Infection and HE: Which Comes First?

Overt hepatic encephalopathy (HE) complicates the course of cirrhosis in one-third of the patients at some point during the clinical course leading to a high risk of mortality. Studies have shown that the rate of survival at 1 year and 5 years are 36% and 15%, respectively.

Infections, including community-acquired and healthcare-related, are another complication of cirrhosis that affects more than 50% of the hospitalized. Most common infections are spontaneous bacterial peritonitis (SBP), urinary tract infections, pneumonia and cellulitis. It has been observed that infections accelerate the progression of HE, other organ failure and mortality in patients with cirrhosis. It has been seen that the presence and severity of minimal HE in cirrhosis are independent of the severity of liver disease and plasma ammonia concentration. However, markers of systemic inflammation are significantly higher in HE patients due to alterations in neurotransmission caused by reactive oxygen/nitrogen species (RONS) and astrocyte swelling. Based on these, it can be deduced that HE comes first because: Hyperammonemia condition in HE impairs neutrophils function which is mediated by activation of the p38 mitogen-activated protein kinase (p38 MAPK) pathway. This contributes to excessive ROS release, systemic inflammation, oxidative stress, high spontaneous oxidative burst and decreased phagocytosis, subsequently leading to infections.