Systemic PCSK9 elevation characterises autoimmune liver disease across sexes

URN zum Zitieren dieses Dokuments:: urn:nbn:de:bvb:355-epub-782014
DOI zum Zitieren dieses Dokuments:: 10.5283/epub.78201

Mester, Patricia ; Pavel, Vlad

; Stoeckert, Petra ; Müller, Martina ; Tews, Hauke Christian ; Buechler, Christa

Lizenz: Creative Commons Namensnennung 4.0 International
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Veröffentlichungsdatum dieses Volltextes: 25 Nov 2025 06:07

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum cholesterol. Its expression is particularly abundant in hepatocytes, yet its role in autoimmune liver diseases remains unclear. Here we investigated serum PCSK9 levels in patients with autoimmune liver diseases and compared them to healthy controls, with attention to sex-specific differences. Serum PCSK9 levels were measured in 100 patients with autoimmune liver diseases — 57 with primary sclerosing cholangitis (PSC), 33 with primary biliary cholangitis (PBC), and 10 with autoimmune hepatitis (AIH)—and 88 healthy controls. Subgroup analyses were conducted based on sex and disease type. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curves. PCSK9 levels were significantly elevated in patients with autoimmune liver diseases compared to healthy controls (p < 0.001). In male patients, serum PCSK9 levels discriminated between patients with PSC and controls. In female patients, they discriminated between patients with PBC and controls. The area under the ROC curve (AUROC) for distinguishing between these groups was 0.765 ± 0.057 and 0.834 ± 0.047, respectively. Patients with almost normal aminotransferase and cholestasis marker levels (n = 47) had significantly higher PCSK9 levels than controls. The AUROC was 0.788 ± 0.039 and a serum PCSK9 level of 224 ng/ml had a sensitivity of 92% and a specificity of 60% for diagnosing autoimmune liver disease. Serum PCSK9 levels did mostly not correlate with serum cholesterol, markers of liver disease severity, the model for end stage liver disease score, or fibrosis stage. Patients who experienced decompensation or required a liver transplant during the course of their disease had PCSK9 levels similar to those who did not experience these adverse events. Serum PCSK9 levels are elevated in both male and female patients with autoimmune liver diseases, independent of cholesterol levels or fibrosis stage. PCSK9 may serve as a biomarker in the diagnosis of autoimmune liver disease, even in patients with almost normal liver function test results.

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