| Methods |
Randomised clinical trial |
| Participants |
Country: USA.
Number randomised: 50.
Post‐randomisation drop‐outs: not stated.
Revised sample size: 50.
Average age: 49 years.
Females: 31 (62%).
NASH: 50 (100%).
Diabetics: 14 (28%).
Average follow‐up period in months: 6.
Inclusion criteria
1. Patients with biopsy proven NASH.
2. Aged ≥ 18 years.
3. ALT > upper limit of normal (19 U/L for women and 30 U/L for men).
4. Presence of hepatic steatosis as defined by ≥ 5% on MRI.
Exclusion criteria
1. Evidence of other forms of liver disease shown by the presence of serum hepatitis B surface antigen, hepatitis C viral RNA, positive auto‐immune serologies with biopsy consistent with autoimmune hepatitis, haemochromatosis by 3+ or 4+ stainable iron on biopsy and homozygosity/heterozygosity on genetic analysis, low ceruloplasmin levels with biopsy suggestive of Wilson's disease, or low alpha‐1‐antitrypsin levels with biopsy suggestive of alpha‐1‐antitrypsin disease.
2. Alcohol intake > 30 g/day in the previous 10 years or > 10 g/day in the previous year.
3. Decompensated cirrhosis with Child‐Pugh score > 7 points.
4. Active substance abuse.
5. Significant systemic illnesses.
6. Renal insufficiency.
7. Positive human immunodeficiency virus test.
8. Pregnancy.
9. Evidence of hepatocellular carcinoma.
10. Ingestion of drugs known to cause hepatic steatosis.
11. Ingestion of drugs known to improve NASH such as vitamin E or pioglitazone.
12. Contraindications to liver biopsy or inability to undergo MRI. |
| Interventions |
Participants were randomly assigned to two groups.
Group 1: ezetimibe (N = 25).
Further details: ezetimibe 10 mg once daily.
Group 2: control (N = 25).
Further details: control: placebo.
Duration of treatment: 6 months. |
| Outcomes |
Outcomes reported: 1. Adverse events 2. Fibrosis score 3.NAS score 4. Resolution of fatty liver disease |
| Notes |
Reasons for post‐randomisation drop‐outs: not stated. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Quote: "computer‐generated numbers". |
| Allocation concealment (selection bias) |
Low risk |
Quote: "Independent investigational drug services pharmacists dispensed either active or placebo treatment pills, which were identical in appearance". |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
Quote: "double‐blind". |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
Quote: "double‐blind". |
| Incomplete outcome data (attrition bias)
All outcomes |
Unclear risk |
Comment: 4 patients did not compelete the treatment. It was not clear whether these patients were included in the results for adverse events. For histological assessment only 17 patients and 18 patients were included in the analysis. |
| Selective reporting (reporting bias) |
High risk |
Comment: protocol was not available; mortality was not reported. |
| For‐profit bias |
High risk |
Quote: "Supported by an investigator‐initiated study grant to R.L. by Merck.". |
| Other bias |
Low risk |
Comment: no other risk of bias. |
