Background
In 2019, VALDIG proposed the term of porto-sinusoidal vascular liver disease (PSVD) to describe a group of rare vascular liver entities characterized by histological lesions involving portal venules and/or sinusoids and absence of cirrhosis, with or without signs of portal hypertension (1). Recently, the Baveno VII consensus workshop preferred the term “disorder” instead of “disease” so that PSVD now stands for “porto-sinusoidal vascular liver disorder”. PSVD is defined as follows:
- Adequate liver biopsy (≥20 mm long, and not too fragmented, or considered adequate for interpretation by an expert pathologist) or liver explant without cirrhosis AND one sign specific for portal hypertension or one histological lesion specific for PSVD;
- Or adequate liver biopsy (≥20 mm long, and not too fragmented, or considered adequate for interpretation by an expert pathologist) or liver explant without cirrhosis AND one sign not specific for portal hypertension AND one histological lesion not specific for PSVD.
Table. Criteria in the definition of PSVD according to Baveno VII conference (2)
| Feature of portal hypertension | Histological lesions suggestive of PSVD assessed by an expert pathologist | |
| Specific | – Gastric, esophageal or ectopic varices
– Portal hypertensive bleeding – Porto-systemic collaterals at imaging |
– Obliterative portal venopathy (thickening of vessel wall, occlusion of the lumen, vanishing of portal veins)
– Nodular regenerative hyperplasia – Incomplete septal fibrosis (also called incomplete septal cirrhosis); this latter feature can only be assessed on liver explants and not on liver biopsies |
| Not specific | – Ascites
– Platelet count < 150’000/mm3 – Spleen size ≥13 cm in the largest axis
|
– Portal tract abnormalities (multiplication, dilatation of arteries, periportal vascular channels, aberrant vessels)
– Architectural disturbance: irregular distribution of the portal tracts and central veins – Non-zonal sinusoidal dilatation – Mild perisinusoidal fibrosis |
In patients with compensated advanced chronic liver disease (cACLD), liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) ≥25 kPa is sufficient to rule in clinically significant portal hypertension (CPSH) (2). The performance of spleen stiffness measurement (SSM) by VCTE to diagnose CSPH is also excellent (3). Moreover, liver stiffness and spleen stiffness are associated with the risk of decompensation in cACLD. In 2 508 patients with more than 8 000 reliable LSM, Semmler et al. observed that a 20% increase in LSM was associated with a 50% increased risk of hepatic decompensation and liver-related death (4). Notably, the performance of LSM dynamics was better than single-time point LSM, and than dynamics in MELD. SSM by VCTE can also predict clinical decompensation in cACLD (5).
Patients with PSVD and portal hypertension usually have liver stiffness values much lower than those with cirrhosis; thus, cut-offs for clinically significant portal hypertension established in patients with cirrhosis cannot be used in this population (6). However, SSM by VCTE is independently associated with high-risk varices in patients with PSVD, and a model combining SSM by VCTE ≤40 kPa and total serum bilirubin <1 mg/dL identifies patients with PSVD and signs of portal hypertension with a probability of HRV <5% (VALDIG study, submitted). In a retrospective VALDIG study gathering 587 patients with PSVD and signs of portal hypertension, LSM by VCTE was available in 393 patients at baseline and was not associated with patients’ outcome (VALDIG study, submitted). However, no study assessed the potential value of changes in LSM over time, nor the interest of SSM, to predict patient outcome.
Design
Part I: Derivation cohort of patients with PSVD
The learning cohort will include 200 patients who underwent a liver biopsy between 2012 and 2023 at Hôpital Beaujon (Clichy, France) showing PSVD and at least one liver and / or spleen stiffness measurements by vibration-controlled transient elastography using FibroScan® and / or by 2D-shear-wave elastography. All liver biopsies have already been reviewed by a pathologist expert in vascular liver diseases (Prof. Valérie Paradis, Hôpital Beaujon, Clichy, France). Diagnosis of PSVD will be based on VALDIG criteria, as stated in Baveno VII consensus.
Part II: Validation cohort of patients with PSVD
The validation cohort will include PSVD patients from participating VALDIG centers fulfilling the same inclusion criteria.
Inclusion criteria
- Patients with PSVD and signs of portal hypertension according to VALDIG criteria (please see above). Signs of portal hypertension should be present at the time of liver biopsy (i.e. within 1 year before or after liver biopsy);
- And at least one liver and / or spleen stiffness measurement by vibration-controlled transient elastography using FibroScan® and / or by 2D-shear-wave elastography.
Non-inclusion criteria
- Cavernoma or complete portal vein thrombosis at the time of liver biopsy or liver / spleen stiffness measurement;
- Other cause of portal hypertension (Budd-Chiari syndrome, cardiac insufficiency, Fontan surgery, hereditary hemorrhagic telangiectasia, Abernethy syndrome, history of bone marrow transplantation, chronic cholestatic disease, liver infiltration by tumor cells, hepatic schistosomiasis diagnosed on liver biopsy);
- History of transjugular intrahepatic portosystemic shunt at the time of liver / spleen stiffness measurement;
- Tense ascites at the time of first liver / spleen stiffness measurement.