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AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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BACKGROUND AND AIM: The 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 METHODS: 53 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. RESULTS: In 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. CONCLUSIONS: The study confirms that the diagnostic criteria of PSVD lead to the inclusion of a greater number of patients than INCPH.

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Objective To with analyzing the gene expression profile of idiopathic non-cirrhotic portal hypertension(INCPH)by bioinformatics methods,we may obtain its key genes and signaling pathways to explore the molecular mechanism of INCPH and predict the potential traditional Chinese medicine.Methods The gene microarray dataset GSE77627 on INCPH was downloaded from gene expression omnibus(GEO)database,the data were normalized and screened for differential genes(DEGs)of INCPH using R language,and all DEGs were analyzed for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment using Metascape database,and protein-protein interaction network was constructed by STRING database;meanwhile DEGs with the top 15 Degree values were screened as key genes using CytoHubba plugin.Subsequently,the key genes were mapped to each other with the medical ontology information retrieval platform(coremine medical)to screen potential Chinese herbal medicines for the treatment of INCPH with P<0.05,and the potent components that potential Chinese medicines have were screened from the TCMSP database,imported into Cytoscape software to construct a Chinese medicine correlation network map and predict the key targets.Results A total of 1880 DEGs were screened,including 1061 up-regulated and 819 down-regulated genes.DEGs were analyzed using the protein interaction database STRING and cytoHubba in Cytoscape software to obtain key genes,which were RPS27A,CDC42,EIF4E,MAPK1,PIK3R1,RPS6,RPS9,RPS8,RPL15,RPL27A,RPL24,RPL27,RPL26,RPL12 and MAPK14.The GO and KEGG analysis mainly involved gamete production and AGE-RAGE signaling pathway in INCPH.Conclusion The potential traditional Chinese medicines screened for INCPH are Ginseng Radix et Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Scutellariae Radix,etc,which may be a potential source of molecular drugs for the treatment of INCPH.

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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.

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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.

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DGUOK deficiency has primarily been associated with lethal hepatic failure with or without hypotonia, nystagmus, and psychomotor retardation, features typical of mitochondrial disease. A study in 3 Turkish children identified homozygosity for a variant in DGUOK as associated with idiopathic non-cirrhotic portal hypertension (INCPH). However, no further instances of INCPH associated with DGUOK variants have been reported. We here describe a fourth patient with DGUOK variants and childhood-onset INCPH, a 12-year-old Han Chinese boy, reporting clinical manifestations, histopathologic findings, and results of genetic studies. The child presented with hepatosplenomegaly; portal hypertension and hypersplenism were found. Vascular changes with hepatic fibrosis (Scheuer score 3) were observed on liver biopsy. Whole-exome sequencing and family analyses revealed compound heterozygosity for the DGUOK (NM_080916.3) variants c.778_781dup, (p.Thr261Serfs*28) and c.831_832del, (p.*278Thrfs*9) in the proband. These observations support ascription of instances of INCPH in children to variation in DGUOK.

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Backgrounds/Aims: Proximal splenorenal shunt (PSRS) is a commonly performed procedure to decompress portal hypertension, in patients with refractory variceal bleed, especially in non-cirrhotic portal hypertension (NCPH). If conventional methods are hindered by any technical or pathological factors, alternative surgical techniques may be required. This study analyzes the effectiveness of various unconventional shunt surgeries performed for NCPH. Methods: A retrospective analysis of NCPH patients who underwent unconventional shunt surgeries during the period July 2011 to June 2022 was conducted. All patients were followed up for a minimum of 12 months with doppler study of the shunt to assess shunt patency, and upper gastrointestinal endoscopy to evaluate the regression of varices. Results: During the study period, 130 patients underwent shunt surgery; among these, 31 underwent unconventional shunts (splenoadrenal shunt [SAS], 12; interposition mesocaval shunt [iMCS], 8; interposition PSRS [iPSRS], 6; jejunal vein-cava shunt [JCS], 3; left gastroepiploic-renal shunt [LGERS], 2). The main indications for unconventional shunts were left renal vein aberration (SAS, 8/12), splenic vein narrowing (iMCS, 5/8), portalhypertensive vascular changes (iPSRS, 6/6), and portomesenteric thrombosis (JCS, 3/3). The median fall in portal pressure was more in SAS (12.1 mm Hg), and operative time more in JCS, 8.4 hours (range, 5-9 hours). During a median follow-up of 36 months (6-54 months), shunt thrombosis had been reported in all cases of LGERS, and less in SAS (3/12). Variceal regression rate was high in SAS, and least in LGERS. Hypersplenism had reversed in all patients, and 6/31 patients had a recurrent bleed. Conclusions: Unconventional shunt surgery is effective in patients unsuited for other shunts, especially PSRS, and it achieves the desired effects in a significant proportion of patients.

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Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive skin fibrosis. It has 2 main clinical subtypes-diffuse cutaneous scleroderma and limited cutaneous scleroderma. Non-cirrhotic portal hypertension (NCPH) is defined as presence of elevated portal vein pressures without cirrhosis. It is often a manifestation of an underlying systemic disease. On histopathology, NCPH may be found to be secondary to multiple abnormalities such as nodular regenerative hyperplasia (NRH) and obliterative portal venopathy. There have been reports of NCPH in patients with both subtypes of SSc secondary to NRH. However, simultaneous presence of obliterative portal venopathy has not been reported. We present a case of NCPH due to NRH and obliterative portal venopathy as a presenting sign of limited cutaneous scleroderma. The patient was initially found to have pancytopenia and splenomegaly and was erroneously labeled as cirrhosis. She underwent workup to rule out leukemia, which was negative. She was referred to our clinic and diagnosed with NCPH. Due to pancytopenia, she could not be started on immunosuppressive therapy for her SSc. Our case describes the presence of these unique pathological findings in the liver and highlights the importance of an aggressive search for an underlying condition in all patients diagnosed with NCPH.

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Porto-Sinusoidal Vascular Disorder (PSVD) is a recently introduced clinical entity. Since it is rare and often underrecognized, there is growing interest in identifying patients at increased risk. We present a case of a 59-years-old male with refractory ascites, pleural effusion, and high-risk varices meeting the diagnostic criteria for PSVD with a concomitant diagnosis of POEMS syndrome. The possible association between PSVD and POEMS syndrome has been described only in eight reports in literature, but it may be underrecognized due to the clinical manifestations overlap. To gain a wider comprehension of PSVD, it is fundamental to cooperate using international networks.

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We report the case of idiopathic non-cirrhotic portal hypertension associated with systemic lupus erythematosus in a 43-year-old woman who suffered from breast cancer. We review this rare condition, as well as its diagnostic and therapeutic approaches.

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BACKGROUND: The 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 PRESENTATION: We 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. CONCLUSION: In 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.

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Hepatoportal sclerosis (HPS) is an idiopathic non-cirrhotic portal hypertension (INCPH) characterized by hypersplenism, portal hypertension, and splenomegaly. Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Non-cirrhotic portal hypertension is an extremely rare cause of HCC. A 36-year-old woman was referred to our hospital with esophageal varices. All serologic tests for etiology were negative. Serum ceruloplasmin and serum Ig A-M-G were normal. In the follow-up, two liver lesions were identified on a triple-phase computer. The lesions had arterial enhancement but no washout in the venous phase. In the magnetic resonance imaging examination, differentiation in favor of HCC was considered at one of the lessions. Radiofrequency ablation therapy was first applied to a patient who had no signs of metastasis. Within 2 months, the patient underwent a living donor liver transplant. In explant pathology, well-differentiated HCC and HPS were considered the cause of non-cirrhotic portal hypertension. The patient has been followed without relapse for 3 years. The development of HCC in INCPH patients is still debatable. Despite the presence of liver cell atypia and pleomorphism in nodular regenerative hyperplasia liver specimens, a causal link between HCC and INCPH is yet to be established.

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Objective Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare cause of portal hypertension, and this study aims to analyze the clinical features of patients with INCPH, and to assist in diagnosis and differential diagnosis. Methods A total of 74 patients who were hospitalized in Beijing YouAn Hospital from January 2019 to July 2022 and were diagnosed with INCPH were enrolled, and 332 patients with liver cirrhosis who were hospitalized during the same period of time were enrolled as control group. Demographic data, laboratory markers, gastroscopy, liver elasticity, pathological examination, and complications were recorded and compared between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the ability of liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the differential diagnosis of INCPH, and the DeLong test was used to compare the area under the ROC curve (AUC). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Results Among the patients with INCPH, 46.55% had no obvious symptoms at disease onset and 43.24% were misdiagnosed with liver cirrhosis. Compared with the patients with liver cirrhosis, the patients with INCPH had a significantly higher proportion of patients with gastrointestinal bleeding (62.16% vs 41.27%, χ 2 =10.67, P < 0.01) and a significantly lower proportion of patients with moderate-to-severe ascites (16.21% vs 29.82%, χ 2 =34.98, P < 0.01), and there were few patients with hepatic encephalopathy. As for pathology, 89.19% (66/74) of the INCPH patients manifested as typical occlusive portal vein disease. The statistical analysis showed that compared with the patients with liver cirrhosis, the patients with INCPH had significantly better liver function parameters, MELD score, and Child-Pugh score and significantly lower LSM [9.05(7.18-12.33) vs 25.32(16.21-47.23), Z =-8.41, P < 0.01], APRI score [0.70(0.41-1.28) vs 1.35(0.80-2.39), Z =-6.21, P < 0.01], and FIB-4 index [2.99(1.62-4.81) vs 6.68(4.06-10.42), Z =-8.39, P < 0.01]. LSM, FIB-4, and APRI had a good ability in differentiating INCPH from liver cirrhosis, and in particular, LSM had an AUC of up to 0.92 (95% confidence interval: 0.87-0.96), with a sensitivity of 92.68% and a specificity of 81.60%. Conclusion INCPH patients tend to have an insidious onset, a relatively high incidence rate of portal hypertension-related complications, and relatively good liver function, especially the patients with LSM < 14.5 kPa. The possibility of INCPH should be considered for such patients in clinical practice.

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Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a rare plasma cell dyscrasia disease involving multiple organs combined with idiopathic non-cirrhotic portal hypertension. It has been reported only four times in the English literature. Here, we present the first case of a 62-year-old male POEMS syndrome patient with portal hypertension treated with the transjugular intrahepatic portosystemic shunt (TIPS), after he presented with a 10-day history of melena. The diagnosis of POEMS syndrome was given because the patient presented with polyneuropathy, monoclonal plasma cell proliferative disorder, sclerotic bone lesions, splenomegaly, lymphadenopathy, ascites, hypothyroidism, and hyperpigmentation. The presence of portal hypertension was confirmed by esophageal varices, congested and edematous stomach body, splenomegaly, and transudate ascites in which the serum-ascites albumin gradient of ascites fluid was over 11 g/L (a concentration considered to be associated with POEMS syndrome), as no other causes were found. The patient fasted and received conservative drug treatments on admission, but symptoms of melena soon recurred within 1 week after resuming his diet. After TIPS and venous embolization were performed, symptoms of bleeding were effectively controlled, while the patient subsequently developed hepatic encephalopathy, which ultimately led to death. The presence of gastrointestinal bleeding in POEMS syndrome with idiopathic non-cirrhotic portal hypertension indicates a poor prognosis. Given that this was the first patient to receive TIPS, and although the incidence of hepatic encephalopathy has increased, TIPS is still acceptable for refractory variceal bleeding.

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Liver disease is one of the possible clinical manifestations of common variable immunodeficiency and can range from mild hepatomegaly and persistent elevation of liver enzymes to cirrhosis, portal hypertension, and nodular regenerative hyperplasia. The last one is the most common histologic presentation of liver involvement by common variable immunodeficiency and its clinical spectrum can range from asymptomatic to cholestasis, liver cirrhosis, or idiopathic non-cirrhotic portal hypertension, with the severe manifestations being less recognised. We present a case of a 48-year-old woman who was referred for an internal medicine consultation for evaluation of rapidly progressing (span of three months) large-volume ascites and marked asthenia. The patient had a past medical history of common variable immunodeficiency and a recent episode of severe haemolytic anaemia. Peritoneal fluid analyses identified portal hypertension as the cause of the ascites. Abdominal Doppler ultrasound and contrasted abdominal computed tomography confirmed the presence of permeable hepatic and portal veins. Liver biopsy revealed regenerative nodular hyperplasia without cirrhosis. A diagnosis of idiopathic non-cirrhotic portal hypertension secondary to common variable immunodeficiency was made. Treatment was adjusted with considerable improvement in ascites. In conclusion, idiopathic non-cirrhotic portal hypertension is a possible and often overlooked complication in patients with common variable immunodeficiency and is an exclusion diagnosis that requires a high level of suspicion, especially in patients with ascites.

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BACKGROUND AND AIMS: Cystic fibrosis liver disease (CFLD) is the third leading cause of death in patients with cystic fibrosis (CF). We aim to determine the prevalence of CFLD in a cohort of adult patients with CF and to characterise liver involvement in this population highlighting the importance of histological diagnosis. METHODS: We retrospectively studied a cohort of patients with CF. Inclusion criteria were age ≥ 18 and minimum 1 year of follow-up. We excluded lung transplant patients. CFLD was defined as having 2 out of 3 criteria: persistent elevation of transaminases and/or gamma-glutamyltransferase; abnormal ultrasound; and abnormal transient elastography. Non-invasive fibrosis biomarkers were calculated in CFLD patients. Adult-onset CFLD (Ad-CFLD) was defined as CFLD ≥18 years. Severe CFLD (s-CFLD) was defined as CFLD with cirrhosis and/or portal hypertension. RESULTS: We included 113 patients. Median age was 29 years, 58 were male. Forty patients had CFLD. Median age at CFLD diagnosis was 10 years. Twenty-one patients had s-CFLD. Two s-CFLD patients had nodular regenerative hyperplasia, 1 had hepatocellular carcinoma and 4 underwent liver transplantation. Six patients had ad-CFLD. Both CFLD and s-CFLD groups were compared to a non-CFLD group. The CFLD group had significantly more males (p = 0.034). S-CFLD group had worse pulmonary function (p = 0.015). CONCLUSION: Thirty five percent of adult patients with CF, mainly males, had CFLD. Nineteen percent had s-CFLD and had worse pulmonary function. With recent reports unravelling different pathophysiological mechanisms in CFLD, we believe it is important to better characterise liver involvement using liver biopsy.

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Objective:To explore the medium-long term efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for gastrointestinal hemorrhage in patients with idiopathic non-cirrhotic portal hypertension (INCPH).Methods:From March 2013 to July 2018, clinical data of 13 INCPH patients, including 5 males, 8 females,with gastrointestinal hemorrhage were retrospectively analyzed, who were diagnosed at the First Affiliated Hospital of Zhengzhou University, Anyang Fifth People′ s Hospital and Yuncheng Central Hospital. All patients received TIPS treatment. The general information, postoperative survival rate, the incidence of rebleeding, shunt dysfunction rate, and incidence of hepatic encephalopathy were analyzed.Results:All 13 patients with INCPH completed TIPS successfully with an average age of 45±8 (33 to 59) years. The hepatic venous pressure gradient (HVPG) decreased from 20.0-26.0 (22.6±1.9) mmHg before procedure to 8.0-14.0 (9.4±3.2) mmHg after. The median follow-up time was 44±7 (31 to 53) months. One patient died of liver failure 27 months after TIPS. Hepatic encephalopathy occurred cumulatively in 1 case (1/13), 1 case (1/13) and 1 case (1/13) in 12, 24 and 36 months after TIPS. Stent restenosis occurred cumulatively in 2 cases (2/13), 3 cases (3/13) and 3 cases (3/13) in 12, 24 and 36 months after TIPS. Portal vein thrombosis occurred cumulatively in 2 cases (2/13), and no primary liver cancer developed.Conclusions:TIPS is safe and effective in the treatment of INCPH with gastrointestinal bleeding with favorable medium-long term outcome.

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The term porto-sinusoidal vascular disease (PSVD) has been recently proposed to replace the term idiopathic non-cirrhotic portal hypertension (INCPH) to describe patients with or without signs of portal hypertension and typical histological lesions involving the portal venules or sinusoids in the absence of cirrhosis. According to the new definition, the presence of known causes of liver disease as well as of portal vein thrombosis does not rule out PSVD. Therefore, the patients in whom the diagnosis of PSVD is possible are much more than the patients strictly fulfilling the diagnostic criteria for INCPH. In this setting, the clinical challenge for the hepatologist is to identify patients at risk of developing PSVD and to indicate liver biopsy to confirm the diagnosis. We describe some possible scenarios in which PSVD should always be suspected, and we provide some tools useful to reach the diagnosis of PSVD.