Abstract
BACKGROUND: Overt hepatic encephalopathy (OHE) is a reversible complication of cirrhosis that often results in hospitalization. Factors associated with progression, resolution and mortality are not known, particularly with confounders such as acute-on-chronic liver failure (ACLF). The aim of the study was to evaluate factors associated with progression, resolution, and mortality of patients with OHE. METHODS: Data for this study were derived from PREDICT, a prospective cohort study of patients with cirrhosis hospitalized for an acute decompensation or ACLF. Progression to OHE or worsening in severity and resolution from OHE were evaluated at 1 week. Cox regression, interaction analyses, and Kaplan-Meier curves were performed. RESULTS: One thousand two hundred seventy-three patients were included [68% males; 59 (51-67) years; 56% alcohol], 16% admitted with OHE and 16% with ACLF. Older age, metabolic dysfunction-associated steatotic liver disease, previous treatment with lactulose, ACLF, white blood cell counts or albumin levels at admission were associated with OHE (P < 0.05). OHE progressed in 3% patients, which was associated with older age, previous treatment with lactulose and bacterial infections (P < 0.05), with a significantly shorter time-to-death (P < 0.001). Patients who resolved OHE (79%) presented a similar prognosis than those without OHE (P = 0.208). Post hoc analysis of the age-adjusted interaction between OHE and ACLF to predict mortality showed higher differences across ACLF grades compared with OHE. CONCLUSION: Presence of ACLF and progression of OHE are associated with high short-term mortality rates, while resolution of OHE is associated with significantly better prognosis. Understanding the natural history of OHE will have profound implications on the development of novel approaches.