Increase brain lactate in hepatic encephalopathy: Cause or consequence?

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome which develops as a result of liver failure or disease. Increased concentrations of brain lactate (microdialysate, cerebrospinal fluid, tissue) are commonly measured in patients with HE induced by either acute or chronic liver failure. Whether an increase in brain lactate is a cause or a consequence of HE remains undetermined. A rise in cerebral lactate may occur due to (1) blood-borne lactate (hyperlactataemia) crossing the blood-brain barrier, (2) increased glycolysis due to energy failure or impairment and (3) increased lactate production/release or decreased lactate utilization/uptake. This review explores the different reasons for lactate accumulation in the brain during liver failure and describes the possible roles of lactate in the pathogenesis of HE.