{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:55:22Z","timestamp":1789768522440,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T00:00:00Z","timestamp":1711152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Biological antioxidant potential (BAP) and Reactive Oxygen Metabolites (dROMs) are two tests complementarily assessing systemic oxidative statuses (SOSs) that are never applied in chronic liver disorders (CLDs). We enrolled 41 ursodeoxycholic acid (UDCA)-na\u00efve Primary Biliary Cholangitis (PBC) patients [age: 58.61 \u00b1 11.26 years; females (F): 39], 40 patients with metabolic-dysfunction-associated steatotic livers (age: 54.30 \u00b1 11.21; F: 20), 52 patients with HBV (age: 52.40 \u00b1 8.22; F: 34), 50 patients with (age: 56.44 \u00b1 7.79, F: 29), and 10 controls (age: 52.50 \u00b1 9.64; F: 7). Liver fibrosis and the steatosis severity were determined using transient elastography, and the SOS was balanced using d-ROMs and the BAP test. The gene expressions of superoxide dismutase (SOD1; SOD2) and glutathione peroxidase (GPx1) were evaluated using real-time PCR in advanced fibrosis (AF: F3F4) in patients with PBC. In contrast to other CLDs, in PBC the dROMs and BAP levels were, respectively, directly and inversely correlated with hepatic fibrosis (dROMs, R: 0.883; BAP, R: \u22120.882) and steatosis (dROMs, R: 0.954; BAP, R: \u22120931) severity (p &lt; 0.0001 all). Patients with PBC also revealed a progressively increasing trend of d-ROMs (F0\u2013F2 vs. F3: p = 0.0008; F3 vs. F4: p = 0.04) and reduction in BAP levels (F0\u2013F2 vs. F3: p = 0.0007; F3 vs. F4 p = 0.04) according to the worsening of liver fibrosis. In AF-PBC, the SOD1, SOD2, and GPx1 expressions were significantly downregulated in patients presenting SOS imbalance (SOD1, p = 0.02; SOD2, p = 0.03; GPx1, p = 0.02). SOS disequilibrium represents a leitmotiv in patients with PBC, perfectly reflecting their liver disease progression status.<\/jats:p>","DOI":"10.3390\/antiox13040387","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:47:11Z","timestamp":1711370831000},"page":"387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Systemic Oxidative Balance Reflects the Liver Disease Progression Status for Primary Biliary Cholangitis (Pbc): The Narcissus Fountain"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4153-815X","authenticated-orcid":false,"given":"Marcello","family":"Dallio","sequence":"first","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2970-9019","authenticated-orcid":false,"given":"Mario","family":"Romeo","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4938-5805","authenticated-orcid":false,"given":"Marina","family":"Cipullo","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2947-431X","authenticated-orcid":false,"given":"Lorenzo","family":"Ventriglia","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4215-9068","authenticated-orcid":false,"given":"Flavia","family":"Scognamiglio","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7600-290X","authenticated-orcid":false,"given":"Paolo","family":"Vaia","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-6613","authenticated-orcid":false,"given":"Giorgia","family":"Iadanza","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-9714","authenticated-orcid":false,"given":"Annachiara","family":"Coppola","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0885-0793","authenticated-orcid":false,"given":"Alessandro","family":"Federico","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ali, S.S., Ahsan, H., Zia, M.K., Siddiqui, T., and Khan, F.H. (2020). Understanding Oxidants and Antioxidants: Classical Team with New Players. J. Food Biochem., 44.","DOI":"10.1111\/jfbc.13145"},{"key":"ref_3","first-page":"33","article-title":"Oxidative Stress and Antioxidant Status in Patients with Autoimmune Liver Diseases","volume":"20","author":"Kaffe","year":"2015","journal-title":"Redox Rep. Commun. Free Radic. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.3382\/ps\/pey407","article-title":"From Oxidative Stress to Inflammation: Redox Balance and Immune System","volume":"98","author":"Lauridsen","year":"2019","journal-title":"Poult. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26087","DOI":"10.3390\/ijms161125942","article-title":"The Role of Oxidative Stress and Antioxidants in Liver Diseases","volume":"16","author":"Li","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1055\/s-0039-1697617","article-title":"The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review","volume":"40","author":"Lleo","year":"2020","journal-title":"Semin. Liver Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0925-4439(02)00225-9","article-title":"Oxidant Stress Is a Significant Feature of Primary Biliary Cirrhosis","volume":"1637","author":"Aboutwerat","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jaut.2008.03.005","article-title":"Activation of ATM Signaling Pathway Is Involved in Oxidative Stress-Induced Expression of Mito-Inhibitory p21WAF1\/Cip1 in Chronic Non-Suppurative Destructive Cholangitis in Primary Biliary Cirrhosis: An Immunohistochemical Study","volume":"31","author":"Sasaki","year":"2008","journal-title":"J. Autoimmun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1016\/S0006-2952(02)01391-6","article-title":"Antioxidant Properties of Ursodeoxycholic Acid","volume":"64","author":"Lapenna","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/j.clinbiochem.2011.09.008","article-title":"Long-Term Ursodeoxycholate Improves Circulating Redox Changes in Primary Biliary Cirrhotic Patients","volume":"44","author":"Grattagliano","year":"2011","journal-title":"Clin. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Hu, X., Chang, J., Chen, J., Han, X., Zhang, T., Shen, J., Shang, N., Han, J., and Wang, H. (2021). The Liver Steatosis Severity and Lipid Characteristics in Primary Biliary Cholangitis. BMC Gastroenterol., 21.","DOI":"10.1186\/s12876-021-01974-4"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1111\/j.1530-0277.1998.tb03973.x","article-title":"Soluble Proteins Modified with Acetaldehyde and Malondialdehyde Are Immunogenic in the Absence of Adjuvant","volume":"22","author":"Thiele","year":"1998","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). EASL Clinical Practice Guidelines: The Diagnosis and Management of Patients with Primary Biliary Cholangitis. J. Hepatol., 67, 145\u2013172.","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2174\/1871530319666181221150352","article-title":"Probiotics Efficacy on Oxidative Stress Values in Inflammatory Bowel Disease: A Randomized Double-Blinded Placebo-Controlled Pilot Study","volume":"19","author":"Ballini","year":"2019","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3164\/jcbn.22-79","article-title":"Balance of the Prooxidant and Antioxidant System Is Associated with Mortality in Critically Ill Patients","volume":"72","author":"Izumino","year":"2023","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_16","first-page":"65","article-title":"Serum Diacron-Reactive Oxygen Metabolites (d-ROMs) and Biological Antioxidant Potential (BAP) in Patients with ATTR-PN","volume":"26","author":"Obayashi","year":"2019","journal-title":"Amyloid Int. J. Exp. Clin. Investig. Off. J. Int. Soc. Amyloidosis"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection. J. Hepatol., 67, 370\u2013398.","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"ref_18","unstructured":"European Association for the Study of the Liver, Clinical Practice Guidelines Panel, and EASL Governing Board representative (2020). EASL Recommendations on Treatment of Hepatitis C: Final Update of the Series\u2606. J. Hepatol., 73, 1170\u20131218."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A Multisociety Delphi Consensus Statement on New Fatty Liver Disease Nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatol. Baltim. Md"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/j.1360-0443.1993.tb02093.x","article-title":"Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption\u2014II","volume":"88","author":"Saunders","year":"1993","journal-title":"Addict. Abingdon Engl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1002\/hep.25993","article-title":"Determination of Reliability Criteria for Liver Stiffness Evaluation by Transient Elastography","volume":"57","author":"Boursier","year":"2013","journal-title":"Hepatol. Baltim. Md"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.ultrasmedbio.2010.07.005","article-title":"Controlled Attenuation Parameter (CAP): A Novel VCTETM Guided Ultrasonic Attenuation Measurement for the Evaluation of Hepatic Steatosis: Preliminary Study and Validation in a Cohort of Patients with Chronic Liver Disease from Various Causes","volume":"36","author":"Sasso","year":"2010","journal-title":"Ultrasound Med. Biol."},{"key":"ref_23","first-page":"71","article-title":"Implication of relationship between oxidative stress and antioxidant status in blood serum","volume":"284","author":"Kajaia","year":"2018","journal-title":"Georgian Med. News"},{"key":"ref_24","unstructured":"Societ\u00e0 Italiana Di Nutrizione Umana (SINU) (2014, August 15). Tabelle LARN 2014. Available online: Http:\/\/Www.Sinu.It\/Html\/Pag\/Tabelle_larn_2014_rev.Asp."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/hep.21151","article-title":"Assessment of Biliary Fibrosis by Transient Elastography in Patients with PBC and PSC","volume":"43","author":"Corpechot","year":"2006","journal-title":"Hepatol. Baltim. Md"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1053\/j.gastro.2019.01.042","article-title":"Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients with Nonalcoholic Fatty Liver Disease","volume":"156","author":"Peter","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_27","first-page":"242","article-title":"Non-Invasive Assessment of Liver Fibrosis by Stiffness Measurement in Patients with Chronic Hepatitis B","volume":"29","author":"Marcellin","year":"2009","journal-title":"Liver Int. Off. J. Int. Assoc. Study Liver"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/hep.20506","article-title":"Noninvasive Assessment of Liver Fibrosis by Measurement of Stiffness in Patients with Chronic Hepatitis C","volume":"41","author":"Ziol","year":"2005","journal-title":"Hepatol. Baltim. Md"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.clinre.2011.08.001","article-title":"The Controlled Attenuation Parameter (CAP): A Novel Tool for the Non-Invasive Evaluation of Steatosis Using Fibroscan","volume":"36","author":"Sasso","year":"2012","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1270391","DOI":"10.3389\/fimmu.2023.1270391","article-title":"Environmental Bisphenol A Exposure Triggers Trained Immunity-Related Pathways in Monocytes","volume":"14","author":"Dallio","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8082","DOI":"10.3748\/wjg.v20.i25.8082","article-title":"Oxidative Stress as a Crucial Factor in Liver Diseases","volume":"20","author":"Michalak","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_32","first-page":"453","article-title":"Malondialdehyde (MDA) as a lipid peroxidation marker","volume":"57","author":"Wardas","year":"2004","journal-title":"Wiadomosci. Lek. Wars. Pol. 1960"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.toxlet.2020.04.006","article-title":"Urinary 8-Isoprostane as a Biomarker for Oxidative Stress. A Systematic Review and Meta-Analysis","volume":"328","author":"Graille","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1111\/j.1872-034X.2010.00717.x","article-title":"Primary Biliary Cirrhosis Is Associated with Oxidative Stress and Endothelial Dysfunction but Not Increased Cardiovascular Risk","volume":"40","author":"Cash","year":"2010","journal-title":"Hepatol. Res. Off. J. Jpn. Soc. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.nut.2015.02.005","article-title":"Exercise and Oxidative Stress: Potential Effects of Antioxidant Dietary Strategies in Sports","volume":"31","author":"Pingitore","year":"2015","journal-title":"Nutr. Burbank Los Angel. Cty. Calif"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.gerinurse.2022.09.013","article-title":"Dietary Diversity, Diet Quality, and Oxidative Stress in Older Adults","volume":"48","author":"Kong","year":"2022","journal-title":"Geriatr. Nurs. N. Y. N"},{"key":"ref_37","first-page":"277","article-title":"Alcohol, Oxidative Stress, and Free Radical Damage. Alcohol Res","volume":"27","author":"Wu","year":"2003","journal-title":"Health J. Natl. Inst. Alcohol Abuse Alcohol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"108365","DOI":"10.1016\/j.mrrev.2021.108365","article-title":"Relationships among Smoking, Oxidative Stress, Inflammation, Macromolecular Damage, and Cancer","volume":"787","author":"Caliri","year":"2021","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.yfrne.2014.04.004","article-title":"Gender Differences in Autoimmune Disease","volume":"35","author":"Ngo","year":"2014","journal-title":"Front. Neuroendocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.cld.2018.03.009","article-title":"Antimitochondrial Antibody-Negative Primary Biliary Cholangitis: Is It Really the Same Disease? Clin","volume":"22","author":"Chascsa","year":"2018","journal-title":"Liver Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5465","DOI":"10.1016\/j.bbagen.2013.04.036","article-title":"Redox Properties of Serum Albumin","volume":"1830","author":"Anraku","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bbadis.2016.11.010","article-title":"Mitochondrial Dysfunction and Oxidative Stress in Metabolic Disorders\u2014A Step towards Mitochondria Based Therapeutic Strategies","volume":"1863","author":"Bhatti","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2152\/jmi.64.7","article-title":"Primary Biliary Cholangitis: Its Pathological Characteristics and Immunopathological Mechanisms","volume":"64","author":"Tsuneyama","year":"2017","journal-title":"J. Med. Investig. JMI"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"818570","DOI":"10.1155\/2015\/818570","article-title":"Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk","volume":"2015","author":"Koenig","year":"2015","journal-title":"Dis. Markers"},{"key":"ref_45","first-page":"509","article-title":"Oxidative Stress Modulates Osteoblastic Differentiation of Vascular and Bone Cells. Free Radic","volume":"31","author":"Mody","year":"2001","journal-title":"Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.14309\/ajg.0000000000001285","article-title":"A Comparison of Prognostic Scores (Mayo, UK-PBC, and GLOBE) in Primary Biliary Cholangitis","volume":"116","author":"Goet","year":"2021","journal-title":"Am. J. Gastroenterol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/4\/387\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:17:34Z","timestamp":1760105854000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/4\/387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,23]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["antiox13040387"],"URL":"https:\/\/doi.org\/10.3390\/antiox13040387","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,23]]}}}