Minimal Hepatic Encephalopathy and Critical Flicker Frequency Are Associated With Survival of Patients With Cirrhosis

BACKGROUND & AIMS: Minimal hepatic encephalopathy (MHE) is associated with falls, traffic accidents, and overt HE. However, the association with survival is controversial. We assessed the effects of MHE on the long-term survival of patients with cirrhosis. METHODS: We performed a prospective study of 117 consecutive patients with cirrhosis seen at a tertiary hospital in Seville, Spain (estimation cohort), followed by a validation study of 114 consecutive patients with cirrhosis seen at 4 hospitals in Spain from January 2004 through December 2007. Patients were examined every 6 months at outpatient clinics through December 2013 (follow-up periods of 5 +/- 2.8 y and 4.4 +/- 3.9 y for each group, respectively). Cirrhosis was identified by liver biopsy, ultrasound, endoscopic analysis, and biochemical parameters. Liver dysfunction was determined based on model for end-stage liver disease (MELD) and ChildPugh scores. All patients were administered the critical flicker frequency (CFF) test and psychometric hepatic encephalopathy scores were used to detect MHE. Survival curves were compared using the log-rank test and multivariable analysis was performed using Cox proportional hazards models. RESULTS: The distributions of Child-Pugh scores were as follows: 66% class A, 31% class B, and 3% class C in the estimation cohort, and 50% class A, 32% class B, and 18% class C in the validation cohort. In the estimation cohort, 24 of 35 patients (68.6%) with a CFF score less than 39 Hz survived for 5 years, whereas 50 of 61 patients (82%) with a CFF score of 39 Hz or higher survived during the follow-up period (log-rank score, 5.07; P = .024). Psychometric hepatic encephalopathy scores did not correlate with survival. In multivariable analysis, older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12; P = .009), CFF score less than 39 Hz (HR, 4.36; 95% CI, 1.67-11.37; P = .003), and MELD score (HR, 1.40; 95% CI, 1.21-1.63; P = .0001) were associated independently with survival during the follow-up period. In the validation cohort, CFF score less than 39 Hz and MELD score also were associated with patient survival during the follow-up period. MHE had no effect on the survival of patients with MELD scores less than 10 (among patients with CFF scores >= 39 Hz, 94.5% survived for 5 years vs 91.9% of patients with CFF scores < 39 Hz; log-rank score, 0.64; P = .423). Fewer patients with MELD scores of 10-15 and MHE survived for 5 years (44.4%; 12 of 27) than those with MELD scores greater than 15 without MHE (61.5%; 8 of 13) (P < .05). Only 2 of 12 patients (16.7%) with MELD scores of 15 or higher and MHE survived for 5 years (log-rank score, 90.56; P = .0001). CONCLUSIONS: MHE is associated with a reduced 5-year survival rate of patients with cirrhosis. Evaluation of MHE could help predict survival times and outcomes of patients with specific MELD scores. The CFF could help physicians determine prognoses of patients with cirrhosis.