Diagnostic methods for liver disorders

Abstract

The present invention relates to methods of diagnosing a liver disorder in a patient, as well as methods of monitoring the progression of a liver disorder and/or methods of monitoring a treatment protocol of a therapeutic agent or a chemotherapeutic regimen. The invention also relates to assay methods used in connection with the diagnostic methods described herein.

1 . A method for diagnosing HCC in a patient, said method comprising
 (a) measuring a level of a first biomarker in a test sample obtained from a patient, wherein said first biomarker is selected from the group consisting of CEA, CA 125, CA 19-9; and   (b) diagnosing from said measuring step the presence or absence of HCC in said patient.   
     
     
         2 . The method of  claim 1  wherein said method further comprises measuring a level of at least one additional biomarker in said sample and determining from said level of said first biomarker and said level of said at least one additional biomarker the presence or absence of HCC in said patient. 
     
     
         3 . The method of  claim 1  wherein said method further comprises comparing said level of said first biomarker in said sample to a level of said first biomarker in a normal control sample and diagnosing the presence or absence of HCC in said patient based on said comparison. 
     
     
         4 . The method of  claim 2  wherein said method further comprises comparing said level of said first biomarker and said at least one additional biomarker in said sample to levels of said first biomarker and said at least one additional biomarker in a normal control sample and diagnosing the presence or absence of HCC in said patient based on said comparison. 
     
     
         5 . The method of  claim 2  wherein said at least one additional biomarker is selected from the group consisting of AFP, OPN, MMP-9, E-cadherin, erbB2, and combinations thereof. 
     
     
         6 . The method of  claim 2  wherein said at least one additional biomarker is selected from the group consisting of CEA, CA 125 and CA 19-9, provided that said additional biomarker is different from said first biomarker. 
     
     
         7 . The method according to  claim 1 , wherein said diagnosing step comprises comparing said level of said first biomarker to a detection cut-off level. 
     
     
         8 . The method according to  claim 2 , wherein said diagnosing step comprises comparing said levels of said first biomarker and said at least one additional biomarker in said sample to detection cut-off levels for said biomarkers. 
     
     
         9 . The method according to  claim 1 , further comprising determining from said level of said first biomarker the disease progression of HCC. 
     
     
         10 . The method according to  claim 1 , wherein said patient has been diagnosed with liver disease. 
     
     
         11 . The method according to  claim 10 , wherein said liver disease is selected from the group consisting of cirrhosis, fibrosis, hepatitis, alcoholic liver disease, fatty liver disease, and combinations thereof. 
     
     
         12 . The method according to  claim 1 , wherein said method further comprises subjecting said patient to an imaging method to evaluate the size, shape and position of the liver and said diagnosing step further comprises evaluating the presence or absence of HCC in said patient based on the results from said imaging method and said measuring step. 
     
     
         13 . The method according to  claim 12 , wherein said imaging method is an ultrasound. 
     
     
         14 . A method for monitoring the progression of HCC in a patient diagnosed with HCC, said method comprising
 (a) measuring the levels of a first biomarker in a plurality of samples obtained, at different times, from said patient, wherein said first biomarker is selected from the group consisting of CEA, CA 125, CA 19-9; and   (b) determining from said levels of said first biomarker the progression or efficacy of treatment of the HCC.   
     
     
         15 . The method of  claim 14 , wherein said method further comprises measuring the levels of at least one additional biomarker in said samples and determining from said levels of said first biomarker and said levels of said at least one additional biomarker the progression of HCC in said patient. 
     
     
         16 . The method of  claim 14 , wherein said method further comprises comparing said levels of said first biomarker in said samples to a level of said first biomarker in a normal control sample and determining the progression of HCC in said patient based on said comparison. 
     
     
         17 . The method of  claim 15 , wherein said method further comprises comparing said levels of said first biomarker and said at least one additional biomarker in said samples to levels of said first biomarker and said at least one additional biomarker in a normal control sample and determining the progression of HCC in said patient based on said comparison. 
     
     
         18 . The method of  claim 15 , wherein said at least one additional biomarker is selected from the group consisting of OPN, MMP-9, E-cadherin, erbB2, and combinations thereof. 
     
     
         19 . The method of  claim 14 , wherein said at least one additional biomarker is selected from the group consisting of CEA, CA 125 and CA 19-9, provided that said additional biomarker is different from said first biomarker. 
     
     
         20 . The method of  claim 14 , wherein said determining step comprises comparing said level of said first biomarker to a detection cut-off level. 
     
     
         21 . The method of  claim 15 , wherein said determining step comprises comparing said levels of said first biomarker and said at least one additional biomarker to detection cut-off levels for said biomarkers. 
     
     
         22 . The method according to  claim 14 , wherein said patient has been diagnosed with liver disease. 
     
     
         23 . The method according to  claim 14 , wherein said liver disease is selected from the group consisting of cirrhosis, fibrosis, hepatitis, alcoholic liver disease, fatty liver disease, and combinations thereof. 
     
     
         24 . The method according to  claim 14 , wherein said method further comprises subjecting said patient to an imaging method to evaluate the size, shape and position of the liver and said diagnosing step further comprises evaluating the presence or absence of HCC in said patient based on the results from said imaging method and said measuring step. 
     
     
         25 . The method according to  claim 24 , wherein said imaging method is an ultrasound. 
     
     
         26 . The method of  claim 1 , wherein said measuring step is used to differentiate HCC from non-cancerous liver diseases. 
     
     
         27 . The method according to any one of  claims 2  and  15 , wherein levels of said first and said at least one additional biomarker are measured in a multiplexed assay. 
     
     
         28 . The method according to any one of  claims 2  and  15 , wherein levels of said first and said at least one additional biomarker are measured in a single assay chamber. 
     
     
         29 . The method according to  claim 28 , wherein said assay chamber is a single well of an assay plate. 
     
     
         30 . The method according to  claim 28 , wherein said assay chamber is an assay chamber of a cartridge. 
     
     
         31 . The method according to any one of  claims 1  and  14 , wherein said sample is selected from the group consisting of blood, serum and plasma. 
     
     
         32 . The method according to any one of  claims 1  and  14 , wherein said sample is selected from a group consisting of biopsy tissue, intestinal mucosa and urine. 
     
     
         33 . The method according to any one of  claims 1  and  14 , wherein said level is measured using an immunoassay. 
     
     
         34 . The method according to any one of  claims 1  and  14 , further comprising determining from said level of said first biomarker the disease progression of HCC. 
     
     
         35 . A method for diagnosing cirrhosis in a patient suspected of having cirrhosis, said method comprising
 (a) measuring a level of a first biomarker in a test sample obtained from a patient, wherein said first biomarker is selected from the group consisting of CEA, CA 125, CA 19-9; and   (b) diagnosing from said measuring step the presence or absence of cirrhosis in said patient.   
     
     
         36 . The method of  claim 35 , wherein said method further comprises measuring a level of at least one additional biomarker in said sample and determining from said level of said first biomarker and said level of said at least one additional biomarker the presence or absence of cirrhosis in said patient. 
     
     
         37 . The method of  claim 35 , wherein said method further comprises comparing said level of said first biomarker in said sample to a level of said first biomarker in a normal control sample and diagnosing the presence or absence of cirrhosis in said patient based on said comparison. 
     
     
         38 . The method of  claim 36 , wherein said method further comprises comparing said level of said first biomarker and said at least one additional biomarker in said sample to levels of said first biomarker and said at least one additional biomarker in a normal control sample and diagnosing the presence or absence of cirrhosis in said patient based on said comparison. 
     
     
         39 . The method of  claim 36 , wherein said at least one additional biomarker is selected from the group consisting of AFP, CEA, CA 125, CA 19-9, OPN, MMP-9, E-cadherin, erbB2, and combinations thereof. 
     
     
         40 . The method according to  claim 35 , wherein said diagnosing step comprises comparing said level of said first biomarker to a detection cut-off level. 
     
     
         41 . The method according to  claim 36 , wherein said diagnosing step comprises comparing said levels of said first biomarker and said at least one additional biomarker in said sample to detection cut-off levels for said biomarkers. 
     
     
         42 . The method according to  claim 35 , further comprising determining from said level of said first biomarker the disease progression of cirrhosis. 
     
     
         43 . A method for monitoring the progression of cirrhosis in a patient diagnosed with cirrhosis, said method comprising
 (a) measuring the level(s) of a first biomarker in a plurality of samples obtained, at different times, from said patient, wherein said first biomarker is selected from the group consisting of CEA, CA 125, CA 19-9; and   (b) determining from said level(s) of said first biomarker the progression or efficacy of treatment of cirrhosis.   
     
     
         44 . The method of  claim 43 , wherein said method further comprises measuring the levels of at least one additional biomarker in said samples and determining from said levels of said first biomarker and said levels of said at least one additional biomarker the progression of cirrhosis in said patient. 
     
     
         45 . The method of  claim 43 , wherein said method further comprises comparing said level of said first biomarker in said samples to a level of said first biomarker in a normal control sample and determining the progression of cirrhosis in said patient based on said comparison. 
     
     
         46 . The method of  claim 44 , wherein said method further comprises comparing said levels of said first biomarker and said at least one additional biomarker in said samples to levels of said first biomarker and said at least one additional biomarker in a normal control sample and determining the progression of cirrhosis in said patient based on said comparison. 
     
     
         47 . The method of  claim 44  wherein said at least one additional biomarker is selected from the group consisting of AFP, CEA, CA 125, CA 19-9, OPN, MMP-9, E-cadherin, erbB2, and combinations thereof. 
     
     
         48 . The method of  claim 43 , wherein said determining step comprises comparing said level of said first biomarker to a detection cut-off level. 
     
     
         49 . The method of  claim 44 , wherein said determining step comprises comparing said levels of said first biomarker and said at least one additional biomarker to detection cut-off levels for said biomarkers. 
     
     
         50 . The method according to any one of  claims 35  and  43 , wherein levels of said first and said at least one additional biomarker are measured in a multiplexed assay. 
     
     
         51 . The method according to any one of  claims 35  and  43 , wherein levels of said first and said at least one additional biomarker are measured in a single assay chamber. 
     
     
         52 . The method according to  claim 51 , wherein said assay chamber is a single well of an assay plate. 
     
     
         53 . The method according to  claim 51 , wherein said assay chamber is a cartridge. 
     
     
         54 . The method according to any one of  claims 35  and  43 , wherein said sample is selected from the group consisting of blood, serum and plasma. 
     
     
         55 . The method according to any one of  claims 35  and  43 , wherein said sample is selected from a group consisting of biopsy tissue, intestinal mucosa and urine. 
     
     
         56 . The method according to any one of  claims 35  and  43 , wherein said level is measured using an immunoassay. 
     
     
         57 . The method according to any one of  claims 35  and  43 , further comprising determining from said level of said first biomarker the disease progression of cirrhosis.