Plasma osteopontin in acute liver failure

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 1055ng/mL; range: 33-19,127), when compared to healthy controls (median in pre-SF patients: 41ng/mL; range 2.6-86.4). RA and SF post op patients had elevated OPN levels (37ng/mL and 198ng/mL respectively), well below those of the ALF patients. Median OPN levels were highest in acetaminophen (3603ng/mL) and ischemia-related ALF (4102ng/mL) as opposed to viral hepatitis (706ng/mL), drug-induced liver injury (353ng/mL) or autoimmune hepatitis (436ng/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.

Keywords: Acute liver failure; Cytokine; Inflammation; Liver necrosis.

Figure 1. Plasma OPN levels in ALF patients and controls

Plasma OPN levels are shown for 105 acute liver failure patients as overall group and as specific etiologies of ALF as well as 40 patients with rheumatoid arthritis (RA) and 35 patients undergoing posterior lumbar spinal fusion (SF). Each dot represents the OPN level. The horizontal line represents the median value in each group. ALF: acute liver failure, APAP: N-acetyl-p-aminophenol, the active compound of acetaminophen; DILI: drug-induced liver injury; IND: indeterminate; RA: rheumatoid arthritis; SP: spinal fusion, prior to surgery.

Figure 2. Correlation of OPN levels and outcomes in ALF patients

Patients who survived without transplantation (SS, n = 52) tended to have higher median admission plasma OPN levels compared to those who died (Death, n = 30) or received liver transplantation (Transplant, n = 23) (P=0.067).

Figure 3. Correlation of OPN values by etiology in spontaneous survivors

Median plasma OPN levels are shown for 52 ALF patients who spontaneously survived as the overall group and by specific etiologies: ALF: acute liver failure, Shock (n = 14), APAP: N-acetyl-p-aminophenol, the active compound of acetaminophen (n = 30); DILI: drug-induced liver injury (n = 12); IND: indeterminate (n = 12); AIH: autoimmune hepatitis (n = 12), Viral (n = 17), and Other (n = 8).