Plasma osteopontin in acute liver failure. Issue 2 (June 2015)

• Record Type: Journal Article
• Authors: Srungaram, Praveen; Rule, Jody A.; Yuan, He Jun; Reimold, Andreas; Dahl, Benny; Sanders, Corron; Lee, William M.
• Is Part Of: Cytokine. Volume 73:Issue 2(2015)
• Page Start: 270
• Page End: 276
• Publication Date: 2015-06
• Subjects: ALF acute liver failure -- ALP alkaline phosphatase -- ALT alanine aminotransferase -- APAP acetaminophen -- AST aspartate aminotransferase -- DAS-28 Disease Activity Score-28 -- HE hepatic encephalopathy -- INR international normalized ratio -- OPN osteopontin -- RA rheumatoid arthritis -- RGD arginine-glycine-aspartic acid domain -- SF spinal fusion -- SIRS systemic inflammatory response syndrome -- SS spontaneous survival -- USALFSG US Acute Liver Failure Study Group -- VARA Veterans Affairs Rheumatoid Arthritis Registry -- WBC white blood cell; Acute liver failure -- Inflammation -- Liver necrosis -- Cytokine; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.02.021
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Osteopontin (OPN) is a cytokine that is elevated in settings associated with inflammation. Plasma OPN levels in acute liver failure patients were increased from 10- to 500-fold over normal. OPN levels in acute or chronic inflammation (RA, post-op) were only minimally elevated. Highest OPN values occurred with severe hepatocyte necrosis (acetaminophen or ischemia). The significance of OPN release remains to be determined, it may play a cytoprotective role. Abstract: Background: Osteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function in the setting of massive hepatocyte injury. Methods: OPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1 and 3 days after undergoing spine fusion (SF) surgery as a model for acute inflammation. Results: Median plasma OPN levels across all etiologies of ALF patients were elevated 10- to 30-fold: overall median 1055 ng/mL; range: 33–19, 127), when compared to healthy controls (median in pre-SF patients: 41 ng/mL; range 2.6–86.4). RA and SF post op patients had elevated OPN levels (37 ng/mL and 198 ng/mL respectively), well below those of the ALF patients. Median OPN levels were highest in acetaminophen (3603 ng/mL) and ischemia-related ALF (4102 ng/mL) as opposed to viral hepatitis (706 ng/mL), drug-induced liver injury (353 ng/mL) or autoimmune hepatitis (436 ng/mL), correlating with the degree of hepatocellular damage, as reflected by aminotransferase values ( R value: 0.47 for AST, p < 0.001). Conclusions: OPN levels appeared to correlate with degree of liver necrosis in ALF. Very high levels were associated with hyperacute injury and good outcomes. Whether OPN exerts a protective effect in limiting disease progression in this setting remains uncertain.