Nonalcoholic Fatty Liver Disease In Women Research Articles

The Effect of Menopausal Status, Insulin Resistance and Body Mass Index on the Prevalence of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is common and presents in a large proportion—up to 30%—of the global adult female population. Several factors have been linked with NAFLD in women, such as age, obesity, and metabolic syndrome. To extract appropriate details about the topic, we conducted an extensive search using various medical subject headings and entry terms including ‘Menopause’, ‘Non-alcoholic fatty liver disease’, ‘Insulin resistance’, and ‘BMI’. This exhaustive search resulted in a total of 180 studies, among which only 19 were able to meet the inclusion criteria. While most of these studies indicated a significant rise in NAFLD prevalence among postmenopausal women, two did not find strong evidence linking menopause with NAFLD. Moreover, it was observed that women with NAFLD had higher insulin resistance levels and BMIs compared to those without the condition. In summary, it is important to consider specific factors like risk profile, hormonal status, and age along with metabolic components when treating women presenting with NAFLD. There is need for data-driven research on how gender affects the sensitivity of biomarkers towards NAFLD as well as the development of sex-specific prediction models—this would help personalize management approaches for women, who stand to benefit greatly from such tailored interventions.

Abstract PO4-04-09: Incidence, prevalence, risk factors, and impact of fatty liver disease in metastatic HR+/HER2− breast cancer patients treated with Endocrine Therapy and CDK 4/6 Inhibitor

Abstract Background: In patients with early-stage breast cancer (BC), non-alcoholic fatty liver disease (NAFLD) is associated with increased recurrence, cardiovascular events, and non-cancer death. Endocrine therapy increases the risk of NAFLD. The impact of cyclin-dependent kinases 4/6 inhibitors (CDKi) combined with endocrine therapy on NAFLD and prognostic association in metastatic breast canceris unknown. Here, we characterize the incidence, prevalence, risk factors, and treatment outcomes of NAFLD in women with metastatic HR+/HER2- BC. Methods: We conducted a retrospective cohort study of patients with advanced HR+/HER2- BC receiving first line endocrine and CDKi at Princess Margaret Cancer Centre, Toronto, Canada between January 2018 – June 2022. Patients were excluded if they had liver disease, prior chemotherapy, or no access to CT scans. Demographic, treatment, toxicity, and survival data were extracted. Liver Attenuation Index (LAI) on contrast-enhanced portal venous phase CT scan was utilized.NAFLD was defined as LAI >25 HU. Univariable binary-logistic regression analysis wasused to assess independent predictive factors of NAFLD. Statistical significance was defined as p< 0.05. Quantitative significance was defined by the Burnand criteria. Time to treatment failure (TTF) was assessed using Cox proportional hazards modeling. Results: Of approximately 90 eligible patients, 40 are included in this analysis. Baseline demographics included median age 61 years, 72% post-menopausal, 58% de-novo metastatic disease, and 27% visceral disease. Of 40 patients, 28 (70%) had NAFLD at anytime (12 at baseline and 16 incident). Associations with NAFLD are shown in Table 1. Presence of NAFLD was associated quantitatively but not statistically with age > 65 (OR 2.6), post-menopausal status (OR 2.6), and inversely associated with prior chemotherapy (OR 0.27) and visceral disease (OR 0.38). Lack of NAFLD at any time was significantly associated with worse TTF (mean TTF 497 versus 1228 days, HR=4.28, 95% CI: 1.89-9.68, p< 0.001). Patients without NAFLD at baseline also had a worse TTF (mean 903 vs 1186 days) compared to those with it at baseline, but this difference was not statistically significance (HR=1.93, 95%CI: 0.77-4.83, p= 0.163). No significant differences were found in grade 3/4 adverse events. Patients who have presented NAFLD at any time received an average of 1.36 subsequent lines of therapy compared to 2.08 in those without. Discussion & Conclusion: This analysis demonstrated an association between presence of NAFLD and longer TTF. This may reflect reverse causation whereby longer exposure to ET and CDKi increases the observation of NAFLD or that these are distinct populations with different molecular pathways leading to differences in response to treatment and prognosis. It is noteworthy that the median time to develop NAFLD in the incident group was 339 days, and the group that never developed NAFLD was on treatment longer than this. Overexpression of CDK 4/6 pathway, could increase sensitivity and duration to treatment with CDKi but produce adverse metabolic changes of increased lipid synthesis, as described in pre-clinical models. If this hypothesis is confirmed, synergistically addressing these metabolic changes with physical exercise, dietary, or pharmacological interventions may improve these patients’ fitness for subsequent lines of therapy. Table 1 Citation Format: Diego Malon Gimenez, Consolacion Molto Valiente, Shopnil Prasla, Danielle Cuthbert, Abhenil Mittal, Faris Tamimi, Massimo Di Iorio, Meredith Li, Neha Pathak, Eitan Amir, Kartik Jhaveri, Michelle Nadler. Incidence, prevalence, risk factors, and impact of fatty liver disease in metastatic HR+/HER2− breast cancer patients treated with Endocrine Therapy and CDK 4/6 Inhibitor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-09.

Polyphenol consumption and Nonalcoholic fatty liver disease risk in adults

In this cross-sectional investigation, the primary objective was to explore the correlation between the consumption of polyphenols and the likelihood of non-alcoholic fatty liver disease (NAFLD) in the adult population participating in the Hoveyzeh cohort. Data from the Hoveyzeh cohort study, part of the Persian Cohort Study, involving 10,009 adults aged 35–70, were analyzed. Exclusions were made for missing data, extreme energy intake, and liver cancer patients. Dietary habits were assessed using a food frequency questionnaire, and polyphenol intake was calculated using the Phenol Explorer database. Logistic regression analyses, adjusted for confounders, were performed to assess the relationship between polyphenol subclasses (total polyphenols, total flavonoids, phenolic acid, and lignin) and NAFLD. Among 9894 participants, those in the highest quintile of total polyphenol (OR 0.65, CI 0.5–0.84; P = 0.007), phenolic acid (OR 0.67, CI 0.52–0.86; P < 0.001), and lignin intake (OR 0.69, CI 0.52–0.87; P = 0.001) demonstrated lower odds of NAFLD compared to the lowest quintile, even after adjusting for confounding factors. However, no significant association was found between total flavonoid intake and NAFLD (OR 1.26, CI 0.96–1.67; P = 0.47). Subgroup analysis indicated a significant inverse association between total polyphenols and NAFLD in women (OR 0.64, CI 0.42–0.93; P = 0.001). Higher intake of total polyphenols, phenolic acid, and lignin was associated with reduced odds of NAFLD among adults in the Hoveyzeh cohort. This suggests that dietary patterns rich in these polyphenols may play a role in mitigating the risk of NAFLD. Further interventional and longitudinal studies are needed to validate these findings and explore potential preventive strategies involving polyphenol-rich diets.

The Association between Educational Attainment and the Risk of Nonalcoholic Fatty Liver Disease among Chinese Adults: Findings from the REACTION Study.

: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. : A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. : Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. : In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Association between sleep duration and a new onset of nonalcoholic fatty liver disease.

Objective A short sleep duration is associated with non-alcoholic fatty liver disease (NAFLD). However, the causal relationship between a short sleep duration and the onset of NAFLD remains unknown because of the lack of any longitudinal studies. Therefore, we evaluated the association between sleep duration and the onset of NAFLD. Methods We evaluated health checkup data for 1,862 NAFLD-free Japanese adults aged 33-86 years at baseline and followed those individuals for a median of 41 months. Hepatic steatosis was examined using ultrasonography (US). The Cox proportional hazards model was used to evaluate the association between sleep duration and NAFLD onset. Results Among the 1,862 participants, 483 (25.9%) developed NAFLD. The proportion of women who developed NAFLD was the highest in the group with a sleep duration of <6 hours and lowest in the group with a sleep duration of 7 to <8 hours. The multivariable-adjusted hazard ratio (95% confidence interval) for the onset of NAFLD in women with a sleep duration <6 hours compared with those with a sleep duration of 7 to <8 hours was 1.55 (1.09-2.20; p=0.02). Conclusions In women, a short sleep duration was independently associated with the onset of NAFLD, thus suggesting that an adequate sleep duration can be a promising preventive factor for the onset of NAFLD in women.

Relationships between nonalcoholic fatty liver disease and polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD) are two common non-infectious pathologies. Their frequency and medico-social significance have increased significantly over the past decades and reflect the effects of radical changes in human lifestyle on human health in a transgenerational aspect. Due to absence a complete understanding of the etiology and pathogenesis of PCOS and NAFLD, modern medicine still does not have etiopathogenetic methods of treating these frequent diseases. Considering epidemiological and pathogenetic data PCOS and NAFLD can be regarded as related pathologies, which creates the prospect of improving the effectiveness of their management if the joint approach to scientific research and implementation of their results in medical practice is applied.The purpose of the review is to summarize the current scientific data on the common pathophysiological and clinical relationships between PCOS and NAFLD, which can contribute to improving the effectiveness management of both diseases.Pathogenetic relationships between PCOS and NAFLD are bidirectional. According to current data, it seems possible to consider PCOS as a significant risk factor for the development of NAFLD in women of reproductive age both in the presence of excess weight and with normal body weight.As is known, that liver is involved in the clearance of androgens by the formation of sex steroid-binding globulin, as well as in the inactivation of insulin. Disruption of these metabolic processes due to liver pathology can lead to the development or strengthening of biochemical and clinical hyperandrogenism and the development of hyperinsulinemia and insulin resistance (IR).Conclusions. The presence of fatty liver and especially steatohepatitis deepens the hormonal disorders inherent in PCOS (primarily, an increase of free androgens, IR and ovulatory dysfunction), as well as potentiates and accelerates the development of cardiometabolic complications, including atherogenic dyslipidemia, dysglycemia, metabolic syndrome and cardiovascular complications. Early detection of NAFLD in women with PCOS, regardless of the presence of obesity, may improve the effectiveness of PCOS management and prevention of its cardiometabolic risks.

Sex differences in the association between adipose insulin resistance and non-alcoholic fatty liver disease in Chinese adults

BackgroundAdipose insulin resistance (Adipo-IR) is associated with multiple metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). The study aimed to evaluate sex differences in the association between Adipo-IR and NAFLD, and further investigated other potential modifiers.MethodsThis cross-sectional study enrolled adults without diabetes who underwent physical examinations in Beijing Chao-Yang Hospital. We calculated the Adipo-IR index as the product of the fasting insulin and free fatty acid concentration. We categorized Adipo-IR into four groups according to quartiles, using the first interquartile range (Q1) as the reference. Logistic regression was used stratified by the modifiers after adjustment for potential confounders.ResultsThere were 5586 participants in the study, 49.8% (n = 2781) of whom were women and 30.4% (n = 1698) with NAFLD. There was a graded positive association between Adipo-IR and NAFLD, with sex (P = 0.01) and hyperlipidemia (P = 0.02) modifying this association. In the hyperlipidemic women, for one unit increase in log-Adipo-IR, the odds of having NAFLD increased by 385% after adjustment for potential confounders (OR = 4.85, 95%CI 3.54–6.73, P < 0.001). However, it turned out that the odds of having NAFLD increased by 131% (OR = 2.31, 95%CI 1.74–3.11, P < 0.001), 216% (OR = 3.16, 95%CI 2.56–3.93, P < 0.001), 181% (OR = 2.81, 95%CI 1.88–4.28, P < 0.001) in normolipidemic men, hyperlipidemic men, and normolipidemic women, respectively. Similarly, the ORs for the association between Adipo-IR and NAFLD in women with age ≥ 50 years were higher than ORs in women with age < 50 years.ConclusionsThe positive correlation between Adipo-IR and NAFLD was stronger in hyperlipidemic women, compared with normolipidemic or hyperlipidemic men, or normolipidemic women. The association also strengthened for women over 50 years. Treatment strategies targeting Adipo-IR to alleviate NAFLD may be of value, especially in hyperlipidemic women after menopause.

Antimullerian Hormone, a Marker of Ovarian Reserve, Is Protective Against Presence and Severity of NASH in Premenopausal Women

Antimüllerian hormone (AMH) is a marker of ovarian reserve with emerging data linking lower levels to some metabolic and inflammatory diseases in women. Whether AMH levels influence nonalcoholic fatty liver disease (NAFLD) is unknown. Leveraging the NASH Clinical Research Network we determined the association of AMH levels within 6 months of liver biopsy with presence and severity of histologic measures of NAFLD in premenopausal women. Outcomes included presence of nonalcoholic steatohepatitis (NASH), presence and severity of fibrosis, and NAFLD Activity Score and its components. Logistic and ordinal logistic regression models were adjusted for age, race/ethnicity, homeostatic model assessment for insulin resistance, body mass index, dyslipidemia, polycystic ovary syndrome, estrogen-progestin use, and menstrual cyclicity. Median cohort age was 35 years; 73% were white and 24% Hispanic. Thirty-three percent had diabetes, 81% had obesity, and 95% had dyslipidemia. On biopsy 71% had NASH, 68% had any fibrosis, and 15% had advanced fibrosis. On adjusted analysis (n= 205), higher AMH quartiles were inversely associated with NAFLD histology including prevalent NASH (adjusted odds ratio [AOR], 0.64; 95% confidence interval [CI], 0.41-1.00), NAFLD Activity Score ≥5 (AOR, 0.52; 95% CI, 0.35-0.77), Mallory hyaline (AOR, 0.54; 95% CI, 0.35-0.82), and higher fibrosis stage (AOR, 0.70; 95% CI, 0.51-0.98). The protective effects of AMH were more pronounced among women without polycystic ovary syndrome (n= 164), including lower odds of NASH (AOR, 0.53; 95% CI, 0.32-0.90) and any NASH fibrosis (AOR, 0.54; 95% CI, 0.32-0.93). AMH may reflect a unique biomarker of NASH in premenopausal women and findings suggest a novel link between reproductive aging and histologic severity of NAFLD in women.

Non-alcoholic fatty liver disease is associated with hyperandrogenism in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53–6.63) in FT; 1.12 (1.04–1.22) in FAI), FLI (OR 2.68 (95% CI 1.43–5.03) in FT; 1.13 (1.06–1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08–5.21) in FT; 1.5 (1.09–1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS.

Association between equol and non-alcoholic fatty liver disease in Japanese women in their 50s and 60s.

Equol is a metabolite of soy isoflavone and has estrogenic activity. The incidence of non-alcoholic fatty liver disease (NAFLD) increases after menopause in women, which is thought to result in a decrease in estrogen. This study aimed to evaluate the association between equol and NAFLD. We evaluated 1185 women aged 50-69years who underwent health check-ups at four health centers in Fukushima, Japan. Equol producers were defined by a urinary equol concentration of 1.0μM or more. In addition to comparison between equol producers and non-producers, the association between equol and NAFLD was estimated using logistic regression analysis adjusting for fast walking and eating habits. Of the 1185 participants, 345 (29.1%) women were equol producers. The proportions of women who had NAFLD (34.8% vs 45.2%) were significantly lower in the equol-producing group than in the non-producing group. Multivariable logistic regression analysis showed that equol production was significantly associated with NAFLD (odds ratio=0.66, 95% confidence interval: 0.51-0.86). Equol production was significantly associated with NAFLD in women in their 50s and 60s.

Long working hours and increased risks of lean non-alcoholic fatty liver disease among Korean men and women

Despite the increasing prevalence of lean nonalcoholic fatty liver disease (NAFLD), its risk factors are not well established. We examined the association between long working hours and incident NAFLD in lean Korean workers with emphasis on sex-based effect modification. This cohort study involved 46,113 non-overweight (BMI < 23 kg/m2) and NAFLD-free Korean workers (mean age, 35.5 years). Working hours were categorized into 35–40 (reference), 41–52, and ≥ 53 h. The presence of fatty liver and its severity were determined using ultrasonography and NAFLD fibrosis score (NFS), respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using parametric proportional hazards models. Incident cases of 5901 lean NAFLD developed over a median follow-up of 3.8 years. The incidence of lean NAFLD increased with increasing working hours with a stronger association in men than in women (P for interaction < 0.001). For men, multivariable-adjusted HRs (95% CIs) for lean NAFLD in time-dependent models comparing working hours of 41–52 and ≥ 53 h compared to the reference category were 1.17 (1.07–1.28) and 1.25 (1.12–1.39), respectively. The excess relative risk of developing lean NAFLD with intermediate/high NFS was observed in working hours of 41–52 and ≥ 53 h with a corresponding HR of 1.66 (1.13–2.43) and 1.54 (0.94–2.51), respectively. Conversely, no significant associations were found between working hours and incidence of lean NAFLD in women. In conclusion, long working hours were significantly associated with an increased incidence of lean NAFLD and its severe form in men but not in women.

Effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood: A systematic review and meta-analysis.

The risk of metabolic disease in adulthood is not only attributed to an unhealthy lifestyle after birth but also to famine exposure during the foetal period. This systematic review and meta-analysis aimed to evaluate the effects of foetal exposure to famine as a risk factor for developing nonalcoholic fatty liver disease (NAFLD) in adulthood. Studies were retrieved from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to evaluate the effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood. Six studies involving 90,582 subjects were included in this meta-analysis. Foetal exposure to famine was associated with an increased risk of NAFLD(RR=1.17, 95% CI: 1.08-1.27, P < 0.0001). Exposure to famine during the foetal period significantly increased the incidence of NAFLD in women (RR=1.27, 95% CI: 1.16-1.40, P <0.00001), while similar results were not observed in the male subgroup (RR =0.99, 95% CI: 0.89-1.11, P=0.88). Foetal exposure to famine was associated with the risk of mild NAFLD (RR=1.17, 95% CI: 1.02-1.33, P=0.02) and moderate to severe NAFLD (RR=1.51, 95% CI: 1.16-1.98, P=0.002). Foetal exposure to famine is associated with an increased risk of NAFLD in adulthood. Women with NAFLD and moderate to severe NAFLD have a more robust association with foetal exposure to famine.

Gender Differences in the Risk for Incident Non-Alcoholic Fatty Liver Disease According to the Transition of Abdominal Obesity Status: A 16-Year Cohort Study.

Waist circumference (WC) is an important predictor of long-term adverse outcomes. We aimed at assessing the correlation between abdominal obesity (AO) patterns and non-alcoholic fatty liver disease (NAFLD). Data from 4467 adults aged 40-69 years and without NAFLD who participated in the Korean Genome and Epidemiology Study were analyzed. Participants were classified according to two-year WC pattern into four groups: persistent lean WC, improved AO, progressed to AO, and persistent AO. NAFLD was defined as NAFLD-liver fat score >-0.640. Multiple Cox proportional hazards regression analysis revealed that the fully adjusted hazard ratio (HR) (95% confidence intervals (CIs)) for NAFLD in persistent AO, progressed to AO, and improved AO groups compared to the persistent lean WC group was 1.33 (1.13-1.57), 1.73 (1.48-2.02), and 1.06 (0.84-1.33), respectively. Women in persistent AO or progressed to AO groups had significantly higher risk for NAFLD than those in persistent lean WC or improved AO groups. Men who had progressed to an AO event over two years had significantly higher risk for NAFLD than those without any AO event over two years. Maintaining lean WC and improving AO would be successful strategies for preventing NAFLD in women, while maintaining lean WC would be more effective in men.

Fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease (25-30% of the global adult general population) with no approved treatment to-date, although its treatment is attractive for the researchers and the pharmaceutical industry. The cessation of ovarian function (natural or iatrogenic menopause, premature ovarian insufficiency) is associated with increased abdominal adipose tissue and changes in carbohydrate and lipid metabolism. These changes lead to a dysmetabolic milieu, characterized by unfavorable lipid profile and the development of NAFLD, which may contribute to the increase in cardiovascular risk observed after menopause. Not only the prevalence of NAFLD seems to be higher in postmenopausal compared with premenopausal women, but also the rates of advanced types of the disease, i.e., nonalcoholic steatohepatitis and hepatic fibrosis, the latter regarded as the main histological prognostic factor of advanced liver disease and a difficult-to-reverse target. These observations may render menopausal hormone therapy (MHT) an appealing way to retard or even restore NAFLD after menopause. Although there are some experimental data favoring this consideration, there are only a few interventional clinical studies evaluating the effect of MHT on NAFLD, which have provided conflicting results. Some of them showed encouraging effects of MHT on liver function tests and/or lower rates of NAFLD in women receiving as compared with those not receiving MHT. However, other studies showed that MHT may adversely affect NAFLD. Regarding the route of administration of MHT, there are currently not comparative data between per os and transdermal use on NAFLD. Until waiting for the publication of relevant studies, based on the favorable effect of transdermal MHT on triglyceride concentrations and the fact that high triglyceride and low high-density lipoprotein-cholesterol concentrations are associated with the severity of NAFLD, the use of transdermal MHT may be preferred in women with NAFLD after the cessation of ovarian function. Of course, MHT could not be recommended as standard treatment of NAFLD in women, because MHT may be used for a certain time frame in a woman’s life. However, given that NAFLD seems to be common after the pause of ovarian function, any potential effect of MHT on NAFLD may be considered before treatment initiation and during the follow-up of these women.

The triglycerides and glucose index is highly associated with non-alcoholic fatty liver disease in overweight and obese women.

Although some previous studies have indicated that the triglycerides and glucose (TyG) index is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), there are still few studies in this field. The goal of this study was to assess whether the TyG index is associated with the presence of non-alcoholic fatty liver disease NAFLD in overweight and obese women. Overweight and obese women aged 20 to 65years were enrolled in a cross-sectional study and allocated into the groups with and without NAFLD. Alcohol consumption, pregnancy, normal-weight, positive markers of viral or autoimmune hepatitis, acute or chronic liver disease, renal disease, cardiovascular disease, neoplasia, and intake of hepatotoxic drugs were exclusion criteria. The diagnosis of NAFLD was established by liver ultrasound and the TyG index was calculated as the Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. A total of 420 participants were enrolled and allocated into the groups with (n = 212) and without (n = 208) NAFLD. In the overall population, the frequency of NAFLD was 50.4%. The logistic regression analysis adjusted by body mass index, waist circumference, and total body fat showed that total cholesterol (OR = 1.004; 95% CI: 1.000-1.007), triglycerides (OR = 1.002; 95% CI: 1.000-1.004), AST (OR = 1.19; 95% CI: 1.15-1.23), ALT (OR = 1.20; 95% CI: 1.15-1.25), and TyG index (OR = 3.15; 95% CI: 1.64-6.06) are significantly associated with NAFLD. The results show that the TyG index is highly associated with the presence of NAFLD in women with overweight and obesity.

Adiponectin–leptin ratio for the early detection of lean non-alcoholic fatty liver disease independent of insulin resistance

Background Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin–leptin ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance. Materials and methods A total of 575 adults without diabetes were enrolled in a community-based study. The subjects were stratified into the lean controls, lean NAFLD, simple overweight/obesity and overweight/obesity NAFLD groups according to body mass index (BMI) and ultrasonographic fatty liver indicators. Serum adiponectin and leptin levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD in relation to the tertiles of serum AL concentration after adjustment. Receiver operating characteristic (ROC) analyses were applied to evaluate the diagnostic performance of the AL ratio for NAFLD. Results The mean age of the participants was 42.8 ± 11.5 years. Comparing with the lean controls, the odds of having lean NAFLD for the highest versus the lowest tertile of AL ratio was 0.28(95%CI: 0.12–0.69) after adjustment. Putting AL ratio, BMI, triglyceride, AST/ALT ratio to the diagnosis performance of NAFLD, the ROC was 0.85 (95% CI: 0.82–0.88), 0.83 (95% CI 0.78–0.87) and 0.86 (95% CI 081–0.91) for all NAFLD, NAFLD in women and NAFLD in men, respectively. (p < .001). Conclusions The study revealed that the AL ratio could be a good biomarker to early distinguish lean NAFLD patients from lean controls independent of insulin resistance. [AQ3] Key messages The prevalence of non-alcoholic fatty liver disease (NAFLD) increases globally and is related to liver diseases and metabolic dysfunctions. Lean subset of NAFLD shares a similar disease burden to those of their overweight counterparts and should be detected early. Adiponectin–leptin ratio were associated with the severity of steatosis and was a predictor of obese NAFLD better than each single adipokine. To date, there is no investigation that explores specifically for the relationship between lean NAFLD and AL ratio. Our study found that adiponectin–leptin ratio is a sole independent marker regardless of insulin resistance in lean NAFLD. Having lean NAFLD for the highest versus the lowest tertile of adiponectin–leptin ratio was 0.28(95%CI: 0.12–0.69) after adjustment of age, sex, current smoking, exercise habits, HOMA-IR and AST/ALT. ROC for the NAFLD performance is good for the early detection (0.85; 95% CI: 0.82–0.88). Further rigorous investigation is necessary and should be promptly performed.

Association between perfluoroalkyl substances exposure and the prevalence of nonalcoholic fatty liver disease in the different sexes: a study from the National Health and Nutrition Examination Survey 2005-2018.

There is evidence that perfluoroalkyl substances (PFASs) have effects on liver toxicity, and the effects may exhibit sex differences. Our study aims to explore the association between exposure to four PFASs (perfluorooctanoic acid, PFOA; perfluorooctane sulfonate, PFOS; perfluorohexane sulfonate, PFHxS; and perfluorononanoate, PFNA) and the risk of nonalcoholic fatty liver disease (NAFLD) in adults ≥ 20years old in the US population. The data were based on the National Health and Nutrition Examination Survey (NHANES) 2005-2018. We used Poisson regression to explore the association between the four PFASs and NAFLD. We included 3464 participants; of these, 1200 (34.64%) individuals were defined as having NAFLD, and the prevalence of NAFLD was 39.52% in men and 30.40% in women. After Poisson regression, among the premenopausal and postmenopausal and total women, PFOA had a significantly positive association with NAFLD (p < 0.05). After principal component analysis, the "composite PFAS" was associated with NAFLD in postmenopausal and total women, and the RRs (95% CIs) were 1.306 (1.075, 1.586) and 1.161 (1.007, 1.339), respectively. In adults, we found that PFASs were associated with NAFLD, and the associations varied by sex, particularly for PFOA and PFNA, which had a positive association with NAFLD in women.

Abstract 12413: Type 2 Diabetes Mellitus and Congestive Heart Failure in Women Are Mutually Independent Predictors of Non-alcoholic Fatty Liver Disease

Introduction: Non-alcoholic fatty liver disease (NAFLD) is associated with both type 2 diabetes mellitus (T2DM) and congestive heart failure (CHF), and T2DM is highly prevalent in CHF patients, in particular among women. However, the single and joint associations of T2DM and CHF with NAFLD in women have not been investigated yet. Hypothesis: We hypothesize that congestive heart failure and T2DM are independent predictors of NAFLD in women. Methods: We investigated 76 female patients with CHF and 321 female controls who did not have signs or symptoms of CHF and in whom significant coronary artery disease was ruled out angiographically. The presence of NAFLD was determined using the validated fatty liver index (FLI). Results: The prevalence of T2DM was 39.5% in women with CHF and 22.1% in controls (p=0.002). FLI values and prevalence rates of NAFLD (FLI≥60) in non-CHF women without T2DM were 43±28 and 31.6%, respectively. They were significantly higher in non-CHF, but T2DM patients (65±28, p&lt;0.001 and 64.8%, p&lt;0.001, respectively), in CHF patients without T2DM (67±25, p&lt;0.001 and 63.0%, p=0.002, respectively) and in CHF patients with T2DM (66±31, p&lt;0.001 and 66.7%, p&lt;0.001, respectively). In multivariate analysis of covariance, T2DM and CHF proved to be mutually independent predictors of FLI after adjustment for age, sex, BMI, LDL-C, history of smoking and hypertension and use of statins (F=7.25; p=0.007 and F=46.89; p&lt;0.001, respectively); concordantly, T2DM and CHF independently predicted the presence of NAFLD in logistic regression analyses, with adjusted odds ratios of 3.22 [1.38-7.50]; p=0.007 and 21.71 [6.58-71.59]; p&lt;0.001, respectively. Conclusions: We conclude that CHF and T2DM are mutually independent predictors of NAFLD in women.

Elevated Serum Low-Density Lipoproteins-Cholesterol Levels and B1B2/B2B2 CETP Genotype Are Positively Associated with Nonalcoholic Fatty Liver Disease in Women with Gallstone Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is generated by the interaction between environmental and genetic factors, and the presence of metabolic alterations. Since Taq1B cholesteryl ester transfer protein (CETP) polymorphism is associated with abnormal serum lipid values, it could be related to NAFLD. The aim of this study was to determine the role of the Taq1B CETP polymorphism with serum lipids, anthropometric variables, and the extent of steatosis in Mexican-mestizo women with gallstone disease (GD). Methods: Sixty-two women were enrolled in this cross-sectional study. Serum lipids were determined by dry chemistry. The Taq1B CETP polymorphism was determined by allelic discrimination. CETP serum levels were measured by enzyme-linked immunosorbent assay, and the extent of steatosis with a biopsy staining with Oil-Red-O. Results: Subjects with the B1B2/B2B2 genotype had higher percentage of degree of steatosis than those with B1B1 (11.95% vs. 2.19%, P = 0.008). The B1B2/B2B2 genotype (odds ratio [OR] 3.90 [confidence interval {CI} 95% 1.891-8.536], P = 0.04) and an elevated low-density lipoproteins (LDL)-cholesterol (OR 3.54 [CI 95% 1.042-2.058, P = 0.039) significantly increase the risk for NAFLD. Conclusions: This study provides evidence that the B1B2/B2B2 genotype of CETP and the elevated LDL-cholesterol serum levels increase the risk of NAFLD in women with GD.

Sex-specific metabolic risk factors and their trajectories towards the non-alcoholic fatty liver disease incidence.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. This study examined sex-specific associations between NAFLD and metabolic factors and investigated the trajectory of risk factors. We retrospectively investigated 16,140 individuals from Beijing Health Management Cohort. Univariate and multivariate time-dependent Cox regression analyses were performed to identify independent risk factors for new-onset NAFLD. The trajectory of risk factors was investigated using the latent growth curve model and growth mixture model. Over a median follow-up of 3.15years, 2,450 (15.18%) participants developed NAFLD. The risk factors for NAFLD in men were increased body mass index (BMI); waist circumference (WC); triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), haemoglobin (Hb), and serum uric acid (SUA) levels; and platelet (PLT) count and decreased serum creatinine-to-body weight (sCr/bw) and high-density lipoprotein cholesterol (HDL-C) levels. In women, the risk factors were increased BMI, WC, and fasting plasma glucose (FPG), TG, LDL-C, SUA, white blood cell (WBC), and PLT and decreased sCr/bw and HDL-C levels. In addition, BMI, LDL-C, sCr/bw and PLT changing trajectories were associated with NAFLD in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends was associated with NAFLD risk in women. Development of NAFLD is associated with BMI, LDL-C, sCr/bw and PLT changing trajectories in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends are associated an increased risk of NAFLD in women. Deterioration of metabolic risk factors status can be a predictor of NAFLD many years before its occurrence.