Table 3.
Summary of Findings with Appraisal of Evidence Quality According to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach
| Outcomes | Number of participants (studies) |
Certainty of the evidence (GRADE) |
Anticipated absolute effects | |
|---|---|---|---|---|
| Risk with | Risk difference with Vitamin co-treatment | |||
| Liver Brightness (Steatosis) assessed with: Ultrasonography follow up: range 3 months to 12 months |
128 (2 RCTs) (Hadzi-Petrushev et al., 2018; Nobili et al., 2006) |
VERY LOW a,b,c | not pooled | not pooled |
| Hepatocyte injury (steatosis, inflammation, ballooning) assessed with: Histological grading follow up: range 6 months to 2 years |
98 (2 RCTs) (Harrison et al., 2003; Nobili et al., 2008) |
VERY LOW c,d,e,f,g | not pooled | not pooled |
| Fibrosis assessed with: Histological grading Scale from: Grade 1 to Grade 4 follow up: range 6 months to 2 years |
98 (2 RCTs) (Harrison et al., 2003; Nobili et al., 2008) |
VERY LOW c,d,f,g | - | SMD 0.01 higher (0.39 lower to 0.41 higher) |
| Aspartate aminotransferase (AST) assessed with: Serum levels follow up: range 3 months to 2 years |
181 (3 RCTs) (Hadzi-Petrushev et al., 2018; Nobili et al., 2006; Nobili et al., 2008) |
VERY LOW c,f,h,i | The mean aspartate aminotransferase (AST) ranged from 23.2 to 37.25 IU/L | MD 0.05 IU/L lower (2.6 lower to 2.49 higher) |
| Alanine aminotransferase (ALT) assessed with: Serum levels follow up: range 3 months to 2 years |
226 (4 RCTs) (Hadzi-Petrushev et al., 2018; Harrison et al., 2003; Nobili et al., 2006; Nobili et al., 2008) |
VERY LOW c,f,i,j,k | The mean alanine aminotransferase (ALT) ranged from 30.3 to 81 IU/L | MD 2.81 IU/L higher (2.1 lower to 7.71 higher) |
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI); CI, Confidence interval; SMD, Standardized mean difference; MD, Mean difference; GRADE Working Group grades of evidence; High certainty: We are very confident that the true effect lies close to that of the estimate of the effect; Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different; Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect; Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect; Explanations: a. Downgraded one level for high risk of bias (selection, performance, detection, and gender biases in Hadzi-Petrushev et al., 2018; b. Downgraded one level for serious indirectness (liver brightness was used as surrogate marker for liver steatosis); c. Downgraded one level for suspected publication bias (small number of small trials); d. Downgraded one level for high risk of bias (selection, performance, and detection biases in Nobili et al., 2008, and selection bias in Harrison et al., 2003; e. Downgraded one level for serious indirectness (Harrison et al., 2003 did not report data on steatosis, while inflammation and hepatocyte degeneration/necrosis scores were combined); f. Downgraded one level for serious imprecision (sample size less than 400 participants); g. Downgraded one level for serious imprecision (CI includes no difference and appreciable harm); h. Downgraded two levels for high risk of bias (selection, performance, and detection biases in Nobili et al., 2008, selection, performance, detection, and gender biases in Hadzi-Petrushev et al., 2018; i. Downgraded one level for serious indirectness (co-intervention in Hadzi-Petrushev et al., 2018 was atorvastatin, as opposed to other trials which administered lifestyle modification); j. Downgraded two levels for high risk of bias (selection, performance, and detection biases in Nobili et al., 2008, selection, performance, and detection, and gender biases in Hadzi-Petrushev et al., 2018, and selection bias in Harrison et al., 2003; k. Downgraded one level for serious heterogeneity (I2 > 50%)