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Background/Objectives: Low fasting blood lysosomal acid lipase (LAL) activity is associated with the pathogenesis of metabolic hepatic steatosis. We measured LAL activity in blood and plasma before and after an oral fat tolerance test (OFTT) in patients with metabolic-dysfunction-associated steatotic liver disease (MASLD). Methods: Twenty-six controls and seventeen patients with MASLD but without diabetes were genotyped for the patatin-like phospholipase 3 (PNPLA3) rs738409 variant by RT-PCR and subjected to an OFTT, measuring LAL activity in blood and plasma with a fluorimetric method. Results: LAL activity in blood both under fasting and 4 h after OFTT (0.846 ± 0.309 nmol/spot/h vs. 1.180 ± 0.503 nmol/spot/h p < 0.01) was lower in patients with MASLD compared to controls. These differences were present only in carriers of the PNPLA3 variant. In controls not carrying the PNPLA3 variant, the postprandial increase in blood LAL activity was negatively correlated with that of serum triglycerides (p < 0.05). Extracellular LAL activity in plasma was lower in patients with MASLD (n = 9) compared to controls (n = 8) in the fasting state (p < 0.01) and 4 h post-meal (p < 0.05). The area under the curve up to 6 h of plasma LAL activity was lower in patients with MASLD than in controls (p < 0.05) and correlated negatively with that of triglycerides only in controls (r = −0.841; p < 0.01). Conclusions: Patients with MASLD have reduced LAL activity in blood and plasma both before and 4 h after a meal. In patients with MASLD, the physiological negative correlation between circulating LAL levels and postprandial hypertriglyceridemia is lost.

Liver cirrhosis development is a multifactorial process resulting from a combination of environmental and genetic factors. The aim of the study was to develop accurate non-invasive diagnostic and prognostic models for alcoholic cirrhosis. Consecutive subjects with at-risk alcohol intake were retrospectively enrolled (110 cirrhotic patients and 411 non-cirrhotics). At enrollment, the data about lifetime drinking history were collected and all patients were tested for Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, Transmembrane 6 Superfamily 2 (TM6SF2) rs58542926, and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567 variants. In cross-sectional analyses, models for the diagnosis of cirrhosis were developed using multivariate logistic regression. A predictive score for cirrhosis development over 24 years was built by evaluating time-dependent AUC curves. The best diagnostic accuracy was demonstrated by the model, which also includes daily alcohol consumption, duration of hazardous alcohol use, and genetic variants, with AUCs of 0.951 (95% CI 0.925–0.977) and 0.887 (95% CI 0.925–0.977) for cirrhosis and compensated cirrhosis, respectively. The predictive model for future cirrhosis development (AUC of 0.836 95% CI: 0.769–0.904) accounted for age at onset of at-risk alcohol consumption and the number of PNPLA3 and HSD17B13 variant alleles. We have developed accurate genetic and alcohol consumption models for the diagnosis of alcoholic cirrhosis and the prediction of its future risk.

Introduction: Liver transplantation (LT) is burdened by the risk of post-operative morbidity. Identifying patients at higher risk of developing complications can help allocate resources in the perioperative phase. Controlling Nutritional Status (CONUT) score, based on lymphocyte count, serum albumin, and cholesterol levels, has been applied to various surgical specialties, proving reliable in predicting complications and prognosis. Our study aims to investigate the role of the CONUT score in predicting the development of early complications (within 90 days) after LT.Methods: This is a retrospective analysis of 209 patients with a calculable CONUT score within 2 months before LT. The ability of the CONUT score to predict severe complications, defined as a Comprehensive Complication Index (CCI) ≥42.1, was examined. Inverse Probability Treatment Weighting was used to balance the study population against potential confounders.Results: Patients with a CCI ≥42.1 had higher CONUT score values (median: 7 vs. 5, P-value < 0.0001). The CONUT score showed a good diagnostic ability regarding post-LT morbidity, with an AUC = 0.72 (95.0%CI = 0.64–0.79; P-value < 0.0001). The CONUT score was the only independent risk factor identified for a complicated post-LT course, with an odds ratio = 1.39 (P-value < 0.0001). The 90-day survival rate was 98.8% and 87.5% for patients with a CONUT score