Factors Associated With Progression, Resolution and Mortality of Patients With Overt Hepatic Encephalopathy

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.

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.

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.

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.