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Liver and atherosclerotic risks of patients with cryptogenic steatotic liver disease

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Abstract

Background and aims

In 2023, a new nomenclature of “metabolic associated steatotic liver disease” (MASLD) has emerged by incorporating cardio-metabolic criteria to redefine “non-alcoholic fatty liver disease” (NAFLD). Among steatotic liver disease (SLD), those having no known causes and without any one of cardio-metabolic criteria are deemed to have cryptogenic SLD. This study aims to compare the liver and atherosclerotic risks between MASLD and cryptogenic SLD patients.

Approach

We analyzed participants with liver ultrasound data from the Taiwan Bio-Bank cohort, excluding those with positive HBsAg, positive anti-HCV, or “frequent drinker”. MASLD involves hepatic steatosis and any of five cardiometabolic risk factors, whereas cryptogenic SLD features hepatic steatosis without these risk factors. Liver fibrosis severity was assessed by using NAFLD fibrosis score (NFS), while atherosclerosis was determined by carotid plaques on duplex ultrasound.

Results

Among 17,595 subjects (age 55.47 ± 10.41; males 31.8%), 7538 participants (42.8%) had SLD, comprising 96.5% of MASLD and 3.5% of cryptogenic SLD. Cryptogenic SLD patients are younger and had a lower percentage of male than those with MASLD. After propensity score matching for age and sex, patients with cryptogenic SLD exhibited milder glucose and lipid profiles, fewer carotid plaques, lower liver steatosis, inflammation, and fibrosis markers than those with MASLD.

Conclusions

In this large population-based study, cryptogenic SLD, the excluded group, occupy only 3.5% in NAFLD patients. It has lower liver and atherosclerotic risks than MASLD, supporting its exclusion from NAFLD and justifying the rationale for the new disease name and diagnostic criteria of MASLD.

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Data availability

We declare the data was available and approved by the Ethics and Governance Council of the TWB (approval numbers: TWBR11102-03).

Abbreviations

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

anti-HCV:

Anti-hepatitis C virus antibody

BMI:

Body mass index

cMASLD:

MASLD combined with other etiologies

CHO:

Cholesterol

DM:

Diabetes mellitus

eGFR:

Estimated glomerular filtration rate

FIB-4:

Fibrosis 4

FLI:

Fatty liver index

GGT:

γ-Glutamyl transferase

HbA1c:

Glycated hemoglobin

HDL:

High-density lipoprotein

HBsAg:

Hepatitis B surface antigen;

IMT:

Intima media thickness

LDL:

Low-density lipoprotein

MAFLD:

Metabolic associated fatty liver disease

MASLD:

Metabolic associated steatotic liver disease

MetALD:

MASLD with excessive alcohol intake

NAFLD:

Non-alcoholic fatty liver disease

NFS:

NAFLD fibrosis score

pMASLD:

Pure MASLD

PS:

Propensity score

SLD:

Steatotic liver disease

TG:

Triglyceride

WC:

Waist circumference

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Funding

This work was supported by grants from Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-112-11, TCRD-TPE-112-RT-7) and the Taiwan Liver Disease Consortium, Ministry of Science and Technology, Taiwan (MOHW112-TDU-B-211-144002).

Author information

Authors and Affiliations

  1. Department of Education, Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan

    Shao-Wen Wang

  2. Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan

    Tsung-Han Hsieh

  3. Department of Gastroenterology and Hepatology, Tung’s Taichung MetroHarbor Hospital, Taichung, Taiwan

    Yu-Ming Cheng

  4. Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, New Taipei City and Hualien, Taiwan

    Chia-Chi Wang

  5. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Jia-Horng Kao

  6. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    Jia-Horng Kao

  7. Medical Department, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, 289 Jianguo Rd., Xindian Area, New Taipei City, 23142, Taiwan

    Chia-Chi Wang

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Contributions

SWW: writing of article; THH and YMC: statistical analysis; CCW: concept, design and writing of article; JHK: revising of article.

Corresponding author

Correspondence to Chia-Chi Wang.

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Conflict of interest

Shao-Wen Wang, Tsung-Han Hsieh, Yu-Ming Cheng, Chia-Chi Wang and Jia-Horng Kao declare no conflict of interest.

Ethical approval

This study was performed in accordance with the principles of the 1975 Declaration of Helsinki and approved with waived informed consent by the Research Ethics Committee of Taipei Tzu Chi Hospital; Buddhist Tzu Chi Medical Foundation (approval numbers: 10-XD-055 and 11-X-074) and the Ethics and Governance Council of the TWB (approval numbers: TWBR11102-03).

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Wang, SW., Hsieh, TH., Cheng, YM. et al. Liver and atherosclerotic risks of patients with cryptogenic steatotic liver disease. Hepatol Int 18, 943–951 (2024). https://doi.org/10.1007/s12072-023-10624-8

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  • DOI: https://doi.org/10.1007/s12072-023-10624-8

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