Author information
1School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, King's College Hospital, 125 Coldharbour Lane, London, SE5 9NU, UK.
2Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
3School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, King's College Hospital, 125 Coldharbour Lane, London, SE5 9NU, UK. debbie.shawcross@kcl.ac.uk.
4Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK. debbie.shawcross@kcl.ac.uk.
Abstract
Hepatic encephalopathy (HE) is a syndrome that is associated with both acute and chronic liver injury. It manifests as a wide spectrum of neuropsychological abnormalities, ranging from subtle impairments in executive higher functions observed in cirrhosis, through to coma in acute liver failure. In acute liver failure, the central role of ammonia in the development of brain oedema has remained undisputed for 130 years. It latterly became apparent that infection and inflammation were profound determinants for the development of severe hepatic encephalopathy, associated with the development of cerebral oedema and intracranial hypertension. The relationship of the development of hepatic encephalopathy with blood ammonia levels in cirrhosis is less clear cut and the synergistic interplay of inflammation and infection with ammonia has been identified as being fundamental in the development and progression of hepatic encephalopathy. A perturbed gut microbiome and the presence of an impaired gut epithelial barrier that facilitates translocation of bacteria and bacterial degradation products into the systemic circulation, inducing systemic inflammation and innate and adaptive immune dysfunction, has now become the focus of therapies that treat hepatic encephalopathy in cirrhosis, and may explain why the prebiotic lactulose and rifaximin are efficacious. This review summarises the current clinical perspective on the roles of inflammation and infection in hepatic encephalopathy and presents the evidence base for existing therapies and those in development in the setting of acute and chronic liver failure.