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The understanding of pathogenesis of portal hypertension in patients with liver cirrhosis continues to evolve. In addition to progressive fibrosis, cirrhosis is characterized by parenchymal extinction and vascular remodelling, causing architectural distortion. Existence of prothrombotic state and more recently, intestinal bacterial dysbiosis are recently described in the pathogenesis of portal hypertension. Clinically significant portal hypertension (CSPH) is an important prognostic milestone in patients with liver cirrhosis. This is a pre-symptomatic phase that predicts the development of varices, ascites and importantly increased risk of Hepatocellular carcinoma (HCC). CSPH is associated with significantly reduced survival. Endoscopic surveillance is necessary in these patients. Non-selective Beta-blocker is the preferred therapy for primary prophylaxis in the management of portal hypertension. Patients with acute variceal bleed should be resuscitated appropriately, followed by vasoactive drugs and endoscopic therapy. Early TIPS should be considered in those with refractory bleed or in endoscopic treatment failure. Application of artificial intelligence and machine learning may be useful in future for identifying patients at risk of variceal hemorrhage., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nonselective beta blockers (NSBBs) exert beneficial effects beyond lowering hepatic venous pressure gradient (HVPG), which may be particularly relevant in patients with decompensated cirrhosis (DC), in whom bacterial translocation and bacterial-induced systemic inflammation drive the development of complications such as acute-on-chronic liver failure (ACLF). We evaluated whether NSBB-related changes in von Willebrand factor (VWF) may serve as a biomarker for these effects. In this retrospective analysis, 159 prospectively characterized patients with clinically stable DC (ie, without acute decompensation) who underwent paired HVPG/VWF assessments before/on NSBB therapy were classified as 'VWF-responders' (as defined by a ≥5% decrease in VWF) versus 'VWF-non-responders.' There were no major differences in baseline characteristics between VWF-responders (61%) and VWF-non-responders. VWF-responders showed more pronounced decreases in inflammation (procalcitonin), whereas rates of HVPG-response were similar. In line, NSBB-related changes in VWF correlated with the dynamics of bacterial translocation/inflammation (lipopolysaccharide-binding protein, C-reactive protein, and procalcitonin), rather than those of HVPG. Interestingly, VWF-responders also showed less pronounced NSBB-related decreases in mean arterial pressure, suggesting an amelioration of systemic vasodilatation. Finally, VWF-response was associated with decreased risks of further decompensation (adjusted hazard ratio [aHR], 0.555; 95% confidence interval [CI], 0.337-0.912; P =.020), ACLF (aHR, 0.302; 95% CI, 0.126-0.721; P =.007), and liver-related death (aHR, 0.332; 95% CI, 0.179-0.616; P <.001) in Cox regression models adjusted for prognostic factors including changes in HVPG. Decreases in VWF upon NSBB therapy reflect their anti-inflammatory activity, are accompanied by less pronounced adverse effects on systemic hemodynamics, and are independently associated with a decreased risk of further decompensation, ACLF, and death. VWF-response may discriminate between decompensated patients who benefit from NSBB treatment and have a favorable prognosis versus patients with poor outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]