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The impact of an increased Fibrosis-4 index and the severity of hepatic steatosis on mortality in individuals living with diabetes

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Abstract

Background and aims

Data on the effects of liver fibrosis and hepatic steatosis on outcomes in individuals living with diabetes are limited. Therefore, we investigated the predictive value of the fibrosis and the severity of hepatic steatosis for all-cause mortality in individuals living with diabetes.

Methods

A total of 1903 patients with diabetes from the Third National Health and Nutrition Examination Survey (NHANES III) dataset were enrolled. Presumed hepatic fibrosis was evaluated with Fibrosis-4 index (FIB-4). The mortality risk and corresponding hazard ratio (HR) were analyzed with the Kaplan–Meier method and multivariable Cox proportional hazard models.

Results

Over a median follow-up of 19.4 years, all-cause deaths occurred in 69.6%. FIB-4 ≥ 1.3 was an independent predictor of mortality in individuals living with diabetes (HR 1.219, 95% confidence interval [CI]: 1.067–1.392, p = 0.004). Overall, FIB-4 ≥ 1.3 without moderate–severe steatosis increased the mortality risk (HR 1.365; 95%CI 1.147–1.623, p < 0.001). The similar results were found in individuals living with diabetes with metabolic dysfunction-associated fatty liver disease (MAFLD) (HR 1.499; 95%CI 1.065–2.110, p = 0.020), metabolic syndrome (MetS) (HR 1.397; 95%CI 1.086–1.796, p = 0.009) or abdominal obesity (HR 1.370; 95%CI 1.077–1.742, p = 0.010).

Conclusions

Liver fibrosis, as estimated by FIB-4, may serve as a more reliable prognostic indicator for individuals living with diabetes than hepatic steatosis. Individuals living with diabetes with FIB-4 ≥ 1.3 without moderate–severe steatosis had a significantly increased all-cause mortality risk. These findings highlight the importance of identifying and monitoring those individuals, as they may benefit from further evaluation and risk stratification.

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Data availability

The data that support the findings of this study are available in the Third National Health and Nutrition Examination Survey (NHANES III) dataset at https://wwwn.cdc.gov/nchs/nhanes/nhanes3/default.aspx.

Abbreviations

HR:

Hazard ratio

CI:

Confidence interval

CLD:

Chronic liver disease

DM2:

Type 2 diabetes mellitus

NAFLD:

Nonalcoholic fatty liver disease

MAFLD:

Metabolic dysfunction- associated fatty liver disease

NHANES III:

Third National Health and Nutrition Examination Survey

NCHS:

National Center for Health Statistics

CDC:

Centers for Disease Control and Prevention

ADA:

American Diabetes Association

BMI:

Body mass index

MS:

Metabolic syndrome

IDF:

International Diabetes Federation

FIB-4:

Fibrosis-4 index

AST:

Aspartate transaminase

ALT:

Alanine transaminase

PLT:

Platelet

NASH:

Nonalcoholic steatohepatitis

CAD:

Coronary artery disease

CRP:

Serum C-reactive protein

TC:

Total cholesterol

TGs:

Triglycerides

HDL:

High- density lipoprotein cholesterol

ALB:

Albumin

SCr:

Serum creatinine

HbA1c:

Glycated hemoglobin

IQR:

Interquartile ranges

PCPs:

Primary care practitioners

TE:

Transient elastography

APASL:

Asian Pacific Association for the Study of the Liver (APASL)

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Funding

This work was supported by the National Natural Science Fund (No.81970545; 82170609), Natural Science Foundation of Shandong Province (Major Project) (No. ZR2020KH006) and Ji’nan Science and Technology Development Project (No.2020190790); Dr. Zhiwen Fan wishes to acknowledge the support from The National Natural Science Foundation of China (82170592, 81700554), The Nanjing Municipal Administration of Health and Human Services (YKK17061), The Fundamental Research Funds for Central Universities (021414380323) and The Research and Practice Innovation Project of Nanjing University (No.CX10284).

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Author notes

  1. Xiaoyan Ma, Yixuan Zhu and Yee Hui Yeo have contributed equally to this work.

Authors and Affiliations

  1. Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, Jiangsu, China

    Xiaoyan Ma, Qi Gu, Xin Tong, Shengxia Yin, Chao Wu & Jie Li

  2. Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, China

    Yixuan Zhu

  3. Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90001, USA

    Yee Hui Yeo

  4. Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, Jiangsu, China

    Zhiwen Fan

  5. Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, Jiangsu, China

    Xiaoming Xu, Fajuan Rui & Wenjing Ni

  6. Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, 210008, Jiangsu, China

    Xin Tong, Shengxia Yin, Chao Wu & Jie Li

  7. Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210008, Jiangsu, China

    Xiaolong Qi

  8. Department of Hepatology, The Affiliated Hospital and Institute of Hepatology and Metabolic Disease, Hangzhou Normal University, Hangzhou, 310015, Zhejiang, China

    Junping Shi

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  1. Xiaoyan Ma
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Contributions

All authors contributed to the study conception and design. Study concept and design (JL, XM); acquisition of data (XM, YZ, YHY, XX); statistical analysis and interpretation of data (XM, YZ, YHY, XX, FR, WN, QG, XT, SY, XQ); drafting of the manuscript (XM, YZ, YHY, ZF); study supervision (XT, SY, XQ, JL, YHY, ZF, CW); critical revision of the manuscript for important intellectual content (JL, CW, JS). All authors were responsible for the interpretation of data, the drafting, critical revision of the manuscript for important intellectual content, and the final approval of the version to be submitted.

Corresponding authors

Correspondence to Junping Shi, Chao Wu or Jie Li.

Ethics declarations

Ethical approval

The study was conducted following the guidelines of the Declaration of Helsinki, and the National Center for Health Statistics Research Ethics Review Board approved the NHANES protocol.

Conflict of interest

Xiaoyan Ma, Yixuan Zhu, Yee Hui Yeo, Zhiwen Fan, Xiaoming Xu, Fajuan Rui, Wenjing Ni, Qi Gu, Xin Tong, Shengxia Yin, Xiaolong Qi, Junping Shi, Chao Wu and Jie Li declare that they have no conflict of interest.

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Ma, X., Zhu, Y., Yeo, Y.H. et al. The impact of an increased Fibrosis-4 index and the severity of hepatic steatosis on mortality in individuals living with diabetes. Hepatol Int (2024). https://doi.org/10.1007/s12072-023-10625-7

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