Serum metabolic disturbances associated with acute-on-chronic liver failure in patients with underlying alcoholic liver diseases: An elaborative NMR-based metabolomics study

Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by acute deterioration of liver function in patients with preexisting chronic liver disease (CLD) or alcoholic liver disease (ALD). Compared to acute liver failure (ALF, which occurs in the absence of preexisting chronic liver disease), ACLF additionally involves extrahepatic organ failure and high short term mortality. The etiology of ACLF is often a precipitating event such as bacterial infection or active alcoholism in patients with underlying alcoholic liver disease. However, no matter the etiology of preexisting chronic liver damage, ACLF patients are always with ascites, jaundice, portal hypertension with variceal bleeding, and/or hepatic encephalopathy or any combination of these. Though recent past has witnessed a significant progress in its basic and clinical research, however, current management of ACLF is rather poor, due to deprived understating of underlying pathogenesis, limited therapeutic options and moreover scarcity of non-invasive and reliable prognostic biomarkers for predicting clinical outcomes and monitoring treatment response resulting in high incidence of short/medium term mortality (>50%). Therefore, there is an urgent need (i) first to identify reliable clinical biomarkers for predicting prognosis in ACLF patients and second (ii) to understand the pathogenesis of liver failure so that the treatment and/or support system can be tailored for rapid and efficient recovery of these patients. As a part of this long-term project, recently, the intestinal permeability of ACLF patients has been investigated to underscore the role of mucosal barrier function in the pathogenesis of ACLF. Continuing further, we have studied the serum metabolic disturbances associated with ACLF, mainly, in patients with alcoholic liver diseases. The study revealed significantly disturbed metabolic homeostasis in ACLF. Key metabolic changes related to severity of hepatic-function impairment were reported as biomarkers for predicting clinical outcomes and guiding treatment of such critically ill ACLF patients.