Why and when to measure ammonemia in cirrhosis?

Hyperammonemia plays a key role in the pathophysiology of hepatic encephalopathy (HE) and most HE treatments are ammonia-lowering drugs. However, the usefulness of measuring ammonemia in routine practice remains controversial and not recommended systematically even when neurological symptoms are present. First, ammonemia measurement should be carefully performed in order to avoid a falsely elevated result. When performed, a normal ammonemia in a cirrhotic patient with neurological symptoms should lead to reconsider the diagnosis of HE. Indeed, literature data show that most cirrhotic patients with HE have an elevated ammonemia, which is however individually poorly correlated with the severity of symptoms. Nevertheless, elevated ammonemia seems to be a factor of bad prognosis in cirrhosis. A decrease in ammonemia after treatments is well proven but it is not determined whether it is associated with clinical efficacy. Repeated measurements could be useful in this context, especially in non-responders, to help differentiating other causes of encephalopathy, such as drug induced. In acute liver failure, the prognostic value of hyperammonemia is well described and could help an early recognition the most severe forms of this disease. We will also discuss how integrating ammonemia into the diagnostic work-up of liver failure and/or encephalopathy. Ammonemia is also essential to diagnose urea cycle disorders or drug toxicity that both need specific interventions.