: 10.5114/ceh.2024.136927
                PMC ID: 11100337
                PubMed ID: 38765911
                SO-VID: b2c69875-80f6-47cc-b03a-db36a5abb9b9
                Copyright © Copyright: © 2024 Clinical and Experimental Hepatology
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                Date received : 20 September 2023
                Date accepted : 09 November 2023
                Categories
                Subject: Original Paper

                Keywords: autoimmune hepatitis,ferritin,immunosuppressive therapy,serum vitamin d
                Data availability:
                Keywords: autoimmune hepatitis, ferritin, immunosuppressive therapy, serum vitamin d

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