Idiopathic Portal Hypertension Research Articles

Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH).

Idiopathic non-cirrhotic portal hypertension (INCPH) is a vascular disorder of uncertain origin. Diagnosis can be challenging on liver biopsy. Despite diverse histomorphologic findings documented in literature, studies on the frequency of these findings are lacking. This study aims to assess both the histomorphologic features and the immunoexpression patterns of CD34 and glutamine synthetase (GS) in liver biopsies and searched for their contribution to the pathologic diagnosis of INCPH. Hematoxylin-eosin, CD34, and GS-stained liver needle biopsy sections of 16 patients clinically diagnosed with INCPH were retrospectively analyzed. Histologic findings such as portal vein narrowing, obliteration, or loss were grouped as major findings, while portal vein herniation, hypervascularized portal tracts, and periportal abnormal vessels were grouped as minor findings, and their frequency were evaluated. Periportal endothelial CD34 stained areas were measured via ocular micrometer. The distribution of GS immunoexpression was evaluated. Eighteen healthy liver donor biopsies were evaluated as controls. In INCPH cases, 58% of portal tracts showed major findings, compared to 15% in the control group (p < 0.001). Minor findings were observed in 16% of INCPH cases and 7% of controls (p = 0.014). The number of portal tracts with histologic findings is significantly higher in INCPH than in control liver biopsies. Abnormal portal tract distribution, like being close to each other, was seen in 75% of INCPH cases but not in controls (p < 0.001). Nodular regenerative hyperplasia (NRH) was present in 31% of cases. Periportal CD34 expression was higher in INCPH, and affected areas were larger than in controls (p < 0.001). Irregular GS staining, i.e. GS staining with patchy distribution in zone 3, and/or periportal and zone 2 hepatocytes, was found in 62% of INCPH cases, while controls showed the usual pattern (p < 0.001). In the biopsy diagnosis of INCPH, in addition to the presence of major histologic findings and the amount of portal tracts displaying these features, the expression of endothelial CD34 in periportal areas, and irregular hepatocellular GS expression can also be considered as supporting feature.

Idiopathic Portal Hypertension: A Case Report of an Adult Indian Rural Female of “Banti Syndrome”

Non-cirrhotic portal fibrosis (NCPF)/idiopathic portal fibrotic hypertension (IPH) is one of the major diseases that include a group of diseases caused by increased portal venous pressure which is thought to be due to intrahepatic or prehepatic lesions in the absence of liver cirrhosis. In the present case a 35-year-old female presented with abdominal fullness and pain in the upper abdomen for the past two months which was not associated with the consumption of water or food, nausea, or vomiting. When we investigated it was seen that she had severe anemia with pancytopenia with no malarial parasite on peripheral smear, liver renal and liver function tests were within the normal range. The diagnosis of Banti’s syndrome was made. However, the patient was then vitally stable and was started on propranolol and was advised for splenectomy due to refractory anemia. The present study provides easy and conventional diagnostic techniques for clinical diagnosis and proves the radiological technique.

Safety and effectiveness of SARS-CoV-2 vaccines for patients with intractable hepatobiliary diseases: A multicenter, questionnaire-based, cross-sectional study.

There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. Patients aged ≥18years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6months after the second vaccination. SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

Post-allogeneic Hematopoietic Stem Cell Transplantation Portal Hypertension Not Associated with Liver Cirrhosis, Veno-occlusive Disease, or Graft-versus-host Disease: A Case Report.

We herein report a rare case of idiopathic portal hypertension (IPH)-like disease that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A 53-year-old woman who underwent allo-HSCT for acute myeloid leukemia showed portal hypertension with radiological and histopathological findings consistent with IPH, distinct from veno-occlusive disease (VOD) and graft-versus-host disease (GVHD) of the liver. This case highlights the importance of considering IPH-like disease as a potential cause of portal hypertension after allo-HSCT. Awareness of this complication can aid in the early diagnosis and appropriate management of patients post allo-HSCT.

Case report: Oxaliplatin-induced idiopathic non-cirrhotic portal hypertension: a case report and literature review

Oxaliplatin has become a widely used agent in neoadjuvant chemotherapy for gastrointestinal tract tumors and is an integral part of the therapeutic approach for managing colorectal cancer recurrences and metastases, resulting in a more favorable prognosis for patients. Nevertheless, oxaliplatin can give rise to idiopathic non-cirrhotic portal hypertension (INCPH). The emergence of INCPH can disrupt tumor chemotherapy and incite persistent adverse reactions in later stages, significantly complicating clinical management. Consequently, we have presented a case report of INCPH induced by oxaliplatin chemotherapy with the aim of advancing the diagnosis and treatment of this condition, with a particular focus on the clinical manifestations. This study has ascertained that the condition is primarily attributed to complications related to portal hypertension, such as gastrointestinal bleeding, splenomegaly, and hypersplenism. The pathological features primarily involve hepatic sinus dilation and congestion, portal obstruction, absence, stenosis, shunting, localized venous and perisinusoidal fibrosis, as well as hepatocellular atrophy. Treatment primarily concentrates on strategies typically employed for cirrhosis. Endoscopic ligation, sclerotherapy, and non-selective beta-blockers (NSBBs) can be selected to prevent and treat variceal hemorrhage. Transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation can also be chosen for severe cases. Notably, despite the timely discontinuation of oxaliplatin, most patients continue to experience disease progression, ultimately resulting in a poor prognosis due to either tumor advancement or the ongoing progression of portal hypertension. This emphasizes the importance for physicians to be aware of and consider the risk of INCPH when prescribing oxaliplatin.

A Narrative Review on Non-Cirrohotic Portal Hypertension: Not All Portal Hypertensions Mean Cirrhosis.

Non-cirrhotic portal hypertension (NCPH), also known as idiopathic non-cirrhotic portal hypertension (INCPH) and porto-sinusoidal vascular disorder (PSVD), is a rare disease characterized by intrahepatic portal hypertension (IPH) in the absence of cirrhosis. The precise etiopathogenesis of IPH is an area of ongoing research. NCPH diagnosis is challenging, as there are no specific tests available to confirm the disease, and a high-quality liver biopsy, detailed clinical information, and an expert pathologist are necessary for diagnosis. Currently, the treatment of NCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied that aimed to modify the natural history of the disease; however, transjugular intrahepatic porto-systemic shunt (TIPS) placement, shunt and liver transplantation are considerable symptomatic options. In this review, we discuss the heterogeneity of NCPH as well as its etiopathogenesis, clinical presentation and management issues. Starting from the assumption that portal hypertension does not always mean cirrhosis, cooperative studies are probably needed to clarify the issues of etiology and the possible genetic background of this rare disease. This knowledge might lead to better treatment and perhaps better prevention.

S3561 Idiopathic Non-Cirrhotic Portal Hypertension With Type B Hepatic Encephalopathy Due to Obliterative Portal Venopathy Secondary to Systemic Lupus Erythematosus and Mixed Connective Tissue Disease

S3561 Idiopathic Non-Cirrhotic Portal Hypertension With Type B Hepatic Encephalopathy Due to Obliterative Portal Venopathy Secondary to Systemic Lupus Erythematosus and Mixed Connective Tissue Disease

P26 Felty’s syndrome as the first presentation of rheumatoid arthritis

Abstract Introduction Felty's syndrome (FS) is a rare, autoimmune disease occurring in &amp;lt; 1% of patients with rheumatoid arthritis (RA) and comprising a triad of persistent idiopathic neutropenia, splenomegaly and RA. In some affected individuals, FS may develop when the symptoms and signs of RA have subsided or are absent. In this case, FS may remain undiagnosed. In rare instances, the development of FS may precede the development of the clinical manifestation of RA. Case description A 73-year-old Caucasian gentleman presented in October 2017 with pancytopenia and splenomegaly. He was investigated by the haematology team with multiple bone marrow biopsies showing no underlying haematological causes for his pancytopenia. He was also investigated by the hepatologists for the possibility of liver cirrhosis as he had a heavy alcohol intake. His liver ultrasound showed fatty liver with splenomegaly, his fibro-scan showed fibrosis with no evidence of cirrhosis and his OGD showed no oesophageal varies. At this point, he was treated with blood transfusions, weekly erythropoietin and filgrastim as needed under the haematologists. In October 2022, he was admitted with febrile neutropenia and he gave a 20-year history of palindromic rheumatism with no evidence of synovitis or previous DMARD treatment. His rheumatoid factor (RF) was &amp;gt;120 iu/ml, anti-cyclic citrullinated peptide (ACCPA) was &amp;gt;340 u/ml and ANA by CIA was weakly positive (20.6 CU) with Hep-2 IFF being homogenous. ENA and dsDNA were negative. His hand X-ray showed evidence of osteoarthritis with no erosion. He subsequently had multiple admissions due to infections. CT chest, abdomen, and pelvis showed splenomegaly with portal vein dilatation suggestive of portal hypertension, normal liver appearance, and left lower lung bronchiectasis. Liver biopsy showed non-specific portal and sinusoidal inflammation, mild fibrosis, and architectural features suggestive of nodular regenerative hyperplasia indicative of FS. Furthermore, his HLA-DRB1*04 was positive. Together, these factors allowed us to diagnose FS. He was started on a tapered course of prednisolone, 30mg daily decreased by 10mg every two weeks, and methotrexate (10mg orally weekly) with careful blood monitoring. Two weeks later, he developed a mild rise in the ALT and alkaline phosphatase. Therefore, the methotrexate dose was reduced to 5mg weekly. Four weeks later, he reported feeling much better, with improvement in all his cell counts and liver function. Discussion While persistent idiopathic neutropenia and splenomegaly (present in 90% of FS patients) are salient features of FS, patients can also present with other extra-articular manifestations such as rheumatoid nodules (74%), hepatomegaly (68%), lymphadenopathy (42%), Sjögren's syndrome (48%), pulmonary fibrosis (50%), pleuritis (22%), peripheral neuropathy (14%) and leg ulcers (16%). Systemic symptoms include fever and weight loss. They also present with idiopathic non-cirrhotic portal hypertension, which can lead to variceal bleeding. The exact pathophysiology of FS is unclear, making the diagnosis and treatment of FS very challenging. A large multi-central cohort study found that FS is associated with HLA-DRB1*0401 and, in two other studies into the pathophysiology of FS, they found that 73% of patients with FS had IgG Anti-G-CSF and autoantibodies that bind to deaminated histones and neutrophil extracellular chromatin traps (NETs), leading to neutrophil sequestration. Therefore, treatment aims to control the underline RA, improve the neutrophil count, and prevent infection. The first challenge, in this case, was to confirm the diagnosis of FS in the absence of any obvious RA joint involvement and a history of heavy alcohol intake. Following an extensive investigation, we discussed his case at the Rare Disease MDT meeting and liaised with the haematology, hepatology, and histopathology teams to exclude the other differential diagnoses. The clues to the diagnosis of FS were the strongly positive RF and ACCPA, the positive HLA-DRB1*04, the liver biopsy, and the exclusion of other causes of neutropenia. The second challenge in this case was to safely start methotrexate, given his mild liver fibrosis and recurrent infections. With close blood test monitoring and follow-up, he achieved improvement in his cell count (WBC from 0.8 to 1.1x10 9/L, HB from 86 to 104 g/L, platelet from 70 to 91X109/L) with stable liver function. Key learning points Rheumatoid arthritis is a multisystem disease with variable presentations. Rarely, FS can occur in the absence of clinical manifestations of the erosive joint involvement of RA. In this situation, careful, thorough investigation to exclude other causes of neutropenia and prove the diagnosis of FS is imperative to justify immunosuppressive treatment. A multidisciplinary team working across specialties was pivotal in the safe diagnosis and treatment of this gentleman.

The Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis

Liver is the largest lymph-producing organ. In cirrhotic patients, lymph production significantly increases concomitant with lymphangiogenesis. The aim of this study was to determine the mechanism of lymphangiogenesis in liver and its implication in liver fibrosis. Liver biopsies from portal hypertensive patients with portal-sinusoidal vascular disease (n = 22) and liver cirrhosis (n = 5) were evaluated for lymphangiogenesis and compared with controls (n = 9 and n = 6, respectively). For mechanistic studies, rats with partial portal vein ligation (PPVL) and bile duct ligation (BDL) were used. A gene profile data set (GSE77627), including 14 histologically normal liver, 18 idiopathic noncirrhotic portal hypertension, and 22 cirrhotic patients, was analyzed. Lymphangiogenesis was significantly increased in livers from patients with portal-sinusoidal vascular disease, cirrhotic patients, as well as PPVL and BDL rats. Importantly, Schwann cells of sympathetic nerves highly expressed vascular endothelial growth factor-C in PPVL rats. Vascular endothelial growth factor-C neutralizing antibody or sympathetic denervation significantly decreased lymphangiogenesis in livers of PPVL and BDL rats, which resulted in progression of liver fibrosis. Liver specimens from cirrhotic patients showed a positive correlation between sympathetic nerve/Schwann cell-positive areas and lymphatic vessel numbers, which was supported by gene set analysis from patients with noncirrhotic portal hypertension and cirrhotic patients. Sympathetic nerves promote hepatic lymphangiogenesis in noncirrhotic and cirrhotic livers. Increased hepatic lymphangiogenesis can be protective against liver fibrosis.

Esophagoduodenal Varices in Non-cirrhotic Portal Hypertension with Myelodysplastic Syndrome: A Case Report

Background: Esophagogastroduodenal varices are dilated submucosal of distal esophageal, gastric, and duodenal veins connecting the portal and systemic circulation. This case report aims to describe a unique case of a child with esophagoduodenal varices due to myelodysplastic syndrome. Case: We reported a case of 3-year-old girl who came to Hasan Sadikin General Hospital on April 3 2022, complaining of black stools 1 time per day for two days before admission. She had previously been diagnosed with esophagogastroduodenal varices since 2019. On initial examination, the patient was fully conscious and appeared pale. The patient's clinical condition improved after adequate treatment of blood transfusion, octreotide, omeprazole and propanolol. However, patient later developed pancytopenia and underwent bone marrow puncture examination which revealed a myelodysplastic syndrome. Discussion: Myelodysplastic syndrome is a condition where ineffective hematopoiesis occurs and can lead to blood malignancy, especially acute myeloblastic leukemia. In this patient, she presented with unequivocal hypertensive gastroesophageal varices, splenomegaly, absence of fibrosis and thrombocytosis supporting subsequent diagnosis of idiopathic non cirrhosis portal hypertension. On the other hand, non-cirrhotic portal hypertension can also be caused by myelodysplastic syndrome as described in this case report. Conclusion: Myeloproliferative malignancies can be a cause of idiopathic non cirrhosis portal hypertension. Pancytopenia often occurs in patients with portal hypertension due to splenomegaly or myelodysplastic syndrome, which can lead to acute myeloblastic leukemia, an example of a myeloproliferative malignancy.

Porto-sinusoidal vascular disorder (PSVD): Application of new diagnostic criteria in a multicenter cohort of patients

Background and aimThe term porto-sinusoidal vascular disorder (PSVD) was recently proposed to replace that of idiopathic non-cirrhotic portal hypertension (INCPH) to describe patients with typical histological lesions in absence of cirrhosis, irrespective of the presence/absence of portal hypertension (PH), and new diagnostic criteria were defined. The study aimed to compare the applicability between the diagnostic criteria of PSVD and those of INCPH. Materials and methods53 patients affected by PSVD were enrolled. Biochemical, clinical, ultrasound and histological data, the presence and type of associated diseases were recorded in a database. According to the new criteria, histological data and signs of PH were divided into specific and non-specific. Percutaneous and transjugular biopsies were compared to establish the usability of the two methods for diagnostic purposes. ResultsIn 85% of the patients the diagnosis of PSVD was obtained by applying the first criterion (25 had specific histological signs with specific signs of PH); one patient presented with specific histological signs but no PH. In 8 patients the diagnosis was obtained by applying the second criterion. 19% of patients had portal vein thrombosis. Finally, the prevalence of the various histological lesions was similar between the patients submitted to percutaneous and transjugular liver biopsy. ConclusionsThe study confirms that the diagnostic criteria of PSVD lead to the inclusion of a greater number of patients than INCPH.

Idiopathic non-cirrhotic portal hypertension in a patient with Talaromyces marneffei infection: a case report

BackgroundThe etiopathogenesis of idiopathic non-cirrhotic portal hypertension (INCPH) is so far poorly understood. Altered immunity, blood diseases, infections, congenital defects and drug exposure have been documented in a part of patients with INCPH owing to increased recognition of the disorder in patients with HIV, or various haematological disorders or autoimmune diseases. We aim to discuss the possible etiopathogenesis of INCPH.Case presentationWe reported that a patient with intestinal infection of T. Marneffei and hyper-IgE syndrome, a group of rare primary immunodeficiency disorders, was finally diagnosed with INCPH for gastroesophageal variceal bleeding. The diagnosis was mainly based on histopathological features. Transjugular intrahepatic portosystemic shunt was performed and there was no recurrence of melena during the six-month follow-up.ConclusionIn the context of immunodeficiency, INCPH may associated with intestinal infections. Thus, screening for enterogenic infection and immunological disorders in patients with unexplained portal hypertension is necessary.

Performance of spleen stiffness measurement by 2D-shear wave elastography in evaluating the presence of high-risk varices: comparative analysis of idiopathic portal hypertension versus hepatitis B virus

BackgroundNoninvasive assessment of high-risk varices (HRV) in idiopathic portal hypertension (IPH) is rare. The purpose of this study was to investigate the performance of spleen stiffness (SS) for evaluating the presence of HRV in IPH patients as compared the measurements in patients with hepatitis B virus (HBV).MethodsA retrospective single-center study was performed to evaluate the performance of SS for assessing HRV in IPH and HBV-infected patients, in comparison with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), LS spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension risk score (PH risk score) and varices risk score, by using upper gastrointestinal endoscopy (UGE) as the gold standard. Finally, 86 IPH and 102 HBV-infected patients were enrolled. UGE, two-dimensional shear wave elastography (2D-SWE) and laboratory data were collected, and noninvasive parameters were calculated. Analysis of receiver operating characteristic (ROC) curves was conducted to acquire the optimal area under the ROC curve (AUC) and cutoff value for predicting the presence of HRV.ResultsIn patients with HRV, the significantly different parameters between IPH (34.9%) and HBV-infected patients (46.1%) were as follows: spleen size (diameter 18.5 ± 3.9 cm vs. 20.8 ± 2.7 cm), SS (50.2 kPa vs. 42.9 kPa), LS (11.1 kPa vs. 18.3 kPa) and PT (prothrombin time 15.1 s vs. 16.7 s). No statistically significant differences were found in liver function, platelet counts, spleen thickness and flow volumes in the portal venous system (p > 0.05). The AUCs of SS were 0.98 and 0.96 for predicting the presence of HRV in IPH (44.0 kPa cutoff value; 0.93 sensitivity; 0.96 specificity) and HBV-infected patients (35.2 kPa cutoff value; 1.00 sensitivity; 0.82 specificity), respectively, which were significantly better than other parameters.ConclusionSS shows the optimal overall performance for predicting the presence of HRV in IPH and HBV-infected patients, in comparison with other noninvasive parameters.

Portal vein thrombosis, hepatic decompensation, and survival in patients with porto-sinusoidal vascular disease and portal hypertension.

Porto-sinusoidal vascular disease (PSVD) is a novel nomenclature to describe non-cirrhotic portal hypertension and characteristic histology without portal vein thrombosis (PVT). It is a more inclusive definition than the previously well-recognized entity idiopathic non-cirrhotic portal hypertension. There is a paucity of data on PSVD patients. A total of 33 patients diagnosed with PSVD and portal hypertension (PH) between 2005 and 2021 were included. Data were retrieved from electronic medical record system and analyzed. Of the 33 patients, 6 (18%) occurred in post-transplant allograft liver. After a median follow-up of 96months (interquartile range, IQR [52, 139]), 14 deaths occurred (42%), 4 directly related to decompensated liver disease. The Kaplan-Meier survival estimates at 1, 5, and 10years were 94%, 87% and 58%. PVT occurred in 10 patients (30%). The Nelson-Aalen cumulative risk estimate for PVT at 1, 5 and 10years were 16%, 25% and 48%. The median model for end-stage liver disease and Child-Pugh score at initial presentation were 8 (IQR [7-12]) and 5 [5-6], and increased to 13 [8, 18] and 7 [5, 8], respectively, at the end of follow-up. Of the 11 patients who presented with splenomegaly and no specific sign of PH, 7 (64%) developed varices and 3 (27%) ascites at a median follow-up of 100months. PSVD with PH is not a benign entity. Mortality, PVT and hepatic decompensation are common. Patients with PSVD must be closely monitored, including those who only have non-specific clinical signs (e.g., splenomegaly) of PH.

Short Telomere Syndromes and Inherited Predisposition to Bone Marrow Diseases: The MDACC Experience

Introduction: Telomeres are noncoding nucleotide repeats at chromosomal ends, which provide genomic stability and are maintained and regulated by specific protein complexes. Their length physiologically decreases with age, although it is known that germline mutations in telomeric regulators can accelerate this process, which is related to a wide variety of clinical situations. Herein we report on the experience of patients diagnosed with Short Telomere Syndromes (STS) evaluated in the Hereditary Hematologic Malignancy Clinic (HHMC) of the MD Anderson Cancer Center. Methods: We retrospectively analyzed clinical characteristics and outcomes of patients with a diagnosis of STS referred or diagnosed in the HHMC. Germline mutation origin was confirmed by genetic analysis of cultured skin fibroblasts or blood/saliva in patients without hematologic disease. Telomere length was assessed by Flow-FISH techniques in a clinically validated external laboratory (John Hopkins Medical Laboratories, Baltimore, MD). Individuals with confirmed STS were recommended to follow a specialized cancer surveillance program to achieve early-diagnosis or prevention of potential complications related to STS. A baseline bone marrow evaluation was recommended to evaluate underlying morphology and assess for somatic comutations. Results: A total of 24 patients with STS were identified (13 males, 54%), with a median age of presentation to the clinic of 53 years old (5-78). Although the reasons of referral for STS testing for each individual patient were diverse, they can be summarized in these categories: unexplained cytopenia (n=9), myeloid malignancy with relevant PMH or FH (n=8), affected sibling (n=5), skin lesions (n=1) and multiple cancer diagnosis (n=1). Pathogenic or likely pathogenic germline variants were confirmed in the TERT gene (n=13, 54%), TERC gene (n=7, 29%), RTEL1 (n=2, 8%), while 2 patients had no telomere-related detectable mutations (Figure 1). Telomere flow-FISH confirmed age-predicted telomere length <1st percentile for age in 67(%). All patients underwent a bone marrow biopsy, being described as hypocellullar in 17 patients (71%). With the bone marrow evaluation, eleven patients were diagnosed with myelodysplastic syndrome (MDS, 46%), two patients with acute leukemia (myeloid and mixed phenotype, 8%), two patients with clonal cytopenia of unknown significance (CCUS, 8%), one aplastic anemia (4%) and eight patients (33%) did not have hematologic malignancy. During the follow-up, three patients underwent an allogeneic stem cell transplantation due to their hematologic disease. Solid neoplasms are frequent in patients with STS, and 11 patients (46%) had a PMH of at least one solid tumor with a median age of 54 (33-78 yrs). Squamous cell carcinoma was the most frequent histology (6/11 patients). Sixteen patients (67%) had a positive FH of cancer in one or more first or second-degree sibling. Pulmonary fibrosis (PF) was diagnosed in 4 patients (17%), two with TERT mutations and two with TERC mutations. Moreover, 7 patients (4 diagnosed with PF,30%) had a positive FH of PF in first degree siblings. Liver diseases were also frequent: 3 patients had non-alcoholic hepatic cirrhosis, one patient had chronic hepatitis with periportal fibrosis and one with idiopathic portal hypertension. One patient had received a liver transplantation and one required a lung transplantation prior to presentation to the HHMC. Finally, twelve patients (50%) were reported to have premature grey hair and eight patients were reported to have nail dysplasia and/or skin abnormalities related to STS (such as unexplained reticular rash). A summary of the described patients is depicted in Figure 2. Conclusion: STS are genetic diseases that can go unnoticed until adulthood. Patients with myeloid malignancies (especially MDS) with hypocellular bone marrow and suspicious findings (i.e. FH or PMH of PF, premature grey hair, long standing cytopenias) should be considered for underlying STS. An early diagnosis is essential to start cancer surveillance programs and provide timely genetic counseling to the patient and relatives. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Bioinformatics Analysis of Common Genetic and Molecular Traits and Association of Portal Hypertension with Pulmonary Hypertension.

Portal hypertension (PH) is an important cause of pulmonary arterial hypertension(PAH), but its mechanism is still unclear. We used genetic data analysis to explore the shared genes and molecular mechanisms of PH and PAH. We downloaded the PH and PAH data from the GEO database, and used the weighted gene coexpression network analysis method (WGCNA) to analyze the coexpression modules of idiopathic noncirrhotic portal hypertension (INCPH) and cirrhotic portal hypertension (CPH) and pulmonary hypertension, respectively. Enrichment analysis was performed on the common genes, and differential gene expressions (DEGs) were used for verification. The target genes of INCPH and PAH were obtained by string and cytoscape software, and the miRNAs of target genes were predicted by miRwalk, miRDB, and TargetScan and their biological functions were analyzed; finally, we used PanglaoDB to predict the expression of target genes in cells. In WGCNA, gene modules significantly related to PAH, CPH, and INCPH were identified, and enrichment function analysis showed that the common pathway of PAH and CPH were “P53 signaling pathway,” “synthesis of neutral lipids”; PAH and INCPH are “terminal,” “Maintenance Regulation of Granules,” and “Toxin Transport.” DEGs confirmed the results of WGCNA; the common miRNA functions of PAH and cirrhosis were enriched for “P53 signaling pathway,” “TGF-β signaling pathway,” “TNF signaling pathway,” and “fatty acid metabolism,” and the miRNAs-mRNAs network suggested that hsa-miR-22a-3p regulates MDM2 and hsa-miR-34a-5p regulates PRDX4; the target genes of PAH and INCPH are EIF5B, HSPA4, GNL3, RARS, UTP20, HNRNPA2B1, HSP90B1, METAP2, NARS, SACM1L, and their target miRNA function enrichment showed EIF5B, HNRNPA2B1, HSP90B1, METAP2, NARS, SACM1L, and HSPA4 are associated with telomeres and inflammation, panglaoDB showed that target genes are located in endothelial cells, smooth muscle cells, etc. In conclusion, the mechanism of pulmonary hypertension induced by portal hypertension may be related to telomere dysfunction and P53 overactivation, and lipid metabolism and intestinal inflammation are also involved in this process.

Noninvasive assessment of the risk of esophageal variceal bleeding from noncirrhotic portal hypertension

Objective: To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH). Methods: 111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results: Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively (P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 (P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups (P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively (P<0.05). Conclusion: Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.

Porto-sinusoidal vascular disorder.

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term.

S3117 Partial Splenic Artery Embolization for Patients With Portal Hypertension Undergoing Organ Transplant Evaluation: A Case Series

Introduction: Partial splenic artery embolization (PSAE) is an infrequently utilized approach to reduce portal hypertension (PHT) by reducing splenic arterial inflow and thereby splenic vein flow into the portal vein. We describe three patients who underwent PSAE to address diverse manifestations of PHT due to contraindications to transjugular intrahepatic portosystemic shunts (TIPS). Case Description/Methods: Case 1: A 50-year-old male with CKD stage 4 and idiopathic PHT had diuretic-refractory ascites and thrombocytopenia, precluding surgery for an arteriovenous fistula (AVF) and kidney transplantation. He was not a candidate for TIPS due to extensive portal vein thrombosis but underwent PSAE leading to resolution of ascites and marked improvement in thrombocytopenia (Figure 1). The patient ultimately received an AVF and was placed on the kidney transplant waitlist. He has been followed for 30 months with sustained clinical improvement. Case 2: A 60-year-old male with prior hepatocellular carcinoma (HCC) status post right partial hepatectomy and hepatitis C cirrhosis complicated by severe thrombocytopenia and refractory ascites, had two previously aborted TIPS procedures due to unusual hepatic vein anatomy. He underwent PSAE that led to a reduction in frequency of therapeutic paracenteses and improvement of thrombocytopenia (Figure 1). Eight months later, TIPS was reattempted and resulted in complete ascites control for over six years. He is currently on the waitlist for liver transplantation. Case 3: A 60-year-old male had cryptogenic cirrhosis complicated by mild ascites, significant thrombocytopenia, and massive splenomegaly with mass effects. He underwent successful PSAE to alleviate splenic compression of the bladder. One year later, he had a repeat PSAE for diaphragmatic compression secondary to splenic hypertrophy. His thrombocytopenia also mildly improved (Figure 1). The patient was declined for liver transplant due to lack of social support. He expired from advanced HCC after two years of follow-up. Discussion: We report three cases of PSAE in patients with PHT awaiting organ transplantation. All three cases had improvement in ascites, splenomegaly, and thrombocytopenia. Although PSAE is not the primary treatment for PHT, it may have a therapeutic role in advanced cases, particularly in transplant candidates when other interventions like TIPS are not possible. Future studies should be conducted to further evaluate the role of PSAE in patients with PHT awaiting organ transplantation.Figure 1.: *2nd PSAE attempt in case 3 represented at time 0.

S3239 A Case of Idiopathic Non-Cirrhotic Portal Hypertension (INCPH) in a Patient With Klebsiella pneumoniae Pyogenic Liver Abscess (PLA)

S3239 A Case of Idiopathic Non-Cirrhotic Portal Hypertension (INCPH) in a Patient With Klebsiella pneumoniae Pyogenic Liver Abscess (PLA)