Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality

Introduction and Objectives: Accumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver dise...

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Main Authors: Hui Han, Qingtao Yu, Nina Qin, Bin Song, Yan Meng, Zuojing Feng, Zhaoping Li, Liyong Chen
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Annals of Hepatology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1665268123002806
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author Hui Han
Qingtao Yu
Nina Qin
Bin Song
Yan Meng
Zuojing Feng
Zhaoping Li
Liyong Chen
author_facet Hui Han
Qingtao Yu
Nina Qin
Bin Song
Yan Meng
Zuojing Feng
Zhaoping Li
Liyong Chen
author_sort Hui Han
collection DOAJ
description Introduction and Objectives: Accumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver disease (NAFLD) risk and all-cause mortality and examine the potential nonlinear relationships between them. Material and Methods: We used nationally representative data from the National Health and Nutrition Examination Survey (NHANES). NAFLD was assessed using the fatty liver index (FLI) and United States fatty liver index (USFLI), respectively. Results: A total of 35 912 and 17 329 participants were included in FLI-NAFLD (case with NAFLD was diagnosed by FLI) and USFLI-NAFLD (case with NAFLD was diagnosed by USFLI) groups, respectively. The mean age of total population was 46.25 years, and 48.51% were male. Compared to participants with lowest quintile of total bilirubin concentration, those with highest quintile had lower risk of NAFLD in both FLI-NAFLD (OR: 0.48, 95% CI: 0.40, 0.59) and USFLI-NAFLD (OR: 0.55, 95% CI: 0.43, 0.70) groups. Compared to participants with lowest quintile of total bilirubin concentration, the association between total bilirubin concentration and all-cause mortality was not significant among those with highest quintile of total bilirubin concentration (HR: 0.89, 95% CI: 0.66, 1.20). The restricted spline curves showed the nonlinear U-shaped association of total bilirubin concentration with NAFLD risk and all-cause mortality. The segmented linear regression analysis showed negative associations between total bilirubin concentration and risk of NAFLD in both FLI-NAFLD (OR: 0.94, 95% CI: 0.93, 0.95) and USFLI-NAFLD (OR: 0.95, 95% CI: 0.93, 0.96) groups when total bilirubin concentration was below the turning point (FLI-NAFLD: 18.81 μmol/L; USFLI-NAFLD: 15.39 μmol/L) and these associations were not significant when total bilirubin concentration was higher than the turning point. Furthermore, all-cause mortality decreased (OR: 0.97, 95%CI: 0.95, 1.00) with increased total bilirubin concentration up to the turning point (11.97 μmol/L), and then all-cause mortality increased with increasing total bilirubin concentration (OR: 1.03, 95%CI: 1.02, 1.04). Conclusions: We found that higher circulating total bilirubin concentration within the physiological range was associated with decreased risk of NAFLD and all-cause mortality among NAFLD patients.
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spelling doaj.art-3ef94fffa8314d00976b8c3c88c272e42024-03-03T04:29:04ZengElsevierAnnals of Hepatology1665-26812024-03-01292101177Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortalityHui Han0Qingtao Yu1Nina Qin2Bin Song3Yan Meng4Zuojing Feng5Zhaoping Li6Liyong Chen7Department of Health, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaDepartment of Internal Medicine, The People's Hospital of Huaiyin, Jinan 250021, ChinaDepartment of Nutrition, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Out-patient, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Nutrition, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Nutrition, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Nutrition, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Health, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Department of Nutrition, Qilu Hospital of Shandong University, Jinan, China; Corresponding author.Introduction and Objectives: Accumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver disease (NAFLD) risk and all-cause mortality and examine the potential nonlinear relationships between them. Material and Methods: We used nationally representative data from the National Health and Nutrition Examination Survey (NHANES). NAFLD was assessed using the fatty liver index (FLI) and United States fatty liver index (USFLI), respectively. Results: A total of 35 912 and 17 329 participants were included in FLI-NAFLD (case with NAFLD was diagnosed by FLI) and USFLI-NAFLD (case with NAFLD was diagnosed by USFLI) groups, respectively. The mean age of total population was 46.25 years, and 48.51% were male. Compared to participants with lowest quintile of total bilirubin concentration, those with highest quintile had lower risk of NAFLD in both FLI-NAFLD (OR: 0.48, 95% CI: 0.40, 0.59) and USFLI-NAFLD (OR: 0.55, 95% CI: 0.43, 0.70) groups. Compared to participants with lowest quintile of total bilirubin concentration, the association between total bilirubin concentration and all-cause mortality was not significant among those with highest quintile of total bilirubin concentration (HR: 0.89, 95% CI: 0.66, 1.20). The restricted spline curves showed the nonlinear U-shaped association of total bilirubin concentration with NAFLD risk and all-cause mortality. The segmented linear regression analysis showed negative associations between total bilirubin concentration and risk of NAFLD in both FLI-NAFLD (OR: 0.94, 95% CI: 0.93, 0.95) and USFLI-NAFLD (OR: 0.95, 95% CI: 0.93, 0.96) groups when total bilirubin concentration was below the turning point (FLI-NAFLD: 18.81 μmol/L; USFLI-NAFLD: 15.39 μmol/L) and these associations were not significant when total bilirubin concentration was higher than the turning point. Furthermore, all-cause mortality decreased (OR: 0.97, 95%CI: 0.95, 1.00) with increased total bilirubin concentration up to the turning point (11.97 μmol/L), and then all-cause mortality increased with increasing total bilirubin concentration (OR: 1.03, 95%CI: 1.02, 1.04). Conclusions: We found that higher circulating total bilirubin concentration within the physiological range was associated with decreased risk of NAFLD and all-cause mortality among NAFLD patients.http://www.sciencedirect.com/science/article/pii/S1665268123002806Total bilirubin concentrationNon-alcoholic fatty liver diseaseAll-cause mortalityNonlinear
spellingShingle Hui Han
Qingtao Yu
Nina Qin
Bin Song
Yan Meng
Zuojing Feng
Zhaoping Li
Liyong Chen
Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality
Annals of Hepatology
Total bilirubin concentration
Non-alcoholic fatty liver disease
All-cause mortality
Nonlinear
title Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality
title_full Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality
title_fullStr Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality
title_full_unstemmed Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality
title_short Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality
title_sort non linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all cause mortality
topic Total bilirubin concentration
Non-alcoholic fatty liver disease
All-cause mortality
Nonlinear
url http://www.sciencedirect.com/science/article/pii/S1665268123002806
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