Original article—liver, pancreas, and biliary tractPlacebo in Nonalcoholic Steatohepatitis: Insight Into Natural History and Implications for Future Clinical Trials
Section snippets
Retrieval of Clinical Trials
The Medline database was searched for articles written in English through May of 2008. Indexing terms included nonalcoholic steatohepatitis or NASH in combination with randomized controlled trials, and nonalcoholic fatty liver disease or NAFLD (nonalcoholic fatty liver disease) in combination with randomized controlled trials. A manual review of the bibliographies of seminal primary and review articles also was performed to identify additional studies.
Criteria for study inclusion in the
Results
Seven studies met the specified criteria on initial screening. We excluded one study because of the short follow-up period11 and a second study because patients had nonalcoholic fatty liver disease and not exclusively NASH.12 Of 5 clinical trials in the pooled analysis, 2 were conducted in North America,13, 14 and 1 each in Switzerland,15 Iran,16 and France.17 Of the 5 studies deemed eligible, 4 were multicenter studies,13, 14, 15, 17 and 1 was a single-center study.16 The quality indicators
Discussion
The main finding of this pooled analysis is that serum ALT and AST levels declined in placebo-treated patients with NASH. Similar reductions were seen in mean changes in NASH-associated histologic parameters. The greatest decline in mean histologic scores was seen in the steatosis score, which was statistically significant. The overall decrease in these parameters was small, but depending on how an outcome measure is defined it may become statistically significant. A 1-point reduction in any of
Conclusions
Serum ALT and AST levels change during follow-up evaluation in NASH patients and may not reflect histologic improvement. Minor improvements in NASH-associated histologic scores are seen in up to a third of patients, although a 2-point improvement in steatosis, ballooning degeneration, or lobular inflammation rarely is seen in placebo-treated individuals. These data have important implications for designing and reporting future clinical trials in NASH and suggest a need for standardization of
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Cited by (0)
This study was supported by the intramural research programs of the National institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute, National Institutes of Health.