Table 2.
Exploratory Biomarkers
| Placebo | OCA 10 mg | OCA 50 mg | ||||||
|---|---|---|---|---|---|---|---|---|
| Baseline | Change From Baseline | Baseline | Change From Baseline | P | Baseline | Change From Baseline | P | |
| Inflammatory and immunomodulatory biomarkers | ||||||||
| hsCRP (mg/L) |
11.2 (5.6, 16.1) n = 21 |
0.0 (−5.7, 2.1) n = 19 |
5.6 (4.0, 7.8) n = 17 |
−3.0 (−5.3, −1.5) n = 15 |
0.1105 |
5.0 (3.6, 9.6) n = 13 |
−1.4 (−4.5, 0.3) n = 11 |
0.3016 |
| TNF‐α (ng/L) |
15.1 (12.6,17.4) n = 18 |
0.4 (−1.0, 3.6) n = 15 |
14.9 (12.0, 19.4) n = 14 |
−1.1 (−3.3, 0.0) n = 13 |
0.1119 |
16.1 (11.7, 21.0) n = 12 |
−2.2 (−3.7, −0.6) n = 9 |
0.0061 |
| TGF−β (μg/L) |
19.0 (16.2, 28.4) n = 10 |
1.0 (0.3, 1.4) n = 10 |
24.0 (19.2, 26.8) n = 8 |
−4.1 (−6.5, 7.0) n = 7 |
0.7327 |
21.5 (19.3, 28.1) n = 6 |
1.9 (0.1, 4.7) n = 6 |
0.7042 |
| IgM (g/L) |
3.0 (2.7, 4.3) n = 17 |
0.0 (−0.3, 0.2) n = 13 |
2.7 (1.9, 3.6) n = 14 |
−0.6 (−0.9, −0.1) n = 11 |
0.0205 |
3.8 (2.7, 6.3) n = 11 |
−1.0 (−1.9, −0.6) n = 9 |
0.0033 |
|
Osteopontin (μg/L) |
229 (169, 324) n = 8 |
60 (−19, 91) n = 7 |
320 (166, 357) n = 7 |
15 (−63, 125) n = 7 |
0.8983 |
217 (180, 264) n = 7 |
181 (134, 252) n = 5 |
0.0348 |
|
Glutathione (μmol/L) |
2.3 (2.0, 4.7) n = 9 |
0.2 (−0.5, 0.7) n = 7 |
2.3 (1.2, 3.1) n = 7 |
1.9 (0.4, 3.0) n = 7 |
0.0151 |
4.2 (1.3, 5.9) n = 7 |
0.2 (0.1, 2.1) n = 5 |
0.6261 |
| Noninvasive measures of liver fibrosis | ||||||||
| ELF score |
9.2 (8.6, 9.8) n = 22 |
−0.1 (−0.2, 0.4) n = 21 |
9.3 (8.2, 9.7) n = 20 |
0.2 (−0.1, 0.5) n = 19 |
0.2334 |
9.2 (8.9, 9.3) n = 14 |
0.0 (−0.4, 0.3) n = 14 |
0.6738 |
| HA (ng/mL) |
49.6 (24.2, 78.0) n = 22 |
0.2 (−11.5, 12.9) n = 21 |
45.8 (24.9, 71.9) n = 20 |
10.2 (−3.2, 30.4) n = 19 |
0.1436 |
40.8 (27.5, 77.2) n = 14 |
1.8 (−12.6, 10.5) n = 14 |
0.8796 |
|
P3NP (ng/mL) |
6.5 (5.8, 11.4) n = 22 |
0.3 (−0.8, 1.3) n = 21 |
7.5 (5.0, 9.0) n = 20 |
−0.2 (−1.2, 2.76) n = 19 |
0.6648 |
8.2 (4.8, 10.7) n = 14 |
−0.4 (−1.2, 1.3) n = 14 |
0.8531 |
|
TIMP‐1 (ng/mL) |
767 (601, 906) n = 22 |
−33 (−133, 73) n = 21 |
799 (661, 897) n = 20 |
−80 (−197, −34) n = 19 |
0.2229 |
785 (689, 854) n = 14 |
−69 (−121, −21) n = 14 |
0.7491 |
| Additional measures of liver function | ||||||||
| Albumin (g/L) |
40.0 (37.0, 42.0) n = 23 |
−1.3 (3.0, 0.0) n = 22 |
38.9 (34.5, 43.2) n = 20 |
−0.6 (−2.1, 1.5) n = 19 |
0.4404 |
40.5 (38.1, 43.5) n = 16 |
−1.0 (−2.8, 1.5) n = 15 |
0.6205 |
| Platelets (109/L) |
314 (213, 386) n = 23 |
−6 (−34, 21) n = 23 |
260 (226, 313) n = 20 |
−6 (−34, 22) n = 19 |
0.9798 |
269 (217, 329) n = 16 |
2 (−10, 35) n = 14 |
0.4154 |
| Serum bile acids (μmol/L) |
8.1 (6.9, 12.9) n = 9 |
0.9 (−1.1, 7.5) n = 6 |
9.4 (7.2, 11.4) n = 7 |
−1.5 (−2.6, 3.6) n = 7 |
0.5203 |
6.0 (5.8, 23.9) n = 7 |
−0.5 (−8.6, 0.4) n = 4 |
0.5940 |
| INR |
1.00 (0.98, 1.07) n = 23 |
−0.02 (−0.05, 0.07) n = 23 |
1.01 (0.98, 1.05) n = 20 |
−0.04 (−0.07, 0.01) n = 19 |
0.1606 |
0.99 (0.96, 1.05) n = 16 |
0.00 (−0.11, 0.07) n = 15 |
0.6977 |
|
NEFA (mmol/L) |
0.5 (0.3, 0.6) n = 9 |
−0.1 (−0.3, 0.1) n = 6 |
0.5 (0.3, 0.9) n = 7 |
0.1 (−0.7, 0.3) n = 7 |
0.7206 |
0.4 (0.1, 0.6) n = 7 |
0.1 (−0.1, 0.5) n = 4 |
0.3359 |
Data are median (Q1, Q3); P values are for median change from baseline to month 3 based on a Wilcoxon‐Mann‐Whitney comparison. Change from baseline values at month 3 include the ET visit data for patients who discontinued. Normal ranges: hsCRP, ≤3.0 mg/L; TNF‐α, ≤8.1 ng/L; TGF‐β, 21.0‐82.0 μg/L; IgM, 0.4‐2.3 g/L; osteopontin, 171‐667 μg/L; glutathione, 2.4‐4.4 μmol/L; albumin, 31.0‐52.0 g/L; platelets, 121‐450 109/L; bile acids, ≤10 μmol/L; INR, 0.76‐1.27; NEFA, 0.1‐0.45 mmol/L (female), 0.1‐0.60 mmol/L (male).
Abbreviations: ELF, enhanced liver fibrosis; HA, hemagglutinin; INR, international normalized ratio; NEFA, nonesterified fatty acids; P3NP, procollagen type 3 N‐terminal peptide; TGF‐β, transforming growth factor‐β; TIMP‐1, tissue inhibitor of metalloproteinase 1.