Liquid Diagnosis of Hepatic Encephalopathy: Are We There Already?

Hepatic encephalopathy (HE) is a neurocognitive syndrome associated with liver disease and/or portosystemic shunts. Its diagnosis is clinical and requires exclusion of many other conditions that can present with similar neuropsychiatric abnormalities [1]. The broad differential diagnosis, and huge clinical overlap with many metabolic, neurologic and psychiatric disorders, is a challenge for clinicians that must decide in which patients further laboratorial, imaging and neurophysiological investigation is warranted. As opposed to overt HE (OHE), minimal HE (MHE) curses with no clinical manifestations, and is diagnosed on the bases of abnormal results on psychometric and neurophysiologic tests [1]. Those tests are quite sensitive but are time-consuming, require training and may be affected by the patients’ age and education, explaining why MHE is the most under-diagnosed form of HE, even though it can afflict up to 80% of patients with chronic liver disease (CLD) [2]. The lack of recognition of MHE may have important implications, since MHE associates with impaired quality of life, decreased ability to perform daily tasks, and increased risk for work and traffic accidents. Furthermore, MHE predicts the development of OHE and increased mortality [3]. Hepatologists’ work would be easier if there were a simple serum biomarker that could identify accurately patients with HE, either OHE in the emergency room, or MHE in the outpatient clinic. It would also help, if that biomarker would correlate with severity of HE in order to objectively monitor response to therapy. Monitoring of therapy response would be most useful in the context of MHE, since, in the case of OHE, once diagnosis is established, clinical evaluation is more straightforward in assessing evolution of HE severity. A biomarker must be accurate, reliable, sensitive/specific, and provide high predictive value. Ammonia is a serum biomarker that 60–95% of clinicians use in their practice to diagnose HE [4], although studies show, that in the context of CLD, ammonia determination does not seem to change the management of the