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. 2024 May 8;16(10):1408.
doi: 10.3390/nu16101408.

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

Roberta Rinaldi  1 , Sara De Nucci  1 , Rossella Donghia  2 , Rosanna Donvito  1 , Nicole Cerabino  1 , Martina Di Chito  1 , Alice Penza  1 , Francesco Pio Mongelli  1 , Endrit Shahini  3 , Marianna Zappimbulso  3 , Pasqua Letizia Pesole  4 , Sergio Coletta  4 , Vincenzo Triggiani  5 , Raffaele Cozzolongo  3 , Gianluigi Giannelli  6 , Giovanni De Pergola  1
Affiliations

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

Roberta Rinaldi et al. Nutrients. .

Abstract

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.

Keywords: gender; metabolic dysfunction-associated steatotic liver disease (MASLD); non-alcoholic fatty liver disease (NAFLD); obesity; transient elastography (FibroScan); very low-calorie ketogenic diet (VLCKD).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any financial relationships that could be construed as potential conflicts of interest. New Penta s.r.l., (Cuneo, Italy) had no role in the design of this study, in the collection, analyses, or interpretation of data, in the writing of this manuscript, or in the decision to publish the results.

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Grants and funding

This research was funded by the Italian Ministry of Health with Ricerca Corrente in 2024.