Thiazolidinediones and Nonalcoholic Steatohepatitis (NASH): A Metaanalysis
Bibliographic record
Abstract
Purpose: To evaluate the efficacy of thiazolidinediones in the treatment of NASH using evidence from randomized controlled trials (RCTs). Methods: The Cochrane database and PubMed were searched for published trials that compared the efficacy of thiazolidinediones versus placebo in the treatment of NASH up to May 2010. Unpublished data was searched from meeting abstracts. Patient demographics, inclusion and exclusion criteria, number of study participants, study drug, dosage and duration, as well as primary, secondary and adverse outcomes were extracted. The methodological quality of the studies was assessed using the Jadad scoring system. The histological parameters examined were steatosis, parenchymal and portal inflammation, hepatocyte injury and fibrosis. Meta-analysis was carried out using Comprehensive Meta Analysis software. A fixed effects model was utilized. P-values of less than 0.05 were considered significant for the pooled estimates of treatment effect and less than 0.1 for the χ2 test of homogeneity. A subgroup analysis was carried out for trials of pioglitazone. Results: Four RCTs, three with pioglitazone and one with rosiglitazone, comprising a total of 335 subjects, were included in the final meta-analysis. Both pioglitazone and rosiglitazone showed improvement in steatosis, pooled OR 3.595 (P<0.001) and inflammation, pooled OR 2.61 (P<0.001). There was no significant heterogeneity of treatment effect. The subgroup analysis of only pioglitazone trials showed similar results for steatosis and inflammation. There was significant heterogeneity of treatment effect for necrosis (P=0.081). All three trials of pioglitazone showed statistically significant improvement in necrosis while the rosiglitazone trial showed a nonsignificant result-favoring placebo. This heterogeneity of treatment effect made the pooled result difficult to interpret. The subgroup analysis of pioglitazone trials showed no significant heterogeneity (P=0.465) and a statistically significant improvement in necrosis, pooled OR 2.42 (P=0.001). All three pioglitazone trials showed improvement in fibrosis. The rosiglitazone trial showed no effect. The pooled OR was 1.61 (P=0.051) with no significant heterogeneity. The subgroup analysis of pioglitazone trials showed a similar but slightly more pronounced effect with a pooled OR 1.72 (P=0.037) with no significant heterogeneity. Conclusion: In patients with NASH, hepatic steatosis and inflammation appear to improve after treatment with both pioglitazone and rosiglitazone. Necrosis and fibrosis appear to improve after treatment with pioglitazione but not rosiglitazone, however this sub-group analysis should be interpreted with caution due to the small number of trials.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.021 | 0.035 |
| Meta-epidemiology (narrow) | 0.005 | 0.002 |
| Meta-epidemiology (broad) | 0.023 | 0.061 |
| Bibliometrics | 0.007 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".