Methods

Randomised clinical trial with three parallel groups

Participants

Participants were free of diabetes mellitus (DM) (ie, fasting glucose levels < 7 mmol/L; 126 mg/dL) and cardiovascular disease (diagnosed on the basis of personal history, clinical examination findings, and non‐invasive methods).

The inclusion criteria were (a) the presence of the metabolic syndrome (MetS) (NCEP ATP III definition) (NCEP ATP III report), (b) low‐density lipoprotein cholesterol (LDL‐C) > 3.4 mmol/L (130 mg/dL), (c) ultrasonographic evidence of fatty liver, and (d) elevated serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) activity.

Other causes of liver disease were excluded.

Interventions

189 participants were randomly allocated to atorvastatin 20 mg/day (n = 63) versus micronised fenofibrate 200 mg/day (n = 62) versus both drugs (n = 61). All participants had both biochemical and ultrasonographic evidence of NAFLD at baseline.

All participants received:

• lifestyle advice, including exercise (walking for at least 30 min, 5 days a week, or equivalent exercise) and a low‐fat and low‐calorie diet (NCEP ATP III report); and

• treatment for hypertension (mainly inhibitors of the renin‐angiotensin system), impaired fasting glucose (metformin), obesity (orlistat), and dyslipidaemia (randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)).

Outcomes

At the end of treatment, 67% of participants taking atorvastatin, 42% taking fenofibrate, and 70% taking combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (P < 0.05 versus baseline for all comparisons).

The percentage of participants who no longer had evidence of NAFLD was significantly higher (P < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers were used for generation of allocation sequence.

Allocation concealment (selection bias)

Unclear risk

The method of allocation concealment was unclear.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

It was an open‐labelled trial.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

It was an open‐labelled trial.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Outcomes, dropouts, and withdrawals were pointed out precisely in the trial.

Selective reporting (reporting bias)

Low risk

All relevant outcomes were available in the trials. No reporting bias was detected.

Other bias

Unclear risk

It is not clear whether sample size calculations were performed.

Methods

Double‐blind randomised placebo‐controlled trial with two parallel groups.

Participants

Sixteen adults, 18 years of age or older, with documented NASH based on liver biopsy using criteria established by Brunt et al (Brunt 2005), were included. All participants had compensated liver disease with haemoglobin values of 12 g/dL or greater in females and 13 g/dL or greater in males; a white blood cell count > 3000/mm³, neutrophil count > 1500/mm³, platelets > 70,000/mm³, albumin > 3.0 g/dL, in addition to normal total bilirubin, prothrombin time, and International normalised ratio. Other requirements included serum creatinine < 1.4 mg/dL and elevated serum lipid panel manifested by total cholesterol > 200 mg/dL, LDL > 130 mg/dL, or TGs > 200 mg/dL.

Interventions

Participants were randomly assigned to receive simvastatin 40 mg (n = 10) versus placebo (n = 6) once daily for 12 months.

Outcomes

Fourteen participants completed the trial, and 10 underwent 1 year repeated liver biopsy. Although a 26% reduction in low‐density lipoprotein was seen in the simvastatin group compared with the placebo group, no statistically significant improvement in serum aminotransferases, hepatic steatosis, necro‐inflammatory activity, or stage of fibrosis was noted within or between groups.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

The method was not reported.

Allocation concealment (selection bias)

Unclear risk

The method was not reported.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

The trial was described as double‐blind, but it was not reported who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

The trial was described as double‐blind, but it was not reported who was blinded.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Reported data about the withdrawals were unclear.

Selective reporting (reporting bias)

High risk

Not all outcomes were reported.

Other bias

Unclear risk

It is not clear whether sample size calculations were performed.