Fasting Ketonuria and the Risk of Incident Nonalcoholic Fatty Liver Disease with and without Liver Fibrosis in Nondiabetic Adults
Fasting Ketonuria and the Risk of Incident Nonalcoholic Fatty Liver Disease with and without Liver Fibrosis in Nondiabetic Adults
Introduction: dietary carbohydrate restriction or ketogenic diets are known to be beneficial in preventing liver fat accumulation. However, the effect of ketonemia on the risk of nonalcoholic fatty liver disease (NAFLD) in nondiabetic population is largely unknown. We investigated the association between fasting ketonuria and the risk of incident NAFLD in healthy adults.
Methods: a cohort of 153,076 nondiabetic Koreans with no hepatic steatosis and low probability of fibrosis at baseline was followed for a median of 4.1 years. The outcome was incident hepatic steatosis with or without liver fibrosis, and it was assessed by liver ultrasound and noninvasive fibrosis indices, including fibrosis-4 and the NAFLD fibrosis score (NFS). Parametric proportional hazard models were used to estimate hazard ratios (HRs) for outcome according to ketonuria status.
Results: within 677,702.1 person-years of follow-up, 31,079 subjects developed hepatic steatosis. Compared with no ketonuria (reference), fasting ketonuria was significantly associated with a decreased risk of incident hepatic steatosis, with multivariable-adjusted HRs (95% confidence interval) of 0.81 (0.78–0.84). The corresponding HRs for incident hepatic steatosis with intermediate-to-high NFS were 0.79 (0.69–0.90). Similar associations were observed replacing NFS with fibrosis-4. In addition, the presence of persistent ketonuria at both baseline and subsequent visit was associated with the greatest decrease in the adjusted HR for incident NAFLD.
Discussion: ketonuria was associated with a reduced risk of developing incident hepatic steatosis with and without intermediate-to-high probability of advanced fibrosis in a large cohort of nondiabetic healthy individuals. The role of hyperketonemia in the prevention of NAFLD requires further exploration.
2270-2278
Kim, Yejin
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Chang, Yoosoo
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Kwon, Min-Jung
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Hong, Yun Soo
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Kim, Mi Kyung
87f544b8-b7cb-4967-b42e-d1eafbe72ea8
Sohn, Won
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Kyun, Yong
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Shin, Hocheol
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Wild, Sarah H.
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Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Ryu, Seungho
d6879218-6f32-4eaf-ac01-5dd6230cac9d
1 November 2021
Kim, Yejin
fcac6419-b6ca-4276-8f9e-27a05148ae1f
Chang, Yoosoo
3d2e7756-3b14-430d-a18c-31fdf3b7a996
Kwon, Min-Jung
0ce883d5-8608-4024-8a8e-aa4ec1b80d04
Hong, Yun Soo
2739acdf-3e03-46b6-be30-79b37908664e
Kim, Mi Kyung
87f544b8-b7cb-4967-b42e-d1eafbe72ea8
Sohn, Won
de174734-f967-4c5d-939c-7e56b1573e59
Kyun, Yong
6eba3ac9-8e25-453d-b3f1-04c3ccf51c7d
Shin, Hocheol
0e085a62-251f-4a00-8b83-5f5338cc7613
Wild, Sarah H.
37c5bc96-2240-4617-908a-20a9e3aa4c6e
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Ryu, Seungho
d6879218-6f32-4eaf-ac01-5dd6230cac9d
Kim, Yejin, Chang, Yoosoo, Kwon, Min-Jung, Hong, Yun Soo, Kim, Mi Kyung, Sohn, Won, Kyun, Yong, Shin, Hocheol, Wild, Sarah H., Byrne, Christopher and Ryu, Seungho
(2021)
Fasting Ketonuria and the Risk of Incident Nonalcoholic Fatty Liver Disease with and without Liver Fibrosis in Nondiabetic Adults.
American Journal of Gastroenterology, 116 (11), .
(doi:10.14309/ajg.0000000000001344).
Abstract
Introduction: dietary carbohydrate restriction or ketogenic diets are known to be beneficial in preventing liver fat accumulation. However, the effect of ketonemia on the risk of nonalcoholic fatty liver disease (NAFLD) in nondiabetic population is largely unknown. We investigated the association between fasting ketonuria and the risk of incident NAFLD in healthy adults.
Methods: a cohort of 153,076 nondiabetic Koreans with no hepatic steatosis and low probability of fibrosis at baseline was followed for a median of 4.1 years. The outcome was incident hepatic steatosis with or without liver fibrosis, and it was assessed by liver ultrasound and noninvasive fibrosis indices, including fibrosis-4 and the NAFLD fibrosis score (NFS). Parametric proportional hazard models were used to estimate hazard ratios (HRs) for outcome according to ketonuria status.
Results: within 677,702.1 person-years of follow-up, 31,079 subjects developed hepatic steatosis. Compared with no ketonuria (reference), fasting ketonuria was significantly associated with a decreased risk of incident hepatic steatosis, with multivariable-adjusted HRs (95% confidence interval) of 0.81 (0.78–0.84). The corresponding HRs for incident hepatic steatosis with intermediate-to-high NFS were 0.79 (0.69–0.90). Similar associations were observed replacing NFS with fibrosis-4. In addition, the presence of persistent ketonuria at both baseline and subsequent visit was associated with the greatest decrease in the adjusted HR for incident NAFLD.
Discussion: ketonuria was associated with a reduced risk of developing incident hepatic steatosis with and without intermediate-to-high probability of advanced fibrosis in a large cohort of nondiabetic healthy individuals. The role of hyperketonemia in the prevention of NAFLD requires further exploration.
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Accepted/In Press date: 15 May 2021
e-pub ahead of print date: 11 June 2021
Published date: 1 November 2021
Additional Information:
Funding Information:
Financial support: This study was supported by SKKU Excellence in Research Award Research Fund, Sungkyunkwan University, 2020 and by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2017R1A2B2008401). C.D.B. was supported in part by the Southampton NIHR Biomedical Research Centre, UK (IS-BRC-20004).
Publisher Copyright:
© 2021 Wolters Kluwer Health. All rights reserved.
Identifiers
Local EPrints ID: 449836
URI: http://eprints.soton.ac.uk/id/eprint/449836
ISSN: 0002-9270
PURE UUID: 8a9bfbcd-9cae-45d7-9dec-59b0388c5169
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Date deposited: 21 Jun 2021 16:31
Last modified: 17 Mar 2024 06:38
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Contributors
Author:
Yejin Kim
Author:
Yoosoo Chang
Author:
Min-Jung Kwon
Author:
Yun Soo Hong
Author:
Mi Kyung Kim
Author:
Won Sohn
Author:
Yong Kyun
Author:
Hocheol Shin
Author:
Sarah H. Wild
Author:
Seungho Ryu
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