Minimal Hepatic Encephalopathy in Patients with Alcohol Related and Non-alcoholic Steatohepatitis Related Cirrhosis by Psychometric Hepatic Cephalopathy Score and Critical Flicker Frequency

Nitin Jagtap, Pintu Bhakhar, Muhammad Miftahussurur, Yashavanth H S, Pankaj Shrimal, Mithun Sharma, Rajesh Gupta, P N Rao, D Nageshwar Reddy


Background: alcohol may have additional neurotoxic ill-effects in patients with alcohol related cirrhosis apart from hepatic encephalopathy. We aimed to evaluate minimal hepatic encephalopathy (MHE) with Psychometric Hepatic Encephalopathy (PHES) score and Critical Flicker Frequency (CFF) in alcohol (ALD) and non-alcoholic steatohepatitis related (NASH) related cirrhosis. Methods: 398 patients were screened between March 2016 and December 2018; of which 71 patients were included in ALD group and 69 in NASH group. All included patients underwent psychometric tests which included number connection test A and B (NCT-A and NCT-B), serial dot test (SDT), digit symbol test (DST), line tracing test (LTT) and CFF. MHE was diagnosed when their PHES was <-4. Results: the prevalence of MHE was significantly higher in ALD group compared to NASH (69.01% vs 40.58%; P=0.007). The performance of individual psychometric tests was significantly poorer in ALD (P<0.05). Overall sensitivity and specificity of CFF was 76.62% (95%CI 65.59 – 85.52) and 46.03% (95%CI 33.39 – 59.06) respectively. Mean CFF was significantly lower in ALD than NASH (37.07 (SD 2.37) vs 39.05 (SD 2.40), P=0.001); also in presence of MHE (36.95 (SD 2.04) vs 37.96 (SD 1.87), P=0.033) and absence of MHE (37.34 (SD 3.01) vs 39.79 (SD 2.46), P=0.001). Conclusion: MHE is significantly more common in patients with ALD cirrhosis than NASH counterparts. Overall CFF values are less in alcohol related cirrhosis than NASH related cirrhosis, even in presence or absence of MHE. We recommend additional caution in managing MHE in ALD cirrhosis.


Minimal Hepatic Encephalopathy; Alcohol Related Cirrhosis, Non-alcohol Steatohepatitis; Critical Flicker Frequency; Psychometric Hepatic Encephalopathy


Mullen KD. Review of the final report of the 1998 Working Party on definition, nomenclature and diagnosis of hepatic encephalopathy. Aliment Pharmacol Ther 2007;25 Suppl 1:11-6.

Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35:716-21.

Dhiman RK, Saraswat VA, Sharma BK, et al. Minimal hepatic encephalopathy: consensus statement of a working party of the Indian National Association for Study of the Liver. J Gastroenterol Hepatol. 2010;25:1029-41.

Groeneweg M, Quero JC, De Bruijn I, et al. Subclinical hepatic encephalopathy impairs daily functioning. Hepatology. 1998;28:45-9.

Cordoba J, Cabrera J, Lataif L, et al. High prevalence of sleep disturbance in cirrhosis. Hepatology. 1998;27:339-45.

Bajaj JS, Heuman DM, Wade JB, et al. Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy. Gastroenterology. 2011;140:478-487 e1.

Guerri C, Pascual M. Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence. Alcohol. 2010;44:15-26.

Cooper C, Bebbington P, Meltzer H, et al. Alcohol in moderation, premorbid intelligence and cognition in older adults: results from the Psychiatric Morbidity Survey. J Neurol Neurosurg Psychiatry. 2009;80:1236-9.

Neiman J. Alcohol as a risk factor for brain damage: neurologic aspects. Alcohol Clin Exp Res. 1998;22:346S-351S.

Hartmann IJ, Groeneweg M, Quero JC, et al. The prognostic significance of subclinical hepatic encephalopathy. Am J Gastroenterol. 2000;95:2029-34.

Quero JC, Hartmann IJ, Meulstee J, et al. The diagnosis of subclinical hepatic encephalopathy in patients with cirrhosis using neuropsychological tests and automated electroencephalogram analysis. Hepatology. 1996;24:556-60.

Kircheis G, Wettstein M, Timmermann L, et al. Critical flicker frequency for quantification of low-grade hepatic encephalopathy. Hepatology. 2002;35:357-66.

Li SW, Wang K, Yu YQ, et al. Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China. World J Gastroenterol. 2013;19:8745-51.

Kunchulia M, Pilz KS, Herzog MH. How alcohol intake affects visual temporal processing. Vision Res. 2012;66:11-6.

Das A, Dhiman RK, Saraswat VA, et al. Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis. J Gastroenterol Hepatol. 2001;16:531-5.

Sharma P, Sharma BC, Puri V, et al. Critical flicker frequency: diagnostic tool for minimal hepatic encephalopathy. J Hepatol. 2007;47:67-73.

Dhiman RK, Kurmi R, Thumburu KK, et al. Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver. Dig Dis Sci. 2010;55:2381-90.

Sharma P, Sharma BC, Sarin SK. Prevalence of abnormal psychometric tests and critical flicker frequency after clinical recovery of overt hepatic encephalopathy. Neurol India. 2010;58:220-4.

Li YY, Nie YQ, Sha WH, et al. Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China. World J Gastroenterol. 2004;10:2397-401.

Torlot FJ, McPhail MJ, Taylor-Robinson SD. Meta-analysis: The diagnostic accuracy of critical flicker frequency in minimal hepatic encephalopathy. Aliment Pharmacol Ther. 2013;37:527-36.

Luo M, Ma P, Li L, et al. Advances in psychometric tests for screening minimal hepatic encephalopathy: From paper-and-pencil to computer-aided assessment. Turk J Gastroenterol. 2019;30:398-407.

Ozel Coskun BD, Ozen M. Critical flicker frequency test for diagnosing minimal hepatic encephalopathy in patients with cirrhosis. Turk J Gastroenterol. 2017;28:191-196.

Amodio P, Wenin H, Del Piccolo F, et al. Variability of Trail Making Test, Symbol Digit Test and Line Trait Test in normal people. A normative study taking into account age-dependent decline and sociobiological variables. Aging Clinical and Experimental Research. 2002;14:117-131.

Campagna F, Montagnese S, Schiff S, et al. Confounders in the detection of minimal hepatic encephalopathy: a neuropsychological and quantified EEG study. Liver Int. 2015;35:1524-32.

Karhunen PJ, Erkinjuntti T, Laippala P. Moderate alcohol consumption and loss of cerebellar Purkinje cells. BMJ. 1994;308:1663-7.

de la Monte SM. Disproportionate atrophy of cerebral white matter in chronic alcoholics. Arch Neurol. 1988;45:990-2.

de la Monte SM, Kril JJ. Human alcohol-related neuropathology. Acta Neuropathol. 2014;127:71-90.

de la Monte SM, Longato L, Tong M, et al. The liver-brain axis of alcohol-mediated neurodegeneration: role of toxic lipids. Int J Environ Res Public Health. 2009;6:2055-75.

Chen CH, Walker J, Momenan R, et al. Relationship between liver function and brain shrinkage in patients with alcohol dependence. Alcohol Clin Exp Res. 2012;36:625-32.

Pearson P, Timney B. Effects of moderate blood alcohol concentrations on spatial and temporal contrast sensitivity. J Stud Alcohol. 1998;59:163-73.

Full Text: PDF


  • There are currently no refbacks.