Methods of treating hepatic encephalopathy

Abstract

The application describes treatment of hepatic encephalopathy using gastrointestinal specific antibiotics. One example of a gastrointestinal specific antibiotic is rifaximin. The instant application also provides methods for determining if a subject has a neurological condition or hepatic encephalopathy by determining the critical flicker frequency and/or the venous ammonia level of the subject at two or more time points. The invention further provides methods for treating these subjects.

1 . A method of reducing the risk of hepatic encephalopathy (HE) recurrence in a subject comprising:
 administering to the subject an effective amount of rifaximin, thereby reducing the risk of hepatic encephalopathy (HE) recurrence.   
     
     
         2 . The method of  claim 1 , wherein the rifaximin reduces the risk of recurrence within 28 days of beginning treatment. 
     
     
         3 . The method of  claim 1 , wherein the HE comprises one or more of minimal, overt, episodic, and/or persistent hepatic encephalopathy. 
     
     
         4 . The method of  claim 2 , wherein the subject is diagnosed with minimal, overt, episodic, and/or persistent hepatic encephalopathy (HE). 
     
     
         5 . The method of  claim 1 , further comprising administering the subject lactulose. 
     
     
         6 . The method of  claim 5 , wherein the lactulose is administered prior to the rifaximin, with the rifaximin or after the rifaximin. 
     
     
         7 . The method of  claim 1 , wherein the subject is administered about 1100 mg of rifaximin per day. 
     
     
         8 . The method of  claim 7 , wherein the about 1100 mg of rifaximin is administered as 550 mg twice daily. 
     
     
         9 . The method of  claim 8 , wherein the 550 mg of rifaximin is administered as one or more tablets or capsules. 
     
     
         10 . The method of  claim 1 , wherein the subject is 18 years old or older. 
     
     
         11 . The method of  claim 1 , wherein the rifaximin is administered with or without food. 
     
     
         12 . The method of  claim 1 , wherein the subject has a Model for End-Stage Liver Disease (MELD) score of greater than 19. 
     
     
         13 . The method of  claim 12 , wherein the MELD score is <25. 
     
     
         14 . The method of  claim 1 , wherein the method decreases the HE-related hospitalizations for the subject. 
     
     
         15 . The method of  claim 4 , wherein the subject has increased exposure to rifaximin as compared to healthy subjects having been administered rifaximin. 
     
     
         16 . The method of  claim 15 , wherein the subject has at least a 9.6 fold increase in rifaximin exposure. 
     
     
         17 . The method of  claim 15 , wherein the subject has at least a 13.1 fold increase in rifaximin exposure.