Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis
Open accessAbstract
UNLABELLED: Estrogens inhibit stellate cell activation and fibrogenesis. Thus, gender and reproductive states may influence the degree of fibrosis in patients with nonalcoholic steatohepatitis (NASH). To investigate the association between gender, menopause, and the severity of liver fibrosis in patients with NASH, we analyzed 541 adult patients enrolled from our Duke Liver Clinics (n = 338) and the Duke Metabolic and Weight Loss Surgery Program (n = 203) who had a histologic diagnosis of NASH. Multiple ordinal logistic regression models were used to assess the association between gender, menopause, and severity of liver fibrosis. Overall, men, premenopausal, and postmenopausal women composed 35.1%, 28.4%, and 36.5% of the population, respectively. The mean age was 48 years and 22% had advanced fibrosis. After adjusting for covariates (enrolling site, grades of portal inflammation, and hepatocyte ballooning) and potential confounders (race, body mass index, diabetes/prediabetes, hypertension), adjusted cumulative odd ratio (ACOR) and 95% confidence interval (CI) for greater fibrosis severity was 1.4 (0.9, 2.1) (P = 0.17) for postmenopausal women and 1.6 (1.0, 2.5) (P = 0.03) for men, having premenopausal women as a reference. There was borderline interaction between gender and age group divided by age 50, the average age at menopause in the U.S. (P = 0.08): ACOR and 95% CI of having greater fibrosis severity in men compared to women was 1.8 (1.1, 2.9) for patients with age <50 years (P = 0.02) and 1.2 (0.7, 2.1) for patients with age ≥50 years (P = 0.59). CONCLUSION: Men are at a higher risk of having more severe fibrosis compared to women before menopause, while postmenopausal women have a similar severity of liver fibrosis compared to men. These findings may be explained by the protective effects of estrogen against fibrogenesis.
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Women aged >50 years have increased odds of advanced fibrosis due to MASLD even after adjustment for covariates.
“Women aged > 50 years have increased odds of advanced fi brosis due to MASLD even after adjustment for covariates.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [68]
The Results report increased odds of more severe fibrosis among women aged ≥50 after adjustment for enrolling site and histologic covariates (ACOR 1.8, p<0.01). With additional potential confounders included, the association was only a trend (ACOR 1.5, p=0.06). The study examined patients with NASH, not the broader MASLD population, and used ≥50 rather than >50 as its cutoff. (LLM, conf=0.88)
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- Authors
- Yang, J. D., Abdelmalek, M. F., Pang, H., Guy, C. D., Smith, A. D., Diehl, A. M., & Suzuki, A.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Duke Medical Center (US)
- Duke University (US)
- Central Arkansas Veterans Healthcare System (US)
- Corresponding author
- Suzuki, Ayako
- ORCID
- Venue
- Hepatology
- Published
- 2014-04
- Volume
- 59
- Issue
- 4
- Pages
- 1406-1414
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC3966932
- OpenAlex
- W2015802619
- Cited by
- 374
- References
- 31
- Citations by year
- 2026: 24 · 2025: 44 · 2024: 37 · 2023: 41 · 2022: 41 · 2021: 38 · 2020: 32 · 2019: 30 · 2018: 22 · 2017: 21 · 2016: 14 · 2015: 21 · 2014: 8
- FWCI
- 10.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- NIH/NIDDK (U01-DK57149, K23-DK062116)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- nonalcoholic steatohepatitis, liver fibrosis, menopause, sex differences, postmenopausal women, estrogen, fibrogenesis, stellate cell activation, fibrosis severity
- MeSH terms
- Adult, Age Factors, Biopsy, Cross-Sectional Studies, Fatty Liver, Female, Humans, Liver, Liver Cirrhosis, Male, Menopause, Middle Aged, Severity of Illness Index, Sex Factors, Estrogen Replacement Therapy, Logistic Models, Non-alcoholic Fatty Liver Disease
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