Animal models of hepatic encephalopathy and hyperammonemia

Animal models of chronic liver disease with hyperammonemia are currently available to investigators. Two in particular have been utilized extensively. Carbon tetrachloride induced (CCl4) cirrhosis in the rat and portacaval shunt in the same species and other animals particularly the dog. In regards to hepatic encephalopathy, however, the CCl4 cirrhosis rat model seems to display few behavioral changes unless very advanced decompensated cirrhosis is produced. Further work should be done on this model to verify the development of encephalopathy and to improve reproducibility. The portacaval shunt rat on the other hand clearly has a consistent albeit subtle set of behavioral changes. Recent improvements in detecting these changes and more importantly showing reversal or improvement by neomycin or a low protein diet are a major advance. Hopefully, more laboratories will be able to reproduce this reversible change in behavior. Experiences gained from 7 years of using the portacaval shunt rat and other models of liver disease are described.