Sarah Shalaby

Background and Aims: Assessing liver congestion and portal hypertension (PHT) in Budd–Chiari syndrome (BCS) remains challenging. We evaluated liver and spleen stiffness measurements (LSM, SSM) obtained by transient elastography as non‐invasive tools for identifying clinically meaningful liver congestion in BCS. Methods: This retrospective study included consecutive patients with BCS followed at our unit. At each visit, patients were classified as having a controlled or uncontrolled clinical status based on clinical, biochemical, imaging and/or hemodynamic data, by absence or presence of clinically significant PHT. LSM and SSM were independently obtained at all visits and diagnostic performance for classifying clinical status was assessed using receiver operating characteristic (ROC) analysis. Results: Sixty‐six patients were included with a median follow‐up of 65.5 months (range:2–182): 34 had persistently controlled status, 11 persistently uncontrolled, 14 initially uncontrolled improved to sustained controlled status and 7 showed fluctuating status. Two‐hundred eighty‐nine LSM were obtained during periods of controlled clinical status (median:15. 1 kPa , IQR :10.9–19.9) and 203 during uncontrolled status (median: 41. 1 kPa , IQR : 34.8–64.5). LSM discriminated controlled from uncontrolled status ( AUC 0.985). LSM cut‐off of 25 kPa yielded 97.5% sensitivity, 92.5% specificity, 97.6% negative predictive value and 90% positive predictive value. SSM showed good discrimination ( AUC 0.854), with values ≤ 30 kPa ruling out and > 40 kPa ruling in uncontrolled status, but accuracy was inferior to LSM . LSM values rapidly decreased following liver congestion resolution after interventional procedures. Conclusions: In BCS, LSM shows excellent concordance with clinical status and periodic assessment may facilitate clinical management. SSM provides complementary information but does not outperform LSM.

Background and Aims: Portal vein thrombosis (PVT) is a frequent complication of cirrhosis, yet its pathophysiology remains elusive. Unlike thrombosis in other vascular beds, anticoagulation often fails to completely recanalize PVT, highlighting the need for greater mechanistic insight and alternative therapeutic approaches. Our study aimed to characterize the structural and cellular changes in the portal venous vascular bed to identify novel physiologically driven therapeutic targets. Approach and Results: Portal vein tissue specimens from explanted livers of patients with cirrhosis with and without PVT and from liver donors were histologically analyzed. PVT is associated with a remarkable eccentric thickening of the tunica intima due to accumulation of extracellular material and tunica intima increased cellularity. Transcriptomic analysis of human portal vein endothelial cells (PVEC) from patients with PVT identified the endothelial-to-mesenchymal transition (EndMT) pathway upregulated in PVECs from patients with PVT. In silico drug repurposing analysis identified statins as potential agents targeting these alterations. In vitro treatment with statins attenuated hallmarks of EndMT in primary human PVECs. Conclusions: In cirrhosis, the portal vein endothelium undergoes maladaptive remodeling marked by eccentric intimal hyperplasia, driven by ECM accumulation and infiltration of inflammatory and myofibroblast-like cells. This process narrows the lumen and may promote PVT. EndMT plays a key role in this transformation and emerges as a novel and promising therapeutic target. Notably, statins can attenuate EndMT, highlighting its potential in PVT treatment.

Hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis presents significant treatment challenges due to the impaired liver function, altered pharmacokinetics, and systemic inflammation associated with advanced liver disease. This review explores the complexities of managing HCC in this high-risk population, focusing on the pharmacological considerations and the impact of cirrhosis on drug metabolism, treatment efficacy, and adverse effects. Studies indicate that drugs metabolized by the liver, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), accumulate in patients with decompensated cirrhosis, increasing the risk of toxicity. Additionally, portal hypertension and systemic inflammation further complicate treatment, limiting the effectiveness of both systemic therapies and immunotherapy. This article discusses potential strategies, including dose adjustments, pharmacokinetic monitoring, and combination therapies, to optimize treatment outcomes.

Venous thromboembolic events (VTE) represent a significant and common complication in patients with hepatocellular carcinoma (HCC) in the context of cirrhosis. While some patient-related risk factors for VTE are shared with the non-cirrhotic population, the presence of HCC amplifies the risk, potentially due to the pro-thrombotic paraneoplastic alterations associated with the tumor. This review aims to examine the current evidence regarding hemostatic disorders observed specifically in cirrhotic patients with HCC. Additionally, the review comprehensively examines VTE events in cirrhotic patients with HCC, specifically emphasizing portal vein thrombosis (PVT). PVT is the most common thrombotic complication in this population and can have significant implications for the eligibility and success of treatment modalities such as liver transplants or surgical interventions. Identifying risk factors associated with PVT occurrence in these patients is essential to guide preventive measures and enhance patient outcomes. This review aims to provide a clear background for further research and investigations into effective prevention and treatment strategies for VTE in cirrhotic patients with HCC by comprehensively revising the current evidence on these topics.

Portal vein thrombosis (PVT) is a frequent event among patients with advanced liver disease, with a prevalence reaching up to 26% in those awaiting liver transplantation (LT). Extensive thrombosis affecting the mesenteric vein confluence correlates with increased morbidity and mortality post-LT, particularly when it impedes physiological anastomosis or contraindicates the LT. Current guidelines advocate for routine PVT screening in all potential liver transplant candidates and prompt treatment upon detection. The main objective in LT candidates is to facilitate physiological portal-to-portal anastomosis. Anticoagulation serves as the first-line therapy, achieving recanalization rates between 33 and 75%. Discontinuation of anticoagulation significantly heightens the risk of rethrombosis in a substantial proportion of patients and therefore, it is recommended to continue anticoagulation until LT for those awaiting LT or potential LT candidates. Nevertheless, 30-60% of patients fail to respond to anticoagulation, with PVT progression occurring in up to 14% despite anticoagulation. In such cases, TIPS placement emerges as a viable alternative to maintain portal vein patency. While the feasibility of TIPS placement diminished with the presence of portal cavernoma or chronic portal vein thrombosis, the introduction of novel interventional radiological techniques to recanalize the portal venous axis through transplenic, transmesenteric and/or transhepatic routes is revolutionizing this landscape. These advancements achieve TIPS placement and recanalization in 90-100% of patients, warranting consideration in cirrhotic patients with chronic PVT for whom LT would otherwise be contraindicated or when physiological anastomosis is not feasible. Export

Acute variceal bleeding in cirrhosis represents a critical clinical event that significantly impacts patient prognosis, with mortality rates increasing further after a second episode. This underscores the need for immediate intervention and optimal prophylaxis. The creation of a transjugular intrahepatic portosystemic shunt (TIPS) has been proven to be highly effective for managing esophageal variceal bleeding. However, the use of TIPS for managing cardiofundal gastric varices and ectopic varices remains debated due to their unique vascular anatomy and the limited data available. These varices, although less prevalent than esophageal varices, are complex and heterogeneous vascular shunts between the splanchnic venous system and the systemic veins. Indeed, while endoscopic therapy with tissue adhesives is widely endorsed for achieving hemostasis in active hemorrhage, there is no consensus regarding the optimal approach for secondary prophylaxis. Recent research emphasizes the efficacy of endovascular techniques over endoscopic treatments, such as TIPS and endovascular variceal embolization techniques. This review examines the use of TIPS in managing acute variceal bleeding in patients with cirrhosis, focusing specifically on cardiofundal gastric varices and ectopic varices, discussing optimal patient care based on the latest evidence, aiming to improve outcomes for this challenging subset of patients.