The why and wherefore of hepatic encephalopathy

Abstract

Hepatic encephalopathy is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease. It was probably first described by Hippocrates over 2000 years ago, who said that "those whose madness arises from phlegm are quiet and neither shout nor make a disturbance, while those whose madness arises from bile shout, play tricks and will not keep still, but are always up to some mischief ". He was presumably describing the differences between patients with pneumonia and acute liver failure. Despite the fact that the syndrome was probably first recognized thousands of years ago, the exact pathogenesis still remains unclear. Furthermore, a precise definition of the syndrome is lacking, as are definitive methods of diagnosing this condition. It is important as both patients with cirrhosis and the general population with whom they interact may be affected as a consequence. At a minimum, the individual may be affected by impaired quality of life, impaired ability to work, and slowed reaction times, which are relevant to the population at large if affected individuals operate heavy machinery or drive a car. Pathogenic mechanisms, diagnostic tools, and treatment options are discussed.

Keywords: ammonia; cirrhosis; hepatic encephalopathy; lactulose; pathology; rifaximin; treatment.

Figure 1

Schematic representation of microglial activation. Notes: Resting microglia are spindly and spiky in appearance on electron microscopy, demonstrating low levels of constitutive PBR binding site activity (TSPO) on their mitochondria. When “activated”, microglia demonstrate an increased number of PBR binding sites. ¹¹C-(R)-PK11195 is a PET ligand that binds to PBRs. Abbreviations: PBR, peripheral benzodiazepine receptor; TSPO, translocator protein; PET, positron emission tomography; TNF-α, tumor necrosis factor-alpha; IL, interleukin; NO, nitric oxide.

Figure 2

Hypothesis of astrocyte swelling contributing to low-grade cerebral edema. Abbreviations: GLN, glutamine; GS, glutamine synthetase; GLU, glutamate; mI, myo-inositol; cho, choline.