Background: Non-alcoholic fatty liver disease (NAFLD) has long been
considered to be most prevalent chronic hepatic disease. However, the overall
prevalence of NAFLD in postmenopausal women was largely unknown.
Objectives: In the current study, we aimed to investigate the overall
prevalence of NAFLD in postmenopausal women in order to provide more information
for clinical work. Methods: A systematic search was conducted in
Medline, Embase, web of science and Cochrane for articles in the English language
from inception until May 2020. Wilson score method was used to calculate the 95%
confidence interval (95% CI) and DerSimonian-Laird random-effects model with
Freeman-Tukey double arcsine transformation was used for estimating pooled
overall prevalence. Results: Our search returned 4465 records. After
removed duplicates and screened titles, abstract and full content of articles, 25
studies were retrieved. Overall, the NAFLD prevalence was 30.81% (95% CI
24.75-37.22). The prevalence of NAFLD in postmenopausal women was 31.64% (95%
CI 25.82-37.77) in Asia countries compared to 27.99% (95% CI 11.21-48.72) in
Non-Asia countries. Ultrasound was the most commonly used diagnostic technique in
diagnosing NAFLD in postmenopausal women, lead a higher prevalence of NAFLD
(32.77%, 95% CI 27.43-38.35) than computed tomography (CT, 5.64%, 95% CI
4.82-6.52) or fatty live index (FLI, 17.33%, 95% CI 11.72-23.78, P
Non-alcoholic fatty liver disease (NAFLD), once considered a disease of western, now is affecting the global population [1, 2]. Although NAFLD has a benign course in the majority of individuals, a subset of patients develops non-alcoholic steatohepatitis (NASH), a more serious form of liver damage with various degrees of fibrosis. They can further develop into end-stage liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC) [3]. Given its high prevalence among general population, even a small proportion of patients developing end-stage liver disease will impose an emerging global health burden.
Liver diseases increased in parallel to age, and its prevalence increased among woman aged range from 40 to 49 years and post menopause, indicating that the metabolism of sexual steroid hormones might play a vital role in NAFLD pathogenesis in woman [4]. Previous studies documented that drastic physiological and biological changes occurred in postmenopausal woman which including fat accumulation and unfavorable metabolic alterations (e.g., dyslipidemia and glucose intolerance), both of which are associated with development of insulin resistance, cardiovascular disease and NAFLD [5, 6, 7]. In this manner, a heightened awareness of complications of metabolic and hormonal changes and their associations with chronic disease is necessary in the evaluation and care of women who are postmenopausal. In current study, we pooled estimates of NAFLD prevalence for postmenopausal women so as to assist stakeholders with bettering comprehend the current circumstances of NAFLD in postmenopausal, which could prompt the advancement of methodologies to build disease mindfulness and intercessions to diminish the ailment trouble. Future investigation ought to be given to defining the economic and public health burden of the NAFLD pandemic.
Systematic search was conducted by a biomedical information specialist of the medical library in database of Medline, Embase, web of science and Cochrane, with an comprehensive arrangement of search terms identified with “NAFLD”, “postmenopausal”, “prevalence”, “epidemiology”. Current study was reported in conformity to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) [8]. Institutional review board approval was not required because our study only included previous published data.
Studies were included in the event that they met following criteria: (1) studies concerning about the prevalence of NAFLD in postmenopausal woman; (2) more than 30 individual included; (3) NAFLD diagnosed by imagological examination (ultrasound, computed tomography scan, and magnetic resonance imaging/spectroscopy), liver biopsy, and/or blood testing/predictive indices (fatty liver index or hepatic steatosis index), transient elastography.
Studies were excluded as follows: (1) Studies are review, systematic review, correspondence, meta-analysis, case reports, perspectives and abstracts; (2) animal study; (3) no primary data or incomplete data; (4) duplicate data; (5) the studies did not identify patients with NAFLD; (6) investigations included other cause of fatty liver disease (e.g. Wilson liver disease or viral hepatitis B and C infection); (7) excess alcohol consumption; (8) patients with preexisting diseases, such as human immunodeficiency virus (HIV) co-infected.
Two authors (XX and LY) worked independently to identify eligible studies, make an assessment of the methodological validity for candidate study, and extracted data by using a specially designed collection forms developed for this study. The authors settled discrepancies by jointly inspecting the study being referred to. On the off chance that no accord was reached, a third author (LH), unaware of prior determinations, worked as an arbiter.
Two authors (XX and YL) independently reviewed and extracted data from the included studies by utilizing the data extract form. When duplicate data were identified, the duplicate with the smallest sample size or shortest duration of follow-up were excluded. The most important part for this meta-analysis was the prevalence of NAFLD in postmenopausal women. In addition, we pooled estimate the prevalence in subgroups, including different countries, continents, country development, country income, study period, study quality and diagnostic techniques. Besides, we also pooled estimate the prevalence of complications among NAFLD patients.
Newcastle-Ottawa Scale, which is comprised of three domains (selection, comparability, and outcome), was used to assess the quality of included studies. This scale assigns a maximum score of five for selection, two for comparability, and two for outcome. Studies scoring 1-3, 4-6 and 7-9 were defined as low quality, average quality and high quality, respectively [9]. To increase transparency and ensure all accessible data in this area was reported, studies were not excluded on the basis of their quality score (Supplementary Table 1 and 2).
All the pooled estimates in current meta-analysis were calculated by using the
Metaprop [10] module in the R-3.5.3 statistical software package. Wilson score
method was used to calculate the 95% confidence interval (95% CI) and
DerSimonian-Laird random-effects model with Freeman-Tukey double arcsine
transformation was used for calculating pooled estimates of prevalence.
Heterogeneity across the included studies was assessed using the Cochran Q
statistics and I
Our search returned 4465 records. 3872 records were retained after removal of duplicates. We screened the titles and abstracts and excluded 3677 ineligible records. Full texts of the remaining 195 records were assessed for eligibility, of which 170 studies were excluded. As a result, 25 studies fulfill our inclusion criteria (Fig. 1).
The flow chart of literature retrieval.
The mean quality of the including studies was 7.76. As a result, 24 high quality and 1 fair quality studies were further included in meta-analysis. All of these included studies were cross-sectional studies in general population by health checkup.
Overall, 25 studies from 7 countries (China [n = 8], Japan [n = 1], South Korea
[n = 100], Mexico [n = 1], USA [n = 1], Montenegro [n = 1], Brazil [n = 3])
comprised of 21550 individuals [11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35]. A total of 5457 participates were
diagnosed as NAFLD with a pooled estimate prevalence rate of 30.81% (95% CI
24.75-37.22, I
Overall non-alcoholic fatty liver disease prevalence among postmenopausal women.
Subgroup analysis for non-alcoholic fatty liver disease prevalence among postmenopausal women.
For subgroup analysis, the prevalence of NAFLD in postmenopausal women was
31.64% (95% CI 25.82-37.77, I
Pooled estimate of prevalence for complications among postmenopausal women with non-alcoholic fatty liver disease.
This systematic review and meta-analysis comprised of 25 studies in order to determine the NAFLD prevalence in postmenopausal woman. From the available data, we estimated that about one third of postmenopausal woman presented with NAFLD. The prevalence of NAFLD in postmenopausal women was 31.64% (95% CI 25.82-37.77) in Asia countries compared to 27.99% (95% CI 11.21-48.72) in Non-Asia countries. Interestingly, we also found that postmenopausal woman diagnosed by US lead a higher prevalence of NAFLD than CT or FLI. Adipose development and deposition was regulated and adjusted by estrogen in women.
Estrogen may support subcutaneous deposition of adipose, thus leading to increased subcutaneous fat and total body fat in women as compared to men [36]. Before menopause, the accumulation of visceral fat among women appears to be inhibited. Yet both the fat distribution and menopause shifted in tandem with age. Women are getting subcutaneous abdominal fat with increased age. After menopause total body fat and visceral fat rise while energy and physical activity decrease [7]. While research indicated that woman developed NAFLD 10 years later than man due to the deficiency of estrogen, the prevalence of NAFLD in postmenopausal was still largely unknown. In the current study, we observed a higher prevalence of NAFLD among postmenopausal women than in general population [37].
The effect of the diagnostic modality used to diagnose NAFLD was one of the
important findings in the current research. Of a technique note, the only gold
standard to diagnose NAFLD is liver biopsy. However, due to its invasiveness and
high cost, it cannot be performed in a large-scale population. Of the imaging
techniques, CT and MRI used for detecting the hepatic steatosis revealed parallel
sensitivity and specificity (
This study has several strengths. This is a comprehensive and up-to-date systematic review and meta-analysis revealing the overall epidemiology of NAFLD in postmenonesaul women. Besides, we also added some new pooled estimation of complications in postmenonesaul women with NAFLD. The limitation for this study including the paucity of information from some continents, like Africa and Oceania which cannot truly reflect the real epidemiology of NAFLD in postmenonesaul women. Besides, unexplained high heterogeneity exists in current study. Although some potential reasons, like diagnostic technique, quality assessment of studies, countries development or countries income could partially explain it. Some other possibilities, like the proficiency and experience of the doctors for diagnosing that cannot take into account in our meta-analysis.
In summary, current meta-analysis indicated a rather high prevalence of NAFLD in postmenonesaul women which calls for the attention of primary care physicians, specialists, and health policy makers.
XX and YL performed the study, acquisition and analysis of data. XX, YL, YW and LH discussed the data; conceive the idea, revising the manuscript and provided technical assistance. XX drafted the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approve the final manuscript.
We would like to express our gratitude to all those who helped us during the writing of this manuscript.
The authors declare no conflict of interest.