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Histological severity of nonalcoholic fatty liver disease is associated with 10-year risk for atherosclerotic cardiovascular disease

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Abstract

Background and aim

Nonalcoholic fatty liver disease (NAFLD) is associated with atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated the association between the histological severity of NAFLD and ASCVD. Therefore, we investigated whether the histological severity of NAFLD is associated with ASCVD risk.

Methods

We performed cross-sectional analysis of prospectively enrolled, biopsy-proven NAFLD patients. The 10-year ASCVD risk was assessed using the Korean Risk Prediction Model. The histological spectrum of NAFLD was classified by the nonalcoholic steatohepatitis (NASH) clinical research network histological scoring system. The association between each histological subgroup and ASCVD risk was analyzed using logistic regression analysis.

Results

This study included 398 Korean subjects (mean age, 57.9 years; male, 44.2%) with biopsy‐proven NAFLD and 102 no-NALFD controls. Subjects with ASCVD risk ≥ 10% showed more severe grades of hepatocellular ballooning and more advanced stages of fibrosis when compared with subjects with ASCVD risk < 10% (p < 0.05 for each). The presence of NASH (odds ratio [OR] 4.07; 95% confidence interval [CI] 1.40–11.88) or advanced fibrosis (OR 8.11; 95% CI 1.83–35.98) was independently associated with a higher risk of ASCVD even after adjustment for age, sex, body mass index, blood pressure, lipids, liver enzymes, systemic inflammation, and insulin resistance.

Conclusions

Patients with NASH or advanced fibrosis are at an increased risk of developing ASCVD compared with no-NAFLD controls or subjects with NAFL, independent of conventional metabolic risk factors for CVD. Histological information on NAFLD may be helpful to promote our understanding of extrahepatic complications, such as ASCVD, resulting from NAFLD progression.

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Data availability

The data can be shared (or provided) upon reasonable request.

Abbreviations

ASCVD:

Atherosclerotic cardiovascular disease

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

BMI:

Body mass index

CVD:

Cardiovascular disease

CI:

Confidence interval

eGFR:

Estimated glomerular filtration rate

HOMA-IR:

Homeostasis model assessment of insulin resistance

hs-CRP:

High-sensitivity C-reactive protein

LDL:

Low-density lipoprotein

NAFL:

Nonalcoholic fatty liver

NAFLD:

Nonalcoholic fatty liver disease

NAS:

Nonalcoholic fatty liver disease activity score

NASH:

Nonalcoholic steatohepatitis

OR:

Odds ratio

SD:

Standard deviation

TG:

Triglycerides

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Funding

This study was supported by an intramural research grant from the Korea National Institute of Health (Grant number 2018-NI007-02).

Author information

Authors and Affiliations

  1. Division of Cardiovascular Disease Research, Department for Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju, Republic of Korea

    Ji Hye Park & Won-Ho Kim

  2. Division of Endocrinology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea

    Bo Kyung Koo

  3. Innovative Target Exploration of NAFLD (ITEN) Consortium, Seoul, Republic of Korea

    Bo Kyung Koo & Won Kim

  4. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, Republic of Korea

    Won Kim

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  1. Ji Hye Park
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  4. Won-Ho Kim
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Consortia

On behalf of the Innovative Target Exploration of NAFLD (ITEN) Consortium

Contributions

JHP was involved in study concept and design, acquisition of data, analysis and interpretation of data, and drafting of the manuscript. BKK was involved in interpretation of data and critical revision of the manuscript. WK was responsible for the Borame cohort. WK and WHK were involved in study concept and design, interpretation of data, drafting of the manuscript, critical revision of the manuscript, and study supervision.

Corresponding authors

Correspondence to Won Kim or Won-Ho Kim.

Ethics declarations

Conflict of interest

Ji Hye Park, Bo Kyung Koo, Won Kim and Won-Ho Kim have nothing to disclose.

Animal research (ethics)

Not applicable.

Consent to participate (ethics)

This study was approved by the Institutional Review Board of Seoul National University Boramae Medical Center (16-2014-86) and was carried out in accordance with the guidelines of the 2013 Declaration of Helsinki. All study participants provided informed consent prior to recruitment into the registry.

Consent to publish (ethics)

All authors contributed to the interpretation of the data and reviewed and approved the manuscript.

Plant reproducibility

Not applicable.

Clinical trials registration

The data were retrieved from the ongoing prospective NAFLD cohort database (Boramae NAFLD registry [NCT 02206841]), which was started from January 2013 (J Hepatol 2017;66:123–131).

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Park, J.H., Koo, B.K., Kim, W. et al. Histological severity of nonalcoholic fatty liver disease is associated with 10-year risk for atherosclerotic cardiovascular disease. Hepatol Int 15, 1148–1159 (2021). https://doi.org/10.1007/s12072-021-10209-3

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  • DOI: https://doi.org/10.1007/s12072-021-10209-3

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