ArticleAlimentary pharmacology & therapeutics2017
Concentration-dependent response to pioglitazone in nonalcoholic steatohepatitis.
Article in Alimentary pharmacology & therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism.Biology of sex differences · 2021Trial
- Development of anFrontiers in pharmacology · 2025Article
- A consensus statement from the Japan Diabetes Society: A proposed algorithm for pharmacotherapy in people with type 2 diabetes - 2nd edition (English version).Journal of diabetes investigation · 2024Article
- A consensus statement from the Japan Diabetes Society (JDS): a proposed algorithm for pharmacotherapy in people with type 2 diabetes-2nd Edition (English version).Diabetology international · 2024Article
- Physiologically Based Pharmacokinetic (PBPK) Model Predictions of Disease Mediated Changes in Drug Disposition in Patients with Nonalcoholic Fatty Liver Disease (NAFLD).Pharmaceutical research · 2024Article
- A gut microbial metabolite of linoleic acid ameliorates liver fibrosis by inhibiting TGF-β signaling in hepatic stellate cells.Scientific reports · 2023Article
- Efficacy of 3 months of additional pioglitazone treatment in type 2 diabetes patients with alcoholic fatty liver disease.Diabetology international · 2023Article
- Considerations for Physiologically Based Modeling in Liver Disease: From Nonalcoholic Fatty Liver (NAFL) to Nonalcoholic Steatohepatitis (NASH).Clinical pharmacology and therapeutics · 2023Review
- Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- Review
- Treating Hepatic Steatosis and Fibrosis by Modulating Mitochondrial Pyruvate Metabolism.Cellular and molecular gastroenterology and hepatology · 2019Review
- A Genetic Score Associates With Pioglitazone Response in Patients With Non-alcoholic Steatohepatitis.Frontiers in pharmacology · 2018Article
- What Are the Current Pharmacological Therapies for Nonalcoholic Fatty Liver Disease?Journal of clinical and experimental hepatologyReview
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPioglitazone is a safe and effective option to manage patients with type 2 diabetes and nonalcoholic steatohepatitis (NASH). However, there is marked variability in treatment response.
aimTo evaluate the relationship between concentrations of pioglitazone and its active metabolites and treatment outcomes in patients with NASH.
methodsPioglitazone concentrations were measured in patients with NASH treated with pioglitazone 45 mg/day for 18 months; liver biopsy samples were obtained at baseline and after treatment. The primary outcome was a ≥2-point reduction in NAFLD activity score (NAS) with at least one-point improvement in more than one liver histology category and without worsening of fibrosis. A novel marker, the pioglitazone exposure index, was calculated to consider the concentrations of pioglitazone as well as the two active metabolites.
resultsThe response to pioglitazone was concentration-dependent as evidenced by the significant relationship between both pioglitazone concentration and pioglitazone exposure index with changes in NAS (r=.48, P=.0002 and r=.51, P<.0001, respectively), steatosis (r=.41, P=.002 and r=.46, P=.0005), and inflammation (r=.44, P=.0009 and r=.40, P=.0003). The pioglitazone exposure index was also associated with a change in ballooning (P=.04). The pioglitazone exposure index was higher in patients with NASH resolution (2.85±1.38 vs 1.78±1.48, P=.018). A predictive model for the primary outcome was developed that incorporated baseline NAS and pioglitazone exposure index (AUC=0.77).
conclusionsThis study demonstrates the importance of pioglitazone exposure to variable response in patients with NASH, and indicates potential factors that may identify patients most likely to benefit from chronic pioglitazone treatment.
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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.