Phd in EXPERIMENTAL AND CLINICAL HEPATO-GASTROENTEROLOGY

Thesis title: Effect of Targeted Nutritional Intervention in Compensated and Early Decompensated Patients with Liver Cirrhosis

Introduction: Frailty and low muscle strength are early, modifiable predictors of poor outcomes in liver cirrhosis, yet they often remain under-recognised in compensated stages of the disease. While supplement-based nutritional interventions have shown benefit, there is limited evidence for diet-only intervention, particularly in Italian patients with cirrhosis. This study evaluated whether individualized dietary intervention along with nutrition counselling could improve muscle strength, frailty, and quality of life in stable cirrhotic outpatients. Methods: A 16-week randomized controlled trial was conducted between March 2023 and March 2025 at the Portal Hypertension Clinic, Policlinico Umberto I, Sapienza University of Rome. Sixty outpatients with compensated or early decompensated liver cirrhosis (Child-Pugh A/B) were randomized to either a structured nutritional intervention group (n = 32) or control group (n = 28). The intervention targeted 30-35 kcal/kg/day and 1.2-1.5 g/kg/day protein through individualized, food-based meal plans and counselling without any supplementation, whereas the control group received no dietary intervention beyond routine clinical follow-up. Handgrip strength (HGS) was the primary endpoint, while the Liver Frailty Index (LFI) and the Chronic Liver Disease Questionnaire-Italian version (CLDQ-I) served as secondary outcomes. Results: Baseline characteristics were comparable between groups. After 16 weeks, the intervention group showed a significant increase in HGS (25.5 ± 10.9 vs 30.4 ± 9.9 kg; Δ +4.9; p < 0.001) compared with the control group (27 ± 11.6 vs 25.7 ± 11.1 kg; Δ −1.36; p = 0.6). A positive, modest correlation was observed between the change in protein intake and change in handgrip strength (r = 0.421, p = 0.002), suggesting that greater improvements in dietary protein intake were associated with larger gains in muscle strength. LFI scores improved in the intervention arm (4.22 ± 0.59 vs 3.71 ± 0.52; Δ −0.51; p < 0.001) versus negligible change in controls (4.2 ± 0.74 vs 4.5 ± 0.86; Δ −0.04; p = 0.38). Quality of life improved significantly in the intervention group (CLDQ-I 2.74 ± 0.75 vs 2.36 ± 0.76; Δ −0.38; p = 0.018), but not in controls (2.7 ± 0.75 vs 2.4 ± 0.79; Δ −0.3; p = 0.018). Protein intake increased from 0.80 ± 0.26 to 1.11 ± 0.25 g/kg/day (p < 0.001) in the intervention group, while remaining unchanged in the control arm. No adverse biochemical or clinical events were reported. Conclusion: A 16-week, dietary nutritional intervention significantly improved muscle strength, frailty, and quality of life compared in patients with liver cirrhosis. These findings underscore the value of individualized dietary counselling as a safe, scalable, and non-pharmacological therapy to preserve physical function and resilience in cirrhotic outpatients. Keywords: liver cirrhosis, nutrition, handgrip strength, quality of life, frailty