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

Victoria Tatiana Kronsten*, Josepmaria Argemi, Ada Sera Kurt, Godhev Mannakat Vijay, Jennifer Marie Ryan, Ramón Bataller, Debbie Lindsay Shawcross

*Corresponding author for this work

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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.

Original languageEnglish
Pages (from-to)21-29
Number of pages9
JournalLiver Research
Issue number1
Early online date3 Feb 2022
Publication statusPublished - 25 Mar 2022


  • Alcohol-related cirrhosis
  • Alcohol-related liver disease (ALD)
  • Alcoholic hepatitis
  • Angiopoietin 1 (ANG1)
  • Angiopoietin 2 (ANG2)


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