The PHES battery does not detect all cirrhotic patients with early neurological deficits, which are different in different patients.
OBJECTIVE
The psychometric hepatic encephalopathy score (PHES) is the "gold standard" for minimal hepatic encephalopathy (MHE) diagnosis. Some reports suggest that some cirrhotic patients "without" MHE according to PHES show neurological deficits and other reports that neurological alterations are not homogeneous in all cirrhotic patients. This work aimed to assess whether: 1) a relevant proportion of cirrhotic patients show neurological deficits not detected by PHES; 2) cirrhotic patients with mild neurological deficits are a homogeneous population or may be classified in sub-groups according to specific deficits.


METHODS
Cirrhotic patients "without" (n = 56) or "with" MHE (n = 41) according to PHES and controls (n = 52) performed psychometric tests assessing attention, concentration, mental processing speed, working memory and bimanual and visuomotor coordination. Heterogeneity of neurological alterations was analysed using Hierarchical Clustering Analysis.


RESULTS
PHES classified as "with" MHE 42% of patients. Around 40% of patients "without" MHE according to PHES fail two psychometric tests. Oral SDMT, d2, bimanual and visuo-motor coordination tests are failed by 54, 51, 51 and 43% of patients, respectively. The earliest neurological alterations are different for different patients. Hierarchical clustering analysis shows that patients "without" MHE according to PHES may be classified in clusters according to the tests failed. In some patients coordination impairment appear before cognitive impairment while in others concentration and attention deficits appear before.


CONCLUSIONS
PHES is not sensitive enough to detect early neurological alterations in a relevant proportion of cirrhotic patients. Oral SDMT, d2 and bimanual and visuo-motor coordination tests are more sensitive. The earliest neurological alterations are different in different cirrhotic patients. These data also have relevant clinical implications. Patients classified as "without MHE" by PHES belonging to clusters 3 and 4 in our study have a high risk of suffering clinical complications, including overt HE and must be diagnosed and clinically followed.
Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Valencia, Spain.
Carla
C
Giménez-Garzó
IDAL, Intelligent Data Analysis Laboratory, Escuela Técnica Superior de Ingeniería, Valencia, Spain.
Juan José
JJ
Garcés
Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Valencia, Spain.|Fundación Investigación Hospital Clínico de Valencia. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain.
Amparo
A
Urios
Fundación Investigación Hospital Clínico de Valencia. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain.
Alba
A
Mangas-Losada
Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Valencia, Spain.
Raquel
R
García-García
Servicio de Digestivo, Hospital Arnau de Vilanova, Valencia, Spain.
Olga
O
González-López
Servicio de Digestivo, Hospital Arnau de Vilanova, Valencia, Spain.
Remedios
R
Giner-Durán
Unidad de Digestivo, Hospital Clínico de Valencia, Departamento de Medicina, Universidad de Valencia, Valencia, Spain.
Desamparados
D
Escudero-García
Unidad de Digestivo, Hospital Clínico de Valencia, Departamento de Medicina, Universidad de Valencia, Valencia, Spain.
Miguel Angel
MA
Serra
IDAL, Intelligent Data Analysis Laboratory, Escuela Técnica Superior de Ingeniería, Valencia, Spain.
Emilio
E
Soria
Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Valencia, Spain.
Vicente
V
Felipo
Fundación Investigación Hospital Clínico de Valencia. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain.|Departamento de Patología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
Carmina
C
Montoliu
D000368:Aged; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D005500:Follow-Up Studies; D006501:Hepatic Encephalopathy / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000209:etiology; D008107:Liver Diseases / Q000150:complications / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D063868:Patient Outcome Assessment; D011594:Psychometrics / Q000379:methods; D011597:Psychomotor Performance; D015203:Reproducibility of Results