Trial reportBMC pharmacology & toxicology2014
Benign elevations in serum aminotransferases and biomarkers of hepatotoxicity in healthy volunteers treated with cholestyramine.
Trial report in BMC pharmacology & toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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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
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Biomarkers of idiosyncratic drug-induced liver injury (DILI) - a systematic review.Expert opinion on drug metabolism & toxicology · 2021Pooled it
- The diagnostic role of miR-122 in drug-induced liver injury: A systematic review and meta-analysis.Medicine · 2018Pooled it
- Linerixibat reduces cholestatic pruritus in patients with primary biliary cholangitis.Translational gastroenterology and hepatology · 2026Article
- Evaluation of Elexacaftor/Tezacaftor/Ivacaftor-Mediated Drug-Induced Liver Injury Using a Liver-On-Chip Model.Clinical and translational science · 2025Article
- Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease.Hepatology (Baltimore, Md.) · 2025Review
- Blood toxicogenomics reveals potential biomarkers for management of idiosyncratic drug-induced liver injury.Frontiers in genetics · 2025Article
- Long-term exposure to high-altitude hypoxic environments reduces blood pressure by inhibiting the renin-angiotensin system in rats.Frontiers in physiology · 2025Article
- Molecular Idiosyncratic Toxicology of Drugs in the Human Liver Compared with Animals: Basic Considerations.International journal of molecular sciences · 2023Review
- Article
- Cannabidiol and Abnormal Liver Chemistries in Healthy Adults: Results of a Phase I Clinical Trial.Clinical pharmacology and therapeutics · 2021Article
- The Challenge of Interpreting Alanine Aminotransferase Elevations in Clinical Trials of New Drug Candidates.Clinical and translational science · 2021Article
- Identification of Serum Biomarkers to Distinguish Hazardous and Benign Aminotransferase Elevations.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Next-Generation DILI Biomarkers: Prioritization of Biomarkers for Qualification and Best Practices for Biospecimen Collection in Drug Development.Clinical pharmacology and therapeutics · 2020Review
- Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments.PloS one · 2020Article
- Previous Drug Exposure in Patients Hospitalised for Acute Liver Injury: A Case-Population Study in the French National Healthcare Data System.Drug safety · 2019Article
- Molecular Biomarkers in Drug-Induced Liver Injury: Challenges and Future Perspectives.Frontiers in pharmacology · 2019Review
- HNF4α Regulates CSAD to Couple Hepatic Taurine Production to Bile Acid Synthesis in Mice.Gene expression · 2018Article
- Bile acids regulate cysteine catabolism and glutathione regeneration to modulate hepatic sensitivity to oxidative injury.JCI insight · 2018Article
- MicroRNAs as biomarkers for clinical studies.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- In silico modeling to optimize interpretation of liver safety biomarkers in clinical trials.Experimental biology and medicine (Maywood, N.J.) · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere are currently no serum biomarkers capable of distinguishing elevations in serum alanine aminotransferase (ALT) that portend serious liver injury potential from benign elevations such as those occurring during cholestyramine treatment. The aim of the research was to test the hypothesis that newly proposed biomarkers of hepatotoxicity would not significantly rise in serum during elevations in serum ALT associated with cholestyramine treatment, which has never been associated with clinically relevant liver injury.
methodsIn a double-blind placebo-controlled trial, cholestyramine (8g) was administered for 11 days to healthy adult volunteers. Serum from subjects with elevations in alanine aminotransferase (ALT) exceeding three-fold the upper limit of normal (ULN) were utilized for biomarker quantification.
resultsIn 11 of 67 subjects, cholestyramine treatment resulted in ALT elevation by >3x ULN (mean 6.9 fold; range 3-28 fold). In these 11 subjects, there was a 22.4-fold mean increase in serum levels of miR-122 relative to baseline, supporting a liver origin of the serum ALT. Significant elevations were noted in mean levels of necrosis biomarkers sorbitol dehydrogenase (8.1 fold), cytokeratin 18 (2.1 fold) and HMGB1 (1.7 fold). Caspase-cleaved cytokeratin 18, a biomarker of apoptosis was also significantly elevated (1.7 fold). A rise in glutamate dehydrogenase (7.3 fold) may support mitochondrial dysfunction.
conclusionAll toxicity biomarkers measured in this study were elevated along with ALT, confirming the liver origin and reflecting both hepatocyte necrosis and apoptosis. Since cholestyramine treatment has no clinical liver safety concerns, we conclude that interpretation of the biomarkers studied may not be straightforward in the context of assessing liver safety of new drugs.
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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.