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Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States

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Kim, Donghee, Kim, Ray W., Kim, Hwa Jung, Therneau, Terry M.·2013·Hepatology

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Abstract

UNLABELLED: The clinical and public health significance of nonalcoholic fatty liver disease (NAFLD) is not well established. We investigated the long-term effect of NAFLD on mortality. This analysis utilized the National Health and Nutrition Examination Survey conducted in 1988-1994 and subsequent follow-up data for mortality through December 31, 2006. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known liver diseases. The presence and severity of hepatic fibrosis in subjects with NAFLD was determined by the NAFLD fibrosis score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and FIB-4 score. Of 11,154 participants, 34.0% had NAFLD--the majority (71.7%) had NFS consistent with lack of significant fibrosis (NFS <-1.455), whereas 3.2% had a score indicative of advanced fibrosis (NFS >0.676). After a median follow-up of 14.5 years, NAFLD was not associated with higher mortality (age- and sex-adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.93-1.19). In contrast, there was a progressive increase in mortality with advancing fibrosis scores. Compared to subjects without fibrosis, those with a high probability of advanced fibrosis had a 69% increase in mortality (for NFS: HR, 1.69, 95% CI: 1.09-2.63; for APRI: HR, 1.85, 95% CI: 1.02-3.37; for FIB-4: HR, 1.66, 95% CI: 0.98-2.82) after adjustment for other known predictors of mortality. These increases in mortality were almost entirely from cardiovascular causes (for NFS: HR, 3.46, 95% CI: 1.91-6.25; for APRI: HR, 2.53, 95% CI: 1.33-4.83; for FIB-4: HR, 2.68, 95% CI: 1.44-4.99). CONCLUSIONS: Ultrasonography-diagnosed NAFLD is not associated with increased mortality. However, advanced fibrosis, as determined by noninvasive fibrosis marker panels, is a significant predictor of mortality, mainly from cardiovascular causes, independent of other known factors.

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Authors: Kim, D., Kim, R. W., Kim, H. J., & Therneau, T. M.
Affiliations: Mayo Clinic (US)
Asan Medical Center (KR)
ORCID: Kim, Donghee
Kim, Hwa Jung
Therneau, Terry M.
Venue: Hepatology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2013-04
Volume: 57
Issue: 4
Pages: 1357-1365
ISSN: 0270-9139 (ISSN-L)
DOI: 10.1002/hep.26156
PMC: PMC3622816
OpenAlex: W1987934823
Cited by: 772
References: 37
Citations by year: 2026: 27 · 2025: 35 · 2024: 51 · 2023: 74 · 2022: 77 · 2021: 80 · 2020: 92 · 2019: 74 · 2018: 52 · 2017: 70 · 2016: 43 · 2015: 46 · 2014: 33 · 2013: 18
FWCI: 23.23
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 883 d)
Locations: Hepatology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Diabetes, Digestive, and Kidney Disease (DK-34238)
Topics: Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords: non-alcoholic fatty liver disease, liver fibrosis, mortality, NAFLD fibrosis score, APRI, FIB-4, cardiovascular mortality, hepatic steatosis, non-invasive fibrosis markers, long-term follow-up, NHANES cohort, liver transplantation, liver cancer
MeSH terms: Adult, Aged, Aspartate Aminotransferases, Blood Platelets, Fatty Liver, Female, Follow-Up Studies, Humans, Liver, Liver Cirrhosis, Male, Middle Aged, Nutrition Surveys, Retrospective Studies, Risk Factors, Severity of Illness Index, Ultrasonography, United States, Prevalence, Survival Rate, Non-alcoholic Fatty Liver Disease

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Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States

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