ArticleJournal of hepatology2022
Complexity of ballooned hepatocyte feature recognition: Defining a training atlas for artificial intelligence-based imaging in NAFLD.
Article in Journal of hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.
- An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography.Journal of hepatology · 2023Pooled it
- Exploration of Multiple Non-Invasive Tests for Assessing Response to Treatment in a Semaglutide Phase 2b Trial in Patients with MASH.Alimentary pharmacology & therapeutics · 2026Trial
- Metabolic Dysfunction-Associated Steatotic Liver Disease in the Aging Population: A Narrative Review of Pathophysiological Synergy, Diagnostic Challenges, and Tailored Management.Current gastroenterology reports · 2026Review
- European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) steatotic liver disease special interest group position paper on screening, diagnosis and investigation of paediatric metabolic dysfunction-associated steatotic liver disease.Journal of pediatric gastroenterology and nutrition · 2026Article
- Review
- Liver Biopsy in Metabolic Dysfunction-Associated Steatohepatitis Clinical Trials: Potential Pitfalls and Solutions.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Prospective validation of imaging and serum diagnostic biomarkers of steatohepatitis and fibrosis in MASLD: the LITMUS Imaging Study.Nature medicine · 2026Article
- Evolving B-mode ultrasound-based techniques for assessing metabolic dysfunction-associated steatotic liver disease: Now and beyond.Liver research (Beijing, China) · 2026Review
- Untargeted plasma lipidomic profiling associated with pediatric metabolic dysfunction-associated steatohepatitis (MASH).Lipids in health and disease · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- The Elucidating Pathways of Steatohepatitis (EPoS) staging system: A reproducible 7-tiered fibrosis scoring system in MASLD.JHEP reports : innovation in hepatology · 2026Article
- Artificial intelligence and digital transformation of gastroenterology and hepatology: A critical review of clinical applications and future challenges.World journal of hepatology · 2026Review
- AI portal tract detection and characterisation for a regional analysis of steatosis and inflammation in MASLD, MASH and AIH.Journal of clinical pathology · 2026Observational
- Development and evaluation of machine learning models for predicting significant liver fibrosis stages: A retrospective analysis.Canadian liver journal · 2026Article
- Article
- Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement.Clinical and molecular hepatology · 2026Article
- Development of automated machine learning models in predicting colorectal adenoma in metabolic-associated steatotic liver disease.Frontiers in medicine · 2026Article
- Disease patterns and entities in adult liver consult cases highlight challenging areas in diagnostic hepatopathology practice.Virchows Archiv : an international journal of pathology · 2025Article
- [Current research progress status in identifying hepatocellular ballooning degeneration in nonalcoholic steatohepatitis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer.Pharmacological reviews · 2025Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 20 institutions in 7 countries.
Funding
Abstract
BACKGROUND &
aimsHistologically assessed hepatocyte ballooning is a key feature discriminating non-alcoholic steatohepatitis (NASH) from steatosis (NAFL). Reliable identification underpins patient inclusion in clinical trials and serves as a key regulatory-approved surrogate endpoint for drug efficacy. High inter/intra-observer variation in ballooning measured using the NASH CRN semi-quantitative score has been reported yet no actionable solutions have been proposed.
methodsA focused evaluation of hepatocyte ballooning recognition was conducted. Digitized slides were evaluated by 9 internationally recognized expert liver pathologists on 2 separate occasions: each pathologist independently marked every ballooned hepatocyte and later provided an overall non-NASH NAFL/NASH assessment. Interobserver variation was assessed and a 'concordance atlas' of ballooned hepatocytes generated to train second harmonic generation/two-photon excitation fluorescence imaging-based artificial intelligence (AI).
resultsThe Fleiss kappa statistic for overall interobserver agreement for presence/absence of ballooning was 0.197 (95% CI 0.094-0.300), rising to 0.362 (0.258-0.465) with a ≥5-cell threshold. However, the intraclass correlation coefficient for consistency was higher (0.718 [0.511-0.900]), indicating 'moderate' agreement on ballooning burden. 133 ballooned cells were identified using a ≥5/9 majority to train AI ballooning detection (AI-pathologist pairwise concordance 19-42%, comparable to inter-pathologist pairwise concordance of between 8-75%). AI quantified change in ballooned cell burden in response to therapy in a separate slide set.
conclusionsThe substantial divergence in hepatocyte ballooning identified amongst expert hepatopathologists suggests that ballooning is a spectrum, too subjective for its presence or complete absence to be unequivocally determined as a trial endpoint. A concordance atlas may be used to train AI assistive technologies to reproducibly quantify ballooned hepatocytes that standardize assessment of therapeutic efficacy. This atlas serves as a reference standard for ongoing work to refine how ballooning is classified by both pathologists and AI. LAY SUMMARY: For the first time, we show that, even amongst expert hepatopathologists, there is poor agreement regarding the number of ballooned hepatocytes seen on the same digitized histology images. This has important implications as the presence of ballooning is needed to establish the diagnosis of non-alcoholic steatohepatitis (NASH), and its unequivocal absence is one of the key requirements to show 'NASH resolution' to support drug efficacy in clinical trials. Artificial intelligence-based approaches may provide a more reliable way to assess the range of injury recorded as "hepatocyte ballooning".
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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.