Methods of diagnosing non-alcoholic steatohepatitis (nash)

Abstract

Non-invasive methods for detecting non-alcoholic fatty liver disease (NAFLD) and identifying the presence or absence of non-alcoholic steatohepatitis (NASH) in a subject utilize one or more biomarkers. The methods can differentiate between subjects with NASH and those with simple steatosis. Kits containing one or more agents for measuring the level of the biomarkers can be utilized to perform the described methods.

What is claimed is: 
     
         1 . A method comprising:
 a. measuring a level of an adipocytokine;   b. determining a level of necrosis by measuring a level of an apoptosis marker and a level of a cell death marker; and   c. analyzing the level of the adipocytokine and the level of necrosis to detect non-alcoholic fatty liver disease (NAFLD).   
     
     
         2 . The method of  claim 1 , wherein analyzing the level of the adipocytokine and the level of necrosis is in conjunction with one or more clinical variables and echographic variables, or any combination thererof. 
     
     
         3 . The method of  claim 1 , wherein determining the level of necrosis comprises subtracting the level of the apoptosis marker from the level of the cell death marker. 
     
     
         4 . The method of  claim 1 , wherein:
 a. the adipocytokine comprises adiponectin and resistin;   b. the apoptosis marker comprises caspase-cleaved CK-18 (M30-antigen); and   c. the cell death marker comprises cytokeratin CK-18 (M65 antigen).   
     
     
         5 . The method of  claim 1 , wherein the NAFLD is simple steatosis, steatosis with non-specific inflammation, non-alcoholic steatohepatitis (NASH), or NASH-related cirrhosis. 
     
     
         6 . The method of  claim 5 , further comprising screening to identify the presence or absence of non-alcoholic steatohepatitis (NASH). 
     
     
         7 . The method of  claim 5 , further comprising evaluating the effect of an agent to treat non-alcoholic steatohepatitis (NASH). 
     
     
         8 . The method of  claim 5 , further comprising monitoring the efficacy of a therapy to treat non-alcoholic steatohepatitis (NASH). 
     
     
         9 . A kit comprising:
 a. a package containing one or more agents to:
 i. measure a level of an adipocytokine; and 
 ii. measure a level of an apoptosis marker and a level of a cell death marker to determine a level of necrosis; and 
   b. instructions to analyze the level of the adipocytokine and the level of necrosis to detect non-alcoholic fatty liver disease (NAFLD).   
     
     
         10 . The kit of  claim 9 , wherein to analyze the level of the adipocytokine and the level of necrosis is to be in conjunction with one or more clinical variables and echographic variables, or any combination thererof. 
     
     
         11 . The kit of  claim 9 , wherein:
 a. the adipocytokine comprises adiponectin and resistin;   b. the apoptosis marker comprises caspase-cleaved CK-18 (M30-antigen); and   c. the cell death marker comprises cytokeratin CK-18 (M65 antigen).   
     
     
         12 . The kit of  claim 9 , wherein the level of necrosis is to be determined by subtracting the level of the apoptosis marker from the level of the cell death marker. 
     
     
         13 . The kit of  claim 9 , wherein the instructions comprise a computer algorithm. 
     
     
         14 . The kit of  claim 9 , wherein the NAFLD is simple steatosis, steatosis with non-specific inflammation, non-alcoholic steatohepatitis (NASH), or NASH-related cirrhosis. 
     
     
         15 . The kit of  claim 14 , further comprising instructions to screen to identify the presence or absence of non-alcoholic steatohepatitis (NASH). 
     
     
         16 . The kit of  claim 14 , further comprising instructions to evaluate the effect of an agent to treat non-alcoholic steatohepatitis (NASH). 
     
     
         17 . The kit of  claim 14 , further comprising instructions to monitor the efficacy of a therapy to treat non-alcoholic steatohepatitis (NASH).