ABSTRACT
INTRODUCTION: Minimal hepatic encephalopathy (MHE) is a common complication of liver cirrhosis not only leading to a decrease in the quality of life, but also predicting development of overt encephalopathy. The diagnosis of MHE usually relies on a combination of neuropsychological tests, while robust serum biomarkers are lacking. We aimed to assess serum concentrations of brain-derived neurotrophic factor (BDNF) in MHE patients. MATERIAL AND METHODS: Serum BDNF was assessed in 78 patients with liver cirrhosis (53 male, median age 55 years) and 40 healthy individuals. 43 subjects underwent extensive evaluation for MHE by psychometric hepatic encephalopathy score (PHES) and inhibitory control test (ICT) or critical flicker frequency (CFF). RESULTS: Serum BDNF was twofold lower in liver cirrhosis compared to healthy subjects [13.6 (7.8-22.6) vs. 33.0 (24.1-40.7) ng/ml, p < 0.001] and its decrease reflected a degree of liver insufficiency assessed by model for end-stage liver disease (MELD). BDNF showed a negative correlation with bilirubin (R = -0.35, p = 0.005) and international normalized ratio (INR) (R = -0.37, p = 0.003), and positive with platelets (PLT) (R = 0.36, p = 0.004), while no associations with age, sex, body mass index (BMI), waist-hip ratio (WHR), creatinine and ammonia were noted. Importantly, subjects with a diagnosis of MHE by at least two modalities showed the lowest levels of BDNF [10.9 (2.5-14.4) vs. 19.9 (9.3-29.4) ng/ml, p < 0.01]. Patients with self-reported sleep disturbances had significantly lower serum BDNF [13.0 (2.5-23.4) vs. 20.0 (8.4-31.3) ng/ml, p = 0.04]. CONCLUSIONS: The lowest serum BDNF concentration was noted in patients with MHE and sleep disturbances, which suggests a role in pathophysiology of hepatic encephalopathy but also as a potential biomarker.
ABSTRACT
Background: Minimal hepatic encephalopathy (MHE) refers to a number of neuropsychiatric and neurophysiological disorders in patients with cirrhosis who do not show abnormalities on physical examination or in clinical tests. The aim of this study was to determine the prevalence, risk factors, and predictive value of minimal hepatic encephalopathy and the usefulness of the inhibitory control test (ICT) in the diagnosis. Methods: Seventy patients (mean age 53 years, range 24-77) with liver cirrhosis were enrolled in the study. MHE was diagnosed based on PHES (psychometric hepatic encephalopathy score) and ICT. PHES and ICT were validated in a group of 56 control subjects. Results: Minimal hepatic encephalopathy was diagnosed using PHES in 21 patients (30%). ICT diagnosed MHE in 30 patients (42%), and the test had a sensitivity of 65% and a specificity of 57% compared to PHES. The ICT score (lures/target accuracy rate) correlated with the age of subjects (R = 0.35, p = 0.002) and only slightly with education (education in years R = -0.22, p = 0.06). MHE diagnosed with PHES or ICT was associated with a significantly higher model of end-stage liver disease (MELD) score in the follow-up. MHE diagnosed with ICT was correlated with a significantly higher incidence of symptoms of decompensated cirrhosis (p = 0.02) in the follow-up. Conclusions: ICT had moderate sensitivity and specificity in diagnosing MHE compared to PHES. Importantly, MHE detected with PHES or ICT was associated with poorer survival and a more severe progression of the disease.
