Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification

Hwi Young Kim; Da Jung Kim; Hye Ah Lee; Joo Youn Cho; Won Kim

doi:10.3390/metabo13030444

Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification

Hwi Young Kim, Da Jung Kim, Hye Ah Lee, Joo Youn Cho, Won Kim

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Noninvasive risk stratification is a challenging issue in the management of patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastography results (n = 160). The baseline median FAST score was 0.37. The PNPLA3 rs738409 genotype was significantly associated with a FAST score > 0.35. Circulating metabolomics significantly associated with a FAST score > 0.35 included SM C24:0 (odds ratio [OR] = 0.642; 95% confidence interval [CI], 0.463–0.891), PC ae C40:6 (OR = 0.477; 95% CI, 0.340–0.669), lysoPC a C18:2 (OR = 0.570; 95% CI, 0.417–0.779), and tyrosine (OR = 2.743; 95% CI, 1.875–4.014). A combination of these metabolites and PNPLA3 genotype yielded a c-index = 0.948 for predicting a FAST score > 0.35. In the follow-up sub-cohort (median follow-up = 23.7 months), 47/76 patients (61.8%) with a baseline FAST score > 0.35 had a follow-up FAST score ≤ 0.35. An improved FAST score at follow-up was significantly associated with age, serum alanine aminotransferase, and tyrosine. In conclusion, baseline risk stratification in NAFLD patients may be assisted using a multiomics-based model. Particularly, patients with increased tyrosine may benefit from an earlier switch to pharmacologic approaches.

Original language	English
Article number	444
Journal	Metabolites
Volume	13
Issue number	3
DOIs	https://doi.org/10.3390/metabo13030444
State	Published - Mar 2023

Bibliographical note

Funding Information:
This research was supported in part by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (Grant No. 2018R1A5A2025286, 2021R1A2C2005820, and 2021M3A9E4021818), the Research Supporting Program of the Korean Association for the Study of the Liver (Grant No. KASL2018-01) and the Technology Innovation Program (or Industrial Strategic Technology Development Program-Bioindustry Strategic Technology Development Program) (Grant No. 20013712) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea). The funding sources had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results.

Publisher Copyright:
© 2023 by the authors.

Keywords

genomics
metabolomics
multiomics
nonalcoholic steatohepatitis
outcome
prediction
risk stratification
steatohepatitis
steatosis
weight change

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

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title = "Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification",

abstract = "Noninvasive risk stratification is a challenging issue in the management of patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastography results (n = 160). The baseline median FAST score was 0.37. The PNPLA3 rs738409 genotype was significantly associated with a FAST score > 0.35. Circulating metabolomics significantly associated with a FAST score > 0.35 included SM C24:0 (odds ratio [OR] = 0.642; 95% confidence interval [CI], 0.463–0.891), PC ae C40:6 (OR = 0.477; 95% CI, 0.340–0.669), lysoPC a C18:2 (OR = 0.570; 95% CI, 0.417–0.779), and tyrosine (OR = 2.743; 95% CI, 1.875–4.014). A combination of these metabolites and PNPLA3 genotype yielded a c-index = 0.948 for predicting a FAST score > 0.35. In the follow-up sub-cohort (median follow-up = 23.7 months), 47/76 patients (61.8%) with a baseline FAST score > 0.35 had a follow-up FAST score ≤ 0.35. An improved FAST score at follow-up was significantly associated with age, serum alanine aminotransferase, and tyrosine. In conclusion, baseline risk stratification in NAFLD patients may be assisted using a multiomics-based model. Particularly, patients with increased tyrosine may benefit from an earlier switch to pharmacologic approaches.",

keywords = "genomics, metabolomics, multiomics, nonalcoholic steatohepatitis, outcome, prediction, risk stratification, steatohepatitis, steatosis, weight change",

author = "Kim, {Hwi Young} and Kim, {Da Jung} and Lee, {Hye Ah} and Cho, {Joo Youn} and Won Kim",

note = "Funding Information: This research was supported in part by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (Grant No. 2018R1A5A2025286, 2021R1A2C2005820, and 2021M3A9E4021818), the Research Supporting Program of the Korean Association for the Study of the Liver (Grant No. KASL2018-01) and the Technology Innovation Program (or Industrial Strategic Technology Development Program-Bioindustry Strategic Technology Development Program) (Grant No. 20013712) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea). The funding sources had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = mar,

doi = "10.3390/metabo13030444",

language = "English",

volume = "13",

journal = "Metabolites",

issn = "2218-1989",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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T1 - Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification

AU - Kim, Hwi Young

AU - Kim, Da Jung

AU - Lee, Hye Ah

AU - Cho, Joo Youn

AU - Kim, Won

N1 - Funding Information: This research was supported in part by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (Grant No. 2018R1A5A2025286, 2021R1A2C2005820, and 2021M3A9E4021818), the Research Supporting Program of the Korean Association for the Study of the Liver (Grant No. KASL2018-01) and the Technology Innovation Program (or Industrial Strategic Technology Development Program-Bioindustry Strategic Technology Development Program) (Grant No. 20013712) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea). The funding sources had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Publisher Copyright: © 2023 by the authors.

PY - 2023/3

Y1 - 2023/3

N2 - Noninvasive risk stratification is a challenging issue in the management of patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastography results (n = 160). The baseline median FAST score was 0.37. The PNPLA3 rs738409 genotype was significantly associated with a FAST score > 0.35. Circulating metabolomics significantly associated with a FAST score > 0.35 included SM C24:0 (odds ratio [OR] = 0.642; 95% confidence interval [CI], 0.463–0.891), PC ae C40:6 (OR = 0.477; 95% CI, 0.340–0.669), lysoPC a C18:2 (OR = 0.570; 95% CI, 0.417–0.779), and tyrosine (OR = 2.743; 95% CI, 1.875–4.014). A combination of these metabolites and PNPLA3 genotype yielded a c-index = 0.948 for predicting a FAST score > 0.35. In the follow-up sub-cohort (median follow-up = 23.7 months), 47/76 patients (61.8%) with a baseline FAST score > 0.35 had a follow-up FAST score ≤ 0.35. An improved FAST score at follow-up was significantly associated with age, serum alanine aminotransferase, and tyrosine. In conclusion, baseline risk stratification in NAFLD patients may be assisted using a multiomics-based model. Particularly, patients with increased tyrosine may benefit from an earlier switch to pharmacologic approaches.

AB - Noninvasive risk stratification is a challenging issue in the management of patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastography results (n = 160). The baseline median FAST score was 0.37. The PNPLA3 rs738409 genotype was significantly associated with a FAST score > 0.35. Circulating metabolomics significantly associated with a FAST score > 0.35 included SM C24:0 (odds ratio [OR] = 0.642; 95% confidence interval [CI], 0.463–0.891), PC ae C40:6 (OR = 0.477; 95% CI, 0.340–0.669), lysoPC a C18:2 (OR = 0.570; 95% CI, 0.417–0.779), and tyrosine (OR = 2.743; 95% CI, 1.875–4.014). A combination of these metabolites and PNPLA3 genotype yielded a c-index = 0.948 for predicting a FAST score > 0.35. In the follow-up sub-cohort (median follow-up = 23.7 months), 47/76 patients (61.8%) with a baseline FAST score > 0.35 had a follow-up FAST score ≤ 0.35. An improved FAST score at follow-up was significantly associated with age, serum alanine aminotransferase, and tyrosine. In conclusion, baseline risk stratification in NAFLD patients may be assisted using a multiomics-based model. Particularly, patients with increased tyrosine may benefit from an earlier switch to pharmacologic approaches.

KW - genomics

KW - metabolomics

KW - multiomics

KW - nonalcoholic steatohepatitis

KW - outcome

KW - prediction

KW - risk stratification

KW - steatohepatitis

KW - steatosis

KW - weight change

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U2 - 10.3390/metabo13030444

DO - 10.3390/metabo13030444

M3 - Article

AN - SCOPUS:85152087023

SN - 2218-1989

VL - 13

JO - Metabolites

JF - Metabolites

IS - 3

M1 - 444

ER -

Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification

Abstract

Bibliographical note

Keywords

UN SDGs

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