ORIGINAL ARTICLE Confounders in the detection of minimal hepatic encephalopathy: a neuropsychological and quantified EEG study Francesca Campagna 1 , Sara Montagnese 1 , Sami Schiff 1 , Manuela Ruzzoli 2 , Anna Biancardi 1 , Pamela Iannizzi 1 , Pietro L. Pujatti 3 , Paolo Angeli 1 , Angelo Gatta 1 , Carlo Merkel 1 , Gioacchino Leandro 4 , Daniela Mapelli 5 and Piero Amodio 1 1 Department of Medicine (DIMED), University of Padua, Padua, Italy 2 Departament de Tecnologies de la Informaci  o i les Comunicacions, Universitat Pompeu Fabra, Barcelona, Spain 3 General Medicine, Hospital of Arzignano, Arzignano, Italy 4 Gastroenterological Department, IRCCS De Bellis Hospital, Castellana Grotte, Italy 5 Department of General Psychology, University of Padua, Padua, Italy Keywords alcohol abuse – cognitive dysfunction – electroencephalogram – HCV infection – minimal hepatic encephalopathy – psychometric tests Correspondence Campagna Francesca, MD. Department of Medicine (DIMED), Via Giustiniani 2, 35128 Padova, Italy Tel: +39 049 8218675 Fax: +39 049 8218292 e-mail: francescacampagna3@gmail.com Received 11 November 2013 Accepted 5 July 2014 DOI:10.1111/liv.12635 Abstract Background & Aims: Chronic alcohol misuse, HCV infection and cirrhosis may cause cognitive alterations. The aim of the present study was to assess the influence of alcohol misuse, HCV infection and cirrhosis per se on the neuropsychological and electroencephalogram (EEG) profile and to evaluate the role of alcohol misuse and HCV infections as potential confounding fac- tors in the detection of minimal hepatic encephalopathy. Methods: A com- prehensive neuropsychological profile and EEG spectral parameters were obtained in six age-matched groups of 30 subjects each: (i) HCV-related hep- atitis without cirrhosis, (ii) chronic alcohol abusers, (iii) patients with HCV- related cirrhosis, (iv) alcohol-related cirrhosis, (v) cirrhosis not related to alcohol or HCV and (vi) healthy subjects. Cirrhotic patients were matched for MELD score. Results: The factor ‘cirrhosis’ was associated with low Pho- nemic Verbal Fluency (PVF) and Difference between Trail Making Test B and A (TMT) (B-A) (P < 0.001). Chronic alcohol misuse was associated with low PVF, TMT (B-A), Memory with Interference Task at 10 (ITM 10) and 30 s (ITM 30) (all P < 0.05). An interaction was found between the factors ‘cirrhosis’, ‘alcohol misuse’ and tests (P < 0.01). HCV hepatitis reduced ITM 10 (P < 0.05), but no interaction was found between ‘cirrhosis’, ‘HCV infec- tion’ and tests (P = 0.14). The EEG parameters were mainly influenced by ‘cirrhosis’ (P < 0.05), and EEG alterations were more pronounced in patients with alcoholic cirrhosis (P = 0.04). Conclusions: Cirrhosis per se, chronic alcohol misuse and HCV infection were found to be associated with cognitive dysfunction. In patients with cirrhosis, the interaction with alcohol misuse further impinged on brain dysfunction. Individuals with cirrhosis and/or portal-systemic shunt- ing may present with initial signs of brain alterations. These subclinical changes are considered the expression of minimal hepatic encephalopathy (MHE). The brain dysfunction detected in MHE includes alterations in brain metabolism (1), neurophysiological changes (2) and/or cognitive dysfunction (3). MHE has high preva- lence in patients with cirrhosis, ranging from 10% to 70% depending on the degree of liver failure (4), portal- systemic shunting, previous overt hepatic encephalopa- thy (OHE) and the technique used to diagnose it (5). Chronic alcohol misuse and HCV infection may act as confounders in the neuropsychological assessment for MHE, as they might directly impair brain function- ing, regardless of the liver disease they have caused (6, 7). It is well known that chronic alcohol misuse is associ- ated with specific changes in brain structure and func- tion, which remain detectable long after patients have stopped drinking (8). The brain areas which are most susceptible to alcohol-related damage are the frontal lobes, periventricular structures and the cerebellum (9). The corresponding, damaged functions are executive function, working memory, strategy, switching, atten- tion and psychomotor speed (10). Alcohol-related cir- rhosis seems to be associated with more severe cognitive dysfunction compared to non-alcoholic cirrhosis based on some studies (11, 12). The hypothesis that alcohol Liver International (2014) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1 Liver International ISSN 1478-3223