Background and Aims: Esophageal varices (EV) are common in adults with Fontan-type circulation and may arise via distinct hemodynamic mechanisms depending on their anatomic location. We aimed to determine the prevalence, anatomical distribution, and hemodynamic correlates of EV in this population. Approach and Results: In this prospective cohort study, 114 consecutive adults with Fontan-type circulation underwent combined hepatic and cardiac catheterization, esophagogastroduodenoscopy, and liver biopsy. Patients were classified by endoscopic findings into those with and without EV, and the EV cohort was further stratified by location (proximal or distal). EV were present in 36.8% (95% CI, 27.9–45.8%), including 28.9% with distal EV and 17.5% with proximal EV. Over a median follow-up of 48.9 months (IQR, 27.1–85.5), only one variceal bleeding event occurred. Patients with distal EV exhibited the highest cardiac index and pulmonary, systemic and hepatic venous pressures, as well as the lowest systemic vascular resistance (all p <0.01). Severe hepatic fibrosis was more frequent in this group (87.9%) than in patients without EV (33.8%) or those with proximal EV (25.0%). Non-invasive fibrosis markers (liver stiffness, FIB-4, Forns index, FonLiver risk score) were significantly elevated in patients with distal EV (all p <0.05), despite similar biochemical profiles. Conclusions: Distal EVs are frequent and characterize a distinct hemodynamic phenotype, featuring elevated Fontan pathway pressures, severe hepatic fibrosis, portal hypertension, and a hyperdynamic circulatory state.

Background and aims: Liver transplantation is effective against hepatocellular carcinoma (HCC), but recurrence remains a challenge. Traditional criteria based on tumor size, nodule number, and AFP levels have had limited success in predicting aggressiveness. [18F]FDG PET/CT has shown promise in identifying high-risk tumor features, including microvascular invasion (MVI), which is a key predictor of recurrence. Methods: In this retrospective, single-center study, all consecutive patients who underwent LT for HCC between 2010 and 2019 were included. Prior to listing, the patients underwent [18F]FDG PET/CT, and explant pathology was analyzed for MVI and other histological features. The primary objective was to identify the predictors of early HCC recurrence (within 24 months after LT). Secondary objectives included identifying predictors of high-risk histological features of the explant, describing recurrence patterns, and assessing post-recurrence survival. Results: The study included 143 patients (median age 59 years [IQR 54–64], 85% males, median MELD 10 [IQR 8–14], median AFP value 8.5 [IQR 4–39] ng/mL) and 40 (28%) with intra-hepatic [18F]FDG PET/CT positivity. HCC recurred post-LT in 25 patients (17%) (median post-LT follow-up 49 months [IQR 28.5–77]) and within 24 months in 12 patients (48%). MVI at the explant stage was independently associated with early recurrence (HR: 7.20, 95% CI 1.82–28.45, p = 0.005), while intra-hepatic [18F]FDG PET/CT positivity before LT independently predicted MVI in explants (OR 3.90, 95% CI 1.30–11.71, p = 0.01). Conclusions: [18F]FDG PET/CT may offer a valuable tool for pre-transplant risk assessment by identifying MVI, which is an independent predictor of early cancer recurrence. Its incorporation into the selection criteria for LT may enhance patient stratification and post-transplant outcomes.

Background and aims: Hepatocellular carcinoma (HCC) patients frequently present with comorbidities that limit therapeutic options and increase mortality. This study evaluated the performance of the Charlson Comorbidity Index (CCI) and a modified CCI (mCCI) in stratifying patients with HCC to predict treatment allocation and survival. Methods: A retrospective single-center cohort study analyzed 401 patients with de novo HCC (74% male, median age 68 years, 80% Child–Pugh-Turcotte (CPT) A, 65% viral etiology, 70% Barcelona Clinic Liver Cancer stage (BCLC) 0/A). CCI and mCCI (with points related to HCC and chronic liver disease excluded), were calculated at diagnosis for each patient. The primary endpoint was overall survival (OS) estimated by Kaplan–Meier method and compared across mCCI classes; Cox uni/multivariable models were applied to identify predictors of mortality. The secondary aim was evaluating the association between mCCI and treatment allocation. Results: While CCI classified 94% of patients as “high-risk”, mCCI reclassified patients into “high-risk” (21%), “intermediate-risk” (48%), and “low-risk” (31%), demonstrating better stratification whilst maintaining a strong correlation with CCI (Kendall’s tau-b = 0.57, p < 0.001). BCLC B patients with “high-risk” mCCI exhibited significantly lower access to first-line curative treatment (14% vs. 47%, p = 0.03). Moreover, “high” or “intermediate-risk” patients according to mCCI experienced significantly shorter OS compared to “low-risk” (median OS 36 vs. 49 vs. 74 months, p < 0.001). “High-risk” and “intermediate-risk” mCCI classes were independent predictors of mortality, alongside alpha-fetoprotein, CPT and BCLC stage. Considering the items composing mCCI, age and cardiovascular diseases were independent predictors of mortality. Conclusions: mCCI provides a more accurate assessment of comorbidities than the standard CCI and is associated with survival, hence it can contribute to designing patient-tailored therapeutic strategies.

The ASAP algorithm incorporating Age, Sex, Alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence/antagonist II (PIVKA-II) has been shown to predict hepatocellular carcinoma (HCC) development. Our study evaluated the prognostic value of ASAP for early HCC recurrence after complete radiological response (CR) to locoregional therapy. This single-center study enrolled patients with newly diagnosed HCC who achieved CR by ablation (MWTA) or chemoembolization (TACE) and available serum samples on the day of treatment. CR was evaluated by CT-scan 1 month after treatment. PIVKA-II and AFP levels were measured using Fujirebio assays. Patients were followed up every three months until recurrence, death, or last follow-up. 127 patients with HCC (median age 66 years, 79 % male, 79 % with viral etiology) who achieved CR were enrolled. At time of treatment, median AFP and PIVKA-II levels were 6.6 ng/mL and 144 mAU/mL, respectively, while median ASAP score was 0.60. During follow-up, HCC recurred in 72 (56.7 %) patients (63 within 24 months, early recurrence). ASAP score was the sole independent predictor of early recurrence [HR 2.57 (95 % CI 1.50-4.40), p=0.001] and its new cutoff of 0.797 (AUC 66 %, sensitivity 57 %, specificity 75 %) outperformed other scores and biomarkers. The ASAP score accurately predicted early HCC recurrence post-CR, warranting further validation.

Background: Liver cirrhosis is frequently associated with cardiovascular abnormalities collectively referred to as cirrhotic cardiomyopathy, characterized by impaired cardiac reserve and subclinical myocardial dysfunction despite preserved conventional systolic function. Advanced myocardial deformation imaging techniques, including two-dimensional speckle-tracking echocardiography (2D-STE) and cardiac magnetic resonance feature tracking (CMR-FT), may allow earlier detection of subtle ventricular impairment. We performed a systematic review and meta-analysis to comprehensively evaluate conventional and deformation-derived indices of biventricular systolic function in cirrhotic patients. Methods: PubMed, Scopus, and EMBASE databases were systematically searched for observational studies evaluating myocardial systolic function in adult cirrhotic patients using 2D-STE and/or CMR-FT. Comparative meta-analyses between cirrhotic patients and controls were performed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Separate analyses were conducted for left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS), left ventricular global circumferential strain (LV-GCS), left ventricular global radial strain (LV-GRS), right ventricular ejection fraction (RVEF), and right ventricular global longitudinal strain (RV-GLS). Weighted pooled descriptive analyses of clinical, laboratory, echocardiographic, and CMR findings were additionally performed. Results: Twenty studies including 1553 cirrhotic patients and 498 controls were included, whereas 14 studies were eligible for quantitative meta-analysis. Conventional LVEF remained globally preserved and showed no significant overall difference between cirrhotic patients and controls, although CMR-based studies demonstrated mildly higher LVEF values in cirrhosis. Meta-analysis revealed no significant overall differences in LV-GLS, LV-GCS, LV-GRS, or RVEF, whereas RV-GLS was significantly reduced in cirrhotic patients. Substantial heterogeneity was observed across most deformation analyses. Meta-regression demonstrated significant associations between LV-GLS variability and age, body mass index, MELD score, diabetes prevalence, heart rate, systolic blood pressure, and software vendor. Descriptive pooled analyses demonstrated larger cardiac chamber dimensions, increased filling pressures, mildly increased pulmonary pressures, and increased extracellular volume fraction values in cirrhotic populations. Conclusions: Patients with liver cirrhosis exhibit preserved conventional systolic function despite evidence of subtle myocardial mechanical abnormalities, particularly involving right ventricular longitudinal mechanics and diastolic function. Advanced deformation imaging with 2D-STE and CMR-FT may improve early detection of subclinical cardiac involvement in cirrhotic cardiomyopathy.

Background and Aims: Accuracy of Baveno criteria for avoiding endoscopy in patients with hepatocellular carcinoma (HCC) is uncertain, and systematic upper gastrointestinal endoscopy (UGE) may not be necessary. We evaluated Baveno VI criteria performance in this population and developed an alternative non-invasive rule to exclude esophagogastric varices of any grade, rather than high-risk varices (HRV). Methods: Patients with BCLC 0-C HCC and compensated advanced chronic liver disease (cACLD) from Italian Liver Cancer (ITA.LI.CA) database, with available liver stiffness measurement (LSM), UGE, and blood tests within six months of diagnosis, were included. Independent predictors of varices identified by logistic regression were combined through grid-search to derive a rule-out strategy (SAPHE-R), validated by bootstrap-resampling and in an independent cohort (Vienna). Results: The derivation cohort comprised 598 patients (age, 69 years; male sex, 75.3%; viral etiology, 69.3%; BCLC 0/A, 77.9%; ALBI 1, 54.2%; varices, 33.4%; HRV, 11.2%). Baveno VI criteria missed 8.5% of varices and 6.0% of HRV, sparing 31.1% of UGE. Independent predictors of varices were incorporated into SAPHE-R (LSM≤16 kPa, platelet count ≥160×10⁹/L, ALBI grade 1), which missed 4.0% of varices (HRV 3.0%, spared UGE 17.6%). In the validation cohort (n=149), SAPHE-R missed 4.8% of varices (HRV 3.1%, spared UGE 14.8%). Results remained consistent in sensitivity analyses. In an exploratory analysis, no HVPG-defined CSPH was observed among SAPHE-R rule-out patients (0/22). Conclusions: Baveno VI criteria showed suboptimal performance in patients with HCC and cACLD, whereas SAPHE-R provided a reliable non-invasive strategy to rule out varices, facilitating variceal risk assessment in patients with HCC.