Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Feb 27;11(2):173-185.
doi: 10.4254/wjh.v11.i2.173.

Hepatic Encephalopathy: Lessons From Preclinical Studies

Free PMC article

Hepatic Encephalopathy: Lessons From Preclinical Studies

Luiza Cioglia Dias Lima et al. World J Hepatol. .
Free PMC article


Hepatic encephalopathy (HE) is a major complication that is closely related to the progression of end-stage liver disease. Metabolic changes in advanced liver failure can promote cognition impairment, attention deficits and motor dysfunction that may result in coma and death. HE can be subdivided according to the type of hepatic injury, namely, type A, which results from acute liver failure, type B, which is associated with a portosystemic shunting without intrinsic liver disease, and type C, which is due to chronic liver disease. Several studies have investigated the pathogenesis of the disease, and most of the mechanisms have been explored using animal models. This article aimed to review the use of preclinical models to investigate HE. The most used animal species are rats and mice. Experimental models of type A HE include surgical procedures and the administration of hepatotoxic medications, whereas models of types B and C HE are generally surgically induced lesions in liver tissue, which evolve to hepatic cirrhosis. Preclinical models have allowed the comprehension of the pathways related to HE.

Keywords: Acute liver failure; Hepatic cirrhosis; Hepatic encephalopathy; Hyperammonemia; Neuroinflammation; Preclinical studies.

Conflict of interest statement

Conflict-of-interest statement: The authors declare that they do not have any conflicts of interest.


Figure 1
Figure 1
Main pathophysiological feature of the available models of hepatic encephalopathy. APAP: Acetaminophen; A/C Hamm: Acute/chronic hyperammonemia; BDL: Bile duct-ligated; CCl4: Carbon tetrachloride; GP-VS: Graded portal-vein stenosis; PCA: Portosystemic anastomosis; TAA: Thioacetamide.

Similar articles

See all similar articles

Cited by 2 articles


    1. Butterworth RF. The concept of "the inflamed brain" in acute liver failure: mechanisms and new therapeutic opportunities. Metab Brain Dis. 2016;31:1283–1287. - PubMed
    1. Wang AJ, Peng AP, Li BM, Gan N, Pei L, Zheng XL, Hong JB, Xiao HY, Zhong JW, Zhu X. Natural history of covert hepatic encephalopathy: An observational study of 366 cirrhotic patients. World J Gastroenterol. 2017;23:6321–6329. - PMC - PubMed
    1. Wong RJ, Gish RG, Ahmed A. Hepatic encephalopathy is associated with significantly increased mortality among patients awaiting liver transplantation. Liver Transpl. 2014;20:1454–1461. - PubMed
    1. Yuan LT, Chuah SK, Yang SC, Liang CM, Wu CK, Tai WC, Hung TH, Nguang SH, Wang JW, Tseng KL, Ku MK, Hsu PI, Wu DC, Hsu CN. Multiple bacterial infections increase the risk of hepatic encephalopathy in patients with cirrhosis. PLoS One. 2018;13:e0197127. - PMC - PubMed
    1. Flamm SL. Considerations for the cost-effective management of hepatic encephalopathy. Am J Manag Care. 2018;24:S51–S61. - PubMed