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BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) is an under-recognized and under-diagnosed disease. The purpose of this study was to investigate the clinical features and prognosis of PSVD. METHODS: The patients who underwent liver biopsies were analyzed retrospectively. The clinical and pathological data were reviewed and screened according to the latest diagnostic criteria of PSVD. RESULTS: A total of 234 patients were diagnosed as PSVD, including 103 patients presented with portal hypertension (PH) and 131 patients without PH. At baseline, the alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) levels were higher in the no-PH group. The liver stiffness increased in the PH group. In histological review, obliterative portal venopathy, sinusoidal dilatation and architectural disturbance were more common in the PH group, while portal tract abnormalities were more widely distributed in the no-PH group. After a median follow-up of 43.6 months, the survival rate of patients with baseline liver decompensation was 76.0%, and that of patients at a liver compensated stage in the PH group was 98.7%. First variceal bleeding occurred in 13.8% of patients with gastric-oesophageal varices. None of the patients in the no-PH group developed portal hypertension during follow-up. CONCLUSIONS: PSVD can manifest as PH or mild liver enzyme abnormalities. There are significant differences in pathological features among patients with different clinical manifestations. Recurrent ascites are the main cause of death in PSVD patients. However, patients without PH have a slow disease progression, with recurrent elevated GGT levels being their main clinical feature.

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Porto-sinusoidal vascular disease (PSVD) is the medical diagnosis for a patient who has portal hypertension in the absence of cirrhosis on liver biopsy. There are several specific histologic findings for PSVD, including obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. Epidemiologic reports vary widely among regions; PSVD comprises less than 10% of causes of portal hypertension in Western countries but incidence has been found to be as high as 48% in India. There is an expansive list of etiologies that have been reported to cause PSVD.

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La enfermedad vascular porto-sinusoidal es una causa infrecuente de hipertensión portal no cirrótica, fue descrita recientemente y es poco diagnosticada por el desconocimiento entre los médicos. Se considera en casos de hipertensión portal clínicamente significativa, en ausencia de cirrosis. El diagnóstico se basa en los hallazgos de la biopsia. El pronóstico de la enfermedad es mejor que el de los pacientes cirróticos, y el tratamiento es similar al de la hipertensión portal y al de las complicaciones que presentan los pacientes con cirrosis. Se presenta el caso de una paciente con várices esofágicas con estudios de imágenes no compatibles con cirrosis y hallazgos específicos en la biopsia de enfermedad vascular porto-sinusoidal. Este caso muestra el ejercicio diagnóstico en un caso de enfermedad vascular porto-sinusoidal de una paciente de Colombia, así como el resultado de las intervenciones terapéuticas y la evolución en el tiempo.

Porto-sinusoidal vascular disease is an uncommon cause of non-cirrhotic portal hypertension. It was recently described and is rarely diagnosed due to lack of knowledge among doctors. It is considered in cases of clinically significant portal hypertension in the absence of cirrhosis, and the diagnosis is based on biopsy findings. The prognosis of the disease is better than that of cirrhotic patients, and the treatment is similar to that of portal hypertension, including the management of complications associated with cirrhosis. We present the case of a patient with esophageal varices, whose imaging studies were not compatible with cirrhosis, alongside specific biopsy findings of porto-sinusoidal vascular disease. This case illustrates the diagnostic process in a patient from Colombia with portosinusoidal vascular disease, as well as the outcomes of therapeutic interventions and the patient´s evolution over time.

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Porphyria caused by inherited disorders in heme biosynthesis can lead to accumulation of porphyrins in various organs. Liver involvement due to porphyria mostly results in cholestasis leading to liver cirrhosis or hepatocellular carcinoma. Congenital erythropoietic porphyria (CEP), a rare porphyria due to deficiency of uroporphyrinogen III synthase, mostly results in cutaneous manifestations. There are reports of liver involvement including varying degree of fibrosis in patients with CEP. We report a unique case of a patient with CEP who developed porto-sinusoidal vascular disease with complications of portal hypertension that necessitated liver transplantation.

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Background & Aims: Porto-sinusoidal vascular disorder (PSVD) encompasses a group of liver diseases with vascular abnormalities that can cause portal hypertension in the absence of cirrhosis. The new diagnostic criteria allow for coexistence with other liver diseases, however its relationship with chronic hepatitis B (CHB) remains unclear. This study aimed to assess HBV prevalence in a PSVD cohort and evaluate its clinical impact. Methods: This retrospective study was conducted on patients with PSVD at Hospital Clínic Barcelona. HBV serology was evaluated, and patients were categorized into HBV chronic infection, past infection, or no HBV exposure. Clinical characteristics and outcomes were compared. Results: We included 155 patients with PSVD. Prevalence of CHB and past HBV infection in patients with PSVD was higher than in the general population (5.8% vs. 0.5%, p <0.0001 and 20% vs. 9.1%, p <0.0001, respectively). Patients with CHB had a significant delay in PSVD diagnosis compared to those without CHB (11 [5-25] vs. 1 [0-3] years, p = 0.002) and had a more advanced disease (MELD score 12 [9-17] vs. 9 [7-11], p = 0.012) at the time of PSVD diagnosis. The clinical evolution of PSVD in patients with CHB was marked by a significantly higher transplantation rate at the last follow-up (33% vs. 4.1%, p = 0.001). Conclusions: Recognizing the coexistence of PSVD and CHB is important for timely diagnosis and optimal management, highlighting the potential benefits of specialized care for potentially improved outcomes. Impact and implications: The new diagnostic criteria for porto-sinusoidal vascular disorder (PSVD) allow for coexistence with other liver diseases. The results of the present study highlight, for the first time, a non-negligible prevalence of chronic hepatitis B in the PSVD population that was previously unknown. Coexistence may challenge and delay the PSVD diagnosis and is associated with a more unfavorable clinical course. Our findings will increase awareness of this coexistence and improve PSVD diagnosis and management. Furthermore, the data will encourage new studies to determine the prevalence and clinical behavior of other chronic liver diseases that coexist with PSVD.

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BACKGROUND: Porto-sinusoidal vascular disease (PSVD) and portal vein thrombosis (PVT) are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system. As PVT may be a consequence of PSVD, in PVT patients at presentation, a pre-existing PSVD should be suspected. In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management, but it could be challenging. In this setting ultrasonography may be valuable in differential diagnosis. The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and "pure" PVT and then to suspect PVT secondary to a pre-existing PSVD. METHODS: Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse (ARFI). RESULTS: ARFI was higher and superior mesenteric vein (SMV) diameter was wider in PSVD patients than in PVT patients. Thus, a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT (the area under the curve = 0.780; 95% confidence interval: 0.690-0.869). CONCLUSIONS: A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.

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BACKGROUND: Porto-sinusoidal vascular disorder (PSVD) involves a group of rare vascular liver diseases of unknown aetiology that may lead to the development of portal hypertension and its life-threatening complications. Its pathophysiology is not well understood, and animal models described to date do not fully recapitulate human disease. METHODS: We developed three different PSVD rat models by either immunosensitization (repetitive intraportal LPS or intramuscular spleen extract injections) or toxic (Selfox: combination of FOLFOX and a selenium-enriched diet) treatment and characterized them at haemodynamic, histological, biochemical and transcriptional levels. We compared these results to human data. RESULTS: All three models developed significant portal hypertension, while only the LPS and the Selfox models displayed PSVD-specific and nonspecific histological alterations in the absence of cirrhosis. Transcriptional comparison between rat models and human data showed that both LPS and Selfox models recapitulate the main transcriptional alterations observed in humans, especially regarding haemostasis, oxidative phosphorylation and cell cycle regulation. Reproducibility and feasibility was higher for the Selfox model. CONCLUSIONS: The Selfox rat model faithfully reproduces the main alterations described in PSVD. Its use as a preclinical model for drug testing in progressing PSVD can be a significant step forward towards the development of new therapeutic targets for this rare condition.

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Porto-sinusoidal vascular disease （PSVD） is a new disease nomenclature proposed in recent years， which is an important supplement to idiopathic non-cirrhotic portal hypertension. PSVD includes the patients with specific pathological conditions， but without portal hypertension symptoms， and the patients with portal vein thrombosis or viral hepatitis. This article elaborates on the naming， epidemiology， etiology， clinical manifestations， prognosis， and treatment of PSVD， in order to improve the understanding of this disease among clinicians.

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Introduction: Porto-sinusoidal vascular syndrome is characterised by specific histological changes that do not include cirrhosis, with or without portal hypertension. Patients are usually asymptomatic until development of portal hypertension complications. Case description: A 69-year-old female with history of JAK2 positive essential thrombocythemia (ET) was referred to internal medicine consultation due to elevated liver enzymes. The patient had no previous history of liver disease. Seven months earlier, she had an ischaemic stroke and started treatment with atorvastatin. After discontinuing medication, liver enzymes returned to normal and atorvastatin-related drug-induced liver disease (DILI) was presumed.During a follow-up visit, iron deficiency anaemia was detected and an endoscopic study was performed. It revealed a gastric varix actively bleeding, which was successfully treated with cyanoacrylate.Two months later, the patient was admitted due to a new episode of variceal bleeding, and a portal hypertension complementary study was made. Discussion: Although the pathogenesis of porto-sinusoidal vascular disease (PSVD) remains poorly understood, vascular changes within the liver have been associated with several predisposing conditions, such as hypercoagulable states. Patients with ET, especially those with JAK2 mutation, are known to be at increased risk of non-cirrhotic vein thrombosis. Concerning PSVD, the association is not clear but it is believed that both PSVD and myeloproliferative neoplasms share a common denominator: a state characterised by hypercoagulability, inflammation, endothelial dysfunction and, in some cases, portal hypertension. Conclusion: Portal hypertension without cirrhosis is a rare condition, presenting diagnostic challenges and significant impact on the patient's prognosis. LEARNING POINTS: The suspicion of PSVD should be raised when signs of portal hypertension are present with normal or mildly elevated liver enzymes and normal liver stiffness measurement. A liver biopsy should be performed in this situation.Although the pathogenesis of PSVD is not clearly understood, it is based on the development of vascular changes within the liver and there might be several predisposing conditions such as coagulation disorders.

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BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) has been described as the prominent pathology in liver explants of patients with cystic fibrosis (CF), but data outside the transplant setting are lacking. We aimed to investigate the prevalence of portal hypertension (PH) in CF-associated liver disease (CFLD) and develop an algorithm to classify liver involvement in CF patients. METHODS: This is a cross-sectional study of consecutive paediatric and adult patients in a tertiary centre between 2018 and 2019, who underwent ultrasound, liver (LSM) and spleen stiffness (SSM) measurement. CFLD was defined according to physical examination, liver tests and ultrasound findings. PSVD was likely if there were PH signs in the absence of advanced chronic liver disease (CF-ACLD, LSM <10 kPa). A historical cohort was used to validate the prognostic significance of the new definitions. RESULTS: Fifty (27.5%) patients met CFLD criteria. At least one sign of PH was found in 47 (26%) patients, but most (81%) had LSM <10 kPa and were likely to have PSVD; only 9 (5%) had CF-ACLD. PSVD and CFLD (LSM <10 kPa) co-existed in most (23/36) cases. In the historical cohort (n = 599 patients), likely PSVD and CFLD+PH were independently associated with a 2-fold and 3.5-fold increase in mortality compared to patients without PH, respectively. In 34 patients with SSM, values <21 and >50 kPa accurately diagnosed specific signs of PH. CONCLUSIONS: PSVD is the prevailing cause of PH in CF patients. We developed a new diagnostic algorithm based on clinical and elastosonography criteria to classify liver involvement in patients with CF.

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BACKGROUND: Hepatic encephalopathy, (HE) although commonly associated with cirrhosis, has also been reported in non-cirrhotic portal hypertension (NCPH). The importance of identifying and treating HE in NCPH lies in the fact that many patients may be wrongly diagnosed as having psychiatric or neurologic disorders. Hence, we aimed to systematically review the prevalence of HE in NCPH. METHODS: A comprehensive search of three databases (Medline, Embase and Scopus) was conducted from inception to November 2022 for studies reporting on the prevalence of minimal HE (MHE) and overt HE (OHE) in patients with NCPH. Results were presented as pooled proportions with their 95% confidence intervals (CI). RESULTS: Total 25 studies (n = 1487) were included after screening 551 records. The pooled prevalence of MHE in NPCH was 32.9% (95% CI: 26.7-39.0) without any difference between adult (32.9%, 95% CI: 23.5-42.3) and pediatric patients (32.6%, 95% CI: 26.1-39.1) (p = 0.941). There was no significant difference in the prevalence between patients with NCPH and compensated cirrhosis with odds ratio of 1.06 (95% CI: 0.77-1.44). The pooled event rate for prior history of OHE in NCPH was 1.2% (95% CI: 0.3-2.1). CONCLUSION: Around one-third of the patients with NCPH have MHE, irrespective of age group. OHE is extremely rare in NCPH and is usually associated with a precipitating factor.

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Although cirrhosis is one of the most common causes of portal hypertension, noncirrhotic portal hypertension can result from hemodynamic perturbations occurring in the prehepatic, intrahepatic, and posthepatic circulation. Intrahepatic portal hypertension can be further subclassified relative to the hepatic sinusoids as presinusoidal, sinusoidal, and postsinusoidal. For many of these differential diagnoses, the etiology is known but the cause of idiopathic noncirrhotic portal hypertension, recently included in porto-sinusoidal vascular disease (PSVD), remains poorly understood. Herein, we discuss the diagnostic pathological features of noncirrhotic portal hypertension, with an emphasis on PSVD.

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INTRODUCTION: In patients with portal hypertension (PH), the differential diagnosis between porto-sinusoidal vascular disease (PSVD) and cirrhosis is challenging. This study aims to evaluate the diagnostic accuracy of the SSM/LSM index in the diagnosis of PSVD. METHODS: Prospective study of patients with PH and PSVD or cirrhosis. Transient liver and spleen elastography were performed and the ratio between spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) was calculated. The relation of SSM/LSM with the diagnosis of PSVD was evaluated. RESULTS: Forty-four patients with PSVD and 44 patients with cirrhosis were evaluated. Median age was 57.5 (IQR 49.0-64.5) years, 66.3% were males. In patients with PSVD, median SSM was 59.4 (33.5-77.7) kPa, median LSM was 6.2 (5.2-10.2) kPa and median SSM/LSM was 5.62 (3.15-9.68). In patients with cirrhosis, median SSM was 47.3 (24.3-60.3) kPa, median LSM was 27.8 (17.7-53.9) kPa and median SSM/LSM was 1.55 (1.06-3.24). The SSM/LSM AUROC was 0.940 (p<0.001). Using 2 as a cut-off, we obtained good sensitivity (86.5%), specificity (92.7%), and accuracy (89.7%) for the diagnosis of PSVD. CONCLUSION: The SSM/LSM index is useful in the differential diagnosis between liver cirrhosis and PSVD. Using the cut-off of 2 we achieved a good sensitivity and specificity for diagnosing PSVD.

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Porto-sinusoidal vascular disease (PSVD) is defined as a vascular liver disease characterized by the absence of cirrhosis and the presence of characteristic histological features, with or without the presence of portal hypertension (PH). Half of the patients with PSVD also have associated disease that may contribute to the development of PSVD. Patients usually remain asymptomatic until complications of PH arise. Variceal bleeding and portal vein thrombosis are major complications associated with PSVD. The treatment is focused on managing complications of PH, mainly through primary prophylaxis of variceal bleeding and treatment of portal vein thrombosis. Currently, there is insufficient evidence to support the use of anticoagulants for thrombosis prevention in these patients. Despite the increase of recognition of PSVD, further research is needed to enable early disease diagnosis, establish optimal screening methods, and develop strategies to slow down disease progression.

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Oxaliplatin, widely used as a chemotherapy drug for colorectal cancer, is known to cause various adverse reactions. In particular, special attention for the development of portal hypertension associated with porto-sinusoidal vascular disease is necessary, as it is a serious adverse life-threating reaction, although rare. We herein report a case of oxaliplatin-related portal hypertension that developed several years after oxaliplatin administration and led to esophageal varices and refractory massive ascites. Clinical physicians should be aware of the possibility of oxaliplatin-induced portal hypertension and its possible development over a long period after discontinuation of the drug.

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Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population. Cystic fibrosis-related liver disease (CFLD) is defined as the pathogenesis related to the underlying CFTR defect in biliary epithelial cells. CFLD needs to be distinguished from other liver manifestations that may not have any pathological significance. The clinical/histological presentation and severity of CFLD vary. The main histological presentation of CFLD is focal biliary fibrosis, which is usually asymptomatic. Portal hypertension develops in a minority of cases (about 10%) and may require specific management including liver transplantation for end-stage liver disease. Portal hypertension is usually the result of the progression of focal biliary fibrosis to multilobular cirrhosis during childhood. Nevertheless, non-cirrhotic portal hypertension as a result of porto-sinusoidal vascular disease is now identified increasingly more frequently, mainly in young adults. To evaluate the effect of new CFTR modulator therapies on the liver, the spectrum of hepatobiliary involvement must first be precisely classified. This paper discusses the phenotypic features of CFLD, its underlying physiopathology and relevant diagnostic and follow-up approaches, with a special focus on imaging.

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BACKGROUND: Oxaliplatin is a key drug for the chemotherapy of colorectal cancer; however, it is also known to cause non-cirrhotic portal hypertension. We aimed to identify the characteristics of patients who developed esophagogastric varices (EGVs) after treatment with oxaliplatin. METHODS: This study retrospectively analyzed patients with colorectal cancer who were treated with chemotherapy including oxaliplatin between 2010 and 2016. All patients were evaluated by contrast-enhanced computed tomography (CE-CT) every 3 months both during and after treatment; and endoscopy was performed when appearance of portal hypertension was suspected. RESULTS: A total of 106 patients were divided into two groups: EGV formation (n = 6) and EGV non-formation (n = 100). In the EGV group, platelet counts decreased and the size of the spleen calculated by CT (CT spleen index; CT-SI) increased markedly. The highest area under the receiver operating characteristic curve (AUC) for the change in platelet counts was 0.81 (80% sensitivity and 83% specificity) at 3 months post treatment, and the maximum AUC for CT-SI was 0.89 (79% sensitivity and 83% specificity) at 6 months post treatment. CONCLUSIONS: EGV formation could be predicted by the assessment of platelet counts and spleen size. If progressive splenomegaly and thrombocytopenia are observed not only during but also after completion of the oxaliplatin-containing chemotherapy, EGVs should be confirmed by endoscopy for avoiding subsequent rupture.

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BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) is a rare disease that requires excluding cirrhosis and other causes of portal hypertension for its diagnosis because it lacks a specific diagnostical test. Although it has been occasionally associated with autoimmune diseases, the pathophysiology of PSVD remains unknown. The aim of this study was to evaluate the potential role of autoimmunity in the pathophysiology and diagnosis of PSVD. METHODS: Thirty-seven consecutive patients with PSVD and 39 with cirrhosis matched by gender, signs of portal hypertension and liver function were included (training set). By using Indirect Immunofluorescence, ELISA and slot-blot methods data 22 autoantibodies were identified in patients with PSVD and cirrhosis. Presence of anti-endothelial cells antibodies (AECA) was assayed by a cell-based ELISA. Thirty-one PSVD, 40 cirrhosis patients, 15 patients with splenomegaly associated with haematological disease and 14 healthy donors were included in a validation set. FINDINGS: The proportion of patients with at least one positive antibody was statistically significantly higher in patients with PSVD compared with cirrhosis (92% vs 56%; P < .01). Specifically, AECA were significantly more frequent in PSVD than in cirrhosis (38% vs 15%; P = .013). Results were confirmed in the validation set. In the overall population, presence of AECA had a 63% positive predictive value for diagnosing PSVD and a 71% negative predictive value, with a specificity of 94% when the 1/16 level is used as cut-off. AECA positive serum samples react with a 68-72 kDa protein of human liver endothelial sinusoidal cells.

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BACKGROUND & AIMS: Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD. METHODS: We obtained liver tissue samples from 20 consecutive patients with PSVD and 21 sex- and age-matched patients with cirrhosis and 13 histologically normal livers (HNL) (initial cohort) and performed transcriptomic analysis. Microarray data were analyzed using weighted gene correlation network analysis to identify clusters of highly correlated genes differently expressed in patients with PSVD. We next evaluated the molecular pathways enriched in patients with PSVD and the core-related genes from the most significantly enriched pathways in patients with PSVD. Our main findings were validated using RNA sequencing in a different cohort of PSVD, cirrhosis and HNL (n = 8 for each group). RESULTS: Patients with PSVD have a distinctive genetic profile enriched mainly in canonical pathways involving hemostasis and coagulation but also lipid metabolism and oxidative phosphorylation. Serpin family (SERPINC1), the apolipoproteins (APOA, APOB, APOC), ATP synthases (ATP5G1, ATP5B), fibrinogen genes (FGB, FGA) and alpha-2-macroglobulin were identified as highly connective genes that may have an important role in PSVD pathogenesis. CONCLUSION: PSVD has a unique transcriptomic profile and we have identified deregulation of pathways involved in vascular homeostasis as the main pathogenic event of disease development. LAY SUMMARY: Porto-sinusoidal vascular disease is a rare but life-shortening disease that affects mainly young people. Knowledge of the disrupted pathways involved in its development will help to identify novel therapeutic targets and new treatments. Using a systems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease.

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Common variable immunodeficiency disorders (CVID) are the most common symptomatic primary antibody deficiency in adults with an estimated prevalence of 1/25,000. The most frequent clinical manifestations are upper respiratory tract infections (including pneumonia, bronchitis, and sinusitis) predominantly with Streptococcus pneumoniae or H. influenzae. However, CVID are complicated in 20 to 30 % of cases of non-infectious manifestations which have been well characterized in recent years. Several complications can be observed including autoimmune, lymphoproliferative, granulomatous or cancerous manifestations involving one or more organs. These complications, mostly antibody-mediated cytopenias, are correlated with a decrease in the number of circulating switched memory B cells. Replacement therapy with polyvalent gammaglobulins has greatly improved the prognosis of these patients but it remains poor in the presence of digestive complications (especially in the case of chronic enteropathy and/or porto-sinusoidal vascular disease), pulmonary complications (bronchiectasis and/or granulomatous lymphocytic interstitial lung disease) and when progression to lymphoma. Much progress is still to be made, in particular on the therapeutic management of non-infectious complications which should benefit in the future from targeted treatments based on knowledge of genetics and immunology.

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