Hepatofugal portal flow is highly predictive of acute-on-chronic liver failure: A new hemodynamic patho-physiological hypothesis

Background and aims: Acute-on-chronic liver failure (ACLF) is a severe complication of advanced liver disease. A significant number of ACLF patients have not clear precipitating factors. The aim of the study was to investigate the role of alterations in porto-hepatic hemodynamics, especially non-forward portal flow (NFPF), in ACLF and liver-related mortality. Methods: 233 cirrhotic patients were included in the study with a median follow-up of 24 months. Color-Doppler ultrasound was used to assess portal vein patency, flow direction and significant porto-systemic collaterals (>8 mm). Patients with active cancer, both at baseline and during follow-up and severe non liver-related comorbidities were excluded. ACLF and liver-related mortality were recorded during follow-up. Results: Fifty-six patients (24%) developed ACLF; 24 (10,3%) had baseline NFPF. In survival analysis, NFPF, but not portal vein thrombosis, was independently associated with ACLF development (HR 2.85 95% C.I. [1.49-5.42], p = 0.001) and liver-related mortality (HR 2.24 95% C.I. [1.16-4.28], p = 0.015), even after adjustment for liver disease severity scores, age and etiology of liver disease. Conclusion: NFPF is independently associated with ACLF development and liver-related mortality, regardless of etiology, severity disease scores and portal vein thrombosis. Although there is no specific measure to reverse NFPF, patients with NFPF should receive prompt intensive management and urgent prioritization for liver transplantation.