Background and Aims: Surveillance programs are strongly recommended in patients with liver cirrhosis for early detection of HCC development. Six-monthly ultrasound sonography is the most reliable and commonly used technique, especially when associated with serum determination of α-fetoprotein, but different score systems have been proposed to overcome the unsatisfactory diagnostic accuracy of α-fetoprotein. The aim of this 12-year prospective study is to compare the gender, age, AFP-L3, AFP, des-gamma-carboxy prothrombin (GALAD) versus age, gender, bilirubin, albumin, and platelets and albumin-bilirubin scores in predicting HCC onset. Approach and Results: A cohort of 545 consecutive patients with compensated advanced chronic liver disease without suspected focal lesions was followed up every 6 months by liver imaging and α-fetoprotein to detect HCC occurrence. Harrell’s C-index for censored data was employed to evaluate the performance of any parameters or scores helping to predict HCC development. ROC curve analysis showed that the GALAD score was more accurate in evaluating HCC development than albumin-bilirubin and age, gender, bilirubin, albumin, and platelets. The AUC ranged from 0.7268 to 0.6851 at 5 and 10 years, both in the total cohort and in the sub-cohorts (viral hepatitis, NASH, and alcohol). The HCC Risk model was constructed using univariate and multivariate Cox proportional hazard regression analysis, showing a strong association of GALAD with HR > 1, p < 0.05, in the total and sub-cohorts, and a better risk prediction in the alcohol cohort, both alone and standardized with other blood parameters. Conclusions: GALAD is the most reliable and accurate score system to detect HCC risk of development in patients with compensated advanced chronic liver disease.

Extra virgin olive oil (EVOO) has healthy benefits for noncommunicable diseases (NCDs). However, limited evidence is available about the effects of liver disease and non-alcoholic fatty liver disease (NAFLD). We evaluate whether dose-increased consumption of EVOO is associated with a lower prevalence of NAFLD and if these effects vary based on body weight. The study included 2436 subjects with a 33% NAFLD prevalence. Daily EVOO was categorized into tertiles: low (0–24 g/day), moderate (25–37 g/day), and high consumption (>37 g/day). Subjects were also classified by body mass index (BMI) as normo-weight (18.5–24.9), overweight (25–29.9), and obese (≥30). Logistic regression analysis was applied to calculate odds ratios (ORs) for NAFLD, considering a 20-gram increment in EVOO intake and accounting for EVOO categories combined with BMI classes. The ORs were 0.83 (0.74;0.93) C.I. p = 0.0018 for continuous EVOO, 0.89 (0.69;1.15) C.I. p = 0.37, and 0.73 (0.55;0.97) C.I. p = 0.03 for moderate and high consumption, respectively, when compared to low consumption. Overall, the percent relative risk reductions (RRR) for NAFLD from low to high EVOO consumption were 18% (16.4%;19.2%) C.I. and 26% (25%;27.4%) C.I. in overweight and obese subjects. High EVOO consumption is associated with a reduced risk of NAFLD. This effect is amplified in overweight subjects and even more in obese subjects.

Background: Migraine is a chronic neurovascular disorder with a multifactorial aetiology. A strong relationship links migraine with aura (MHA) and patent foramen ovale (PFO), with migraine regression after PFO closure. Increased platelet aggregation and oxidative stress were documented in migraineurs. Current guidelines suggest the use of aspirin or P2Y12-antagonists. To date, however, no clear mechanisms connecting MHA to PFO has been demonstrated. Purpose: To perform a comprehensive analysis of platelet activation, inflammation and oxidative stress status in 78 aspirin-treated MHA-patients before (T0) and 6-months after (T1) PFO closure (LEARNER Study-NCT03521193-clinicaltrials.gov). Primary endpoint was migraine regression rate in relation to these parameters. Methods: P-selectinpos-, activated-glycoproteinIIbIIIa (aGPIIbIIIa)pos-, Tissue Factor (TF)pos-, reactive oxygen species (ROS)pos-platelets, platelet-leukocyte aggregates (PLA) and microvesicles (MVs) were evaluated by flow cytometry; thrombin generation (TG) by Calibrated Automated Thrombogram (CAT) assay; oxidative stress status by mass spectrometry. Twelve aspirin-treated-healthy subjects (HS) were enrolled for comparison. To test the effect of PFO patients' plasma on platelet activation, blood from HS was plasma-depleted and replaced with a pool of plasma from PFO patients. Results: Migraine resolution occurred in 69.7%, significant reduction in 27%, while no effect was observed in 2 patients (3.2%). Only ROSpos-platelets, and TFpos-platelets and -MVs were significantly higher at T0, sustaining a TG capacity that was associated with an altered blood GSSG/GSH (Oxidized/Reduced Glutathione) ratio. This phenotype reverted to HS levels at T1 (Fig. 1). MHA-PFO plasma, added to HS blood, mirrored the in vivo platelet activation and N-acetylcysteine blunted it. In vitro GSSG treatment of HS platelets reproduced the in vivo condition. Aspirin had little effect on the platelet prothrombotic phenotype which was effectively inhibited by a P2Y12-antagonist (Fig.2). Conclusions: MHA-PFO patients show a platelet-associated prothrombotic phenotype, characterized by a marked thrombin generation capacity sustained by an elevated number of platelets and MVs expressing a functionally active Tissue Factor and sustained by altered oxidative stress status. This phenotype, not fully controlled by aspirin but by P2Y12-antagonism, reverted after PFO closure together with a complete migraine remission. Funding Acknowledgement: Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health