Porto-Sinusoidal Vascular Disorder-Spectrum Portal Venopathy as a Structural Substrate for Portal Hypertension in Anti-Centromere Antibody-Positive Primary Biliary Cholangitis.

Abstract

Anti-centromere antibody (ACA) positivity in primary biliary cholangitis (PBC) has been associated with a portal hypertension-dominant clinical trajectory, even without advanced fibrosis. This study investigated whether porto-sinusoidal vascular disorder (PSVD)-spectrum portal venopathy may underlie this phenotype. This retrospective case-series study included three ACA-positive PBC-spectrum patients who underwent liver biopsy. The clinical characteristics, imaging findings, liver and spleen stiffness, hepatic venography, and hepatic venous pressure gradient (HVPG) were evaluated. Liver specimens were assessed for PSVD-spectrum portal venopathy and PBC-related bile duct injury. All patients presented with PSVD-spectrum portal venopathy on liver biopsy; PBC-defining bile duct lesions were present in two patients, and the presence of ductular reaction was suggestive of a biliary disease but not diagnostic for PBC in one patient. All patients had manifestations of portal hypertension with preserved liver synthetic function and noncirrhotic liver stiffness. The portal sandwich sign was present in all patients. When available, spleen stiffness was markedly elevated, indicating spleen-liver stiffness dissociation. HVPG was heterogeneous, with normal values in two patients and marked elevation in one patient. In summary, PSVD-spectrum portal venopathy may contribute to disproportionate portal hypertension in ACA-positive PBC-spectrum patients but constitutes a diagnostic gray zone because PBC is defined as exclusionary in PSVD definitions.