Associations of serum liver enzyme levels and their changes over time with all-cause and cause-specific mortality in the general population: A large-scale national health screening cohort study

Kyoung Nam Kim, Jungmin Joo, Ho Kyung Sung, Chee Hae Kim, Haebin Kim, Yong Jin Kwon

Research output: Contribution to journalArticle

Abstract

Objectives To investigate the associations of the levels of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT), at baseline and their changes over time with mortality. Design Cohort study. Setting, participants and outcome measures We analysed the data of 484 472 individuals from the National Health Insurance Service-National Health Screening Cohort (2002-2013). We used two exposure indices: (1) deciles of baseline ALT, AST and GGT levels measured in 2002 or 2003 and (2) deciles of changes in ALT, AST and GGT levels over a 4 year period (2002-2006 or 2003-2007). We constructed Cox models to evaluate the associations of these exposure indices with mortality (2008-2013). Results We found non-monotonic dose-response associations between the baseline levels of ALT and AST and all-cause mortality. We also found a monotonic non-linear association between the baseline levels of GGT and all-cause mortality (10th decile: HR=2.05, 95% CI: 1.93 to 2.18). Compared with the ninth, sixth and fourth deciles of changes in ALT (8-13 U/L), AST (1 U/L) and GGT (-3 to -2 U/L) over time, respectively, the risks of all-cause mortality increased in both the higher and lower deciles of changes in the corresponding liver enzyme levels (10th decile: HR=1.36, 95% CI 1.24 to 1.48; 1st decile: HR=1.46, 95% CI 1.34 to 1.59 for ALT; 10th decile: 1.55, 95% CI 1.40 to 1.71; 1st decile: HR=1.53, 95% CI 1.38 to 1.69 for AST; 10th decile: HR=1.71, 95% CI 1.56 to 1.88; 1st decile: HR=1.67, 95% CI 1.52 to 1.84 for GGT). These non-monotonic dose-response associations remained when analyses were stratified by the medians or quartiles of the baseline liver enzyme levels. Conclusions The levels of liver enzymes at baseline and over time showed non-linear associations with mortality.

Original languageEnglish
Article numbere026965
JournalBMJ Open
Volume9
Issue number5
DOIs
StatePublished - 1 May 2019

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gamma-Glutamyltransferase
Aspartate Aminotransferases
Alanine Transaminase
Cohort Studies
Mortality
Liver
Health
Enzymes
Serum
Population
National Health Programs
Proportional Hazards Models
Aspartic Acid
Outcome Assessment (Health Care)

Keywords

  • alanine aminotransferase
  • aspartate aminotransferase
  • gamma glutamyltransferase
  • mortality
  • non-linear associations

Cite this

@article{39ed70ccf86440b18e8bf0d2d56b922d,
title = "Associations of serum liver enzyme levels and their changes over time with all-cause and cause-specific mortality in the general population: A large-scale national health screening cohort study",
abstract = "Objectives To investigate the associations of the levels of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT), at baseline and their changes over time with mortality. Design Cohort study. Setting, participants and outcome measures We analysed the data of 484 472 individuals from the National Health Insurance Service-National Health Screening Cohort (2002-2013). We used two exposure indices: (1) deciles of baseline ALT, AST and GGT levels measured in 2002 or 2003 and (2) deciles of changes in ALT, AST and GGT levels over a 4 year period (2002-2006 or 2003-2007). We constructed Cox models to evaluate the associations of these exposure indices with mortality (2008-2013). Results We found non-monotonic dose-response associations between the baseline levels of ALT and AST and all-cause mortality. We also found a monotonic non-linear association between the baseline levels of GGT and all-cause mortality (10th decile: HR=2.05, 95{\%} CI: 1.93 to 2.18). Compared with the ninth, sixth and fourth deciles of changes in ALT (8-13 U/L), AST (1 U/L) and GGT (-3 to -2 U/L) over time, respectively, the risks of all-cause mortality increased in both the higher and lower deciles of changes in the corresponding liver enzyme levels (10th decile: HR=1.36, 95{\%} CI 1.24 to 1.48; 1st decile: HR=1.46, 95{\%} CI 1.34 to 1.59 for ALT; 10th decile: 1.55, 95{\%} CI 1.40 to 1.71; 1st decile: HR=1.53, 95{\%} CI 1.38 to 1.69 for AST; 10th decile: HR=1.71, 95{\%} CI 1.56 to 1.88; 1st decile: HR=1.67, 95{\%} CI 1.52 to 1.84 for GGT). These non-monotonic dose-response associations remained when analyses were stratified by the medians or quartiles of the baseline liver enzyme levels. Conclusions The levels of liver enzymes at baseline and over time showed non-linear associations with mortality.",
keywords = "alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, mortality, non-linear associations",
author = "Kim, {Kyoung Nam} and Jungmin Joo and Sung, {Ho Kyung} and Kim, {Chee Hae} and Haebin Kim and Kwon, {Yong Jin}",
year = "2019",
month = "5",
day = "1",
doi = "10.1136/bmjopen-2018-026965",
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Associations of serum liver enzyme levels and their changes over time with all-cause and cause-specific mortality in the general population : A large-scale national health screening cohort study. / Kim, Kyoung Nam; Joo, Jungmin; Sung, Ho Kyung; Kim, Chee Hae; Kim, Haebin; Kwon, Yong Jin.

In: BMJ Open, Vol. 9, No. 5, e026965, 01.05.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Associations of serum liver enzyme levels and their changes over time with all-cause and cause-specific mortality in the general population

T2 - A large-scale national health screening cohort study

AU - Kim, Kyoung Nam

AU - Joo, Jungmin

AU - Sung, Ho Kyung

AU - Kim, Chee Hae

AU - Kim, Haebin

AU - Kwon, Yong Jin

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Objectives To investigate the associations of the levels of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT), at baseline and their changes over time with mortality. Design Cohort study. Setting, participants and outcome measures We analysed the data of 484 472 individuals from the National Health Insurance Service-National Health Screening Cohort (2002-2013). We used two exposure indices: (1) deciles of baseline ALT, AST and GGT levels measured in 2002 or 2003 and (2) deciles of changes in ALT, AST and GGT levels over a 4 year period (2002-2006 or 2003-2007). We constructed Cox models to evaluate the associations of these exposure indices with mortality (2008-2013). Results We found non-monotonic dose-response associations between the baseline levels of ALT and AST and all-cause mortality. We also found a monotonic non-linear association between the baseline levels of GGT and all-cause mortality (10th decile: HR=2.05, 95% CI: 1.93 to 2.18). Compared with the ninth, sixth and fourth deciles of changes in ALT (8-13 U/L), AST (1 U/L) and GGT (-3 to -2 U/L) over time, respectively, the risks of all-cause mortality increased in both the higher and lower deciles of changes in the corresponding liver enzyme levels (10th decile: HR=1.36, 95% CI 1.24 to 1.48; 1st decile: HR=1.46, 95% CI 1.34 to 1.59 for ALT; 10th decile: 1.55, 95% CI 1.40 to 1.71; 1st decile: HR=1.53, 95% CI 1.38 to 1.69 for AST; 10th decile: HR=1.71, 95% CI 1.56 to 1.88; 1st decile: HR=1.67, 95% CI 1.52 to 1.84 for GGT). These non-monotonic dose-response associations remained when analyses were stratified by the medians or quartiles of the baseline liver enzyme levels. Conclusions The levels of liver enzymes at baseline and over time showed non-linear associations with mortality.

AB - Objectives To investigate the associations of the levels of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT), at baseline and their changes over time with mortality. Design Cohort study. Setting, participants and outcome measures We analysed the data of 484 472 individuals from the National Health Insurance Service-National Health Screening Cohort (2002-2013). We used two exposure indices: (1) deciles of baseline ALT, AST and GGT levels measured in 2002 or 2003 and (2) deciles of changes in ALT, AST and GGT levels over a 4 year period (2002-2006 or 2003-2007). We constructed Cox models to evaluate the associations of these exposure indices with mortality (2008-2013). Results We found non-monotonic dose-response associations between the baseline levels of ALT and AST and all-cause mortality. We also found a monotonic non-linear association between the baseline levels of GGT and all-cause mortality (10th decile: HR=2.05, 95% CI: 1.93 to 2.18). Compared with the ninth, sixth and fourth deciles of changes in ALT (8-13 U/L), AST (1 U/L) and GGT (-3 to -2 U/L) over time, respectively, the risks of all-cause mortality increased in both the higher and lower deciles of changes in the corresponding liver enzyme levels (10th decile: HR=1.36, 95% CI 1.24 to 1.48; 1st decile: HR=1.46, 95% CI 1.34 to 1.59 for ALT; 10th decile: 1.55, 95% CI 1.40 to 1.71; 1st decile: HR=1.53, 95% CI 1.38 to 1.69 for AST; 10th decile: HR=1.71, 95% CI 1.56 to 1.88; 1st decile: HR=1.67, 95% CI 1.52 to 1.84 for GGT). These non-monotonic dose-response associations remained when analyses were stratified by the medians or quartiles of the baseline liver enzyme levels. Conclusions The levels of liver enzymes at baseline and over time showed non-linear associations with mortality.

KW - alanine aminotransferase

KW - aspartate aminotransferase

KW - gamma glutamyltransferase

KW - mortality

KW - non-linear associations

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U2 - 10.1136/bmjopen-2018-026965

DO - 10.1136/bmjopen-2018-026965

M3 - Article

C2 - 31154308

AN - SCOPUS:85066754679

VL - 9

JO - BMJ open

JF - BMJ open

SN - 2044-6055

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ER -