Porto-Sinusoidal Vascular Disorder-Spectrum Portal Venopathy as a Structural Substrate for Portal Hypertension in Anti-Centromere Antibody-Positive Primary Biliary Cholangitis.
Ando Y, Mabuchi S, et al. • Pathology international • 2026
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.
Key Findings
Results
All three ACA-positive PBC-spectrum patients who underwent liver biopsy demonstrated PSVD-spectrum portal venopathy.
This was a retrospective case-series study with three patients total.
All patients had ACA positivity in the context of primary biliary cholangitis (PBC) or PBC-spectrum disease.
Liver specimens were assessed for both PSVD-spectrum portal venopathy and PBC-related bile duct injury.
PBC-defining bile duct lesions were present in two of the three patients; the third had ductular reaction suggestive of biliary disease but not diagnostic for PBC.
Results
All three patients manifested portal hypertension with preserved liver synthetic function and noncirrhotic liver stiffness.
Portal hypertension was present in all patients despite the absence of advanced fibrosis.
Liver stiffness measurements were in the noncirrhotic range for all three patients.
This pattern is consistent with a portal hypertension-dominant clinical trajectory previously associated with ACA positivity in PBC.
Preserved liver synthetic function indicated that parenchymal liver disease was not the primary driver of the clinical presentation.
Results
The portal sandwich sign was present in all three patients on imaging.
The portal sandwich sign was identified as a consistent imaging finding across all cases.
This sign was evaluated as part of a multimodal assessment including imaging findings, liver and spleen stiffness, hepatic venography, and hepatic venous pressure gradient (HVPG).
Results
Spleen stiffness was markedly elevated when available, indicating spleen-liver stiffness dissociation.
Spleen-liver stiffness dissociation was identified as a notable finding in cases where spleen stiffness measurement was available.
Markedly elevated spleen stiffness in the setting of noncirrhotic liver stiffness constitutes the dissociation pattern described.
This pattern may reflect significant portal hypertension disproportionate to the degree of hepatic fibrosis.
Results
HVPG values were heterogeneous across the three patients, with normal values in two patients and marked elevation in one.
Two of three patients had normal HVPG values despite clinical manifestations of portal hypertension.
One patient had markedly elevated HVPG.
Heterogeneous HVPG findings suggest that portal hypertension in this population may be presinusoidal in origin in some cases, consistent with PSVD pathophysiology.
Normal HVPG in the setting of clinical portal hypertension is characteristic of presinusoidal or sinusoidal-level vascular disorders such as PSVD.
Discussion
The co-occurrence of PSVD-spectrum portal venopathy and PBC creates a diagnostic gray zone because current PSVD definitions exclude PBC as a diagnosis.
PSVD is formally defined as an exclusionary diagnosis, with PBC listed among the conditions that preclude a PSVD diagnosis.
The study identifies this as a 'diagnostic gray zone' for patients with concurrent histological evidence of both conditions.
The authors suggest that PSVD-spectrum portal venopathy may contribute to disproportionate portal hypertension in ACA-positive PBC-spectrum patients.
This finding raises questions about whether current nosological boundaries between PSVD and PBC adequately capture overlapping or concurrent pathology.
What This Means
This research suggests that a specific type of liver blood vessel disorder, called porto-sinusoidal vascular disorder (PSVD), may help explain why some patients with a liver disease called primary biliary cholangitis (PBC) develop high blood pressure in the portal vein (the large vein supplying the liver) even when their liver scarring is minimal. The study focused on patients who tested positive for a particular antibody called anti-centromere antibody (ACA), which has previously been linked to this unusual pattern of high portal pressure without severe liver damage. In all three patients examined, the liver biopsies showed features of PSVD alongside signs of PBC, and all patients had evidence of portal hypertension despite their livers not appearing cirrhotic by standard stiffness measurements. A notable additional finding was that the spleen — which enlarges when portal pressure is high — appeared much stiffer than expected relative to the liver, and a specific imaging pattern called the 'portal sandwich sign' was seen in all cases.
The study also found that a standard test for portal pressure (the hepatic venous pressure gradient, or HVPG) gave normal results in two of the three patients even though they clearly had signs of portal hypertension. This suggests the high pressure was occurring in a part of the circulation that this test does not fully capture, which is typical of PSVD. Together, these findings point to PSVD as a likely structural contributor to the unusual clinical course seen in ACA-positive PBC patients.
However, this research highlights a significant diagnostic challenge: current medical definitions of PSVD explicitly exclude patients who have PBC, meaning these patients fall into a 'diagnostic gray zone' where neither diagnosis fully applies. This matters because the correct diagnosis influences treatment decisions and disease monitoring. The findings suggest that future diagnostic frameworks may need to reconsider how these two overlapping conditions are classified, and that clinicians evaluating ACA-positive PBC patients with unexplained portal hypertension should consider the possibility of concurrent vascular liver disease.