Emerging drugs for hepatic encephalopathy.
BACKGROUND
Hepatic encephalopathy (HE) is a severe complication of cirrhosis, seriously affecting the patients' quality of life. The classical approach aimed at reducing the production of gut-derived toxins, such as ammonia, is under debate as, at the moment, the information obtained from the clinical trials does not support any specific treatment for HE.


OBJECTIVE
i) To discuss present therapeutic strategies and possible future developments; ii) to identify areas of medical needs and iii) to suggest the ideal design and methodology for randomized controlled trials (RCTs) in HE.


METHODS
Current approaches were obtained from already available RCTs or from experimental animal studies. Those approaches developed from studies on HE pathophysiology were considered as working hypotheses for future therapies.


CONCLUSIONS
Our competence in testing old and new treatment modalities by RCTs with appropriate clinically relevant end points should urgently be improved. The patients at risk of HE are identifiable, and studies specifically aimed at establishing whether HE may be prevented or not are needed. As far as new treatment modalities are concerned, RCTs on the modulators of the intestinal bacterial flora and on the molecular adsorbent recirculating system are already available, but further studies are needed to confirm these promising approaches.
Riggio
Oliviero
O
Sapienza Università di Roma, Dipartimento di Medicina Clinica, II Gastroenterologia, Viale dell' Università 37, 00185 Roma, Italy. oliviero.riggio@uniroma1.it
Ridola
Lorenzo
L
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D004345:Drug Industry / Q000639:trends; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D009584:Nitrogen / Q000378:metabolism; D055502:Secondary Prevention; D009435:Synaptic Transmission / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D001427:Bacterial Toxins; D009584:Nitrogen