Diagnosis of Minimal Hepatic Encephalopathy: A Systematic Review of Point-of-Care Diagnostic Tests

Objectives: Minimal hepatic encephalopathy (HE) is common, characterized by deficits in reaction time and executive function, and strongly associated with disability and mortality. Point-of-care diagnostics performed without specialized skills or equipment are now available, albeit with limited data regarding their generalizability. Methods: We systematically reviewed MEDLINE, EMBASE, Cochrane Library, and Scopus for diagnostic studies of MHE using broad search terms including HE and minimal, covert, or the names of published diagnostic modalities. We included tests that provide results during clinical visits without requiring neuropsychologists to administer and/or special equipment. These include the Inhibitory Control Test (ICT, n=16), EncephalApp Stroop (n=3), an algorithm based on the Sickness Impact Profile (n=2), and the Animal Naming Test (ANT, n=1). Results: The populations enrolled in the included study were highly selected, excluding patients with recent (6-months) alcohol or psychoactive medications use. Cutoffs for MHE for each test varied widely. For the ICT, the optimal cutoffs for MHE varied by 300%, whereas healthy control performance varied >400%. The optimal cutoffs for the EncephalApp also varied (by 50%). The gold standards for MHE varied substantially between studies, and clinical outcomes were never used to develop test cutoffs. Data comparing the performance of each modality are lacking. Longitudinal data are limited but suggest that good performance on the ICT, EncephalApp or ANT is associated with reduced risk of developing overt HE. Conclusion: The point-of-care tests for MHE are promising tools. However, additional longitudinal studies are needed in clinically representative populations of at-risk patients with cutoffs validated based on the development of clinical outcomes.