2D shear wave liver elastography by aixplorer to detect portal hypertension in cirrhosis: an individual patient data meta-analysis

Background & Aims: Liver stiffness measured with 2-dimensional shear wave elas- tography by Supersonic Imagine (2DSWE-SSI) is well-established for fibrosis diagnos- tics, but non-conclusive for portal hypertension. Methods: We performed an individual patient data meta-analysis of 2DSWE-SSI to identify clinically significant portal hypertension (CSPH), severe portal hyperten- sion and large varices in cirrhosis patients, using hepatic venous pressure gradient and upper endoscopy as reference. We used meta-analytical integration of diagnos- tic accuracies with optimized rule-out (sensitivity-90%) and rule-in (specificity-90%) cut-offs. Results: Five studies from seven centres shared data on 519 patients. After exclu- sion, we included 328 patients. Eighty-nine (27%) were compensated and 286 (87%) had CSPH. 2DSWE-SSI < 14 kPa ruled out CSPH with a summary AUROC (sROC), sensitivity and specificity of 0.88, 91% and 37%, and correctly classified 85% of pa- tients, with minimal between-study heterogeneity. The false negative rate was 60%, of which decompensated patients accounted for 78%. 2DSWE-SSI ≥ 32 kPa ruled in CSPH with sROC, sensitivity, specificity and correct classifications of 0.83, 47%, 89% and 55%. In a subgroup analysis, the 14 kPa cut-off showed consistent sensitivity and higher specificity for patients with compensated cirrhosis, without ascites, viral 2 aetiology or BMI < 25 kg/m . 2DSWE-SSI ruled out severe portal hypertension and large varices with fewer correctly classified and lower sROC, and with minimal benefit for ruling in. Conclusion: Liver stiffness using 2-dimensional shear wave elastography below 14 kPa may be used to rule out clinically significant portal hypertension in cirrhosis patients, but this would need validation in populations of compensated liver disease. 2DSWE-SSI cannot predict varices needing treatment

Bidimensional shear wave ultrasound elastography with supersonic imaging to predict presence of oesophageal varices in cirrhosis

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Regression of portal hypertension: underlying mechanisms and therapeutic strategies.

Portal hypertension is the main non-neoplastic complication of chronic liver disease, being the cause of important life-threatening events including the development of ascites or variceal bleeding. The primary factor in the development of portal hypertension is a pathological increase in the intrahepatic vascular resistance, due to liver microcirculatory dysfunction, which is subsequently aggravated by extra-hepatic vascular disturbances including elevation of portal blood inflow. Evidence from pre-clinical models of cirrhosis has demonstrated that portal hypertension and chronic liver disease can be reversible if the injurious etiological agent is removed and can be further promoted using pharmacological therapy. These important observations have been partially demonstrated in clinical studies. This paper aims at providing an updated review of the currently available data regarding spontaneous and drug-promoted regression of portal hypertension, paying special attention to the clinical evidence. It also considers pathophysiological caveats that highlight the need for caution in establishing a new dogma that human chronic liver disease and portal hypertension is reversible

The Interplay between Liver Sinusoidal Endothelial Cells, Platelets, and Neutrophil Extracellular Traps in the Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a societal burden due to the lack of effective treatment and incomplete pathophysiology understanding. This review explores the intricate connections among liver sinusoidal endothelial cells (LSECs), platelets, neutrophil extracellular traps (NETs), and coagulation disruptions in MASLD pathogenesis. In MASLD’s early stages, LSECs undergo capillarization and dysfunction due to excessive dietary macronutrients and gut-derived products. Capillarization leads to ischemic changes in hepatocytes, triggering pro-inflammatory responses in Kupffer cells (KCs) and activating hepatic stellate cells (HSCs). Capillarized LSECs show a pro-inflammatory phenotype through adhesion molecule overexpression, autophagy loss, and increased cytokines production. Platelet interaction favors leucocyte recruitment, NETs formation, and liver inflammatory foci. Liver fibrosis is facilitated by reduced nitric oxide, HSC activation, profibrogenic mediators, and increased angiogenesis. Moreover, platelet attachment, activation, α-granule cargo release, and NETs formation contribute to MASLD progression. Platelets foster fibrosis and microthrombosis, leading to parenchymal extinction and fibrotic healing. Additionally, platelets promote tumor growth, epithelial–mesenchymal transition, and tumor cell metastasis. MASLD’s prothrombotic features are exacerbated by insulin resistance, diabetes, and obesity, manifesting as increased von Willebrand factor, platelet hyperaggregability, hypo-fibrinolysis, and a prothrombotic fibrin clot structure. Improving LSEC health and using antiplatelet treatment appear promising for preventing MASLD development and progression

Is Fasting Good When One Is at Risk of Liver Cancer?

Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related deaths worldwide, is a multistep process that usually develops in the background of cirrhosis, but also in a non-cirrhotic state in patients with non-alcoholic fatty liver disease (NAFLD) or viral hepatis. Emerging evidence suggests that intermittent fasting can reduce the risk of cancer development and could improve response and tolerance to treatment through the metabolic and hormonal adaptations induced by the low energy availability that finally impairs cancer cells’ adaptability, survival and growth. The current review will outline the beneficial effects of fasting in NAFLD/NASH patients and the possible mechanisms that can prevent HCC development, including circadian clock re-synchronization, with a special focus on the possibility of applying this dietary intervention to cirrhotic patients

Presence of Hepatocellular Carcinoma Does Not Affect Course and Response to Anticoagulation of Bland Portal Vein Thrombosis in Cirrhotic Patients

Background: Malignancies are generally considered a risk factor for deep vein thrombosis and may hamper the recanalisation of thrombosed veins. Aim: We investigate whether the natural course and response to anticoagulant treatment of bland portal vein thrombosis (PVT) in patients with cirrhosis complicated by hepatocellular carcinoma (HCC) differ from those without HCC. Methods: Retrospective study in two hepatology referral centres, in Italy and Romania where patients with a diagnosis of PVT on cirrhosis and follow-up of at least 3 months with repeated imaging were included. Results: A total of 162 patients with PVT and matching inclusion and exclusion criteria were identified: 30 with HCC were compared to 132 without HCC. Etiologies, Child-Pugh Score (7 vs 7) and MELD scores (11 vs 12, p=0.3679) did not differ. Anticoagulation was administered to 43% HCC vs 42% nonHCC. The extension of PVT in the main portal trunk was similar: partial/total involvement was 73.3/6.7% in HCC vs 67.4/6.1% in nonHCC, p=0.760. The remainder had intrahepatic PVT. The recanalization rate was 61.5% and 60.7% in HCC/nonHCC in anticoagulated patients (p=1). Overall PVT recanalisation, including treated and untreated patients, was observed in 30% of HCC vs 37.9% of nonHCC, p=0.530. Major bleeding incidence was almost identical (3.3% vs 3.8%, p=1). Progression of PVT after stopping anticoagulation did not differ (10% vs 15.9%, respectively, HCC/nHCC, p=0.109). Conclusion: The course of bland non-malignant PVT in cirrhosis is not affected by the presence of active HCC. Treatment with anticoagulation in patients with active HCC is safe and as effective as in nonHCC patients, this can potentially allow us to use otherwise contraindicated therapies (ie TACE) if a complete recanalization is achieved with anticoagulation