首页|Highly Increased Levels of Inter-α-inhibitor Heavy Chain 4 (ITIH4) in Autoimmune Cholestatic Liver Diseases

Highly Increased Levels of Inter-α-inhibitor Heavy Chain 4 (ITIH4) in Autoimmune Cholestatic Liver Diseases

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Background and Aims: There is an unmet need for new bi-omarkers to improve diagnostics and prognostics in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Inter-α-inhibitor heavy chain 4 (ITIH4) is an abun-dant, liver-produced protein, and its synthesis may be al-tered in liver diseases. We investigated whether ITIH4 plas-ma concentrations were affected in PBC and PSC patients. Methods: We developed an immunoassay specific for ITIH4 and determined ITIH4 plasma concentrations in 66 PBC, 126 PSC, 92 autoimmune hepatitis (AIH), 67 chronic hepatitis C (CHC), 33 alcoholic hepatitis (AH) patients and 138 healthy controls (HCs). Hepatic ITIH4 expression was investigated by immunohistochemistry in PBC. Results: The mean plas-ma concentration of ITIH4 was almost doubled in PBC [409 µg/mL (95％ CI: 388–431)] and 35％ higher in PSC [308 µg/mL, (95％ CI: 296–319)] compared with HCs [226 µg/mL (95％ CI: 221–231); p<0.001]. In PBC patients, ITIH4 correlated with IgM (rho=0.49, p<0.001). Responders to ursodeoxycholic acid treatment (UDCA) had lower levels of ITIH4 than incomplete responders [395 µg/mL (95％ CI: 364–425)] vs. 460 µg/mL (95％ CI: 421–498); p=0.02]. Four weeks of UDCA treatment had no effect (p=0.19). In-creased ITIH4 immunohistochemical staining was seen in a liver biopsy from a PBC patient. ITIH4 levels in AIH [224 µg/mL (95％ CI: 208–241)] and HCs were similar (p=0.8). ITIH4 levels were lower in AH [199 µg/mL (95％ CI: 175–223)] and CHC [202 µg/mL (192–212)] patients than in HCs (p<0.05). Conclusions: The plasma concentration of ITIH4 was highly elevated in patients with PBC and PSC, suggesting that ITIH4 should be further investigated as a biomarker in cholestatic liver disease.

Primary biliary cholangitisPrimary sclerosing cholangitisAutoim-mune hepatitisUrsodeoxycholic acid treatmentAlcoholic hepatitisChronic viral hepatitis

Tea Lund Laursen、Lars Bossen、Rasmus Pihl、Anne Troldborg、Thomas Damgaard Sandahl、Annette Gudmann Hansen、Trine Folserass、Mette Vesterhus、Henning Gr?nb?k、Steffen Thiel

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Department of Hepatology and Gastroenterology,Aarhus University Hospital,Aarhus,Denmark

Department of Biomedi-cine,Aarhus University,Aarhus,Denmark

Department of Rheumatology,Aarhus University Hospital,Aarhus,Denmark

Department of Clinical Medicine,Aarhus University,Aarhus,Denmark

Norwegian PSC Research Center,Department of Transplantation Medicine,Division of Surgery,Inflammatory Diseases and Transplantation,Oslo University Hospital Rik-shospitalet,Oslo,Norway

Haraldsplass Deaconess Hospital,Bergen,Norway

Department of Clinical Science,University of Bergen,Bergen,Norway

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2022

10.14218/JCTH.2021.00515

临床与转化肝病杂志(英文版)

临床与转化肝病杂志(英文版)

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年,卷(期)：2022.10(5)
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