Grade | Bias |
---|---|
• | Random sequence generation (selection bias) |
• | Allocation concealment (selection bias) |
○ | Blinding of participants and personnel (performance bias) |
○ | Blinding of outcome assessment (detection bias) |
○ | Incomplete outcome data (attrition bias) |
• | Selective reporting (reporting bias) |
Author (year) | Outcomes | Main findings | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
% of steatosis | Steatosis grading | NAS | Necroinflammatory activity grade | Fibrosis stage | Total cholesterol | Triglyceride | HDL | LDL | ALT | AST | |||
Nelson et al. (2009) [18] | Yes | No | No | Yes | Yes | Yes | Yes | No | Yes | Yes | Yes | - 26% reduction in LDL between simvastatin vs placebo | |
- No statistically significant improvement in ALT, AST, hepatic steatosis, necroinflammatory activity, or stage of fibrosis within or between groups | |||||||||||||
Ekstedt et al. (2007) [13] | Yes | No | No | No | Yes | Yes | Yes | No | No | Yes | Yes | - Significant reduction in quantitative steatosis in the statin cohort between baseline and follow-up | |
- AST/ALT did not differ significantly between the two cohorts | |||||||||||||
Hyogo et al. (2011) [14] | No | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | - Significant decrease in ALT and lipid profiles | |
- NAS tended to be decreased but statistical significance was not shown | |||||||||||||
- Fibrosis stage did not change significantly | |||||||||||||
Nakahara et al. (2012) [15] | No | Yes | Yes | No | Yes | Yes | Yes | Yes | Yes | Yes | Yes | - Mean AST/ALT did not significantly change during the treatment | |
- NAS and fibrotic stage tended to decrease after the treatment but statistical significance was not shown | |||||||||||||
Hyogo et al. (2012) [16] | No | No | Yes | No | No | Yes | Yes | Yes | Yes | Yes | Yes | - Significant decrease in AST and ALT | |
- Significant improvement in NAS | |||||||||||||
Kargiotis et al. (2015) [17] | No | Yes | Yes | No | No | Yes | Yes | Yes | Yes | No | No | - Complete resolution of NASH in 19 of 20 patients | |
- AST, ALT, and lipid profiles were normalized by the 3rd month of treatment |
Outcomes | Studies, n | Patients, n | Standardized mean change† | Assessment of heterogeneity | ||
---|---|---|---|---|---|---|
% of steatosis | 2 | 27 | –0.580 (–1.599, 0.439) | 0.265 | 93 | <0.001 |
Steatosis grading | 3 | 42 | –2.580 (–4.623, –0.536) | 0.013 | 98 | <0.001 |
NAFLD activity score | 4 | 84 | –1.488 (–2.506, –0.471) | 0.004 | 96 | <0.001 |
Necroinflammatory activity grade | 2 | 23 | –0.112 (–0.372, 0.148) | 0.398 | 0 | 0.454 |
Fibrosis stage | 4 | 49 | 0.156 (–0.553, 0.865) | 0.667 | 92 | <0.001 |
Total cholesterol | 6 | 111 | –1.540 (–2.221, –0.859) | <0.001 | 93 | <0.001 |
Triglyceride | 6 | 111 | –0.764 (–1.334, –0.195) | 0.009 | 94 | <0.001 |
High-density lipoprotein | 4 | 84 | 0.423 (–0.070, 0.917) | 0.093 | 89 | <0.001 |
Low-density lipoprotein | 5 | 94 | –1.865 (–2.416, –1.313) | <0.001 | 83 | <0.001 |
Alanine transaminase | 5 | 91 | –0.511 (–0.650, –0.373) | <0.001 | 0 | 0.680 |
Aspartate aminotransferase | 5 | 91 | –0.462 (–0.599, –0.325) | <0.001 | 0 | 0.594 |
Author | Year [ref] | Country | Study design | Patients, n Number of patients in statin treatment arm, | Type of statin (mg/dL) | Follow-up time (year) | Statin duration (year) | Study quality Quality assessment using Cochrane Collaboration’s tool for assessing risk of bias for RCT and Cochrane assessment of bias for non-randomized studies tool (ROBINS-I). | |
---|---|---|---|---|---|---|---|---|---|
Nelson et al | 2009 [18] | USA | RCT | 10 data from the statin arm. | Simvastatin (40) | 1 | 1 | Low Risk of bias legend for RCT illustrated in | |
Ekstedt et al | 2007 [13] | Sweden | Retrospective | 17 | NA | 10.3–16.3 | 1–15.9 | Ser Risk of bias legend for nonrandomized studies illustrated in | |
cohort | |||||||||
Hyogo et al | 2011 [14] | Japan | Prospective | 13 | Pitavastatin (2) | 1 | 1 | Mod Risk of bias legend for nonrandomized studies illustrated in | |
cohort | |||||||||
Nakahara et al | 2012 [15] | Japan | Prospective | 9 | Rosuvastatin (2.5) | 2 | 2 | Mod Risk of bias legend for nonrandomized studies illustrated in | |
cohort | |||||||||
Hyogo et al | 2012 [16] | Japan | Prospective | 42 | Atorvastatin (10) | 1 | 1 | Mod Risk of bias legend for nonrandomized studies illustrated in | |
cohort | |||||||||
Kargiotis et al | 2015 [17] | Greece | Prospective | 20 | Rosuvastatin (10) | 1 | 1 | Mod Risk of bias legend for nonrandomized studies illustrated in | |
cohort |
Domain | Ekstedt et al. [13] | Hyogo et al. [14] | Nakahara et al. [15] | Hyogo et al. [16] | Kargiotis et al. [17] |
---|---|---|---|---|---|
Confounding | Moderate | Moderate | Moderate | Moderate | Moderate |
Selection | Serious | Low | Low | Low | Low |
Measurement of interventions | Serious | Low | Low | Low | Low |
Performance | Low | Low | Low | Low | Low |
Missing data | Low | Low | Low | Low | Low |
Measurement of outcomes | Low | Low | Low | Low | Low |
Reporting | Low | Low | Low | Low | Low |
Overall | Serious | Moderate | Moderate | Moderate | Moderate |