Membranous Obstruction Of The Inferior Vena Cava Research Articles

MiR‑3133 inhibits proliferation and angiogenesis by targeting the JUNB/VEGF pathway in human umbilical vein endothelial cells.

Membranous obstruction of the inferior vena cava (MOVC) has the highest incidence rate among the different types of Budd‑Chiari syndrome (BCS) in China. The inferior vena cava septum of patients with MOVC contains capillaries and the two surfaces of the membrane are composed of vascular endothelial tissue. Membrane formation occurs due to endothelial damage. MicroRNAs (miRNAs/miRs) have been verified to be involved in the pathogenesis and progression of various human diseases. A previous study by our group suggested that miR‑3133 was downregulated in the serum of patients with MOVC. In the present study, the possible mechanistic implication of miR‑3133 in MOVC‑associated processes was further explored. It was observed that miR‑3133 overexpression inhibited, whereas miR‑3133 knockdown enhanced the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the CCK‑8 and tube formation assays. JUNB, a member of activator protein 1 and an important upstream transcriptional molecule of vascular endothelial growth factor (VEGF), was proven to be a direct target gene of miR‑3133 using a bioinformatics prediction and luciferase reporter assay. Meanwhile, the mRNA and protein expression of JUNB and VEGF was determined by PCR, ELISA and western blot analyses. Of note, miR‑3133 overexpression downregulated, while miR‑3133 knockdown elevated the expression of JUNB and VEGF significantly. Furthermore, it was demonstrated that JUNB upregulated the expression and secretion of VEGF to promote HUVEC proliferation and angiogenesis. miR‑3133 was able to inhibit the effect of JUNB overexpression to promote cell proliferation, angiogenesis and the expression of VEGF. In conclusion, the present study demonstrated that miR‑3133 regulated endothelial cell proliferation and angiogenesis through the JUNB/VEGF pathway, which may provide an approach for inhibiting diaphragm formation of the inferior vena cava in MOVC.

Circulating microRNA profile in patients with membranous obstruction of the inferior vena cava.

Membranous obstruction of the inferior vena cava (MOVC) is a common type of Budd-Chiari syndrome. However, the pathogenesis of MOVC has not been fully elucidated. Recent studies demonstrated that microRNAs (miRNAs or miRs) are involved in multiple diseases. To the best of our knowledge, specific changes in the expression of miRNAs in MOVC patients have not been previously assessed. The present study used a microarray analysis, followed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation, with the aim to access the miRNA expression levels in the plasma of 34 MOVC patients, compared with those in healthy controls. The results revealed a total of 16 differentially expressed miRNAs in MOVC patients. Subsequently, RT-qPCR analysis verified the statistically consistent expression of 5 selected miRNAs (miR-125a-5p, miR-133b, miR-423-5p, miR-1228-5p and miR-1266), in line with the results of the microarray analysis. These 5 miRNAs, which were described as crucial regulators in numerous biological processes and vascular diseases, may play an important role in the pathogenesis of MOVC. Bioinformatics analysis of target genes of the differentially expressed miRNAs revealed that these predicted targets were significantly enriched and involved in several key signaling pathways important for MOVC, including the ErbB, Wnt, MAPK and VEGF signaling pathway. In conclusion, miRNAs may involve in multiple signaling pathways contributing to the pathological processes of MOVC. The present study offers an intriguing new perspective on the involvement of miRNAs in MOVC; however, the precise underlying mechanisms require further validation.

Hepatocellular Carcinoma Associated with Membranous Obstruction of the Inferior Vena Cava: Incidence, Characteristics, and Risk Factors and Clinical Efficacy of TACE

To analyze the characteristics associated with membranous obstruction of the inferior vena cava (MOVC)-associated hepatocellular carcinoma (HCC) and to evaluate the clinical efficacy of transcatheter arterial chemoembolization (TACE). This retrospective study was approved by an institutional review board, and informed consent was waived. Ninety-eight patients (mean age, 48.5 years +/- 12.9 [standard deviation]) with MOVC were retrospectively evaluated. The diagnosis of Budd-Chiari syndrome was confirmed with results from Doppler ultrasonography, computed tomography, magnetic resonance imaging, and/or inferior venacavography. The cumulative incidences of HCC and the patient survival period were calculated by using the Kaplan-Meier method. Factors associated with the development of HCC were evaluated by using multivariate Cox regression analysis. Among 98 patients with MOVC, liver nodules were detected in 37 patients (38%), 23 of whom had HCC associated with MOVC and 14 of whom had benign nodules. The cumulative incidence of HCC at 1, 5, and 10 years was 7.3%, 13.5%, and 31.8%, respectively. Female sex was the only significant factor associated with the development of HCC (odds ratio, 6.02; P <.001). HCC was of the single nodular type and of peripheral location. Among 23 patients with HCC, 20 patients were treated with only TACE and three with liver transplantation after TACE. After TACE, 14 (61%) of the study patients had a complete response, and survival rates at 1, 2, 3, 4, and 5 years were 90%, 85%, 61%, 61%, and 46%, respectively. The incidence of HCC in patients with MOVC was similar to that found in other studies. TACE resulted in an effective tumor response for HCC and seemed to be effective in prolonging patient survival. Female sex was the only significant factor associated with the development of HCC. A single nodular tumor with a peripheral location appears to have a higher probability of HCC.

Is Familial Mediterranean Fever a Possible Cofactor for Budd‐Chiari Syndrome?

Budd-Chiari syndrome (BCS) is characterized by obstruction of hepatic venous outflow at any level of the hepatic veins or the inferior vena cava (IVC). Clinical presentation ranges from asymptomatic cases to fulminant hepatic failure or end-stage liver disease (1). Primary endophlebitis or congenital malformations may be responsible for BCS (1). Although several hypercoagulable states such as antithrombin III, protein C and S deficiency, factor V Leiden (FVL), and prothrombin gene 20210A mutations have been linked to BCS, recent data show that primary BCS is a multifactorial disease and the combination of several prothrombotic factors play a role in the development of thrombosis (1). Familial Mediterranean fever (FMF) is an autoinflammatory disorder characterized by episodic fever and polyserositis. Hypercoagulability has been recently reported in patients with FMF, yet thrombotic events were rarely reported in the literature. Although large vessel thrombosis in patients with FMF without amyloidosis is an unexpected event, an occurrence of superior vena cava thrombosis in a patient with FMF has also been reported (2-4). Our report is one of the few articles in the literature in which a major thrombotic event has occurred in the setting of FMF without amyloidosis.

Membranous obstruction of the inferior vena cava and its causal relation to hepatocellular carcinoma

Although rare in most countries, membranous obstruction of the inferior vena cava (MOIVC) occurs more frequently in Nepal, South Africa, Japan, India, China, and Korea. The occlusive lesion always occurs at approximately the level of the diaphragm. It commonly takes the form of a membrane, but may be a fibrotic occlusion of variable length. Controversy exists as to whether MOIVC is a developmental abnormality or a result of organization of a thrombus in the hepatic portion of the inferior vena cava. The outstanding physical sign associated with MOIVC are large truncal collateral vessels with a cephalad flow. A dilated vena azygous is seen on chest radiography. Definitive diagnosis is made by contrast inferior vena cavography. The long-standing obstruction to hepatic venous flow causes severe centrolobular fibrosis and predisposes to the development of hepatocellular carcinoma (HCC). Percutaneous balloon angioplasty, transatrial membranotomy, or more complex vena caval and portal decompression surgery should be performed to prevent these complications. HCC occurs in more than 40% of South African Black and Japanese patients with MOIVC, but less often in other populations. It is thought to result from the tumour-promoting effect of continuous hepatocyte necrosis, although the associated environmental risk factors have not been identified.

Proposal of a new nomenclature for Budd-Chiari syndrome: hepatic vein thrombosis versus thrombosis of the inferior vena cava at its hepatic portion.

Budd-Chiari syndrome (BCS) was initially defined as a symptomatic occlusion of the hepatic veins, but subsequent reports on various obliterative changes that occur in the hepatic portion of the inferior vena cava (IVC) and hepatic vein orifices have resulted in a broadened and ambiguous definition. Membranous obstruction of the inferior vena cava has been regarded by many as a congenital vascular malformation, but its relation to the classical BCS has remained obscure. With modern imaging and recent histological study of new cases, membranous obstruction of the IVC is now considered to be a sequela to thrombosis. How to classify various forms of occlusion and stenosis of the IVC and hepatic vein ostia is a major challenge. In this review, we emphasize that primary hepatic vein thrombosis (classical Budd-Chiari) and an obliterative disease predominantly affecting the hepatic portion of the IVC, both of which account for most patients with venous outflow block, are clinically quite different. In the West, the former is more common than the latter, which constitutes the vast majority of cases of outflow block in developing countries such as Nepal, South Africa, China, and India. The latter is frequently complicated by hepatocellular carcinoma (HCC), and primary hepatic vein thrombosis is not. The major cause of thrombosis is a hypercoagulable state in hepatic vein thrombosis, but more of the latter cases are idiopathic. The clinical presentation of the latter is milder, and onset is frequently inapparent, whereas the former is more severe, sometimes causing acute hepatic failure. Markedly enlarged subcutaneous veins over the body trunk characterize the latter. We propose that these two disorders be clinically distinguished with a suggested term "obliterative hepato-cavopathy" for the latter against classical BCS.

Successful Treatment by Percutaneous Balloon Angioplasty of Budd-Chiari Syndrome Caused by Membranous Obstruction of Inferior Vena Cava: 8-Year Follow-Up Study

ObjectivesThis study sought to report the long-term result (up to 8 years) of percutaneous transluminal balloon angioplasty (PTBA) for Budd-Chiari syndrome (BCS) caused by membranous obstruction of the inferior vena cava (MOVC). BackgroundWe previously reported on this nonoperative form of therapy in a smaller series of patients and found the short-term results to be excellent. MethodsWe studied the long-term results of PTBA in the treatment of BCS caused by MOVC in 42 patients who underwent PTBA with the Inoue balloon catheter between June 1988 and February 1996. There were 28 men and 14 women with a mean age of 35.6 years (range 16 to 56). MOVC was incomplete in 27 patients and complete in 15. PTBA was successful in 38 patients (91%). The longest follow-up period was 8 years. ResultsAll 38 patients who successfully underwent PTBA showed marked symptomatic improvement. Immediately after PTBA, the diameter of the inferior vena cava at the MOVC increased from 1.7±2 to 19.9±3.5 mm (p<0.0001), the caval pressure below the MOVC decreased from 23.6±8.5 to 12.0±6.5 mm Hg (p<0.0001), and the enlarged liver size decreased from 6.5±1.5 to 2.0±1.5 cm below the right costal margin at the midclavicular line (p<0.0001). Over a follow-up period of up to 8 years (7 to 8 years in 4 patients, 5 to 7 years in 12, 3 to 5 years in 11, 2 to 3 years in 6 and <2 years in 9), MOVC returned in only 1 patient. This patient, our first, required a second PTBA 3 years later and a third 4.25 years after the second PTBA, in combination with stent placement for recurrence of stenosis. ConclusionsPTBA with the Inoue balloon catheter is an effective, safe and long-lasting alternative to surgical treatment of patients with BCS due to MOVC.

Hepatic outflow obstruction (Budd-Chiari syndrome). Experience with 177 patients and a review of the literature.

Budd-Chiari syndrome (BCS) may not be as uncommon as was once believed. Our study has substantiated the existence of 2 major clinical forms. The acute syndrome is invariably associated with extensive blockage of the major hepatic veins, resulting in congestive liver cell necrosis. In a small, but significant, number of patients the inferior vena cava (IVC) is also occluded. The important etiologic factors are related to hypercoagulability of blood. Immediate placement of a shunt improves survival. The chronic syndrome is characterized by portal hypertension and is associated with a variable abnormal vascular anatomy. The causes of the chronic syndrome are not clear, but a substantial number of cases are related to the presence of an IVC membrane. Shunt surgery is effective but procedures aimed at the primary pathology are likely to be even more so. The natural history of BCS should be viewed over a long period of time. The very long survival of several patients urges a more cautious approach to surgical remedies. Budd-Chiari syndrome probably represents a spectrum of disease caused primarily by a hypercoagulable state and having a varied presentation depending on the balance between rate of formation and the extent of the thrombosis and the body's own rate of thrombolysis and recanalization. The extent and efficacy of the individual's collateral circulation and the rate of development of liver fibrosis are other determinants. It is thus possible to view BCS as a continuum of a single pathogenetic spectrum. Pregnancy-related BCS in India probably has strong social determinants, and is usually acute and fulminant. We have, however, documented a chronic form not described earlier. Children usually do not have acute BCS, but chronic BCS in children and adolescents is similar to that in adults. Membranous obstruction of the inferior vena cava (MOVC) is common and was found even at a young age. The association of MOVC with hepatocellular carcinoma, however, did not appear to be as clear as was previously believed. There has been a wide geographical variability in the causes and manifestations of BCS. Our study has clearly shown that--Kipling's categorical statement to the contrary--East and West do meet in India, in the Budd-Chiari syndrome.

Nonoperative treatment of membranous obstruction of the inferior vena cava by percutaneous balloon transluminal angioplasty

Percutaneous transluminal angioplasty (PTA) was performed with the inoue balloon catheter in nine patients with membranous obstruction of the inferior vena cava (MOVC) between November 1988 and April 1991. There were five men and four women, aged 30.8 ± 8.5 years. Two patients had had previous surgical treatment. Three patients had complete and six had incomplete MOVC. The caval pressure below the MOVC was 24.0 ± 5.6 and 11.8 ± 5.3 mm Hg ( p < 0.0001) before and after PTA, respectively. The caval diameter at the site of MOVC increased from 1.5 ± 1.7 to 20.3 ± 2.6 mm ( p < 0.0001), and the maximal caval diameter below the MOVC decreased from 28.7 ± 12.9 to 19.8 ± 9.9 mm ( p = 0.006), before and after PTA, respectively. One patient died of massive pulmonary embolism following successful PTA. All the other eight patients remained asymptomatic during an 18.5 ± 11.5 months (range 3.5 to 32) follow-up period. Two-dimensional ultrasonograms showed no recurrence of MOVC. We conclude that PTA with the inoue balloon catheter is an effective and safe alternative to surgical treatment of MOVC.

Membranous Obstruction of the Inferior Vena Cava with Budd-Chiari Syndrome: MR Imaging Findings

Membranous obstruction of the inferior vena cava (IVC) is a curable cause of a primary type of Budd-Chiari syndrome. Magnetic resonance (MR) imaging and vena cavography were performed on nine patients with membranous obstruction of the IVC. The MR findings were retrospectively analyzed and compared with computed tomographic findings in seven patients. The morphologic features of membranous obstruction of the IVC on spin-echo MR images were a curvilinear soft-tissue membrane (five cases) or an obliterated lumen of a hepatic segment of the IVC (four cases) in transverse or sagittal views. The lumen below the obstruction revealed flow-related signal (seven cases), intraluminal thrombus (one case), and thrombotic occlusion (one case). The hepatic veins were narrow and disoriented without connection to the hepatic segment of the IVC just below the diaphragm. On T2-weighted images, inhomogeneity with high signal intensity was shown more prominently in the hepatic parenchyma in Simson type II or III membranous obstruction. Other findings were hepatosplenomegaly, enlarged caudate lobe, cirrhotic liver, associated hepatoma, and presence of various collaterals.

Membranous obstruction of the inferior vena cava in the United States.

The pathogenesis of membranous obstruction of the inferior vena cava (MOVC) is unclear. Although the lesion is rare in the United States compared to Japan, India, and black South Africa, it has been responsible for 23% of cases of hepatic outflow obstruction we have encountered in the ethnically heterogeneous indigent population of Los Angeles. Most patients with MOVC are male. In contrast, recent series of patients with Budd-Chiari Syndrome (BCS) have demonstrated a female predominance. Compared to BCS without involvement of the inferior vena cava (IVC), patients with MOVC have more chronic symptoms. Large truncal collaterals, particularly on the back, strongly suggest MOVC. In patients without this sign, a high index of diagnostic suspicion is required. Chronic hepatitis B infection occurs with increased frequency in these patients. Chest radiograph may show an enlarged azygous shadow. Liver-spleen scan is not helpful, and the liver biopsy is frequently nondiagnostic. A useful screening procedure for hepatic outflow block is transhepatic portal pressure measurement demonstrating aberrant hepatic veins with pressures higher than in the portal vein and, occasionally, hepatofugal portal flow. Transcardiac membranotomy appears to be symptomatically effective in patients with MOVC and at least one patent hepatic vein. It is not known whether this operation will prolong life and prevent the development of hepatocellular cancer, which may occur in up to 48% of these patients. The correct therapeutic approach has not been established for those patients whose lesion is not amenable to surgery because of extensive IVC occlusion or absence of patent hepatic veins.

The use of radionuclide venography in the differential diagnosis of inferior vena caval obstruction

In using radionuclide imaging of the inferior vena cava (RIVC) to investigate the prevalence of membranous obstruction of the inferior vena cava (IVC) in patients with hepatocellular carcinoma, it was necessary first to determine if this technique would distinguish membranous obstruction of the IVC both from other causes of IVC obstruction likely to be encountered in these patients and from the picture obtained with severe ascites. RIVC readily distinguished an obstructed from a normally patent IVC. However, membranous obstruction of the IVC could not in most instances be differentiated from extrinsic compression of the IVC by an enlarged tumourous liver, occlusion of the lumen of the IVC by tumour, or the effect of severe ascites. In a proportion of the patients with membranous obstruction of the IVC, flow of the radionuclide through large superficial collateral vessels was seen, enabling this diagnosis to be made with confidence. Thus, if RIVC shows the IVC to be obstructed or if severe ascites is present, contrast venography will usually be necessary to determine the nature of the obstructing lesion.

Membranous obstruction of the inferior vena cava.

Membranous obstruction of the inferior vena cava (MOVC) is a rare clinical entity. The incidence is higher in Japan and Africa than that in USA and Europe. MOVC is considered to be different from the Budd-Chiari syndrome. There are differences in clinical manifestation and pathologic changes in the liver. Findings of the liver revealed cirrhosis in all patients but in one. Ascites and esophageal varices could be observed in 79% and in 58% of the patients, respectively. According to Sugiura's classification, they consisted of Type Ia in 63%, Type Ib in 11%, Type II in 11%, and Type III in 16%. Portopulmonary shunt by splenopneumopexy was successfully performed on 19 patients with MOVC in this clinic, of which diagnosis was established by cavography.