Association between Non-invasive Fibrosis Markers and Mortality among Adults with Non-alcoholic Fatty Liver Disease in the United States

By Donghee Kim, W. Kim, H. Kim, Terry M. Therneau. Hepatology, 2013

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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. (HEPATOLOGY 2013)

Subfields: Epidemiology, Hepatology, Oncology

View Paper: https://www.semanticscholar.org/paper/e8b9017b33a24c08d1311f486d95e9be1db139cd

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Citations in the corpus

Sex Differences in Nonalcoholic Fatty Liver Disease: State of the Art and Identification of Research Gaps (2019, neutral): “( 93 ) US A 5, 29 6/ 5, 85 8 20 -7 4 N o N on -H is pa ni c”
Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence? (2018, result): “However, in a subsequent analysis of the same cohort of NHANES-III participants, advanced liver fibrosis, estimated by non-invasive fibrosis marker panels, was a significant predictor of mortality, mainly from CVD, independently of other known risk factors.(109) Interestingly, other smaller cohort s”
EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. (2015, background): “Advanced fibrosis, as determined by non-invasive serum biomarker, has been shown to predict liver-related complications and mortality [222,223].”
Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. (2016, background): “2013 [37] Population-based cohort, n = 11,154 United States adults (NHANES 1988-94); mean 43 years, 48% men 14.”
Easl Clinical Practice Guidelines (Cpgs) On Non-Invasive Tests For Evaluation Of Liver Disease Severity And Prognosis- 2020 Update. (2021, background): “A large US cohort study in 11,154 individuals (NHANES cohort) of whom 34% had NAFLD on ultrasound reported that those diagnosed as having advanced fibrosis using NFS had higher overall, liverrelated and cardiovascular mortality [160].”
EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. (2016, neutral): “87 66 91 73 87 - Developed in hepatitis C [46]; predicts liverrelated events [37, 40] McPherson 2010 [47] AST/ALT ratio AST, ALT 145 >0.”
Fibrosis stage is the strongest predictor for disease‐specific mortality in NAFLD after up to 33 years of follow‐up (2015, result): “Our study demonstrates that in NAFLD fibrosis stage is a more robust predictor than the NAS of both overall and disease-specific mortality, which is in accordance with a recent publication based on the National Health And Nutrition Examinations Survey (NHANES).(39) The present study is also the firs”
NAFLD: a multisystem disease. (2015, background): “Interestingly, however, the latest analyses of the same NHANES-III database found that NAFLD with advanced hepatic fibrosis (defined by non-invasive scoring systems) was independently associated with a 70% increased risk of all-cause mortality, and that this increase in mortality was almost entirely”