Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) imposes significant healthcare burdens. Early detection of advanced fibrosis and cirrhosis in MASLD is essential due to their unfavourable outcomes. This multi-level random-effects meta-analysis aimed to provide the best evidence for the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE) in detecting liver fibrosis in biopsy-proven MASLD. Approach & Results: Systematic search in PubMed/MEDLINE, Embase, Scopus, Web of Science, LILACS, and Cochrane Library electronic databases for full-text articles published in any language up to the 26^th of February 2024. Included studies reported liver stiffness measurement (LSM) by 2D-SWE and used histological diagnosis as gold standard. A linear mixed-effects multiple thresholds model was employed, and summary estimates for sensitivity (Se), specificity (Sp), and summary area under the curve (sAUC) were computed. 20 observational studies (SuperSonic Imagine, General Electric Healthcare, Canon Medical Systems) fulfilled the inclusion criteria, comprising 2223 participants with biopsy-proven MASLD. The prevalence of mild fibrosis (F1), significant fibrosis (F2), advanced fibrosis (F3), and cirrhosis (F4) was 30.0%, 18.5%, 17.9%, and 10.9%, respectively. The sAUCs [95%CI] in detecting ≥F1, ≥F2, ≥F3, and F4 for all ultrasound machines considered together were 0.82 [0.16-0.98], 0.82 [0.76-0.88], 0.86 [0.77-0.93], and 0.89 [0.80-0.95], respectively. The optimal cut-off values were 6.432 kPa for ≥F1, 8.174 kPa for ≥F2, 9.418 kPa for ≥F3, and 11.548 kPa for F4, respectively. Conclusions: Our meta-analysis identified optimised cut-offs for fibrosis staging by 2D-SWE in etiology-specific chronic liver diseases (MASLD), with excellent diagnostic performance, underscoring the potential for standardising cut-off values. Export

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.

Non-alcoholic fatty liver disease (NAFLD), and its progressive form, non-alcoholic steatohepatitis (NASH), represent, nowadays, real challenges for the healthcare system. Liver fibrosis is the most important prognostic factor for NAFLD, and advanced fibrosis is associated with higher liver-related mortality rates. Therefore, the key issues in NAFLD are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. We critically reviewed the ultrasound (US) elastography techniques for the quantitative characterization of fibrosis, steatosis, and inflammation in NAFLD and NASH, with a specific focus on how to differentiate advanced fibrosis in adult patients. Vibration-controlled transient elastography (VCTE) is still the most utilized and validated elastography method for liver fibrosis assessment. The recently developed point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) techniques that use multiparametric approaches could bring essential improvements to diagnosis and risk stratification.

Non-alcoholic fatty liver disease (NAFLD), with its progressive form, non-alcoholic steatohepatitis (NASH), has emerged as a significant public health concern, affecting over 30% of the global population. Hepatocellular carcinoma (HCC), a complication associated with both cirrhotic and non-cirrhotic NAFLD, has shown a significant increase in incidence. A substantial proportion of NAFLD-related HCC occurs in non-cirrhotic livers, highlighting the need for improved risk stratification and surveillance strategies. This comprehensive review explores the potential role of liver ultrasound elastography as a risk assessment tool for HCC development in NAFLD and highlights the importance of effective screening tools for early, cost-effective detection and improved management of NAFLD-related HCC. The integration of non-invasive tools and algorithms into risk stratification strategies could have the capacity to enhance NAFLD-related HCC screening and surveillance effectiveness. Alongside exploring the potential advancement of non-invasive tools and algorithms for effectively stratifying HCC risk in NAFLD, we offer essential perspectives that could enable readers to improve the personalized assessment of NAFLD-related HCC risk through a more methodical screening approach.

The COVID-19 pandemic has raised awareness of the virus’s long-term non-pulmonary consequences. This study examined the relationship between genetic polymorphisms of VEGF and cardiac dysfunction and subclinical atherosclerosis in patients recovering from COVID-19. This study included 67 patients previously diagnosed with COVID-19. VEGF-936C/T, VEGF-634G/C, and VEGF-2578C/A statuses were determined. Conventional echocardiography and arterial parameters assessments were performed at inclusion and at six months after the first assessment. For VEGF-936C/T, dominant and over-dominant models showed a significant increase in ejection fraction at six months after COVID (p = 0.044 and 0.048) and was also a predictive independent factor for the augmentation index (β = 3.07; p = 0.024). The dominant model showed a rise in RV-RA gradient (3.702 mmHg) (p = 0.028 95% CI: 0.040–7.363), with the over-dominant model indicating a greater difference (4.254 mmHg) (p = 0.025 95% CI: 0.624–7.884). The findings for VEGF-634G/C were not statistically significant, except for a difference in TAPSE during initial evaluation, using the codominant model. For VEGF-2578C/A, a difference in ventricular filling pressure (E/E’ratio) was best described under the recessive model. Our research suggests that the VEG-936C/T genotype may impact the baseline level and subsequent changes in cardiac function and subclinical atherosclerosis. These findings offer valuable insights into the complex correlation between genetic polymorphisms and cardiovascular disfunction in long COVID patients.

Bile salt export pump (BSEP) deficiency, also termed progressive familial intrahepatic cholestasis type 2 (PFIC2), is a rare genetic disorder caused by mutations in the ATP-binding cassette, sub-family B member 11 (ABCB11) gene, predisposing to cholestasis and progressive liver damage. Although parvovirus B19 is a recognized but rare cause of acute hepatitis in children, its role in adult liver disease remains uncertain. To expand the knowledge on this topic, we performed a narrative review of published adult cases of B19-associated hepatitis and report the case of a 46-year-old immunocompetent man who developed acute cholestatic hepatitis during B19 infection. The clinical course was not fully attributable to the viral insult alone, prompting further evaluation. Liver histology demonstrated marked loss of BSEP immunoreactivity, and genetic testing identified a heterozygous ABCB11 variant. Despite treatment with ursodeoxycholic acid and cholestyramine, the symptoms persisted, leading to the introduction of the ileal bile acid transporter (IBAT) inhibitor, odevixibat, which resulted in rapid relief of pruritus and near-complete biochemical normalization within 2 months. Our review identified 32 published adult cases of B19-associated hepatitis. Most patients were immunocompetent, with presentations ranging from mild hepatic dysfunction to fulminant liver failure requiring transplantation. In more than half of the patients, predisposing factors such as hematologic disorders or viral co-infections were identified. This review highlights the importance of considering parvovirus B19 infection in the differential diagnosis of acute hepatitis in adults and of investigating potential underlying predisposing factors when the clinical course cannot be fully explained by the viral infection alone.