Polycystic ovary syndrome with hyperandrogenism as a risk factor for non-obese non-alcoholic fatty liver disease.

Lean Fatty Liver Disease: Through Thick and Thin

To investigate the effect of obesity on nonalcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS). The patient data were acquired from 306 women with PCOS by Rotterdam consensus criteria and 286 women selected as controls. Basal endocrine, oral glucose tolerance test (OGTT), insulin release test, lipid profile, blood pressure and body mass index (BMI) were tested. The essays of liver chemistries, B-hepatitis and c-hepatitis were performed and alcoholic liver diseases excluded. Fatty liver was diagnosed by ultrasound. Patients with PCOS showed a higher prevalence of NAFLD than control group (30.7% vs 17.5%), including 56 mild cases (59.6%), 34 moderate cases (36.2%) and 4 severe cases (4.2%). The prevalence of NAFLD in PCOS increased with BMI, waist hip ratio, triglyceride and HOMA-IR. The prevalence of NAFLD in abdominal obese PCOS patients was significantly higher than those with normal waist. In addition to the prevalence of insulin resistance, metabolic syndrome in PCOS women significantly increased with BMI. These findings indicate that Chinese women with PCOS have a high prevalence of NAFLD, especially in abdominal and II obese PCOS patients. The prevalence and severity of NAFLD are positively correlated with BMI. It seems that insulin resistance and metabolic abnormalities are closely associated with NAFLD in PCOS. It is essential to give a high priority to the screening and treatment of NAFLD in obese PCOS patients.

Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis

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.

Non-alcoholic fatty liver disease (NAFLD) is an insidious pathologic condition that can manifest from simple steatosis to steatohepatitis (NASH) with potential progression to cirrhosis. Like the polycystic ovary syndrome (PCOS), NAFLD is associated with obesity, diabetes mellitus, insulin resistance and metabolic syndrome. PCOS women have an increased risk of NAFLD, but it is debatable which features of PCOS, either specific (androgen excess) or unspecific (metabolic derangements) affect the NAFLD risk. We performed a systematic review and meta-analysis of studies that addressed the association of PCOS and NAFLD. We selected 17 studies published between 2007 and 2017 that included 2734 PCOS patients and 2561 controls of similar age and body mass index (BMI). PCOS patients have increased prevalence of NAFLD (odds ratio 2.54, 95% confidence interval 2.19-2.95). PCOS women with hyperandrogenism (classic phenotype) have a higher prevalence of NAFLD compared to women with PCOS without hyperandrogenism, even after correction for confounding variables. Among women with PCOS, those with NAFLD have higher serum total testosterone (mean difference 0.40 nmol/L, 95% CI 0.29-0.50 nmol/L) and free androgen index (mean difference 4.46, 95% CI 3.53-5.39) than those without NAFLD. The studies that used multivariate analysis controlling for age, BMI, triglycerides, and insulin resistance index confirmed that serum androgens are independent predictors of NAFLD in women with PCOS. The prevalence of NAFLD is increased in women with PCOS and the presence of NAFLD is associated with high serum androgen levels, in addition to obesity and insulin resistance.

IntroductionSince there is a paucity of data on the epidemiology of the non-alcoholic fatty liver disease (NAFLD), particularly in rural areas in Asia, we undertook such a study among the...

Nonalcoholic Fatty Liver Disease: Indian Perspective.

Abnormal aminotransferase activity in women with polycystic ovary syndrome

BackgroundNon-obese non-alcoholic fatty liver disease (NAFLD) has been reported to share clinical outcomes with its obese counterpart in the general population. However, conflicting results have been observed regarding the cardio-metabolic risk profile of non-obese NAFLD as compared to obese NAFLD. Moreover, in the context of type 2 diabetes mellitus (T2DM), this issue has been even less addressed. We hence aimed to examine the association of NAFLD with the cardio-metabolic risk profile in patients with T2DM according to their obesity status.MethodsA total of 2,708 patients with T2DM who were hospitalized between June 2018 and May 2021 were cross-sectionally assessed.ResultsThe prevalence of NAFLD was 49.3%. NAFLD was found in 34.1% of non-obese patients and 66.0% of obese patients. Non-obese NAFLD patients had more and worse metabolic disorders than obese patients without NAFLD in both men and women. Comparable cardio-metabolic risk profiles were noted between non-obese and obese NAFLD subjects. The associations of worse cardio-metabolic risk profiles with NAFLD were overall stronger in non-obese than in obese subjects among women with T2DM, while more pronounced in obese than in non-obese subjects among men with T2DM.ConclusionIn patients with T2DM, non-obese NAFLD had no better cardio-metabolic risk profile than obese NAFLD. The associations of metabolic disorders with NAFLD were stronger in non-obese than in obese patients in women patients with T2DM.

Objective To compare the prevalence of non-alcoholic fatty liver disease (NAFLD) in women with or without polycystic ovary syndrome (PCOS), and to evaluate association between PCOS and NAFLD. Methods A cross-sectional study was performed including 122 PCOS patients (PCOS group) and 107 age, and body mass index (BMI)-matched women (control group). Anthropometric parameters, liver enzyme, lipid profile, glucose and insulin levels, sex hormones and hepatic ultrasonography were measured in all subjects. The clinical features, laboratory parameters and prevalence of NAFLD were compared between PCOS group and control group. The related factors were evaluated between PCOS and NAFLD, finally the role of insulin resistance (IR) and hyperandrogenism (HA) was analysed. Results Women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (62.6% vs. 76.2%, P=0.025). Logistic regression found that HOMA-IR and FAI were associated with NAFLD in PCOS women (OR=1.686, 95% CI=1.279-2.223; OR=1.167, 95% CI=1.039-1.311), however, there was no significant correlation between FAI and NAFLD after adjustment for HOMA-IR (P>0.05). Conclusion NAFLD is more prevalent in women with PCOS than in those without. Insulin resistance and HA drive risk of NAFLD in young female with PCOS. IR may be an independent risk factor for NAFLD, and the association between HA and NAFLD is not independent but is mediated by IR. Key words: Polycystic ovary syndrome; Non-alcoholic fatty liver disease; Insulin resistance; Hyperandrogenism

These recommendations are based on the following: (1) a formal review and analysis of the recently published world literature on the topic [Medline search up to June 2011]; (2) the American College of Physicians’ Manual for Assessing Health Practices and Designing Practice Guidelines; (3) guideline policies of the three societies approving this document; and (4) the experience of the authors and independent reviewers with regards to NAFLD. Intended for use by physicians and allied health professionals, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible and adjustable for individual patients. Specific recommendations are evidence-based wherever possible, and when such evidence is not available or inconsistent, recommendations are made based on the consensus opinion of the authors. To best characterize the evidence cited in support of the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1). The strength of recommendations in the GRADE system is classified as strong (1) or weak (2). The quality of evidence supporting strong or weak recommendations is designated by one of three levels: high (A), moderate (B) or low-quality (C). This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently.

Polycystic ovary syndrome (PCOS) is a prevalent condition in women of reproductive age. It is characterized by androgen excess and chronic anovulation. Some trace elements, macroelements, and heavy metals have been linked to pathophysiological mechanisms of PCOS .
 To study the alterations in the serum levels of the trace element manganese (Mn), some macroelements, magnesium(Mg) and calcium (Ca), and the heavy metals cadmium (Cd) and lead (Pb), in obese and non-obese PCOS patients; and the association of these alterations with some of the hormonal changes occurring in PCOS.
 The study was carried out at Kamal Al-Samarrai Hospital (Center for Infertility treatment and in vitro Fertilization "IVF") Baghdad- Iraq. Eighty-two women were enrolled in the study. Fifty-four of them were diagnosed by a specialist gynecologist as PCOS patients; they were subdivided into two subgroups according to their body mass index (BMI); twenty-seven obese PCOS patients with BMI > 30 kg/m2, and another twenty seven non obese patients PCOS with BMI <30 kg/m2. Whereas, twenty-eight apparently healthy women with regular menstruation and of comparable age, were selected to serve as control groups; they were subdivided into, fourteen obese women with BMI > 30kg/m2, and fourteen non obese women with BMI <30 kg/m2.
 Blood lead and cadmium levels were significantly higher in both of the obese and the non-obese PCOS groups, than in their corresponding control groups. While, serum magnesium, calcium and manganese levels were significantly lower in both of the obese and the non-obese PCOS groups, as compared to their corresponding control groups. The results revealed no significant difference in the levels of the measured elements, between the obese PCOS group and the non-obese PCOS group. The serum FSH levels was significantly lower in obese PCOS patients than in the obese and non-obese control groups. There was a positive correlation between blood lead and serum TSH levels in non-obese PCOS women; and between serum total testosterone and cadmium levels in obese PCOS women. Finally, there was negative correlation between serum magnesium and serum LH levels in non-obese PCOS women.
 the study has demonstrated higher blood levels of lead and cadmium; and lower serum levels of magnesium, calcium and manganese in PCOS groups than control subject. There were no significant differences between obese PCOS women and non-obese PCOS women in the levels of the studied hormones, elements and heavy metals.

Background: While commonly associated with obesity, non-alcoholic fatty liver disease (NAFLD) is increasingly recognized in non-obese individuals, but data are limited. Using a systematic review and meta-analytic approach, we determined the global prevalence, incidence, and clinical outcomes of NAFLD in non-obese or lean persons. Methods: We searched four databases (PubMed, EMBASE, SCOPUS, and the Cochrane Library) from inception to May 1, 2019 and included relevant original research articles without language restriction. Literature search and data extraction performed independently by two investigators. Findings: We found a total of 134 studies (N=11,947,163) from 26 countries/areas: 124 (N=11,799,621) for prevalence analysis, 14 (N=110,588) for incidence analysis, and eight (N=36,954) for outcome analysis. Within the NAFLD population, non-obese (lean plus overweight) NAFLD prevalence was 40·75% varying from about ≤25% (Malaysia, Pakistan, Bangladesh) to over 50% (e.g. Mexico, Austria, Sweden); and lean (not overweight or obese) NAFLD prevalence was 19·19%. In the general population (NAFLD and non-NAFLD), non-obese NAFLD prevalence was 12·12% and also varied geographically, and lean NAFLD prevalence was 5·12%. Among people with non-obese or lean NALFD, the prevalence of metabolic disease was similar to those with obese NAFLD, 38·98% had NASH, 29·23% had significant fibrosis (stage ≥2) and, and 3·16% had cirrhosis. The incidence rate of NAFLD among non-obese people with NAFLD at baseline was 24·6 per 1000 person-years. The incidence per 1000 person-years was 12·1 for all-cause mortality, 4·1 for liver-related mortality, 4·0 for cardiovascular death, and 56·1 for hypertension development for persons with non-obese or lean NAFLD. Interpretation: Overall, close to half of the NAFLD population were not obese and one-fifth were lean, but they carried substantial long-term liver and non-liver comorbidities. Therefore, BMI should not be the sole criterion for NAFLD screening and NAFLD treatment trials should include NAFLD persons that cover the BMI spectrum. Funding Statement: No external funding to disclose. Declaration of Interests: Tetsuya Hosaka: Speaking fees and educational fund from Gilead. Ramsey Cheung: Research support from Gilead Mindie H. Nguyen: Research support: Gilead, Pfizer; Consulting/advisory board: Intercept, Gilead. All other authors have nothing to disclose. Ethics Approval Statement: The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards.

Prevalence of non alcoholic fatty liver disease in premenopausal, posmenopausal and polycystic ovary syndrome women. The role of estrogens

Data on risk of developing chronic kidney disease (CKD) between non-obese and obese non-alcoholic fatty liver disease (NAFLD) patients are limited. We aimed to reveal the risk difference of incident CKD between non-obese and obese NAFLD patients. We searched PubMed, Embase, and Web of Science databases for studies which reported the incidence of CKD in non-obese and obese NAFLD from inception to 10 March 2024. The primary and secondary outcomes were pooled. Subgroup analysis was used to examine the heterogeneity. A total of 15 studies were incorporated. The incidence of CKD in non-obese and obese NAFLD were 1,450/38,720 (3.74%) and 3,067/84,154 (3.64%), respectively. Non-obese NAFLD patients had a comparable risk of CKD as obese NAFLD (odds ratio [OR] 0.92, 95% confidence interval [95% CI] [0.72-1.19], I2 = 88%). No differences in estimated glomerular filtration rate and serum creatinine between non-obese and obese NAFLD were found. The mean differences (MD) and 95% CI were 0.01 [-0.02 to 0.04] and 0.50 [-0.90 to 1.90], respectively. In subgroup analyses, non-obese NAFLD had higher eGFR when diagnosed with ultrasound (MD 1.45, 95% CI [0.11-2.79], I2 = 21%). Non-obese NAFLD had higher creatinine in non-Asian (MD 0.06, 95% CI [0.01-0.11], I2 = 55%) and when taking BMI > 30 as the criterion for obesity (MD 0.06, 95% CI [0.00-0.12], I2 = 76%). The occurrence of CKD did not differ when non-obese NAFLD were categorized into overweight and normal-weight types. Non-obese NAFLD patients experienced the same risk of CKD compared to obese NAFLD.