Multimodal Approach Including MR-spectroscopy for the Diagnosis of Minimal Hepatic Encephalopathy

BACKGROUND: There is no gold-standard for the diagnosis of hepatic encephalopathy (HE) and especially in case of minimal HE (MHE) where the value of paraclinical examinations is debated. MR-spectroscopy has been proposed as a valuable diagnostic tool for the diagnosis of HE by showing increased glutamate/glutamine peak and decreased myoinositol and choline peaks. However, access to MRI is difficult and few data on real life experience has been reported. We studied the interest of a multimodal approach combining clinical, neuropsychological, biological and MR-spectroscopy in the diagnosis of MHE. METHODS: We conducted a retrospective study in a single tertiary university hospital in Paris, France, where all out-patients referred to a specific hepato-neurology consultation dedicated to the diagnostic of MHE underwent a clinical examination, psychometric tests (Critical Flicker Frequency-CFF, Psychometric Hepatic Encephalopathy Score-PHES), ammonemia and cerebral MRI with spectroscopy (MRS). Patients were classified as having MHE or not by consensus between two experts. RESULTS: We included 56 patients between February 2013 and April 2016. Median age was 57 years [49–63]. Forty-four (79%) had a cirrhosis (etiology: alcohol 35%, NASH 9%, viral 23%, alcoholic and non-alcoholic steatohepatitis 26%, other 7%) with a median MELD of 10 [7–12]. Twelve (21%) had non-cirrhotic portal hypertension (Budd-Chiari 33%, extra-hepatic portal hypertension 33%, idiopathic portal hypertension 16%, portal agenesia 9% and nodular regenerative hyperplasia 9%). According to the experts, 57% had an MHE, whereas 43% hadn't. Among the clinical informations, only the presence of a portosystemic shunt (TIPS or surgical) was associated with MHE. A venous ammonemia >50 μmol/l, MRI T1 hyperintensity of the basal ganglia and an MRS HE profil suggestive of HE were all statistically associated with the diagnosis of MHE ( P < 0.0001). The best diagnostic performance was achieved by combining MRS with either MRI T1 hyperintensity (AUC = 0.93) or ammonemia (AUC = 0.91). CONCLUSION: A multimodal approach combining clinical data, ammonemia and cerebral MRI with MRS seems to have good accuracy for the diagnosis of MHE. Further prospective studies are mandatory.