ArticleThe lancet. Gastroenterology & hepatology2018
Risk stratification after paracetamol overdose using mechanistic biomarkers: results from two prospective cohort studies.
Article in The lancet. Gastroenterology & hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 3 of them syntheses that pooled it.
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57 citing papers in PubMed, 3 syntheses or guidelines pooled it, 132 citations in OpenAlex.
- Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update.Hepatology international · 2024Guideline
- [Chinese guideline for diagnosis and management of drug-induced liver injury (2023 version)].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Guideline
- The diagnostic role of miR-122 in drug-induced liver injury: A systematic review and meta-analysis.Medicine · 2018Pooled it
- Cytokeratin-18 is a sensitive biomarker of alanine transaminase increase in a placebo-controlled, randomized, crossover trial of therapeutic paracetamol dosing (PATH-BP biomarker substudy).Toxicological sciences : an official journal of the Society of Toxicology · 2024Trial
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- Identification of Pre-Diagnostic Protein Biomarkers for Liver Cirrhosis Based on Prospective Analysis of a Large-Scale Plasma Proteomics in the UK Biobank.Proteomics. Clinical applications · 2026Article
- Short communication: Dynamic chemical labelling allows the measurement of the paracetamol toxicity biomarker microRNA-122 in hospital clinical laboratories.British journal of clinical pharmacology · 2026Article
- Toxicoproteomics of APAP-exposed HepG2 cells identifies candidate translational biomarkers of liver injury and recovery.Frontiers in pharmacology · 2026Article
- Article
- The endothelial growth factor angiopoietin-2 is an accurate prognostic biomarker in patients with acetaminophen-induced acute liver failure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- A point-of-care diagnostic for drug-induced liver injury using surface-enhanced Raman scattering lateral flow immunoassay.Nature communications · 2025Article
- Hepatotoxicity induced by arsenic trioxide: clinical features, mechanisms, preventive and potential therapeutic strategies.Frontiers in pharmacology · 2025Review
- Short communication: miRNA122 interrogation via PCR-Free method to track liver recovery.PloS one · 2025Article
- Multimorbidity in tuberculosis (TB) and its impact on patient care (MITICare): a cross-sectional study nested within a prospective cohort study protocol.Wellcome open research · 2025Article
- Regulated cell death and DAMPs as biomarkers and therapeutic targets in normothermic perfusion of transplant organs. Part 2: implementation strategies.Frontiers in transplantation · 2025Review
- Clinical and biochemical characteristics, and outcome in 33 patients with ceftriaxone-induced liver injury.European journal of clinical pharmacology · 2024Article
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Biomarkers of Hepatic Toxicity: An Overview.Current therapeutic research, clinical and experimental · 2024Review
- Article
- The Role of Carbamoyl Phosphate Synthetase 1 as a Prognostic Biomarker in Patients With Acetaminophen-induced Acute Liver Failure.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023Article
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14 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundParacetamol overdose is common but patient stratification is suboptimal. We investigated the usefulness of new biomarkers that have either enhanced liver specificity (microRNA-122 [miR-122]) or provide mechanistic insights (keratin-18 [K18], high mobility group box-1 [HMGB1], and glutamate dehydrogenase [GLDH]). The use of these biomarkers could help stratify patients for their risk of liver injury at hospital presentation.
methodsUsing data from two prospective cohort studies, we assessed the potential for biomarkers to stratify patients who overdose with paracetamol. We completed two independent prospective studies: a derivation study (MAPP) in eight UK hospitals and a validation study (BIOPAR) in ten UK hospitals. Patients in both cohorts were adults (≥18 years in England, ≥16 years in Scotland), were diagnosed with paracetamol overdose, and gave written informed consent. Patients who needed intravenous acetylcysteine treatment for paracetamol overdose had circulating biomarkers measured at hospital presentation. The primary endpoint was acute liver injury indicating need for continued acetylcysteine treatment beyond the standard course (alanine aminotransferase [ALT] activity >100 U/L). Receiver operating characteristic (ROC) curves, category-free net reclassification index (cfNRI), and integrated discrimination index (IDI) were applied to assess endpoint prediction.
findingsBetween June 2, 2010, and May 29, 2014, 1187 patients who required acetylcysteine treatment for paracetamol overdose were recruited (985 in the MAPP cohort; 202 in the BIOPAR cohort). In the derivation and validation cohorts, acute liver injury was predicted at hospital presentation by miR-122 (derivation cohort ROC-area under the curve [AUC] 0·97 [95% CI 0·95-0·98]), HMGB1 (0·95 [0·93-0·98]), and full-length K18 (0·95 [0·92-0·97]). Results were similar in the validation cohort (miR-122 AUC 0·97 [95% CI 0·95-0·99], HMGB1 0·98 [0·96-0·99], and full-length K18 0·93 [0·86-0·99]). A combined model of miR-122, HMGB1, and K18 predicted acute liver injury better than ALT alone (cfNRI 1·95 [95% CI 1·87-2·03], p<0·0001 in the MAPP cohort; 1·54 [1·08-2·00], p<0·0001 in the BIOPAR cohort).
interpretationPersonalised treatment pathways could be developed by use of miR-122, HMGB1, and full-length K18 at hospital presentation for patient stratification. This prospective study supports their use for hepatic safety assessment of new medicines.
fundingEdinburgh and Lothians Health Foundation, UK Medical Research Council.
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