Plasma Pentraxin3 is a novel marker for nonalcoholic steatohepatitis (NASH)

Abstract

Background: The changes in the liver in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However it has remained difficult to differentiate between NASH and non-progressive NAFLD on the basis of the clinical findings alone.

Aims: In this study we investigated the clinical usefulness of plasma Pentraxin3 (PTX3) levels to predict NASH. Plasma PTX3 was measured in 70 patients with histologically verified NAFLD (28 with non-NASH and 42 with NASH) and 10 healthy control subjects.

Results: The plasma PTX3 level was significantly higher in the NASH cases than in the non-NASH cases (p = 0.0021) and control subjects (p = 0.045). And the plasma PTX3 level was significantly higher in the stages 3-4 NAFLD cases than in the stages 0-2 NAFLD cases (p < 0.0001). The PTX3 values were closely correlated with the stages of liver fibrosis (p < 0.0001, Kruskal-Wallis test). To detect NASH compared with non-NASH, the area under the curve for plasma PTX3 were 0.755, and to detect stages 3-4 NAFLD compared with stages 0-2 NAFLD, the area under the curve for plasma PTX3 were 0.850.

Conclusion: This is the first study to demonstrate consistent and profound elevation of plasma PTX3 levels in NASH in comparison with non-NASH. The results suggest that plasma PTX3 levels may not only be laboratory values that differentiate NASH from non-NASH, but marker of the severity of hepatic fibrosis in NASH.

Figure 1

Plasma PTX3 levels in healthy control subjects, non-NASH patients, and NASH patients. Box plots of plasma PTX3 levels showing interquartile range (box), median (thick line), range (thin lines) and outliers (circles). The length of the box represents the interquatile range within which 50% of the values were located. Plasma PTX3 levels of healthy control subjects, non-NASH and NASH patients.

Figure 2

Plasma PTX3 levels in stages 0–2 and stages 3–4 NAFLD. Box plots of plasma PTX3 levels showing interquartile range (box), median (thick line), range (thin lines) and outliers (circles). The length of the box represents the interquatile range within which 50% of the values were located. Plasma PTX3 levels in stages 0-2 NAFLD and stages 3-4 NAFLD.

Figure 3

Relation between Plasma PTX3 levels and fibrosis stage. Comparison between plasma PTX3 levels in various stages of fibrosis. Box plots of plasma PTX3 levels showing interquartile range (box), median (thick line), range (thin lines) and outliers (circles). The length of the box represents the interquatile range within which 50% of the values were located. A steady stepwise increase in serum high-sensitivity CRP levels was observed with increasing severity of hepatic fibrosis (p = 0.0049).

Figure 4

ROC curve for differentiating steatosis and NASH according to the plasma PTX3 level. ROC curve for differentiating between steatosis and NASH on the basis of the plasma PTX3 level (area under the curve = 0.719).

Figure 5

ROC curve for differentiating between advanced NAFLD and non-advanced NAFLD on the basis of the plasma PTX3 level. ROC curve for differentiating between non-advanced NAFLD and advanced NAFLD on the basis of the plasma PTX3 level (area under the curve = 0.849).

Figure 6

Correlation between the plasma PTX3 levels and the serum CRP levels. No correlation was found between plasma PTX3 levels and serum CRP levels (r = 0.220, p = 0.1431)