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The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995–2040

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Abstract

Background

NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD.

Methods

We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD—8 studies) patients.

Results

The overall NAFLD prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001), and increased over time (p = 0.015), but not by per-person income or gross prefectural productivity, which increased by 0.64% per year (1983–2012) and is forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC, and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively. Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the NAFLD population, with lean NAFLD persons being older and with a higher all-cause mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02). Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality, but not lean NAFLD.

Conclusion

NAFLD prevalence has increased in Japan and may affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the NAFLD population, were older, and had higher mortality.

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Abbreviations

NAFLD:

Non-alcoholic fatty liver disease

DM:

Diabetes mellitus

PRISMA:

Preferred reporting items for systematic reviews and meta-analyses

CDS:

Collaboration with a medical librarian

FLI:

Fatty Liver Index

HIV:

Human immunodeficiency virus

QA:

Quality assessment

BMI:

Body Mass Index

GPP:

Gross prefecture product

CI:

Confidence interval

OR:

Odds ratios

HR:

Hazard ratio

HCC:

Hepatocellular carcinoma

US:

Ultrasonography

FIB-4:

Fibrosis-4

PNPLA3:

Patatin-like phospholipase domain containing 3

SNPs:

Single nucleotide polymorphisms

NAFL:

Non-alcoholic fatty liver

NASH:

Non-alcoholic steatohepatitis

FPG:

Fasting plasma glucose

FBG:

Fasting blood glucose

FBS:

Fasting blood sugar

HBA1C:

Hemoglobin A1C

AST:

Aspartate aminotransferase

ALT:

Alanine transaminase

GGT:

Gamma glutamyl transferase

HOMA-IR:

Homeostatic model assessment of insulin resistance

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Acknowledgements

We wish to acknowledge http://www.mapchart.net for the generous sharing of the map tools used to generate all maps in this article.

Funding

No external funding to disclose.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Takanori Ito, Masatoshi Ishigami, Taku Tanaka & Mitsuhiro Fujishiro

  2. Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 780 Welch Road, CJ250K, Palo Alto, CA, 94304, USA

    Biyao Zou, Mayumi Maeda, Khin Naing Thin, Scott D. Barnett, Ramsey C. Cheung & Mindie H. Nguyen

  3. Liver Center, Saga University Hospital, Saga, Japan

    Hirokazu Takahashi & Yuichiro Eguchi

  4. Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan

    Hirokazu Takahashi, Kenichi Tanaka & Yuichiro Eguchi

  5. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan

    Masayuki Kurosaki & Yuka Takahashi

  6. Yangon Specialty Hospital, Yangon, Myanmar

    Khin Naing Thin

  7. Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Yoshito Itoh & Yuya Seko

  8. Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan

    Kentaro Oniki & Junji Saruwatari

  9. Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan

    Miwa Kawanaka

  10. Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan

    Masanori Atsukawa

  11. Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hiroshima, Japan

    Hideyuki Hyogo

  12. Department of Internal Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan

    Masafumi Ono

  13. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan

    Eiichi Ogawa

  14. Lane Medical Library, Stanford University School of Medicine, Palo Alto, CA, USA

    Christopher D. Stave

  15. Palo Alto Veterans Affairs Healthcare System, Palo Alto, CA, USA

    Ramsey C. Cheung

  16. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan

    Hidenori Toyoda

Authors
  1. Takanori Ito
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  26. Mindie H. Nguyen
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Contributions

Guarantor of article: MHN. Specific author contributions: Study design: TI, MI, HT, and MHN. Data collection: all authors. Data analysis: BZ, SB, TT, TI, and MHN. Drafting of the article: TI and MHN. Data interpretation, review and/or revision of the manuscript: all authors. Study concept and study supervision: MHN.

Corresponding author

Correspondence to Mindie H. Nguyen.

Ethics declarations

Conflict of interest

Mindie Nguyen: Research grants: Enanta, Gilead, Pfizer; Consultation and/or advisory board with Gilead, Intercept. Junji Saruwatari: Research grants: Tsumura & Co. Eiichi Ogawa: Speaker's fee: Gilead Sciences, Abbvie. Ramsey C. Cheung: Research grants: Gilead. Hidenori Toyoda: Speaker's fee: Gilead Sciences, Abbvie, Bayer. All other authors have nothing to disclose.

Ethical standards

The study was performed according to the 1964 Declaration of Helsinki.

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The study was approved by the Institutional Review Board at Stanford University, Palo Alto, California, USA and at each participating study center.

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Ito, T., Ishigami, M., Zou, B. et al. The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995–2040. Hepatol Int 15, 366–379 (2021). https://doi.org/10.1007/s12072-021-10143-4

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  • DOI: https://doi.org/10.1007/s12072-021-10143-4

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