Evidence map›Paper›PMID 36317632›Full record

ArticleThe Journal of clinical investigation2022

Risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease.

Nobuharu Tamaki, Noora Ahlholm, Panu K Luukkonen, Kimmo Porthan, Suzanne R Sharpton, Veeral Ajmera, Yuko Kono, Shravan Dave, Aijaz Ahmed, Vinay Sundaram and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
8.6field-weighted citation impact, top 1% of its field
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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.

  1. Guideline
  2. Guideline
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Deep Learning Reveals Liver MRI Features Associated With PNPLA3 I148M in Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  14. Observational
  15. Review
  16. Fat, fibrosis, and the future: navigating the maze of MASLD/MASH.The Journal of clinical investigation · 2025
    Article
  17. Targeting PNPLA3 to Treat MASH and MASH Related Fibrosis and Cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  18. Diagnostic Uptake of Targeted Sequencing in Adults With Steatotic Liver Disease and a Suspected Genetic Contribution.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  19. The Role of Myokines in Liver Diseases.International journal of molecular sciences · 2025
    Review
  20. Article
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

24 authors at 5 institutions in 3 countries.

Nobuharu TamakiNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Noora AhlholmDepartment of Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Panu K LuukkonenDepartment of Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Kimmo PorthanDepartment of Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Suzanne R SharptonNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Veeral AjmeraNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Yuko KonoDivision of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Shravan DaveDivision of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Aijaz AhmedDivision of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA.
Vinay SundaramKarsh Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Michael J WilkinsonDivision of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Heather PattonGastroenterology Section, VA San Diego Healthcare System, San Diego, California, USA.
Hersh GuptaNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Vanessa CervantesNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Christie HernandezNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Scarlett J LopezNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Ria LoombaNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Amanda BaumgartnerNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Lisa RichardsNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Perttu Et ArkkilaDepartment of Gastroenterology and.
Katriina NemesDepartment of Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Helena IsoniemiTransplantation and Liver Surgery Unit, Abdominal Center, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Hannele Yki-JärvinenDepartment of Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Rohit LoombaNonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
University of California San Diego · USUniversity of Helsinki · FICedars-Sinai Medical Center · USStanford University · USVA San Diego Healthcare System · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Pediatric Trials in Non-Alcoholic Steatohepatitis (NASH)U01DK061734 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROHIT LOOMBA · 2002 to 2026
$24.4M
Tissue-specific roles of FXR in CVD and NASHP01HL147835 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOOMBA, ROHIT · 2020 to 2024
$12.2M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
HIV MASLD Clinical Research Network (HCRN)R01DK121378 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI NAGA P CHALASANI, ROHIT LOOMBA · 2020 to 2026
$8.7M
Novel IL-23 inhibitor for the treatment of alcohol associated liver diseaseU01AA029019 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA, LOOMBA, ROHIT · 2020 to 2024
$3.7M
QUS Technology for Diagnosis and Grading of Hepatic Steatosis in NAFLDR01DK106419 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOOMBA, ROHIT, SIRLIN, CLAUDE B · 2015 to 2019
$3.4M
San Diego Cirrhosis Clinical Research NetworkU01DK130190 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROHIT LOOMBA · 2021 to 2026
$2.3M
Non-invasive screening of diabetics for advanced fibrosis due to NAFLDR01DK124318 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOOMBA, ROHIT · 2020 to 2022
$1.7M
A Novel Multimodal Approach to Characterize NAFLD Severity and PrognosisK23DK119460 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AJMERA, VEERAL HARESH · 2019 to 2023
$1.1M
NCATS NIH HHS UL1 TR001442NHLBI NIH HHS P01 HL147835NIAAA NIH HHS U01 AA029019NIDDK NIH HHS K23 DK119460NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R01 DK106419NIDDK NIH HHS R01 DK121378NIDDK NIH HHS R01 DK124318NIDDK NIH HHS U01 DK061734NIDDK NIH HHS U01 DK130190
6 · The paper itself

Abstract

BACKGROUNDA pilot, single-center study showed that first-degree relatives of probands with nonalcoholic fatty liver disease (NAFLD) cirrhosis have a high risk of advanced fibrosis. We aimed to validate these findings using 2 independent cohorts from the US and Europe.METHODSThis prospective study included probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 first-degree relative. A total of 396 first-degree relatives - 220 in a derivation cohort and 176 in a validation cohort - were enrolled in the study, and liver fibrosis was evaluated using magnetic resonance elastography and other noninvasive imaging modalities. The primary outcome was prevalence of advanced fibrosis in first-degree relatives.RESULTSPrevalence of advanced fibrosis in first-degree relatives of probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD was 15.6%, 5.9%, and 1.3%, respectively (P = 0.002), in the derivation cohort, and 14.0%, 2.6%, and 1.3%, respectively (P = 0.004), in the validation cohort. In multivariable-adjusted logistic regression models, age of ≥50 years (adjusted OR [aOR]: 2.63, 95% CI 1.0-6.7), male sex (aOR: 3.79, 95% CI 1.6-9.2), diabetes mellitus (aOR: 3.37, 95% CI 1.3-9), and a first-degree relative with NAFLD with advanced fibrosis (aOR: 11.8, 95% CI 2.5-57) were significant predictors of presence of advanced fibrosis (all P < 0.05).CONCLUSIONFirst-degree relatives of probands with NAFLD with advanced fibrosis have significantly increased risk of advanced fibrosis. Routine screening should be done in the first-degree relatives of patients with advanced fibrosis.FUNDINGSupported by NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515, K23DK119460), NHLBI (P01HL147835), and NIAAA (U01AA029019); Academy of Finland grant 309263; the Novo Nordisk, EVO, and Sigrid Jusélius Foundations; and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 777377. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and the EFPIA.

Indexed as

Elasticity Imaging TechniquesNon-alcoholic Fatty Liver DiseaseFibrosisHumansLiver CirrhosisMaleMiddle AgedProspective StudiesEpidemiologyFibrosisGastroenterologyHepatologyLiver cancer

Identifiers

PMID36317632
PMCPMC9621132
OpenAlexW4307717780

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.