Evidence map›Paper›PMID 15915461›Full record

ArticleHepatology (Baltimore, Md.)2005

Design and validation of a histological scoring system for nonalcoholic fatty liver disease.

David E Kleiner, Elizabeth M Brunt, Mark Van Natta, Cynthia Behling, Melissa J Contos, Oscar W Cummings, Linda D Ferrell, Yao-Chang Liu, Michael S Torbenson, Aynur Unalp-Arida and 4 more

11 registry-linked trialsAbstract readMulticenter StudyValidation Study
PubMed Publisher
In one paragraph

Article in Hepatology (Baltimore, Md.), 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 11 registered trials, which are not on this map. Cited by 4,975 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4,975citing papers in PubMed, 3 pooled it
–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.

NCT02964715 phase4unknown statusstarted 2016, after this paper: background citation

The Effect of Empagliflozin on NAFLD in Asian Patients With Type 2 Diabetes

Ran2016Enrolled25Registered outcomes17Posted comparisons0ConditionsNAFLD, Type2 DiabetesArmsempagliflozin
Open the trial in the graph
NCT00244569 phase3completednot on this map

Development of a Breath Test for Monitoring Liver Metabolic Function in Patients With Chronic Liver Disease and Cirrhosis

TypeinterventionalSponsorVirginia Commonwealth UniversityRan2005 to 2007Enrolled120ConditionsFatty Liver, CirrhosisArms13C-Methacetin, Breath ID Machine
NCT00266019 phase2completednot on this map

Weight Management in Nonalcoholic Steatohepatitis (NASH)

TypeinterventionalSponsorNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Ran2005 to 2007Enrolled30ConditionsFatty LiverArmsWeight Management (diet, exercise, and behavior modification)
NCT01051219 phase3completednot on this mapstarted 2011, after this paper: background citation

A Randomised, Controlled Trial of Losartan as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis

TypeinterventionalSponsorNewcastle-upon-Tyne Hospitals NHS TrustRan2011 to 2014Enrolled45ConditionsNonalcoholic SteatohepatitisArmsLosartan
NCT01210989 nacompletednot on this mapstarted 2010, after this paper: background citation

A Randomized,Placebo-controlled,Double-blind Trial of Phyllanthus Urinaria (Hepaguard®) in Adults With Nonalcoholic Steatohepatitis

TypeinterventionalSponsorChinese University of Hong KongRan2010 to 2012Enrolled60ConditionsNonalcoholic Fatty Liver DiseaseArmsPhyllanthus urinaria, Placebo
NCT01523639 phase2terminatednot on this mapstarted 2012, after this paper: background citation

A Randomized, Placebo-controlled, Double-blind Multicenter Phase II Study to Investigate the Protectivity and Efficacy of Metformin Against Steatosis in Combination With FOLFIRI and Cetuximab in Subjects With First-line Palliative Treated, KRAS-Wild-Type, Metastatic Colorectal Cancer

TypeinterventionalSponsorAustrian Breast & Colorectal Cancer Study GroupRan2012 to 2014Enrolled8ConditionsColorectal Cancer, SteatohepatitisArmsMetformin/Placebo
NCT03198572 phase4unknown statusnot on this mapstarted 2017, after this paper: background citation

Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis: a Multicentre, Randomised, Placebo-controlled Trial

TypeinterventionalSponsorFudan UniversityRan2017 to 2024Enrolled120ConditionsNon-alcoholic SteatohepatitisArmsLifestyle intervention, Placebo, Berberine
NCT03375008 nacompletednot on this mapstarted 2016, after this paper: background citation

Development of Non-invasive Magnetic Resonance Imaging Diagnostic Method for Nonalcoholic Steatohepatitis(NASH)

TypeinterventionalSponsorKorea University Guro HospitalRan2016 to 2018Enrolled47ConditionsNonalcoholic SteatohepatitisArmsImaging diagnostic and biopsy
NCT03725631 naunknown statusnot on this mapstarted 2016, after this paper: background citation

Non-invasive Evaluation of Liver Fibrosis, Steatosis, and Nonalcoholic Steatohepatitis in Biopsy-Proven NAFLD Patients

TypeinterventionalSponsorKorea University Guro HospitalRan2016 to 2019Enrolled150ConditionsNonalcoholic Fatty Liver, Nonalcoholic SteatohepatitisArmsImaging and serologic evaluation of fibrosis and steatosis
NCT05317260 completednot on this map

Prognostic Relevance of Fatty Liver Disease for Patients With Chronic Hepatitis B

TypeobservationalSponsorMahidol UniversityRan2002 to 2021Enrolled408ConditionsFatty Liver, Chronic Hepatitis bArmsAntiviral Agents
NCT07119957 narecruitingnot on this mapstarted 2025, after this paper: background citation

ProspEXPO : PROSPective Study of the Associations Between Hepatocellular Carcinoma and Chemical and Psychosocial Environmental EXPOsome

TypeinterventionalSponsorUniversity Hospital, AngersRan2025 to 2029Enrolled300ConditionsCirrhoses, Liver, Carcinoma LiverArmsBlood, urine and stool biocollection
3 · Its place in the literature

Who cites it

4,975 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. [Construction norms for the tiered diagnosis and treatment and standardized management center of metabolic-associated fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Guideline
  2. Pooled it
  3. Pooled it
  4. Trial
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  16. Ethanol reshapes FFC-driven steatohepatitis through time-dependent fibrosis and lipid-droplet remodeling.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Article
  17. Article
  18. Article
  19. Article
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4,915 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

David E KleinerLaboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA. KleinerD@mail.nih.gov
Elizabeth M Brunt
Mark Van Natta
Cynthia Behling
Melissa J Contos
Oscar W Cummings
Linda D Ferrell
Yao-Chang Liu
Michael S Torbenson
Aynur Unalp-Arida
Matthew Yeh
Arthur J McCullough
Arun J Sanyal
Nonalcoholic Steatohepatitis Clinical Research Network

Funding

Pediatric Trials in Non-Alcoholic Steatohepatitis (NASH)U01DK061734 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROHIT LOOMBA · 2002 to 2026
$24.4M
Continuation of the Non-Alcoholic Steatohepatitis Clinical Research Network (NASHU01DK061730 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI TONASCIA, JAMES A · 2002 to 2018
$23.2M
Non Alcoholic Steatohepatitis Clinical Research NetworkU01DK061732 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy · 2002 to 2026
$12.2M
The Saint Louis University Component of the NASH CRNU01DK061718 · NIDDK · SAINT LOUIS UNIVERSITY · PI BRENT A NEUSCHWANDER-TETRI · 2002 to 2026
$12.0M
Nonalcoholic Steatohepatittis Clinical Research Network (NASH CRN)U01DK061731 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI ARUN J SANYAL · 2002 to 2026
$11.2M
Pathogenesis, prognosis, and treatment of NAFLD patientsU01DK061713 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ANNA MAE ELIZABETH DIEHL · 2002 to 2026
$10.3M
Collaborative Clinical Research on Non Alcoholic StratohepatitisU01DK061737 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI NAGA P CHALASANI · 2002 to 2026
$10.2M
Clinical Research Network in Non-Alcoholic SteatohepatitisU01DK061728 · NIDDK · UNIVERSITY OF WASHINGTON · PI KRIS KOWDLEY · 2002 to 2026
$9.0M
Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)U01DK061738 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Norah A. Terrault · 2002 to 2026
$8.9M
Histology Core LaboratoryZ01BC010687 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KLEINER, DAVID E · 2006 to 2008
$2.2M
NHLBI NIH HHS N01HR761019NIDDK NIH HHS 1U01DK061718NIDDK NIH HHS 1U01DK061728NIDDK NIH HHS 1U01DK061731NIDDK NIH HHS 1U01DK061732NIDDK NIH HHS 1U01DK061734NIDDK NIH HHS 1U01DK061737NIDDK NIH HHS 1U01DK061738NIDDK NIH HHS 5U01DK061730NIDDK NIH HHS 7U01DK061713NIDDK NIH HHS U01 DK061730NIDDK NIH HHS U01 DK061732
6 · The paper itself

Abstract

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."

Indexed as

Severity of Illness IndexAdultChildFatty LiverFibrosisHumansInflammationLiverLogistic ModelsObserver Variation

Identifiers

PMID15915461

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

and 5 more above

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 Socratic graph.