Porto-sinusoidal vascular disorder (PSVD) is a rare, non-cirrhotic vascular liver disease characterised by portal venule and sinusoidal abnormalities leading to portal hypertension. Despite its clinical significance, the underlying pathophysiology has remained poorly understood.
Porto-sinusoidal vascular disorder (PSVD) is a rare, non-cirrhotic vascular liver disease characterised by portal venule and sinusoidal abnormalities leading to portal hypertension. Despite its clinical significance, the underlying pathophysiology has remained poorly understood. In this comprehensive review, Ciriaci et al. systematically evaluate genetic mutations associated with PSVD, offering critical insights into its mechanistic basis.
The authors identify 34 genes and one chromosomal abnormality previously linked to PSVD and report an additional mutation in TBL1XR1 (Pierpont syndrome). Genetic associations fall into two broad categories:
Syndromic PSVD – occurring in multisystem disorders (e.g., telomere biology disorders, immune deficiencies, cystic fibrosis, Williams-Beuren syndrome, Turner syndrome).
Isolated PSVD – involving mutations such as KCNN3, DGUOK, GIMAP5, FCHSD1, TRMT5, and HRG.
Most cases present clinically with complications of portal hypertension rather than early liver dysfunction. Importantly, gene expression analyses reveal predominant involvement of immune cells, suggesting that immune-mediated vascular remodelling may play a central role in disease development. Pathway analyses further support two mechanistic subtypes: one driven by morphogenetic vascular abnormalities, and another secondary to immune dysregulation.
Clinically, the review recommends next-generation sequencing panels for patients with early-onset PSVD, syndromic features, or a family history.
This work redefines PSVD as a genetically heterogeneous disorder and highlights immune pathways as promising targets for future research and therapeutic development.
Introduction: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary liver cancer with poor prognosis and limited treatment options. While ICC has traditionally been considered a malignancy of biliary epithelial cells, increasing evidence suggests that hepatocytes can...
Introduction: Liver fibrosis is the key determinant of long-term outcomes in metabolic dysfunction-associated steatohepatitis (MASH). Activated hepatic stellate cells (HSCs) drive fibrogenesis, but effective antifibrotic therapies remain unavailable. This study investigated whether blocking the succinate–GPR91...
Introduction: The progression from metabolic dysfunction-associated fatty liver (MAFL) to metabolic dysfunction-associated steatohepatitis (MASH) is driven by complex interactions between hepatocytes and immune cells. This study identifies a novel spatial mechanism in the periportal (PP)...
Introduction: Cardiovascular–Kidney–Metabolic (CKM) syndrome recognizes the close interaction between obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. This review highlights the emerging role of the gut microbiome, particularly butyrate-producing bacteria, as a central...
• Small intestinal adenocarcinoma (SIA) is a rare gastrointestinal cancer with limited disease-specific prognostic biomarkers and generally poor outcomes. • This nationwide Dutch population-based study evaluated whether three routinely available immunohistochemical markers—CK7, CK20, and CDX2—have...
Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is closely linked to insulin resistance and type 2 diabetes, with the liver traditionally viewed as a key regulator of blood glucose through hepatic glucose production. However, emerging...
We are pioneers in clinical intelligence, dedicated to helping gastroenterologists harness the power of artificial intelligence to drive precision, efficiency, and patient growth.