Table 2.
Changes in histological features of the liver after 72 weeks of treatment
| Obeticholic acid | Placebo | Relative risks or mean changes from baseline* (95% CI) (obeticholic acid vs placebo) | p value* | |
|---|---|---|---|---|
|
Primary outcome†
| ||||
| Number of patients at risk‡ | 110 | 109 | ||
| Patients with improvement | 50 (45%) | 23 (21%) | 1·9 (1·3 to 2·8) | 0·0002 |
|
| ||||
|
Changes from baseline in histological features
| ||||
| Number of patients with biopsy specimens at baseline and 72 weeks | 102 | 98 | ||
| Resolution§ of definite non-alcoholic steatohepatitis | 22 (22%) | 13 (13%) | 1·5 (0·9 to 2·6) | 0·08 |
| Fibrosis¶ | ||||
| Patients with improvement | 36 (35%) | 19 (19%) | 1·8 (1·1 to 2·7) | 0·004 |
| Change in score | −0·2 (1·0) | 0·1 (0·9) | −0·3 (−0·6 to −0·1) | 0·01 |
| Total NAFLD activity score | ||||
| Change in score | −1·7 (1·8) | −0·7 (1·8) | −0·9 (−1·3 to −0·5) | <0·0001 |
| Hepatocellular ballooning | ||||
| Patients with improvement | 47 (46%) | 30 (31%) | 1·5 (1·0 to 2·1) | 0·03 |
| Change in score | −0·5 (0·9) | −0·2 (0·9) | −0·2 (−0·5 to 0·0) | 0·03 |
| Steatosis | ||||
| Patients with improvement | 62 (61%) | 37 (38%) | 1·7 (1·2 to 2·3) | 0·001 |
| Change in score | −0·8 (1·0) | −0·4 (0·8) | −0·4 (−0·6 to −0·2) | 0·0004 |
| Lobular inflammation | ||||
| Patients with improvement | 54 (53%) | 34 (35%) | 1·6 (1·1 to 2·2) | 0·006 |
| Change in score | −0·5 (0·8) | −0·2 (0·9) | −0·3 (−0·5 to −0·1) | 0·0006 |
| Portal inflammation|| | ||||
| Patients with improvement | 12 (12%) | 13 (13%) | 1·0 (0·6 to 1·7) | 0·90 |
| Change in score | 0·2 (0·7) | 0·2 (0·7) | 0·0 (−0·1 to 0·2) | 0·59 |
Data are n (%) or mean (SD).
p values and relative benefit were calculated with the Cochran-Mantel-Haenszel chi-square test, stratified by clinic and diabetes status, for binary outcomes; p values and mean changes from baseline were calculated using ANCOVA, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome, for outcome scores.
The primary outcome was an improvement in histological findings, which required a decrease of 2 or more points in the total non-alcoholic fatty liver disease (NAFLD) activity score and no worsening in the fibrosis score; 11 patients in the placebo group and eight in the obeticholic acid group had missing histological data at week 72, and the results for these patients were imputed as a lack of improvement; NAFLD activity score was assessed on a scale of 0–8, with higher scores showing more severe disease (the components of this measure are steatosis [assessed on a scale of 0–3], lobular inflammation [assessed on a scale of 0–3], and hepatocellular ballooning [assessed on a scale of 0–2]).
Number of randomly assigned patients with observed or expected week 72 visit before protocol modified on Jan 6, 2014, to eliminate week 72 biopsy.
Resolution defined as either not NAFLD, or NAFLD but not non-alcoholic steatohepatitis on week 72 biopsy.
Fibrosis was assessed on a scale of 0–4, with higher scores showing more severe fibrosis.
Portal inflammation was assessed on a scale of 0–2, with higher scores showing more severe inflammation.