Liver Disease

Abstract

Methods of treating a liver disease or condition, or a symptom thereof, in a subject in need of treatment, are disclosed and described. One method comprises orally administering to a subject, a pharmaceutical composition having an amount of a testosterone, or an ester thereof, sufficient to treat the liver disease or condition, or symptom thereof.

What is claimed is: 
     
         1 . A pharmaceutical composition for treating at least one of NASH, NASH post-liver transplantation, hepatitis, alcoholic steatohepatitis, viral steatohepatitis, genetic steatohepatitis, non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, viral fatty liver disease, genetic fatty liver disease, and a symptom thereof, comprising at least one of a testosterone, a testosterone ester, a testosterone ester and tocopherol (TET) or a tocopherol derivative, and a combination thereof. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein said pharmaceutical composition treats at least one co-morbid condition of obesity, type 2 diabetes, dyslipidemia, cardiovascular disease, thyroid dysfunction, chronic kidney disease, liver disease, osteoporosis, hypogonadism, hypertension, sarcopenia, and cachexia. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein said at least one of a testosterone ester comprises at least one of testosterone undecanoate (TU), testosterone dodecanoate (TD), and testosterone tridecanoate (TT). 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein said at least one testosterone ester is administered with at least one pharmaceutical agent of metformin, glibenclamide, gliclazide, rosiglitazone, pioglitazone, troglitazone, acarbose, miglitol, nateglinide, repaglinide, exenatide, sitagliptin, pramlintide, atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, pitavastatin, butanoic acid, CER209, evogliptin, DUR928, MK-4074, OPRX-106, PF06865571, PF06882961, PXS-5382A, RG-125, RYI-018, seladelpar, SGM-1019, aramchol, ARX618, BI 1467335, DS102, EDP-305, Emricasan, gemcabene, GR-MD-02, GRI-0621, GS-0976, GS-9674, IMM-124E, IONIS-DGAT2Rx, IVA-337, Lipaglyn, LJN452, LMB763, MGL-3196, MN-001, MSDC-0602K, NC101, NGM282, NS-0200, Ozempic, PF-05221304, PF-06835919, remogliflozin etabonate, SHP626, TVB-2640, VK2809, cenicriviroc, elafibranor, ocaliva (obeticholic acid), selonsertib, and a combination thereof. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein if said pharmaceutical composition comprises a single testosterone ester, loading of said single testosterone ester per unit dosage form of said pharmaceutical composition comprises at least one of 1-50% w/w, 5-30% w/w, 10-30% w/w, and 5-15% w/w. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein if said pharmaceutical composition comprises a plurality of testosterone esters and includes TU, loading of said TU per unit dosage form of said pharmaceutical composition comprises at least one of 1-50% w/w, 5-30% w/w, 10-30% w/w, and 5-15% w/w, and wherein if said pharmaceutical composition comprises a plurality of testosterone esters and includes TD, loading of said TD per unit dosage form of said pharmaceutical composition comprises at least one of 1-50% w/w, 5-30% w/w, 10-30% w/w, and 5-15% w/w, and wherein if said pharmaceutical composition comprises a plurality of testosterone esters and includes TT, loading of said TT per unit dosage form of said pharmaceutical composition comprises at least one of 1-50% w/w, 5-30% w/w, 10-30% w/w, and 5-15% w/w. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein if said pharmaceutical composition is prepared for a male subject and comprises TU, daily dosage of said TU comprises at least one of 10 mg to 1,000 mg, 200 mg to 750 mg, and 300 mg to 600 mg, and wherein if said pharmaceutical composition is prepared for a male subject and comprises TD, daily dosage of said TD comprises 10 mg to 1,000 mg, and wherein if said pharmaceutical composition is prepared for a male subject and comprises TT, daily dosage of said TT comprises at least one of 10 mg to 1,000 mg, 400 mg to 2,000 mg, and 600 mg to 1,800 mg, and wherein if said pharmaceutical composition is prepared for a female subject and comprises TU, daily dosage of said TU comprises 1/10th- 1/15th of at least one of 10 mg to 1,000 mg, 200 mg to 750 mg, and 300 mg to 600 mg, and wherein if said pharmaceutical composition is prepared for a female subject and comprises TD, daily dosage of said TD comprises 1/10th- 1/15th of 10 mg to 1,000 mg, and wherein if said pharmaceutical composition is prepared for a female subject and comprises TT, daily dosage of said TT comprises 1/10th- 1/15th of at least one of 10 mg to 1,000 mg, 400 mg to 2,000 mg, and 600 mg to 1,800 mg. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein in response to administration of said pharmaceutical composition to a male subject having a testosterone concentration baseline below at least one of 350 ng/dL, 300 ng/dL, 250 ng/dL, 200 ng/dL, 150 ng/dL, and 100 ng/dL, said testosterone concentration (C ave0-24 ) of said male subject is increased over said subject's baseline. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein said testosterone concentration (C ave0-24 ) increase comprises an increase of at least one of 30, 50, 75, 100, 150, 200, 300, 400 or 500 ng/dL. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein said pharmaceutical composition comprises at least one pharmaceutically acceptable carrier. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein said pharmaceutical composition comprises at least one of a hydrophilic carrier, a lipophilic carrier, and an additive. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein said hydrophilic carrier comprises at least one of a polyoxylated mono-glyceride, a polyoxylated di-glyceride, a polyoxylated tri-glyceride, a polyoxylated vegetable oil, a polyoxylated hydrogenated vegetable oil, a polyoxylated mono-fatty acid, a polyoxylated di-fatty acid, a polyoxylated tri-fatty acid, a hydrogenated vegetable oil, Cremophor, Span, Tween, SLS, Poloxamer, Polymer, and a combination thereof. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein said hydrogenated vegetable oil comprises at least one of hydrogenated castor oil, hydrogenated coconut oil, hydrogenated cottonseed oil, hydrogenated palm oil, hydrogenated soybean oil, and a combination thereof. 
     
     
         14 . The pharmaceutical composition of  claim 12 , wherein said polyoxylated hydrogenated vegetable oil comprises at least one of polyoxylated 35 hydrogenated castor oil, polyoxylated 40 hydrogenated castor oil and polyoxylated 60 hydrogenated castor oil, and a combination thereof, and wherein said Tween comprises at least one of Tween-20, Tween-21, Tween-40, Tween-60, Tween-61, Tween-65, Tween-80, Tween-81, Tween-85, Tween-120, and a combination thereof. 
     
     
         15 . The pharmaceutical composition of  claim 11 , wherein said lipophilic carrier comprises at least one of a vegetable oil, a fatty acid, a fatty alcohol, a mono-glyceride, a di-glyceride, a tri-glyceride, a hydrogenated vegetable oil, a Vitamin E compound, polyoxylated fatty acid, polyoxylated triglyceride, polyoxylated vegetable oil, glyceryl fatty acid, propylene glycol fatty acid, a PEG sorbitan fatty acid, an omega-3 fatty acid, a PEG glycol alkyl ether, a polyglycerized fatty acid, and a combination thereof. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein said vegetable oil comprises at least one of castor oil, coconut oil, borage oil, cottonseed oil, peppermint oil, corn oil, peanut oil, linseed oil, olive oil, palm oil, sesame oil, soybean oil, and a combination thereof. 
     
     
         17 . The pharmaceutical composition of  claim 15 , wherein said fatty acid comprises at least one of caprylic acid, capric acid, lauric acid, palmitic acid, stearic acid, arachidic acid, behenic acid, myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, linoleic acid, linoelaidic acid, and a combination thereof, and wherein said omega-3 fatty acid comprises at least one of omega-3 EPA, omega-3 DHA, and a combination thereof. 
     
     
         18 . The pharmaceutical composition of  claim 15 , wherein said hydrogenated vegetable oil comprises at least one of hydrogenated castor oil, hydrogenated coconut oil, hydrogeneated cottonseed oil, hydrogenated palm oil, hydrogenated soybean oil, and a combination thereof. 
     
     
         19 . The pharmaceutical composition of  claim 15 , wherein said glyceryl fatty acid comprises at least one of glyceryl stearate, glyceryl oleate, glyceryl caprate, glyceryl caprylate, glyceryl laurate, glyceryl stearate, glyceryl palmitate, glyceryl linoleate, glyceryl myristate, and a combination thereof, and wherein said propylene glyceryl fatty acid comprises at least one of propylene glyceryl stearate, propylene glyceryl oleate, propylene glyceryl caprate, propylene glyceryl caprylate, propylene glyceryl laurate, propylene glyceryl stearate, propylene glyceryl palmitate, propylene glyceryl ricinoleate, propylene glyceryl myristate, and a combination thereof. 
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein said glyceryl fatty acid comprises at least one of a glyceryl mono-fatty acid, a glyceryl di-fatty acid, and a glyceryl tri-fatty acid, and wherein said propylene glyceryl fatty acid comprises at least one of a propylene glyceryl mono-fatty acid, a propylene glyceryl di-fatty acid, and a propylene glyceryl tri-fatty acid. 
     
     
         21 . A Method of treating at least one of NASH and a symptom thereof in a subject in need of treatment thereof comprising orally administering to said subject a pharmaceutical composition resulting in a therapeutically effective testosterone concentration in said subject. 
     
     
         22 . The method of  claim 21 , wherein said method further includes administering a therapeutically effective amount of a combination of androgen receptor agonists to said subject. 
     
     
         23 . The method of  claim 22 , wherein said androgen receptor agonists comprise at least one of a testosterone, a testosterone ester, a testosterone ester and tocopherol (TET) or a tocopherol derivative, and a combination thereof. 
     
     
         24 . The method of  claim 23 , wherein said at least one of a testosterone ester is administered with at least one pharmaceutical agent of metformin, glibenclamide, gliclazide, rosiglitazone, pioglitazone, troglitazone, acarbose, miglitol, nateglinide, repaglinide, exenatide, sitagliptin, pramlintide, atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, pitavastatin, butanoic acid, CER209, evogliptin, DUR928, MK-4074, OPRX-106, PF06865571, PF06882961, PXS-5382A, RG-125, RYI-018, seladelpar, SGM-1019, aramchol, ARX618, BI 1467335, DS102, EDP-305, Emricasan, gemcabene, GR-MD-02, GRI-0621, GS-0976, GS-9674, IMM-124E, IONIS-DGAT2Rx, IVA-337, Lipaglyn, LJN452, LMB763, MGL-3196, MN-001, MSDC-0602K, NC101, NGM282, NS-0200, Ozempic, PF-05221304, PF-06835919, remogliflozin etabonate, SHP626, TVB-2640, VK2809, cenicriviroc, elafibranor, ocaliva (obeticholic acid), selonsertib, and a combination thereof 
     
     
         25 . The method of  claim 21 , wherein said subject has at least one co-morbid condition selected from obesity, type 2 diabetes, dyslipidemia, cardiovascular disease, thyroid dysfunction, chronic kidney disease, liver disease, osteoporosis, hypogonadism, hypertension, sarcopenia, and cachexia. 
     
     
         26 . The method of  claim 21 , wherein said subject comprises at least one of a post-transplantation subject, pending transplantation subject, a transplantation rejection subject, and a combination thereof. 
     
     
         27 . The method of  claim 21 , wherein said treatment results in improvement or amelioration of changes in body composition, muscle mass, appendicular lean mass, total lean mass, fat mass, high VAT (visceral adipose fat), waist circumference, weight gain, BMI, mobility/frailty, hand grip strength, liver frailty index, balance, and chair stand ability, and a patient reported outcome (PRO). 
     
     
         28 . The method of  claim 27 , wherein said PRO comprises at least one of a functional status of patient-COA-symptom only known to said patient, a quality of life (QOL) assessed by CLDQ, a perceived HRQoL score, depression, degree of mobility, sexual dysfunction, and FIS fatigue questionnaire. 
     
     
         29 . The method of  claim 21 , wherein said treatment results in improvement or amelioration of at least one biomarker comprising a liver injury marker, lipoprotein-associated phospholipase A2, triglyceride, LDL, total cholesterol, cholesterol, hematocrit, hemoglobin, albumin, VLDL, non-HDL, SHBG, an imaging biomarker, liver stiffness, liver biopsy, inflammation, fibrosis, bilirubin, and a liver histology biomarker. 
     
     
         30 . The method of  claim 29 , wherein said liver injury marker comprises at least one of ALT, AST, ALP, and GGT, and wherein said fibrosis biomarker comprises at least one of CK18, AST/ALT ratio, NAFLD fibrosis score (NFS), BARD, Fibrometer test, Fibrotest (FT), Fibrospect-II, PGA-index, PGAA-index, Pohl score, ELF score, SHASTA, Fibrosis probability index (FPI), APRI score, FIB-4 score, and platelet count. 
     
     
         31 . A Method of treating at least one of NASH and a symptom thereof in a subject in need of treatment thereof comprising administering to said subject a pharmaceutical composition comprising at least one of TU, TD, TT, TET, and a combination thereof. 
     
     
         32 . The method of  claim 31 , wherein said pharmaceutical composition treats at least one co-morbid condition of obesity, type 2 diabetes, dyslipidemia, cardiovascular disease, thyroid dysfunction, chronic kidney disease, liver disease, osteoporosis, hypogonadism, hypertension, sarcopenia, and cachexia. 
     
     
         33 . The method of  claim 31 , wherein said pharmaceutical composition is administered with at least one pharmaceutical agent of metformin, glibenclamide, gliclazide, rosiglitazone, pioglitazone, troglitazone, acarbose, miglitol, nateglinide, repaglinide, exenatide, sitagliptin, pramlintide, atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, pitavastatin, butanoic acid, CER209, evogliptin, DUR928, MK-4074, OPRX-106, PF06865571, PF06882961, PXS-5382A, RG-125, RYI-018, seladelpar, SGM-1019, aramchol, ARX618, BI 1467335, DS102, EDP-305, Emricasan, gemcabene, GR-MD-02, GRI-0621, GS-0976, GS-9674, IMM-124E, IONIS-DGAT2Rx, IVA-337, Lipaglyn, LJN452, LMB763, MGL-3196, MN-001, MSDC-0602K, NC101, NGM282, NS-0200, Ozempic, PF-05221304, PF-06835919, remogliflozin etabonate, SHP626, TVB-2640, VK2809, cenicriviroc, elafibranor, ocaliva (obeticholic acid), selonsertib, and a combination thereof. 
     
     
         34 . The method of  claim 31 , wherein if said pharmaceutical composition comprises a single testosterone ester, loading of said single testosterone ester per unit dosage form of said pharmaceutical composition comprises at least one of 1-50% w/w, 5-30% w/w, 10-30% w/w, and 5-15% w/w. 
     
     
         35 . The method of  claim 31 , wherein if said pharmaceutical composition comprises a plurality of testosterone esters and includes TU, loading of said TU per unit dosage form of said pharmaceutical composition comprises at least one of 1-50% w/w, 5-30% w/w, 10-30% w/w, and 5-15% w/w, and wherein if said pharmaceutical composition comprises a plurality of testosterone esters and includes TD, loading of said TD per unit dosage form of said pharmaceutical composition comprises at least one of 1-50% w/w, 5-30% w/w, 10-30% w/w, and 5-15% w/w, and wherein if said pharmaceutical composition comprises a plurality of testosterone esters and includes TT, loading of said TT per unit dosage form of said pharmaceutical composition comprises at least one of 1-50% w/w, 5-30% w/w, 10-30% w/w, and 5-15% w/w. 
     
     
         36 . The method of  claim 31 , wherein if said pharmaceutical composition is prepared for a male subject and comprises TU, daily dosage of said TU comprises at least one of 10 mg to 1,000 mg, 200 mg to 750 mg, and 300 mg to 600 mg, and wherein if said pharmaceutical composition is prepared for a male subject and comprises TD, daily dosage of said TD comprises 10 mg to 1,000 mg, and wherein if said pharmaceutical composition is prepared for a male subject and comprises TT, daily dosage of said TT comprises at least one of 10 mg to 1,000 mg, 400 mg to 2,000 mg, and 600 mg to 1,800 mg, and wherein if said pharmaceutical composition is prepared for a female subject and comprises TU, daily dosage of said TU comprises 1/10th- 1/15th of at least one of 10 mg to 1,000 mg, 200 mg to 750 mg, and 300 mg to 600 mg, and wherein if said pharmaceutical composition is prepared for a female subject and comprises TD, daily dosage of said TD comprises 1/10th- 1/15th of 10 mg to 1,000 mg, and wherein if said pharmaceutical composition is prepared for a female subject and comprises TT, daily dosage of said TT comprises 1/10th- 1/15th of at least one of 10 mg to 1,000 mg, 400 mg to 2,000 mg, and 600 mg to 1,800 mg. 
     
     
         37 . The method of  claim 31 , wherein in response to administration of said pharmaceutical composition to a male subject having a testosterone concentration baseline below at least one of 350 ng/dL, 300 ng/dL, 250 ng/dL, 200 ng/dL, 150 ng/dL, and 100 ng/dL, said testosterone concentration (C ave0-24 ) of said male subject is increased over said subject's baseline. 
     
     
         38 . The method of  claim 37 , wherein said testosterone concentration (C ave0-24 ) increase comprises an increase of at least one of 30, 50, 75, 100, 150, 200, 300, 400 or 500 ng/dL. 
     
     
         39 . The method of  claim 31 , wherein said pharmaceutical composition comprises at least one pharmaceutically acceptable carrier. 
     
     
         40 . The method of  claim 31 , wherein said pharmaceutical composition comprises at least one of a hydrophilic carrier, a lipophilic carrier, and an additive. 
     
     
         41 . The method of  claim 40 , wherein said hydrophilic carrier comprises at least one of a polyoxylated mono-glyceride, a polyoxylated di-glyceride, a polyoxylated tri-glyceride, a polyoxylated vegetable oil, a polyoxylated hydrogenated vegetable oil, a polyoxylated mono-fatty acid, a polyoxylated di-fatty acid, a polyoxylated tri-fatty acid, a hydrogenated vegetable oil, Cremophor, Span, Tween, SLS, Poloxamer, Polymer, and a combination thereof. 
     
     
         42 . The method of  claim 41 , wherein said hydrogenated vegetable oil comprises at least one of hydrogenated castor oil, hydrogenated coconut oil, hydrogenated cottonseed oil, hydrogenated palm oil, hydrogenated soybean oil, and a combination thereof. 
     
     
         43 . The method of  claim 41 , wherein said polyoxylated hydrogenated vegetable oil comprises at least one of polyoxylated 35 hydrogenated castor oil, polyoxylated 40 hydrogenated castor oil and polyoxylated 60 hydrogenated castor oil, and a combination thereof, and wherein said Tween comprises at least one of Tween-20, Tween-21, Tween-40, Tween-60, Tween-61, Tween-65, Tween-80, Tween-81, Tween-85, Tween-120, and a combination thereof. 
     
     
         44 . The method of  claim 40 , wherein said lipophilic carrier comprises at least one of a vegetable oil, a fatty acid, a fatty alcohol, a mono-glyceride, a di-glyceride, a tri-glyceride, a hydrogenated vegetable oil, a Vitamin E compound, polyoxylated fatty acid, polyoxylated triglyceride, polyoxylated vegetable oil, glyceryl fatty acid, propylene glycol fatty acid, a PEG sorbitan fatty acid esters, a omega-3 fatty acid, a PEG glycol alkyl ether, a polyglycerized fatty acid, and a combination thereof. 
     
     
         45 . The method of  claim 44 , wherein said vegetable oil comprises at least one of castor oil, coconut oil, borage oil, cottonseed oil, peppermint oil, corn oil, peanut oil, linseed oil, olive oil, palm oil, sesame oil, soybean oil, and a combination thereof. 
     
     
         46 . The method of  claim 44 , wherein said fatty acid comprises at least one of caprylic acid, capric acid, lauric acid, palmitic acid, stearic acid, arachidic acid, behenic acid, myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, linoleic acid, linoelaidic acid, and a combination thereof, and wherein said omega-3 fatty acid comprises at least one of omega-3 EPA, omega-3 DHA, and a combination thereof. 
     
     
         47 . The method of  claim 44 , wherein said hydrogenated vegetable oil comprises at least one of hydrogeneated castor oil, hydrogeneated coconut oil, hydrogeneated cottonseed oil, hydrogenated palm oil, hydrogenated soybean oil, and a combination thereof. 
     
     
         48 . The method of  claim 44 , wherein said glyceryl fatty acid comprises at least one of glyceryl stearate, glyceryl oleate, glyceryl caprate, glyceryl caprylate, glyceryl laurate, glyceryl stearate, glyceryl palmitate, glyceryl linoleate, glyceryl myristate, and a combination thereof, and wherein said propylene glyceryl fatty acid comprises at least one of propylene glyceryl stearate, propylene glyceryl oleate, propylene glyceryl caprate, propylene glyceryl caprylate, propylene glyceryl laurate, propylene glyceryl stearate, propylene glyceryl palmitate, propylene glyceryl ricinoleate, propylene glyceryl myristate, and a combination thereof. 
     
     
         49 . The method of  claim 48 , wherein said glyceryl fatty acid comprises at least one of a glyceryl mono-fatty acid, a glyceryl di-fatty acid, and a glyceryl tri-fatty acid, and wherein said propylene glyceryl fatty acid comprises at least one of a propylene glyceryl mono-fatty acid, a propylene glyceryl di-fatty acid, and a propylene glyceryl tri-fatty acid. 
     
     
         50 . The method of  claim 31 , wherein said method further includes administering a therapeutically effective amount of a combination of androgen receptor agonists to said subject. 
     
     
         51 . The method of  claim 31 , wherein said subject has at least one co-morbid condition selected from obesity, type 2 diabetes, dyslipidemia, cardiovascular disease, thyroid dysfunction, chronic kidney disease, liver disease, osteoporosis, hypogonadism, hypertension, sarcopenia, and cachexia. 
     
     
         52 . The method of  claim 31 , wherein said subject comprises at least one of a post-transplantation subject, pending transplantation subject, a transplantation rejection subject, and a combination thereof. 
     
     
         53 . The method of  claim 31 , wherein said treatment results in improvement or amelioration of changes in body composition, muscle mass, appendicular lean mass, total lean mass, fat mass, high VAT (visceral adipose fat), waist circumference, weight gain, BMI, mobility/frailty, hand grip strength, liver frailty index, balance, and chair stand ability, and a patient reported outcome (PRO). 
     
     
         54 . The method of  claim 53 , wherein said PRO comprises at least one of a functional status of patient-COA-symptom only known to said patient, a quality of life (QOL) assessed by CLDQ, a perceived HRQoL score, depression, degree of mobility, sexual dysfunction, and FIS fatigue questionnaire. 
     
     
         55 . The method of  claim 31 , wherein said treatment results in improvement or amelioration of at least one biomarker comprising a liver injury marker, lipoprotein-associated phospholipase A2, triglyceride, LDL, total cholesterol, cholesterol, hematocrit, hemoglobin, albumin, VLDL, non-HDL, SHBG, an imaging biomarker, liver stiffness, liver biopsy, inflammation, fibrosis, bilirubin, and a liver histology biomarker. 
     
     
         56 . The method of  claim 55 , wherein said liver injury marker comprises at least one of ALT, AST, ALP, and GGT, and wherein said fibrosis biomarker comprises at least one of CK18, AST/ALT ratio, NAFLD fibrosis score (NFS), BARD, Fibrometer test, Fibrotest (FT), Fibrospect-II, PGA-index, PGAA-index, Pohl score, ELF score, SHASTA, Fibrosis probability index (FPI), APRI score, FIB-4 score, and platelet count. 
     
     
         57 . The method of  claim 31 , wherein said administering comprises an oral administration.