Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The hypervascular nature of the majority of HCCs and the peculiar vascular derangement occurring during liver carcinogenesis underscore the importance of angiogenesis in the development and progression of these tumors. Indeed, several angiogenic molecular pathways have been identified as deregulated in HCC. The hypervascular nature and the peculiar vascularization of HCC, as well as deregulated angiogenic pathways, represent major therapeutic targets. To a large extent, intra-arterial locoregional treatments (transarterial-(chemo)embolization) rely on tumor ischemia caused by embolization of tumor feeding arteries, even though this may represent the “primum movens” of tumor recurrence through the activation of neoangiogenesis. Considering systemic therapies, the currently available tyrosine kinase inhibitors (sorafenib, regorafenib, cabozantinib and lenvatinib) and monoclonal antibodies (ramucirumab and bevacizumab, in combination with the anti-PD-L1, atezolizumab) primarily target, among others, angiogenic pathways. Considering the importance of angiogenesis in the pathogenesis and treatment of liver cancer, in this paper, we aim to review the role of angiogenesis in HCC, addressing the molecular mechanisms, available antiangiogenic therapies and prognostic biomarkers in patients receiving these treatments.

Portal cavernoma cholangiopathy (PCC) is a rare condition characterized by abnormalities of the intrahepatic and extrahepatic bile ducts and the gallbladder, resulting from long-standing chronic portal vein thrombosis (cPVT). These vascular changes often occur in the setting of non-cirrhotic, non-neoplastic portal hypertension. Its prevalence among cPVT patients ranges from 4% to 92%, with an unweighted average of 45.2%, increasing to 67.0% in studies using magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP). Although most patients remain asymptomatic, about 25% develop symptoms. Diagnosis mainly depends on imaging, with MRCP being the most accurate choice. The classification proposed by Llop and colleagues provides a useful framework by integrating anatomical involvement with the severity of biliary disease. However, combining this classification with the pathophysiological one could support a more personalized treatment approach. Management depends on symptom presentation. Asymptomatic patients are managed conservatively. Symptomatic cases may require endoscopic interventions; plastic stents are most commonly used, although they have around a 30% risk of hemobilia and a high re-intervention rate of ~50%. Interventional radiology techniques, particularly portal vein recanalization with transjugular intrahepatic portosystemic shunt (TIPS), exhibit high technical success rates (median 91%) and patency rates (median 81.8%). Surgical portosystemic shunts remain a key option for a subgroup of patients, with about 65% achieving symptom resolution after decompression alone, whereas liver transplantation is rarely indicated. Given the rarity of this condition and the limited quality of existing studies, we conducted this systematic review to provide a comprehensive overview of the current literature and to promote a more standardized approach to managing PCC. This review aims to fill knowledge gaps and enhance consistency in treatment strategies for this complex condition.