BACKGROUND Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE). Minimal hepatic encephalopathy patients do not demonstrate clinically overt symptoms of HE but present with abnormal neuropsychological and/or neurophysiological tests indicative of cerebral dysfunction. This study was performed in such patients to identify regions of abnormal cerebral perfusion and to correlate regional cerebral blood flow (rCBF) changes with psychometric hepatic encephalopathy score (PHES), Child-Turcotte-Pugh's score (CTP), and model for end-stage liver disease (MELD) score. We also compared abnormal patterns of rCBF in cirrhotic patients of alcoholic etiology with non-alcoholic etiology. METHODS This prospective study was performed to evaluate rCBF in 50 cirrhotic patients and 13 controls using technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography. All the patients underwent a battery of psychometry tests, PHES. Minimal hepatic encephalopathy was diagnosed if PHES was ≤-5. The rCBF changes were evaluated using region of interest (ROI) based semi-quantitative method of region/cerebellum and region/cortex ratios in 16 regions of the brain. RESULTS Cirrhotic patients with MHE showed impaired perfusion in the superior prefrontal cortex and increased perfusion in the thalamus, brain-stem, medial temporal cortex, and the hippocampus when compared with the controls. Cerebral perfusion in superior prefrontal cortex correlated negatively with MELD score (r=-0.323, P=0.022). We found significant positive correlation between PHES score and rCBF values in the left superior prefrontal cortex (r=0.385, P=0.006). Cirrhotic patients with alcohol etiology showed significantly decreased rCBF in right inferior prefrontal cortex, right superior prefrontal cortex, and the anterior cingulate cortex while increased rCBF was noted in the right medial temporal cortex and hippocampus. CONCLUSIONS Our results suggest that alterations in cognition in cirrhotic patients with MHE may be associated with impaired abnormalities of rCBF.