Biomarkers and methods for determining disease progression in nonalcoholic steatohepatitis (NASH)
Diets high in saturated fat and fructose have been implicated in the development of obesity and nonalcoholic steatohepatitis (NASH) in humans. Provided herein are biomarkers, methods, and animal models useful for the investigation and non-invasive detection of NASH, including a non-invasive biomarker that could be used to establish disease severity, follow progression, and evaluate response to treatment in clinical trials for this increasingly prevalent disease.
1. A method of determining the presence of fatty liver disease (FLD) in a patient, comprising:
providing a sample from a patient;
measuring the level of coenzyme Q (CoQ) in the sample; and
comparing the CoQ value from the patient with a threshold value, wherein if the CoQ value meets the threshold value the patient is determined to be at risk for fatty liver disease.
2. The method of claim 1 , wherein the CoQ measurement is a measurement of reduced CoQ.
3. The method of claim 1 , wherein the CoQ measurement is a measurement of total CoQ.
4. The method of claim 1 , wherein the CoQ measurement is a measurement of oxidized CoQ.
5. The method of claim 1 , wherein the CoQ measurement is a measurement of coenzyme Q10 (CoQ10).
6. The method of claim 1 , wherein the CoQ measurement is the ratio of reduced CoQ10:total CoQ10.
7. The method of claim 1 , wherein the sample is selected from the group consisting of blood, plasma, serum, or a tissue.
8. The method of claim 7 , wherein the sample is plasma.
9. The method of claim 1 , wherein the threshold value is determined using a value calculated using a receiver operating characteristic (ROC) analysis.
10. The method of claim 2 , further comprising adjusting the measurement of reduced CoQ based on a lipid level in the sample to form an adjusted CoQ value.
11. The method of claim 10 , wherein the measurement of reduced CoQ is adjusted for the total cholesterol level in the sample.
12. The method of claim 11 , wherein the threshold value is a median reduced CoQ of less than about 0.17 μmol CoQ10/mmol lipid.
13. The method of claim 10 , wherein the measurement of reduced CoQ is adjusted for the low-density lipoprotein (LDL) level in the sample.
14. The method of claim 13 , wherein the threshold value is a median reduced CoQ of less than about 0.293 μmol CoQ10/mmol lipid.
15. The method of claim 10 , wherein the measurement of reduced CoQ is adjusted for the triglyceride level in the sample.
16. The method of claim 15 , wherein the threshold value is a median reduced CoQ of less than about 0.63 μmol CoQ10/mmol lipid.
17. The method of claim 10 , wherein the measurement of reduced CoQ is adjusted for the total cholesterol level and the triglyceride level in the sample.
18. The method of claim 17 , wherein the threshold value is a median reduced CoQ of less than about 0.131 μmol CoQ10/mmol lipid.
19. The method of claim 10 , wherein the measurement of reduced CoQ is adjusted for the high-density lipoprotein (HDL) level in the sample.
20. The method of claim 19 , wherein the threshold value is a median reduced CoQ of more than about 0.639 μmol of CoQ10/mmol lipid.
21. The method of claim 3 , further comprising adjusting the measurement of total CoQ based on a lipid level in the sample to form an adjusted CoQ value.
22. The method of claim 21 , wherein the measurement of total CoQ is adjusted for the total cholesterol level in the sample.
23. The method of claim 22 , wherein the threshold value is a median total CoQ of less than about 0.176 μmol CoQ10/mmol lipid.
24. The method of claim 21 , wherein the measurement of total CoQ is adjusted for the low-density lipoprotein (LDL) level in the sample.
25. The method of claim 24 , wherein the threshold value is a median total CoQ of less than about 0.307 μmol CoQ10/mmol lipid.
26. The method of claim 21 , wherein the measurement of total CoQ is adjusted for the triglyceride level in the sample.
27. The method of claim 26 , wherein the threshold value is a median total CoQ of less than about 0.92 μmol CoQ10/mmol lipid.
28. The method of claim 21 , wherein the measurement of total CoQ is adjusted for the total cholesterol level and the triglyceride level in the sample.
29. The method of claim 28 , wherein the threshold value is a median total CoQ of less than about 0.142 μmol CoQ10/mmol lipid.
30. The method of claim 21 , wherein the measurement of total CoQ is adjusted for the high-density lipoprotein (HDL) level in the sample.
31. The method of claim 30 , wherein the threshold value is a median total CoQ of more than about 0.678 μmol CoQ10/mmol lipid.
32. The method of claim 4 , further comprising adjusting the measurement of oxidized CoQ based on a lipid level in the sample to form an adjusted CoQ value.
33. The method of claim 32 , wherein the measurement of oxidized CoQ is adjusted for the total cholesterol level in the sample.
34. The method of claim 33 , wherein the threshold value is a median oxidized CoQ of less than about 0.016 μmol CoQ10/mmol lipid.
35. The method of claim 32 , wherein the measurement of oxidized CoQ is adjusted for the low-density lipoprotein (LDL) level in the sample.
36. The method of claim 35 , wherein the threshold value is a median oxidized CoQ of less than about 0.015 μmol CoQ10/mmol lipid.
37. The method of claim 32 , wherein the measurement of oxidized CoQ is adjusted for the triglyceride level in the sample.
38. The method of claim 37 , wherein the threshold value is a median oxidized CoQ of less than about 0.051 μmol CoQ10/mmol lipid.
39. The method of claim 32 , wherein the measurement of oxidized CoQ is adjusted for the total cholesterol level and the triglyceride level in the sample.
40. The method of claim 39 , wherein the threshold value is a median oxidized CoQ of less than about 0.006 μmol CoQ10/mmol lipid.
41. The method of claim 32 , wherein the measurement of oxidized CoQ is adjusted for the high-density lipoprotein (HDL) level in the sample.
42. The method of claim 41 , wherein the threshold value is a median oxidized CoQ of more than about 0.051 μmol of oxidized CoQ10/mmol lipid.
43. The method of claim 6 , wherein the ratio of reduced CoQ10:total CoQ10 is less than about 0.935.
44. The method of claim 1 , further comprising determining the stage of FLD in the patient.
45. The method of claim 44 , wherein the stage of FLD is nonalcoholic fatty liver disease (NAFLD).
46. The method of claim 44 , wherein the stage of FLD is nonalcoholic steatohepatitis (NASH).
47. The method of claim 46 , further comprising determining the stage of fibrosis in NASH in the patient.