Porto-sinusoidal vascular disease (PSVD) has recently been redefined as the grouping of diverse conditions previously included within noncirrhotic portal hypertension. It is characterized by vascular alterations at the sinusoidal level and in the portal microcirculation, in the absence of cirrhosis and with no evidence of portal vein thrombosis. A distinctive aspect of the new definition is that PSVD may occur in patients with portal hypertension, as well as in those without it, as long as there are characteristic histologic lesions.1,2

The recent conceptualization of PSVD seeks to standardize the diagnosis through the integration of clinical, radiologic, and histopathologic data. Even though its pathophysiology is not fully understood, consistent lesions, such as obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis, have been described. Diagnosis requires the ruling out of cirrhosis through adequate liver biopsy and the identification of either specific clinical signs or the histologic alterations that have been described.2,3

PSVD is considered a rare disorder that predominantly affects young adults and whose clinical spectrum is heterogeneous. Its recognition is essential, given that the prognosis and therapeutic approach differ substantially from those of cirrhosis, making differential diagnosis more relevant. In general, patients with PSVD have better preserved liver function, a lower risk of hepatocellular carcinoma, and a more favorable long-term prognosis.4,5

We conducted a retrospective review of 10 cases clinically diagnosed with PSVD at the Hospital General Dr. Manuel Gea González, within the time frame of 2022 and 2024.

Diagnosis was made in accordance with the recently defined criteria, requiring liver biopsy that confirmed the absence of cirrhosis and at least one of the following:

• 1)

  Specific clinical signs of portal hypertension (esophageal or gastric varices, upper gastrointestinal bleeding due to portal hypertension, portosystemic collaterals)

• 2)

  Nonspecific signs of portal hypertension (ascites, platelets <150,000/µL, spleen >13 cm) accompanied by a nonspecific histologic lesion (portal tract and central vein abnormalities or irregular distribution, non-zonal sinusoidal dilation, mild perisinusoidal fibrosis)

• 3)

  A specific histologic lesion of PSVD (obliterative portal venopathy, nodular regenerative hyperplasia, incomplete septal fibrosis).2,3

Clinical, laboratory, imaging data (Fig. 1), and histopathologic findings (Fig. 2) were systematically collected. The present case-by-case review enabled phenotype heterogeneity to be characterized and highlighted the importance of integrating radiologic and histologic methods for making the diagnosis.

Figure 1.

Selected radiologic findings. (A) Contrast-enhanced CT in the venous phase showing chronic portal vein thrombosis with multiple collateral vessels at the hepatic hilum. (B) Coronal contrast-enhanced CT in the portal phase showing a patent portal vein and smooth hepatic surface. (C) Ultrasound showing splenomegaly. (D) Doppler ultrasound revealing slow flow. (E) Venous-phase CT showing hypertrophy of the caudate lobe. (F and G) Doppler ultrasound of the hepatic veins showing loss of normal triphasic pattern. (H) Two-dimensional shear-wave elastography (2D-SWE) showing normal liver stiffness. (I–K) B-mode ultrasound demonstrating thickening of the portal vein wall. (L) B-mode ultrasound showing a markedly dilated splenic vein.

Figure 2.

Illustrative liver biopsy findings. (A and B) Nodular regenerative hyperplasia with irregular nodular parenchyma and large hepatocytes forming nodules, surrounded by atrophic cells (H&E 40× and 20×). (C and D) Pericentral collapse and nodular pattern of the parenchyma; atrophic hepatocytes positive for CK7 and nodular regeneration, with sinusoidal CD34 expression (20× and 40×). (E) Irregular portal tracts with sclerosis and partial stenosis (H&E 400×). (F) Obliterative portal venopathy with marked portal vein stenosis (PAS 400×). (G) Incomplete septal fibrosis with sinusoidal dilation and loss of portal venules (H&E 40×). (H) Portal herniation with aberrant vessels in direct contact with hepatocytes (PAS 200×). (I) Sinusoidal dilation with endothelial prominence and a spongiform pattern in zones 2 and 3 (H&E 40×). (J) Lymphocytic margination and apoptotic debris within sinusoids (H&E 400×). (K and L) Bridging fibrosis (incomplete septal fibrosis), with multiple thin-walled vascular structures, megasinusoids, and periportal phlebosclerotic changes (Masson 40× and 400×).

In this case series of ten Mexican patients with PSVD, female sex was predominant (F7:M3), mean age at disease presentation was 49.7 years (34–65), and mean spleen size was 12.87 cm (10.8–15). The most frequent clinical presentation was signs of portal hypertension: large esophageal varices in 6 patients, small varices in one patient, and no varices in 3 patients; ascites was documented in 2 cases and splenomegaly in 6 patients. The most frequent laboratory abnormality was mild thrombocytopenia, with a mean platelet count of 167.6 ± 6.3 × 103/μL. Portosystemic collaterals were identified in 4 patients and portal vein thrombosis in 2 patients, findings that reflect significant vascular involvement (Table 1). Human immunodeficiency virus (HIV) infection, prothrombotic disorders, hematologic diseases, drug-related causes, and immunologic diseases were ruled out in all cases. No histologic findings compatible with schistosomiasis were observed.

Women made up 70% of the cases, suggesting a possible sex-associated predisposition. Imaging studies revealed portal vein patency in most of the cases, with diameters between 0.7 and 1.56 cm. Noninvasive liver stiffness assessment was carried out through vibration-controlled transient elastography (VCTE) and shear wave elastography (SWE). VCTE showed mean liver stiffness of 6.01 kPa (3.5–12.1), and SWE showed mean liver stiffness of 5.67 kPa (2.7–9.1), both consistent with the absence of cirrhosis. Controlled attenuation parameter (CAP) values varied from 180 to 284 dB/m, corresponding to absent or grade 1 steatosis. Liver biopsy revealed obliterative portal venopathy, anomalous vascular spaces, portal fibrosis, and perisinusoidal fibrosis, as well as nodular regenerative hyperplasia or mild steatosis is some cases. The most frequent microscopic findings included megasinusoids and mild portal fibrosis (Fig. 2). Those results show the marked clinical, radiologic, and histologic heterogeneity of PSVD and underscore the importance of integrating multiple diagnostic modalities for an individualized approach, especially in patients with portal vein thrombosis or chronic liver disease.

Th present study describes the clinical, radiologic, and histologic characteristics of a Mexican cohort with PSVD, reaffirming its heterogeneity and associated diagnostic challenges. Upper gastrointestinal bleeding was the most frequent presentation, consistent with previous case series showing that signs of portal hypertension tend to be disproportionate to preserved liver function. The combination of splenomegaly and mild thrombocytopenia, commonly observed in our cohort, should lead to suspicion of PSVD, especially in patients with no history of liver disease.

The presence of portal vein thrombosis in some cases confirms the participation of complex vascular mechanisms. Even though management is predominantly supportive, liver transplantation is considered in refractory cases.6

PSVD etiology is broad and includes hematologic disorders, prothrombotic states, immunologic diseases, drug-related conditions, and genetic syndromes. The identification of more than 30 associated genes, including TBL1XR1, strengthens the hypothesis of immune-mediated endothelial injury as a key mechanism. Unlike cirrhosis, PSVP tends to have a favorable prognosis, with a low risk of hepatocellular carcinoma, but the presence of ascites and comorbidities may worsen outcomes.2,5

Hepatosplenic schistosomiasis continues to be the main differential diagnosis worldwide. However, given that the disease is not endemic in Mexico, the absence of such cases in our case series highlights the relevance of considering PSVD in non-exposed populations.7,8

The diagnostic approach utilized, which integrated liver biopsy and imaging studies, enabled high diagnostic accuracy. In particular, periportal hyperintensity on magnetic resonance imaging was useful for distinguishing PSVD from cirrhosis, a finding consistent with those of other case series. Internationally described mortality rates (15–20% at 8 years) and transplant rates (5–37%) coincide with the disease evolution observed in our cohort.

Advanced age, comorbidities, and ascites were associated with poorer prognosis, in line with previously described predictors. Nevertheless, important knowledge gaps remain that require multicenter studies for a deeper pathophysiologic analysis, better characterization of clinical phenotypes, and optimized therapeutic strategies.9,10

The recent redefinition of PSVD enables a more accurate diagnosis to be made in patients with hepatic vascular alterations in the absence of cirrhosis. In our case series, the predominant manifestations included upper gastrointestinal bleeding, thrombocytopenia, portosystemic collaterals, and portal vein thrombosis, consistent with international case series.

The current diagnostic criteria, integrating histologic findings and signs of portal hypertension, have broadened the spectrum of identified cases. Magnetic resonance imaging revealing periportal hyperintensity was particularly useful for differentiating PSVD from cirrhosis.

The increasing identification of associated genes supports the role of immune system and endothelial dysfunction mechanisms in the pathogenesis. Early recognition is essential due to the persistent underdiagnosis and the possibility of preventing complications through adequate surveillance.

Multicenter studies with a larger number of cases are needed to more provide a deeper understanding of the pathophysiologic mechanisms, refine the diagnostic criteria, and improve management. A better understanding of PSVD will contribute to more accurate identification and improved clinical results in this still under-recognized disease.

No experiments were conducted on animals or humans for the present article, and the data publication protocol of our work center were followed, preserving patient anonymity.

No specific grants were received from public sector agencies, the business sector, or non-profit organizations in relation to this study.