Plasma angiopoietin 2 as a novel prognostic biomarker in alcohol-related cirrhosis and hepatitis.

BACKGROUND AND AIM: Severe alcoholic hepatitis (SAH), the most florid form of alcohol-related liver disease (ALD), has a mortality rate of 16% at 28 days. The angiopoietin-Tie 2 system regulates angiogenesis and inflammation, both of which are implicated in the pathogenesis of ALD. This study examined plasma and hepatic gene expression of angiopoietin 1 (ANG1) and angiopoietin 2 (ANG2) in patients with SAH and ALD and investigated their roles as prognostic biomarkers.

METHODS

A case-control study was performed measuring plasma levels of ANG1 and ANG2 by enzyme-linked immunosorbent assay (ELISA) from 30 patients with SAH (Maddrey's discriminant function ≥32), 32 patients with ALD cirrhosis and 15 healthy controls (HC). RNA sequencing for ANG1, ANG2, TIE1 (codes for Tie1 receptor) and TEK (codes for Tie2 receptor) gene expression from a separate cohort study of 79 patients was also performed.

RESULTS

Plasma levels of ANG1 were lower (P = 0.010) and ANG2 were higher (P < 0.0001) in patients with ALD/SAH compared to HC. The ANG2: ANG1 ratio was higher in those with ALD/SAH compared to HC (P < 0.0001). ANG2 levels were the highest in patients who developed sepsis (P = 0.030) and those dying within 90 days (P = 0.020). ANG2 levels correlated positively with model for end-stage liver disease (MELD) score (r = 0.30, P = 0.020), Child-Pugh score (r = 0.38, P = 0.003), international normalized ratio (r = 0.41, P = 0.001) and white blood cell count (r = 0.28, P = 0.040) and inversely correlated with albumin (r = -0.26, P = 0.040).ANG1 gene expression from liver biopsies was higher in SAH than that in HC (P < 0.0001), and greater in severe disease (P < 0.0001). ANG2 gene expression trended towards being lower in SAH than that in HC (P = 0.070) though was upregulated in severe disease (P = 0.0003).

CONCLUSIONS

Plasma ANG2 is raised in SAH and ALD and could be useful as a prognostic biomarker in this patient population.