Evidence map›Paper›PMID 39932652›Full record

ReviewDrug safety2025

Emerging Tools to Support DILI Assessment in Clinical Trials with Abnormal Baseline Serum Liver Tests or Pre-existing Liver Diseases.

Jasmine Amirzadegan, Bereket Tesfaldet, Y Veronica Pei, Eileen Navarro Almario, Mark I Avigan, Paul H Hayashi

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Drug safety, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Jasmine AmirzadeganCenter for Drug Evaluation and Research, Office of New Drugs, Division of Hepatology and Nutrition, Food and Drug Administration, White Oak, Silver Spring, MD, USA.
Bereket TesfaldetCenter for Food Safety and Applied Nutrition, Office of Analysis and Outreach, Biostatistics and Bioinformatics, Food and Drug Administration, White Oak, Silver Spring, MD, USA.
Y Veronica PeiCenter for Drug Evaluation and Research, Office of New Drugs, Biomedical Informatics and Regulatory Review Science, Food and Drug Administration, White Oak, Silver Spring, MD, USA.
Eileen Navarro AlmarioCenter for Drug Evaluation and Research, Office of New Drugs, Division of Hepatology and Nutrition, Food and Drug Administration, White Oak, Silver Spring, MD, USA.
Mark I AviganCenter for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Office of Pharmacovigilance and Epidemiology, Food and Drug Administration, White Oak, Silver Spring, MD, USA.
Paul H HayashiCenter for Drug Evaluation and Research, Office of New Drugs, Division of Hepatology and Nutrition, Food and Drug Administration, White Oak, Silver Spring, MD, USA. Paul.Hayashi@fda.hhs.gov.ORCID http://orcid.org/0000-0002-5371-1020

Funding

Oak Ridge Institute for Science and Education CDER-OND-M-24-11192
6 · The paper itself

Abstract

Based on the late Dr. Hyman Zimmerman's observation that hepatocellular drug-induced liver injury (DILI) leading to jaundice carries a ≥ 10% fatality risk (coined as Hy's law by others), evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) continues to play a central role in the assessment of a study drug's liability for acute hepatocellular DILI. The eDISH identifies drugs in clinical trials with DILI fatality (death or transplant) risk that may be unacceptable in a post-market setting. As a two-dimensional graph that plots peak total bilirubin (TB) versus peak serum aminotransferase levels for each patient during study drug or comparator treatment, eDISH identifies potential cases of acute, modest, and serious hepatocellular DILI for in-depth analysis of liver tests (LT) and clinical course so that the likelihood of causal association with the study drug can be determined. Unfortunately, the generalizable utility of this tool only pertains to trials enrolling patients with normal or near normal (NNN) baseline (BL) serum LTs. The eDISH does not necessarily apply to trials of patients with abnormal baseline (ABN-BL) LTs that often coincide with underlying liver disorders. Because drug development programs being reviewed by the FDA increasingly target liver disorders, we are often challenged to evaluate DILI risk in trials of patients with ABN-BL LTs. Also, the high background prevalence of metabolic dysfunction associated steatotic liver disease (MASLD) means patients with LTs above NNN may need to be enrolled in trials treating non-liver disorders to reflect the target population. Such study populations create challenges for industry and regulators because eDISH may not reliably categorize or identify potential cases of DILI for further analysis, as it so efficiently does in NNN-BL trials. We describe the main functionalities of eDISH in NNN-BL trials to understand what should be emulated by new tools or eDISH modifications. We then discuss non-eDISH-based plots that may be useful in ABN-BL trials.

Indexed as

Chemical and Drug Induced Liver InjuryClinical Trials as TopicLiver DiseasesHumansLiver Function Tests

Identifiers

PMID39932652
PMCPMC11982145

What OpenQuestion holds

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Registered trials

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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.