Methods of treating hepatic encephalopathy

Abstract

Treatment of hepatic encephalopathy using gastrointestinal specific antibiotics is disclosed. 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 further provided are methods for treating these subjects.

1 . A method of decreasing blood ammonia levels in a subject comprising:
 administering to the subject an effective amount of rifaximin, thereby reducing ammonia blood levels.   
     
     
         2 - 4 . (canceled) 
     
     
         5 . A method of decreasing fatigue in a subject having hepatic encephalopathy comprising:
 administering to the subject an effective amount of rifaximin, thereby reducing fatigue in a subject.   
     
     
         6 . A method for treating a subject having HE, comprising:
 administering a GI specific antibiotic with lactulose, thereby treating a subject having HE.   
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 6 , further comprising advising a health care worker to administer the GI specific antibiotic prior to, with, or after administration of lactulose. 
     
     
         10 - 14 . (canceled) 
     
     
         15 . The method of  claim 6  wherein the GI specific antibiotic is rifaximin. 
     
     
         16 . A method of diagnosing hepatic encephalopathy (HE) in a subject comprising: determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has hepatic encephalopathy. 
     
     
         17 . The method of  claim 16 , wherein the CFF comprises the CFF time weighted average. 
     
     
         18 . The method of  claim 17 , wherein the CFF time weighted average comprises less than about 24 Hz. 
     
     
         19 . A method of determining a subject's risk of an HE breakthrough event, comprising:
 determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has an increased risk of an HE breakthrough event.   
     
     
         20 . The method of  claim 19 , wherein the CFF comprises the CFF time weighted average. 
     
     
         21 . The method of  claim 20 , wherein the CFF time weighted average comprises less than about 24 Hz. 
     
     
         22 . The method of  claim 19 , wherein a average CFF time weighted average 10 Hz is indicative that the subject has the greatest risk of a HE breakthrough event. 
     
     
         23 . A method of determining the prognosis of a subject having HE, comprising:
 determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has a poor prognosis.   
     
     
         24 . The method of  claim 23 , wherein the CFF is the CFF time weighted average. 
     
     
         25 . The method of  claim 24 , wherein the CFF time weighted average comprises less than about 24 Hz. 
     
     
         26 . The method of  claim 24 , wherein the CFF time weighted average comprises less than about 20 Hz. 
     
     
         27 . A method of treating or preventing an HE event, comprising:
 determining the critical flicker frequency (CFF) of a subject at two or more time points,   administering to a subject having a decrease in the CFF average between the time points an effective amount of a GI specific antibiotic,   thereby treating or preventing an HE event.   
     
     
         28 . The method of  claim 27 , wherein the CFF comprises the CFF time weighted average. 
     
     
         29 . The method of  claim 28 , wherein the CFF time weighted average comprises less than about 24 Hz. 
     
     
         30 . The method of  claim 28 , wherein the subject is administered a GI specific antibiotic when the CFF time weighted average comprises less than 24 Hz. 
     
     
         31 . The method of  claim 30 , wherein the GI specific antibiotic is rifaximin. 
     
     
         32 . The method of  claim 16 , wherein the risk is increased as compared to a control subject without HE. 
     
     
         33 . The method of  claim 16 , wherein the two or more time points occur within one week. 
     
     
         34 . The method of  claim 16 , wherein the two or more time points occur within four weeks. 
     
     
         35 . The method of  claim 16 , wherein the two or more time points occur within six months or more. 
     
     
         36 . A method of diagnosing hepatic encephalopathy (HE) in a subject comprising:
 determining the venous ammonia levels of a subject at two or more time points, wherein an increase in the venous ammonia levels is indicative that the subject has hepatic encephalopathy.   
     
     
         37 . The method of  claim 36 , wherein the venous ammonia level comprises the time weighted average venous ammonia levels. 
     
     
         38 . The method of  claim 37 , wherein the time weighted average venous ammonia level comprises more than about 100 μmol/L. 
     
     
         39 - 44 . (canceled) 
     
     
         45 . A method of treating or preventing an HE event, comprising:
 determining the venous ammonia level of a subject at two or more time points,   administering to a subject having an increase in the venous ammonia level between the time points an effective amount of a GI specific antibiotic,   thereby treating or preventing an HE event.   
     
     
         46 . The method of  claim 45 , wherein the GI specific antibiotic is rifaximin. 
     
     
         47 . The method of  claim 46 , wherein the venous ammonia level comprises the time weighted average venous ammonia levels. 
     
     
         48 . The method of  claim 47 , wherein the time weighted average venous ammonia level is more than about 100 μmol/L. 
     
     
         49 . The method of  claim 45 , further comprising administering lactulose. 
     
     
         50 . The method of  claim 36 , wherein the two or more time points occur within one week. 
     
     
         51 . The method of  claim 36 , wherein the two or more time points occur within four weeks. 
     
     
         52 . The method of  claim 36 , wherein the two or more time points occur within six months or more. 
     
     
         53 - 57 . (canceled) 
     
     
         58 . A method of diagnosing a neurological disease in a subject, comprising:
 determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has a neurological disease.   
     
     
         59 . (canceled) 
     
     
         60 . The method of  claim 58 , wherein the neurological disease or disorder is Alzheimer's disease, Parkinson's disease, brain trauma, migraine, chronic headache, insomnia and other sleep disorders, and/or epilepsy. 
     
     
         61 . A method of determining the prognosis of a subject having a neurological disease, comprising:
 determining the critical flicker frequency (CFF) of a subject at two or more time points, wherein a decrease in the CFF is indicative that the subject has a poor prognosis.   
     
     
         62 . The method of  claim 61 , wherein the CFF is the CFF time weighted average. 
     
     
         63 . The method of  claim 61 , wherein the neurological disease or disorder is Alzheimer's disease or Parkinson's disease. 
     
     
         64 - 66 . (canceled) 
     
     
         67 . A computerized method for identifying subjects having a neurological disease comprising:
 maintaining a database of CFFs for subjects at various time points and stages of disease progression;   comparing the results of an individuals CFF results taken at two or more time points to the database;   obtaining the diagnosis of a neurological disease from the computer if subject has CFF results that decrease between measurements.   
     
     
         68 . The method of  claim 67 , wherein the CFF comprises the CFF time weighted average. 
     
     
         69 . (canceled) 
     
     
         70 . The method of  claim 67 , further comprising controlling a printing device to print a report based on the results of the method. 
     
     
         71 . A business method for decreasing healthcare costs comprising:
 determining the critical flicker frequency (CFF) of a subject at two or more time points;   storing patient information on a computer processor;   determining if the subject has a neurological disease by determining if the CFF value has decreased between time points; and   treating the subject as necessary to avoid or delay hospitalization.   
     
     
         72 . (canceled) 
     
     
         73 . A device for determining the risk of an HE event, comprising:
 a flicker box, a measurement device to determine CFF, and a computer with an algorithm.   
     
     
         74 . (canceled)