Impact of autoimmune phenomena on the clinical presentation and prognosis of Wilson’s disease: a retrospective cohort study

Abstract

Aim: To investigate the clinical relevance of autoimmune phenomena (AP), including autoantibody positivity and elevated serum immunoglobulins, in patients with Wilson’s disease (WD), particularly with respect to disease severity and prognosis.

Methods: We retrospectively enrolled treatment-naïve WD patients (Leipzig score ≥ 4) and classified them as WD with AP (AP-WD) or WD without AP (NAP-WD) based on autoantibody positivity (titer ≥ 1:100) and/or immunoglobulin G (IgG) above the upper limit of normal. Baseline laboratory data, clinical complications, and liver histopathology were compared. Patients received standard anti-copper therapy and were followed longitudinally to evaluate the impact of AP on liver-related outcomes.

Results: Eighty-six treatment-naïve WD patients were included (48 AP-WD, 38 NAP-WD). At baseline, AP-WD patients exhibited more severe laboratory and clinical features, including lower platelet counts, reduced albumin, prolonged international normalized ratio, higher aspartate aminotransferase-to-platelet ratio index (APRI), Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD), and Child-Pugh scores, and greater prevalence of ascites (all P < 0.05). Histopathological analysis demonstrated increased plasma cell infiltration and heightened portal inflammatory activity in the AP-WD group (P < 0.05). Longitudinal follow-up revealed that the presence of AP was independently associated with an increased risk of adverse liver-related events, including liver transplantation, or death.

Conclusion: AP is common in WD and correlates with more severe hepatic dysfunction and poorer long-term outcomes. Screening for autoantibodies and IgG levels in newly diagnosed WD patients may provide important prognostic insight and facilitate early risk stratification, guiding tailored monitoring and management strategies.

Keywords

Wilson’s disease / autoimmune / prognosis / clinical features / liver histology

References

[1] Tang S,Yu H.The potential serum sphingolipid biomarkers for distinguishing Wilson disease.Clin Chim Acta2024;553:117740

[2] Li S,Chen S.Clinical characteristics and prognosis of early diagnosed Wilson’s disease: a large cohort study.Liver Int2024;44:2424-33

[3] Yang RM,Cai W.Chinese multidisciplinary expert consensus on orphan/anticopper drugs and other non-drug management of hepatolenticular degeneration.Curr Neuropharmacol2025;23:1683-708 PMCID:PMC12645139

[4] Roberts EA.Current and emerging issues in Wilson’s disease.N Engl J Med2023;389:922-38

[5] Cai H,Wang XP.ATP7B gene therapy of autologous reprogrammed hepatocytes alleviates copper accumulation in a mouse model of Wilson’s disease.Hepatology2022;76:1046-57 PMCID:PMC9790736

[6] Brennan PN,Manship T.Guideline review: EASL clinical practice guidelines: drug-induced liver injury (DILI).Frontline Gastroenterol2022;13:332-6 PMCID:PMC9186030

[7] Antczak-Kowalska M,Eyileten C.Autoantibodies in Wilson disease: impact on clinical course.JIMD Rep2022;63:508-17 PMCID:PMC9458613

[8] Jańczyk W,Trojanowska I,Cukrowska B.Prevalence and significance of autoantibody seropositivity in children with Wilson’s disease.Diagnostics2023;13:768 PMCID:PMC9955693

[9] Santos BC,Faria LC.Wilson’s disease presentation resembling autoimmune hepatitis.BMJ Case Rep2019;12:e230721 PMCID:PMC6827793

[10] Milkiewicz P,Hubscher SG.Wilson’s disease with superimposed autoimmune features: report of two cases and review.J Gastroenterol Hepatol2000;15:570-4

[11] Lopes SR,Sequeira C,Gamito É.Diagnostic pitfalls in Wilson disease with autoimmune features: a case report.GE Port J Gastroenterol2025;Epub ahead of print: PMCID:PMC12252758

[12] Ferenci P,Loudianos G.Diagnosis and phenotypic classification of Wilson disease.Liver Int2003;23:139-42

[13] European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis.J Hepatol2018;69:406-60. (in Chinese)

[14] Medical Association Tuberculosis Branch. [Guidelines for diagnosis and management of drug-induced liver injury caused by anti-tuberculosis drugs (2024 version)].Zhonghua Jie He He Hu Xi Za Zhi2024;47:1069-90

[15] Hadjout T,Saad M.Is there an alternative to the indirect immunofluorescence ANA HEp-2 assay for the diagnosis of connective tissue diseases?.Front Immunol2025;16:1669124 PMCID:PMC12620368

[16] Inherited Metabolic Liver Disease Collaboration Group, Chinese Society of Hepatology, Chinese Medical Association. [Guidelines for the diagnosis and treatment of hepatolenticular degeneration (2022 edition)].Zhonghua Gan Zang Bing Za Zhi2022;30:9-20. (in Chinese)

[17] Chowdhury AB.Liver biopsy for assessment of chronic liver diseases: a synopsis.Clin Exp Med2023;23:273-85 PMCID:PMC10224864

[18] Arase Y,Anzai K.Clinicopathological features of autoimmune hepatitis with IgG4-positive plasma cell infiltration.Dig Dis2021;39:225-33 PMCID:PMC8117379

[19] Rinella ME,Siddiqui MS.AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease.Hepatology2023;77:1797-835 PMCID:PMC10735173

[20] Pashnina IA,Fedotkina TV.Antinuclear autoantibodies in health: autoimmunity is not a synonym of autoimmune disease.Antibodies2021;10:9 PMCID:PMC8006153

[21] Association for the Study of the Liver. EASL-ERN Clinical Practice Guidelines on Wilson’s disease.J Hepatol2025;Epub ahead of print:

[22] Dara N,Sayyari AA,Hosseini AH.Simultaneous presentation of Wilson’s disease and autoimmune hepatitis; a case report and review of literature.Hepat Mon2015;15:e29043 PMCID:PMC4532869

[23] Rosenblum MD,Abbas AK.Mechanisms of human autoimmunity.J Clin Invest2015;125:2228-33 PMCID:PMC4518692

[24] Shlomchik MJ,Mamula MJ.From T to B and back again: positive feedback in systemic autoimmune disease.Nat Rev Immunol2001;1:147-53

[25] Han K.Restricted mean survival time for survival analysis: a quick guide for clinical researchers.Korean J Radiol2022;23:495-9 PMCID:PMC9081686