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 1055 ng/mL; range: 33 – 19127), 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.

Candidate biomarkers for the diagnosis and prognosis of drug‐induced liver injury: An international collaborative effort

“…The increase in OPN observed in this study is in contrast to recent data demonstrating that patients with acute liver failure (from various etiologies) who died/received a transplant had reduced levels of plasma OPN compared with those who recovered . The difference between these studies may be related to the timing of sample collection.…”

Serum biomarkers of drug‐induced liver injury: Current status and future directions

“…Elevated levels of OPN may simply correlate with the extent of hepatocyte loss not otherwise reflected in biomarkers such as TBIL. It is of note that the association of liver failure with the increase in OPN levels observed in this study contrasts with data demonstrating that patients with acute liver failure (from various etiologies) who died or received a transplant had reduced levels of plasma OPN compared with those who recovered . The difference between this study and the DILIN study may be related to the timing of the sample collection.…”

“…It is of note that the association of liver failure with the increase in OPN levels observed in this study contrasts with data demonstrating that patients with acute liver failure (from various etiologies) who died or received a transplant had reduced levels of plasma OPN compared with those who recovered. 80 The difference between this study and the DILIN study may be related to the timing of the sample collection. Entry into the previously conducted studies required acute liver failure to be occurring at enrollment (INR ≥1.5…”

Serum osteopontin is a predictor of prognosis for HBV‑associated acute‑on‑chronic liver failure

“…Previous studies have demonstrated that two forms of OPN coexist: An intracellular form (iOPN) and a secreted form (sOPN) (15,29,30). Although sOPN was measured in the present study, further studies are imperative to investigate the role of iOPN in lymphocytes and dendritic cells.…”

“…Nevertheless, in mice models of liver injury induced by diethylnitrosamine or ischemia/reperfusion, OPN exerted a protective effect by ameliorating the production of IL-6 and TNF-α in macrophages and inhibiting inflammation (11,12). Furthermore, OPN may serve a key role in the expansion of hepatic progenitor cells (HPC) and in promoting liver regeneration during liver cancer (13,14) and acute liver failure (15,16).…”