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

Tapper, Elliot B, MD1,2,3; Parikh, Neehar D, MD, MS1,2,3; Waljee, Akbar K, MD, MS1,2,3; Volk, Michael, MD MS4; Carlozzi, Noelle E, PhD5; Lok, Anna S-F, MD1,2

American Journal of Gastroenterology: April 2018 - Volume 113 - Issue 4 - p 529–538
doi: 10.1038/ajg.2018.6

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.

1Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA

2Institute for Healthcare Policy and Innovation, Ann Arbor, MI, USA

3Veterans Affairs Hospital, Ann Arbor, MI, USA

4Division of Gastroenterology, Loma Linda University, Loma Linda, CA, USA

5Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA

Correspondence: Dr Elliot B. Tapper, MD, Division of Gastroenterology and Hepatology, University of Michigan, Institute for Healthcare Policy and Innovation, Veterans Affairs Hospital, 3912 Taubman, SPC 5362, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA. E-mail:

published online 13 March 2018

SUPPLEMENTARY MATERIAL accompanies this paper at

Received 25 August 2017; accepted 12 December 2017

© The American College of Gastroenterology 2018. All Rights Reserved.
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