Gender Differences in Liver Steatosis and Fibrosis in Overweight and Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease before and after 8 Weeks of Very Low-Calorie Ketogenic Diet.

Obesity and metabolic syndrome are linked to steatotic liver disease (SLD), the most common form of chronic liver disease. Lifestyle modifications and dieting are strategies that can prevent metabolic dysfunction-associated steatotic liver disease (MASLD). The very low-calorie ketogenic diet (VLCKD) is a helpful treatment for MASLD and has been recommended for people affected by obesity; we evaluated the effect of gender on steatosis and fibrosis in a cohort of 112 overweight or obese patients undergoing an eight-week treatment with a VLCKD. Differences between the genders in terms of anthropometric measures, body composition, and metabolic indicators were examined before, during, and after the nutritional intervention. At baseline, there were significant differences between men and women in terms of anthropometric parameters, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting insulin, hepatic markers, and lipid profile. Men had considerably higher levels of liver steatosis (measured by CAP) and liver stiffness (measured by E) under basal conditions than women. After the VLCKD, there were reductions in both genders of controlled attenuation parameter (CAP), body weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, insulin resistance, fat mass (FM), free fat mass (FFM), and fasting blood glucose, insulin, glycated hemoglobin (HbA1c), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, alanine transaminase (ALT), gamma-glutamyl transferase (γGT), and uric acid levels. Only in men, liver stiffness, aspartate aminotransferase (AST), creatinine, and C-reactive protein (CRP) levels significantly decreased. Moreover, men had significantly greater levels of liver steatosis: the male gender featured an increase of 23.96 points of the Fibroscan CAP. Men exhibited higher levels of steatosis and fibrosis than women, and these differences persist despite VLCKD. These gender-specific variations in steatosis and fibrosis levels could be caused by hormonal and metabolic factors, suggesting that different therapeutic strategies might be required depending on the gender.

Higher-Level Steatosis Is Associated with a Greater Decrease in Metabolic Dysfunction-Associated Steatoic Liver Disease after Eight Weeks of a Very Low-Calorie Ketogenic Diet (VLCKD) in Subjects Affected by Overweight and Obesity.

The most common form of chronic liver disease, recently defined as MASLD, is strongly linked to obesity and metabolic syndrome. Lifestyle changes are part of MASLD prevention. The very low-calorie ketogenic diet (VLCKD) is a useful option for treating MASLD and reducing liver steatosis in patients with obesity. We assessed whether a greater degree of steatosis could have a positive or negative impact on how well 8 weeks of using the VLCKD improve steatosis and fibrosis in a patient population of overweight and obese individuals. Anthropometric parameters, along with changes in hormone and metabolic biomarkers, were also assessed both before and after the dietary change. The study population included 111 overweight (14.41%) or obese subjects (85.59%) aged between 18 and 64 years; the 75 women and 36 men involved were not taking any medicine. In both the raw (0.37 95% CI 0.21; 0.52) and the multivariate models (model a: 0.439 95% CI 0.26; 0.62; model b: 0.437 95% CI 0.25; 0.63), there was a positive and statistically significant correlation between the CAP delta value and the CAP before using the VLCKD. Additionally, the liver stiffness delta was found to be positively and statistically significantly correlated with liver stiffness before the use of the VLCKD in both models: the multivariate model (model a: 0.560 95% CI 0.40; 0.71; model b: 0.498 95% CI 0.34; 0.65) and the raw model (0.52 95% CI 0.39; 0.65). Systolic and diastolic blood pressure, insulin resistance (measured by HOMA-IR), insulin, HbA1c, fasting blood glucose, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, BMI, waist circumference, and fat mass, were all decreased (p < 0.001) following the use of the VLCKD. However, following the use of the VLCKD, there was an increase in vitamin D levels. (p < 0.001). We found that using the VLCKD for 8 weeks has a greater effect on improving steatosis and fibrosis in subjects who initially have more severe forms of these conditions.

Effects of an Eight Week Very Low-Calorie Ketogenic Diet (VLCKD) on White Blood Cell and Platelet Counts in Relation to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Subjects with Overweight and Obesity.

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are frequently associated conditions characterized by low-grade inflammation. Very low-calorie ketogenic diet (VLCKD) strategies are commonly used to simultaneously obtain weight loss and an improvement of liver steatosis. We evaluated the efficacy of 8 weeks' VLCKD in decreasing the white blood cell (WBC) and platelet (PLT) counts, as well as liver steatosis and fibrosis, diagnosed using transient elastography (FibroScan). Metabolic and anthropometric parameters commonly associated with MASLD were also evaluated. This study included 87 participants; 58 women and 29 men aged between 18 and 64 years with overweight (18%) or obesity (82%), but not taking any medication. Anthropometric measurements, bioimpedance analysis, and biochemical assays were performed before and after the dietary intervention. BMI (kg/m2) (p-value < 0.001), waist circumference (cm) (p-value < 0.001), and fat mass (kg) (p-value < 0.001) were significantly decreased following VLCKD. After VLCKD, the FibroScan parameter CAP (db/m), which measures the accumulation of fatty liver, significantly decreased (p-value < 0.001), as did liver stiffness (kPA), the FibroScan parameter quantifying liver fibrosis (p-value < 0.05). Seemingly, WBC (p-value < 0.001) and PLT (p-value < 0.001) counts were lowered by VLCKD in the whole group; however, the decrease in WBC and platelet counts were significant only in patients with steatosis (CAP ≥ 215 dB/m). Fasting blood glucose (p-value < 0.001), insulin (p-value < 0.001), HbA1c (p-value < 0.001), triglycerides (p-value < 0.001), total cholesterol (p-value < 0.001), LDL-cholesterol (p-value < 0.001), HDL-cholesterol (p-value < 0.001); γGT (p-value < 0.001) blood levels and insulin resistance (as measured by HOMAIR) (p-value < 0.001); and systolic (p-value < 0.001), and diastolic (p-value < 0.001) blood pressure levels, were all significantly lower after VLCKD. In contrast, blood levels of vitamin D were higher following the diet (p-value < 0.001). We conclude that treating subjects with overweight and obesity with VLCKD is followed by a simultaneous reduction in WBCs and platelets, the expression of low-grade inflammation, and of liver steatosis and fibrosis. Therefore, we can hypothesize that VLCKD decreases general and liver low-grade inflammation, thus improving liver health.