Trial reportHepatology (Baltimore, Md.)2012
A phase 2, randomized, double-blind, placebo-controlled study of GS-9450 in subjects with nonalcoholic steatohepatitis.
Trial report in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 162 citations in OpenAlex.
- KASL clinical practice guidelines: management of nonalcoholic fatty liver disease.Clinical and molecular hepatology · 2013Guideline
- Pooled it
- Randomised clinical trial: emricasan versus placebo significantly decreases ALT and caspase 3/7 activation in subjects with non-alcoholic fatty liver disease.Alimentary pharmacology & therapeutics · 2019Trial
- Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease.Journal of applied physiology (Bethesda, Md. : 1985) · 2012Trial
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Different forms of cardiomyocyte death in post-myocardial infarction ventricular remodeling: mechanisms and therapeutic strategies.Frontiers in cardiovascular medicine · 2026Review
- NLRP3 Inflammasome Activation in Liver Disorders: From Molecular Pathways to Therapeutic Strategies.Journal of inflammation research · 2025Review
- Cell Death in Liver Disease and Liver Surgery.Biomedicines · 2024Review
- Distinct Types of Cell Death and Implications in Liver Diseases: An Overview of Mechanisms and Application.Journal of clinical and translational hepatology · 2023Review
- Hepatic Macrophages as Targets for the MSC-Based Cell Therapy in Non-Alcoholic Steatohepatitis.Biomedicines · 2023Review
- Review
- Pyroptosis and gasdermins-Emerging insights and therapeutic opportunities in metabolic dysfunction-associated steatohepatitis.Frontiers in cell and developmental biology · 2023Review
- PINK1 ameliorates acute-on-chronic liver failure by inhibiting apoptosis through mTORC2/AKT signaling.Cell death discovery · 2022Article
- Pharmacological effects of Chinese medicine modulating NLRP3 inflammasomes in fatty liver treatment.Frontiers in pharmacology · 2022Review
- A long way to go: caspase inhibitors in clinical use.Cell death & disease · 2021Review
- Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis.Advanced drug delivery reviews · 2021Review
- Too much death can kill you: inhibiting intrinsic apoptosis to treat disease.The EMBO journal · 2021Review
- Targeting programmed cell death in metabolic dysfunction-associated fatty liver disease (MAFLD): a promising new therapy.Cellular & molecular biology letters · 2021Review
- RIP1 kinase activity promotes steatohepatitis through mediating cell death and inflammation in macrophages.Cell death and differentiation · 2021Article
- Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 12 institutions in 2 countries.
Funding
Abstract
unlabelledIn nonalcoholic steatohepatitis (NASH), the extent of hepatocyte apoptosis correlates with disease severity. Reducing hepatocyte apoptosis with the selective caspase inhibitor GS-9450 has a potential for altering the course of the liver disease. In this phase 2, double-blind study, 124 subjects with biopsy-proven NASH were randomized to once-daily placebo or 1, 5, 10, or 40 mg GS-9450 for 4 weeks. Absolute and percent changes from baseline in ALT levels, AST levels, and caspase-3-cleaved cytokeratin (CK)-18 fragments at week 4 were assessed by an analysis of covariance model with adjustment for baseline values. In the 40-mg group, mean (SD) ALT decreased by 47 (43) U/L from baseline to week 4 (P < 0.0001 versus placebo), and the proportion of subjects with normal ALT increased from 0% to 35% at week 4. In the 40-mg group, mean AST decreased by 13 U/L from baseline (not significant), and the proportion with normal AST increased from 20% at baseline to 48% at week 4. By week 4, mean CK-18 fragment levels had decreased to 393 (723) U/L in the GS-9450 10-mg group and 125 (212) U/L in the 40-mg group, but these reductions were not statistically significant. No serious adverse events were reported during treatment, and the percentage of subjects with at least one treatment-emergent grade 3 or 4 laboratory abnormality ranged from 11.5% to 17% across the GS-9450 treatment groups versus 35% in the placebo group.
conclusionGS-9450 treatment induced significant reductions in ALT levels in NASH patients. Reductions in CK-18 fragment levels also occurred, although they were not statistically significant. At appropriate therapeutic indices, selective caspase inhibitors may be a promising treatment option in patients with NASH.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.