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

Figures

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  Fig. 1. Kaplan–Meier survival curve of all-cause mortality for all SAH patients and ALD cirrhosis patients at 90 days (log rank Mantel-CoxP= 0.020). Abbreviations: ALD, alcohol-related liver disease; SAH, severe alcoholic hepatitis.

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  Fig. 2. Plasma ANG levels in HC and patients (SAH and ALD cirrhosis). Plasma (A) ANG1 and (B) ANG2 levels in HC and patients. (C) Plasma ANG2: ANG1 ratio in HC and patients. (D) Plasma ANG2 levels in non-septic and septic patients. (E) Plasma ANG2 levels in surviving and non-surviving patients at 90 days. For box-and-whisker plots: midline, median; perimeters, 25th to 75th centile; whiskers, minimum to maximum values. The Mann–Whitney U test was used for statistical analysis. ∗P < 0.05, ∗∗∗∗P < 0.0001. Abbreviations: ALD, alcohol-related liver disease; ANG, angiopoietin; HC, healthy control; SAH, severe alcoholic hepatitis.

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  Fig. 3. ROC analysis showing the discriminatory power of ANG2 between surviving and non-surviving patients at 90 days(AUC 0.72;95% CI: 0.59–0.85;P= 0.020). Abbreviations: ANG, angiopoietin; AUC, area under the curve; CI, confidence interval; ROC, receiver operating characteristic.

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  Fig. 4. Correlation between plasma ANG2 levels and liver disease severity scores and biochemical markers of severity.(A) Correlation between MELD score and ANG2 levels in patient group (r = 0.30, P = 0.020). (B) Correlation between Child-Pugh score and ANG2 levels in patient group (r = 0.38, P = 0.003). (C) Correlation between INR and ANG2 levels in patient group (r = 0.41, P = 0.001). (D) Correlation between albumin and ANG2 levels in patient group (r = −0.26, P = 0.040). Spearman's rank correlation test was used for statistical analysis. One patient (SAH) was not included in analysis for MELD score, Child-Pugh score and albumin due to missing data. Abbreviations: ANG, angiopoietin; INR, international normalized ratio; MELD, model for end-stage liver disease.

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  Fig. 5. ANG1RNA andANG2RNA results.(A)ANG1 expression in all groups. (B)ANG2 expression in all groups. Gene expression levels are presented as transcripts per million (tpm). For box-and-whisker plots: midline, median; perimeters, 25th to 75th centile; whiskers, minimum to maximum values. The Kruskal-Wallis test and Dunn's multiple comparison test were used for statistical analysis. ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, ∗∗∗∗ P < 0.0001. Abbreviations: AH, alcoholic hepatitis; ANG, angiopoietin; exAH, explants from patients with SAH who underwent transplantation; HC, healthy control; HCV, non cirrhotic HCV infection group; HCV-C, compensated HCV-related cirrhosis group; NAFLD, non-alcoholic fatty liver disease; RNA, ribonucleic acid; SAH, severe alcoholic hepatitis.

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  Fig. 6. TIE1RNA andTEKRNA results.(A)TIE1 expression in all groups. (B)TEK expression in all groups. Gene expression levels are presented as transcripts per million (tpm). For box-and-whisker plots: midline, median; perimeters, 25th to 75th centile; whiskers, minimum to maximum values. The Kruskal–Wallis test and Dunn's multiple comparison test were used for statistical analysis. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, ∗∗∗∗P < 0.0001. Abbreviations: AH, alcoholic hepatitis group; ANG, angiopoietin; exAH, explants from patients with SAH who underwent transplantation; HC, healthy controls; HCV, non cirrhotic HCV infection group; HCV-C, compensated HCV-related cirrhosis group; NAFLD, non-alcoholic fatty liver disease; ns, not significant; RNA, ribonucleic acid; SAH, severe alcoholic hepatitis.