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Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

  1. Layli Eslami1,*,
  2. Shahin Merat2,
  3. Reza Malekzadeh2,
  4. Siavosh Nasseri-Moghaddam2,
  5. Hermineh Aramin2

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 27 DEC 2013

Assessed as up-to-date: 12 JUN 2010

DOI: 10.1002/14651858.CD008623.pub2


How to Cite

Eslami L, Merat S, Malekzadeh R, Nasseri-Moghaddam S, Aramin H. Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD008623. DOI: 10.1002/14651858.CD008623.pub2.

Author Information

  1. 1

    Golestan University of Medical Science, Taleghani Hospital, Gonbad e Kavous, Golestan province, Iran

  2. 2

    Shariati Hospital, Tehran University of Medical Sciences, Digestive Diseases Research Centre, Tehran, Tehran, Iran

*Layli Eslami, Golestan University of Medical Science, Taleghani Hospital, North Khayyam crossroad, East Taleghani Avenue, Gonbad e Kavous, Golestan province, 49791-31983, Iran. laylieslami@gmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 27 DEC 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Athyros 2006

MethodsRandomised clinical trial with three parallel groups


ParticipantsParticipants 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.


Interventions189 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)).


OutcomesAt 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

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers were used for generation of allocation sequence.

Allocation concealment (selection bias)Unclear riskThe method of allocation concealment was unclear.

Blinding of participants and personnel (performance bias)
All outcomes
High riskIt was an open-labelled trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskIt was an open-labelled trial.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcomes, dropouts, and withdrawals were pointed out precisely in the trial.

Selective reporting (reporting bias)Low riskAll relevant outcomes were available in the trials. No reporting bias was detected.

Other biasUnclear riskIt is not clear whether sample size calculations were performed.

Nelson 2009

MethodsDouble-blind randomised placebo-controlled trial with two parallel groups.


ParticipantsSixteen 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.


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


OutcomesFourteen 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

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method was not reported.

Allocation concealment (selection bias)Unclear riskThe method was not reported.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskThe trial was described as double-blind, but it was not reported who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskThe trial was described as double-blind, but it was not reported who was blinded.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskReported data about the withdrawals were unclear.

Selective reporting (reporting bias)High riskNot all outcomes were reported.

Other biasUnclear riskIt is not clear whether sample size calculations were performed.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Antonopoulos 2006Inappropriate study design (uncontrolled clinical trial).

Athyros 2010A few participants in the control group received statin.

Carnelutti 2012Only an abstract of the study was available.

Gomez 2006Inappropriate study design (uncontrolled clinical trial).

Han 2012Both intervention and control groups received statin.

Harlander 2001Inappropriate study design (uncontrolled clinical trial).

Hatzitolios 2004Inappropriate study design (controlled before and after clinical trial).

Kiyici 2003Inappropriate study design (uncontrolled clinical trial).

Lewis 2007Inappropriate participants (patients with chronic liver disease).

Rallidis 2004Inappropriate study design (uncontrolled clinical trial).

Tavakkoli 2009Inappropriate study design (uncontrolled clinical trial).

 
Table 1. Search results

Source of the searchNumber of records

CHBG Controlled Trial Register51

Cochrane Central Register of Controlled Trials78

MEDLINE (Ovid)116

EMBASE (Ovid)518

Science Citation Index EXPANDED91

Total number of references identified851

Number of duplicates excluded198

Number of references in final list653

 
Table 2. Baseline and after treatment laboratory variables in Nelson et al trial

 Statin (n = 10)Placebo  (n = 6)


Before treatmentAfter treatmentMean decreaseBefore treatmentAfter treatmentMean decrease

ALT (U/L)70.449.520.966.875.3-8.5

AST (U/L)43.336.56.842.849.3-6.5

ALP (U/L)86.189.7-3.674.3731.3

TG (mg/dL)388.7490-101.3335.3361.7-26.4

 ALT = alanine aminotransferase
AST = aspartate aminotransferase
ALP = alkaline phosphatase
TG = triglycerides
 
Table 3. Baseline and after treatment laboratory variables in Athyros et al trial

 Statin (n = 63)Fenofibrate  (n = 62)


Before treatmentAfter treatmentMean decreaseBefore treatmentAfter treatmentMean decrease

ALT (U/L)543222523616

AST (U/L)382513392712

ALP (U/L)11075351087830

TG (mg/dL)203.8142.261.6194.9115.679.3

 ALT = alanine aminotransferase
AST = aspartate aminotransferase
ALP = alkaline phosphatases
TG = triglycerides
 
Table 4. Level of evidence for each outcome

OutcomeBiochemical improvement

 
Radiological improvementNo improvement in histologySerious adverse effects

EvidenceLow-quality systematic reviewLow-quality randomised clinical trialSmall sample size in low-quality randomised clinical trialLow-quality systematic review

 

Level of evidence2222

Grade of recommendationBBBB