Management of hepatic encephalopathy: role of rifaximin.
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, which develops in patients with acute or chronic liver failure. It is widely accepted to be due to impairment of hepatic clearance of toxic products from the gut such as ammonia. Accumulation of ammonia induces a glutamate neurotoxicity leading to an increased tone of the gamma-aminobutyric acid A (GABA-A) receptor system in the brain which results in HE. Factors either increasing the ammonia levels (protein load, constipation, sepsis, or gastrointestinal bleeding) or potentiating the functional activity of the GABAergic system [natural benzodiazepine-like compounds (NBZDs) or exogenous benzodiazepines] may act as precipitating factors of HE. NBZDs are present in trace amounts in the blood of normal subjects and have been found to be increased in the blood of patients with liver cirrhosis, with or without HE. These compounds may derive either from the diet since they have been found in plants, vegetables and animals or from gut bacteria. The observation that intestinal bacterial flora is involved in the production of both primary agent of HE (ammonia) and precipitating factors (NBZDs) suggests that the use of nonabsorbable antibiotics such as rifaximin may be useful in preventing episodes of HE in patients with liver cirrhosis.
Zeneroli
Maria Luisa
ML
Department of Medicine and Medical Specialities, University of Modena and Reggio Emilia, Modena, Italy. zeneroli.marialuisa@unimore.it
Avallone
Rossella
R
Corsi
Lorenzo
L
Venturini
Ivo
I
Baraldi
Claudia
C
Baraldi
Mario
M
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000009:adverse effects / Q000097:blood; D001419:Bacteria / Q000378:metabolism; D001569:Benzodiazepines / Q000009:adverse effects / Q000097:blood; D002986:Clinical Trials as Topic; D006501:Hepatic Encephalopathy / Q000517:prevention & control*; D006801:Humans; D007408:Intestinal Absorption; D007422:Intestines / Q000382:microbiology; D012294:Rifamycins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000078262:Rifaximin
D000900:Anti-Bacterial Agents; D000928:Antidepressive Agents; D012294:Rifamycins; D001569:Benzodiazepines; D000641:Ammonia; D000078262:Rifaximin