Repeated measurements and data integration to monitor and study MASLD patients experiencing weight loss

Introduction MASLD is a multifactorial disease for which there are no approved pharmacological therapies and for which lifestyle changes still represent the most effective remedy. Nutritional studies could be essential to increase knowledge and assess causality in the field of MASLD. Aim Our aim is to monitor patients diagnosed with MASLD who attend a weight-loss program at our Hepatology Unit, through repeated measurements of clinical parameters, transient elastography (TE), controlled attenuation parameter (CAP), and blood tests. The interaction between genetics and TE/CAP is also considered. Patients and Methods Overweight or obese MASLD patients, aged ≥ 18, without decompensated cirrhosis or active cancer, were proposed to start a low-glycemic index, nutritionist-guided diet. Weight, BMI, TE/CAP, and blood tests recorded at baseline were compared with the same measurements obtained after 6 months. Weight loss was categorized into classes of weight change compared to baseline (<5%, 5%–10%, >10%). A genetic risk score (GRS) was calculated for each patient and related to changes in TE/CAP Results Among the 131 patients who underwent the first nutritional visit, 50 attended the 6-months control visit to date. At this time-point, as we previously observed in earlier follow-up visits, a significant difference compared to baseline was found in weight, BMI, and CAP (respectively -7.47 kg [-8.10%], -2.67 Kg/m2, and -45.88 dB/m; all p<0.0001). The latter improved proportionally to the extent of weight loss; mean liver stiffness, on the contrary, remained almost unchanged, but it decreased in the >10% weight reduction class. Patients with high GRS experienced a greater decrease in TE/CAP values after 6 months of diet. Liver biochemistry also improved. Conclusions Diet-induced weight loss has beneficial effects on MASLD, and liver disease improves proportionally to its extent. Genetics appear to modulate change in liver disease severity in patients on diet. Weight loss data represent the backbone of our ongoing studies on changes in metabolomics and gut microbiota for these patients, aimed at further investigate the pathophysiology of the disease.