ArticlePloS one2020
Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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.
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
16 citing papers in PubMed, 27 citations in OpenAlex.
- Polygenic risk score and risk of drug-induced liver injury after initiating antiretroviral therapy in people living with HIV.Pharmacogenomics · 2026Article
- Bariatric Surgery and Incident Development of Obesity-Related Comorbidities.JAMA network open · 2025Article
- A cross-tissue transcriptome-wide association study identifies novel susceptibility genes for atrial fibrillation.Journal of arrhythmia · 2025Article
- Integrating PNPLA3 into clinical risk prediction.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Liver-specific deletion of Agpat5 protects against liquid sucrose-induced hyperinsulinemia and glucose intolerance.Biochemical and biophysical research communications · 2024Article
- The interaction of genetics and physical activity in the pathogenesis of metabolic dysfunction associated liver disease.Scientific reports · 2024Article
- Clinical and genetic risk factors for progressive fibrosis in metabolic dysfunction-associated steatotic liver disease.Hepatology communications · 2024Article
- The Impact of Weight Loss Programs on BMI Trajectory in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Veterans Health Administration Study.The American journal of gastroenterology · 2024Article
- Profiling the genome and proteome of metabolic dysfunction-associated steatotic liver disease identifies potential therapeutic targets.medRxiv : the preprint server for health sciences · 2023Article
- Large-scale identification of undiagnosed hepatic steatosis using natural language processing.EClinicalMedicine · 2023Article
- PNPLA3 Genotype and Diabetes Identify Patients With Nonalcoholic Fatty Liver Disease at High Risk of Incident Cirrhosis.Gastroenterology · 2023Article
- Review article: the role of HSD17B13 on global epidemiology, natural history, pathogenesis and treatment of NAFLD.Alimentary pharmacology & therapeutics · 2023Review
- Update on Non-Alcoholic Fatty Liver Disease-Associated Single Nucleotide Polymorphisms and Their Involvement in Liver Steatosis, Inflammation, and Fibrosis: A Narrative ReviewIranian biomedical journal · 2022Review
- Interactions of physical activity, muscular fitness, adiposity, and genetic risk for NAFLD.Hepatology communications · 2022Article
- A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation.Nature genetics · 2022Article
- Identification of 90 NAFLD GWAS loci and establishment of NAFLD PRS and causal role of NAFLD in coronary artery disease.HGG advances · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 15 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsGiven ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans.
methodsMVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts.
resultsAmong 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis.
conclusionsWe validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.
Indexed as
Identifiers
What OpenQuestion holds
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.