Retrospective comparative study of efficacy, safety and outcome of percutaneous intervention for Budd-Chiari syndrome patients with bilirubin less than 3 and 3-6 mg/dl.

OBJECTIVE: Comparing the efficacy, safety and outcome of percutaneous intrervention for Budd-Chiari Syndrome (BCS) patients with bilirubin less than 3 and 3-6 mg dl-1. METHODS AND MATERIALS: 188 BCS patients having serum bilirubin ≤6 mg dl-1 and underwent percutaneous interventions were divided into two groups based on bilirubin level: 151 patients having bilirubin <3 mg dl-1 were included in Group 1; and 37 patients having bilirubin 3-6 mg dl-1 were included in Group 2. Both group were compare for technical success (successful recanalization of hepatic venous stenosis or creation of portocaval shunt with post-procedure gradient ≤5 mm of Hg), Safety (procedure-related mortality/morbidity or patient required transplantation) and outcome (resolution of clinical symptoms and survival). RESULTS: Technical success was 94.7% in Group 1-89.1% in Group 2 with overall success rate was 93.6%. No significant differences observed between the two groups in regards to procedure related complication. Overall transplant-free survival at 1 and 5 years after intervention in both groups was 96.3 and 91.2% respectively. 1-year and 5-year survivals in Group 1 was 96.7%, and 93.1%, whereas Group 2 was 94.6 and 90.1% with no statically significantly difference between the two groups (p = 0.59). Percutaneous intervention results are good in patients having bilirubin up to 6 mg dl-1, i.e. mild to moderate liver dysfunctions. CONCLUSION: Technical success, survival and outcome of percutaneous intervention in BCS patients having serum bilirubin 3-6 mg dl-1 was comparable to patients having bilirubin level <3 mg dl-1. ADVANCES IN KNOWLEDGE: Percutaneous intervention treatment is suitable for treatment for symptomatic BCS patients having bilirubin up to 6 mg dl-1.

A Preclinical Porcine Model of Portal Vein Thrombosis in Liver Cirrhosis.

BACKGROUND: This study aimed at presenting a novel method of developing a porcine model of portal vein thrombosis (PVT) in cirrhosis by intravenous administration of thrombin and insertion of a fibered coil. We further investigated changes of biochemical parameters, coagulation, and proinflammatory cytokine expression in the cirrhosis-PVT group. METHODS: Twelve male pigs were randomized into the control group (n = 3) and cirrhosis group (n = 9). In cirrhotic pigs, three were randomly selected to establish PVT by ultrasound-guided percutaneous puncture of the main portal vein (MPV) followed by intravenous thrombin administration and fibered coil insertion. Thrombosis in the MPV was detected by abdominal enhanced computer tomography (CT). The changes of hepatic function, coagulation system, and inflammation cytokines were compared among normal, cirrhosis, and cirrhosis with PVT groups. RESULTS: As manifested by the presence of a filling defect in MPV on portal venous-phase CT angiography, fibrin thrombi were formed in the MPV in cirrhotic pigs within one week and persisted for four weeks. Five weeks after surgery, abnormal liver functions occurred in association with PVT formation in cirrhosis. Both coagulation and thromboelastography parameters showed that cirrhosis-PVT pigs exhibited a procoagulant state through hyperfunction of platelets and clotting factors. Interleukin 6 (IL-6) as a potential inflammatory marker stimulated PVT-mediated inflammation activation in cirrhosis. CONCLUSIONS: Our study provides in vivo evidence that intravenous injection of a coil and thrombin into MPV under interventional guided devices enables a feasible method in thrombus creation. Further exploration and validation of large-sample cases are required to characterize utilities of this model.

From Budd-Chiari syndrome to acquired von Willebrand syndrome: thrombosis and bleeding complications in the myeloproliferative neoplasms.

Thrombotic and hemorrhagic complications are prevalent in patients with essential thrombocythemia, polycythemia vera, and myelofibrosis. Given the impact on morbidity and mortality, reducing the risk of thrombosis and/or hemorrhage is a major therapeutic goal. Historically, patients have been risk stratified on the basis of traditional factors, such as advanced age and thrombosis history. However, multiple factors contribute to the thrombotic tendency, including gender, mutational profile, inflammatory stress, and abnormal cell adhesion. Management includes cardiovascular risk reduction and use of antiplatelet therapy, depending on myeloproliferative neoplasm subtype and mutational status. Anticoagulation is a mainstay of therapy for those with venous thrombosis, but practice patterns remain heterogeneous. Cytoreduction is indicated for higher-risk patients, but efficacy may depend on the involved vascular bed. Management of special situations, such as unusual site thrombosis, bleeding, the perioperative period, and pregnancy, are especially challenging. In this article, risk factors and treatment strategies for myeloproliferative neoplasm thrombosis and bleeding, including special situations, are reviewed. Insights gained from recent studies may lead to the development of a more precise risk classification and tailored therapy.

Homocysteine Serum Levels as Prognostic Marker of Hepatocellular Carcinoma with Portal Vein Thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication of endstage hepatocellular carcinoma (HCC). The aim of our study was to evaluate the role of Homocysteine (Hcy) in HCC patient with PVT. Hcy is a sulphur amino-acid involved in two pathways, trans-sulphuration and remethylation, that involve vitamins B6, B12 and folates. METHODS: We recruited 54 patients with HCC and PVT, 60 patients with HCC and without PVT and 60 control subjects. We measured serum levels of Hcy, folate, vitamins B6 and B12. RESULTS: The comparison between HCC patients with PVT versus HCC without PVT was shown that mean values of Hcy were 6.4 nmol/L (p<0.0073) higher, LDL cholesterol were 4.8 mg/dl (p<0.0079) lower, vitamin B6 were 4.6 nmol/L(p=0.0544) lower, vitamins B 12 were 22.1 pg/ml (p=0.0001) lower. CONCLUSION: High serum levels of Hcy are an established thrombotic risk factor in the general population. We found significantly higher levels of Hcy in HCC patients with PVT versus both HCC patients without PVT and controls.

Current knowledge in pathophysiology and management of Budd-Chiari syndrome and non-cirrhotic non-tumoral splanchnic vein thrombosis.

Budd-Chiari syndrome and non-cirrhotic non-tumoral portal vein thrombosis are 2 rare disorders, with several similarities that are categorized under the term splanchnic vein thrombosis. Both disorders are frequently associated with an underlying prothrombotic disorder. They can cause severe portal hypertension and usually affect young patients, negatively influencing life expectancy when the diagnosis and treatment are not performed at an early stage. Yet, they have specific features that require individual consideration. The current review will focus on the available knowledge on pathophysiology, diagnosis and management of both entities.

Changes in arterial oxygenation after portal decompression in Budd-Chiari syndrome patients with hepatopulmonary syndrome.

OBJECTIVES: To evaluate the changes in arterial oxygenation after portal decompression in Budd-Chiari syndrome (BCS) patients with hepatopulmonary syndrome (HPS). METHODS: From June 2014 to June 2015, all patients with BCS who underwent balloon angioplasty or transjugular intrahepatic portosystemic shunt (TIPS) creation at our institution were eligible for inclusion in this study. Arterial blood gas analysis was performed with the patient in an upright position and breathing room air at 2-3 days and 1 and 3 months after the procedure. RESULTS: Eleven patients with HPS and 14 patients without HPS were included in this study. The procedure was technically successful in 24 patients. One patient with HPS had technically unsuccessful TIPS creation. Reobstruction or TIPS dysfunction was not detected in any patient within 3 months after the procedure. For patients with HPS, the alveolar-arterial oxygen gradient (A-aO2) remained comparable to baseline 2-3 days after the procedure (-3.2 ± 11.9 mmHg; p = .412), significantly improved 1 month after the procedure (-11.7 ± 6.4 mmHg; p < .001), and then returned to baseline 3 months after the procedure (-1.3 ± 12.5 mmHg; p = .757). For patients without HPS, the A-aO2 remained comparable to baseline at all three time points after the procedure (+1.4 ± 8.3 mmHg, +3.5 ± 8.1 mmHg, and +1.3 ± 8.2 mmHg; p = .543, p = .137, and p = .565). CONCLUSIONS: Arterial oxygenation transiently improves after portal decompression in BCS patients with HPS. KEY POINTS: • Intrapulmonary vascular dilation and hepatopulmonary syndrome are common in patients with Budd-Chiari syndrome. • Arterial oxygenation transiently improves after portal decompression in Budd-Chiari syndrome patients with hepatopulmonary syndrome.

The relationship between the levels and function of endothelial progenitor cells and factor V Leiden and protein C deficiency in patients with primary Budd-Chiari syndrome.

OBJECTIVE: Budd-Chiari syndrome (BCS) is a life-threatening hepatic disease characterized by hepatic venous obstruction at the level of hepatic vein, hepatic venules, or inferior vena cava. No evidence reported the relationship between the endothelial progenitor cells and the deficiency of factor V Leiden and protein C in patients with primary Budd-Chiari syndrome. PATIENTS AND METHODS: We recruited participants between June 2014 and July 2015. For primary BCS group, 28 patients were collected. 20 patients were included in the NAFLD group. Another 73 healthy participants were recruited into the control group. None of the patients and participants had received interventional therapy or had undergone surgery prior to being recruited. Levels and functions of endothelial progenitor cells (EPCs) were examined. The factor V Leiden mutation, protein C deficiency and protein S deficiency were evaluated. Finally, the relationship between the levels and function of endothelial progenitor cells and factor V Leiden and protein C deficiency in patients with primary Budd-Chiari syndrome was analyzed. RESULTS: The results showed that no significant differences were found between the BCS (and NAFLD) and control group considering age, sex, BMI, smoking (p>0.05 for variables). However, significant differences were observed in TG, TC, HDL-C, white blood cells, hemoglobin, ALT, AST, ALP, γ-GT, total bilirubin, and albumin (p<0.05 for variables). Compared with the healthy participants, significant downregulation was found in BCS and NAFLD patients regarding CD34+/CD45-, late outgrowth endothelial cells (OECs) colonies, OECs proliferation, and OECs tubulogenesis (p<0.001 for variables). Among the 28 BCS patients, factor V Leiden mutation (n=10, 35.71%, OR 12.67, 95% CI 5.24-27.93) and hereditary protein C deficiency (n=4, 14.29%, OR 7.48, 95% CI 2.02-21.43) were more prevalent than those in the control group. These results suggested that factor V Leiden mutation and protein C deficiency were major risk factors for BCS. Finally, we demonstrated that factor V Leiden and protein C deficiency may negatively regulate the OECs levels and functions in BCS patients. CONCLUSIONS: It's important to improve the OECs levels and functions, and to prevent the deficiency of factor V Leiden and protein C in the treatment of BCS.

A single-center retrospective study: Clinical features of different types of Budd-Chiari syndrome in Chinese patients in the Hubei area.

Background The characteristics and prevalence of Budd-Chiari syndrome in China remain unclear. This study aimed to analyze the clinical features of Budd-Chiari syndrome in Chinese patients in the Hubei area. Methods One-hundred and thirty patients with Budd-Chiari syndrome, admitted to Union Hospital from January 2002 to January 2011, were included in this retrospective study. Clinical features, laboratory data, imaging characteristics, and cumulative patency rates were analyzed. Results Of the 130 patients with Budd-Chiari syndrome, 77 were men (59.2%) and 53 women (40.8%). Budd-Chiari syndrome was more commonly associated with inferior vena cava block (56.9%, 74/130) than hepatic vein block (19.2%, 25/130) and combined inferior vena cava/hepatic vein block (23.9%, 31/130). The clinical features of Budd-Chiari syndrome varied based on the location of the obstruction. The incidence of bilirubin abnormality, elevated alkaline phosphatase, and γ-glutamyl peptide transferase levels was common in patients with Budd-Chiari syndrome. Liver injury was more severe in cases with combined inferior vena cava/hepatic vein block than in the other two types of Budd-Chiari syndrome. Color Doppler ultrasound imaging was better for the diagnosis of hepatic vein obstruction, while computed tomography and magnetic resonance imaging were superior in diagnosing inferior vena cava obstruction. The cumulative 1-, 5-, and 10-year patency rates were 97%, 69%, and 59%, respectively. Univariate analysis indicated that liver cirrhosis was an independent risk factor of recurrence. Conclusion The most prevalent type of Budd-Chiari syndrome is inferior vena cava obstruction in Chinese patients in the Hubei area. Different types of Budd-Chiari syndrome have diverse clinical and biochemical features, which may assist clinicians in diagnosing Budd-Chiari syndrome. Liver cirrhosis was found as an independent risk factor of recurrence.

Characteristics of hepatocellular carcinoma in Egyptian patients with primary Budd-Chiari syndrome.

BACKGROUND & AIM: Budd-Chiari syndrome (BCS) is caused by hepatic venous outflow obstruction. This work aimed at analyzing characteristics and factors associated with development of hepatocellular carcinoma (HCC) in patients with primary BCS. METHODS: A total of 348 Egyptian BCS patients were included. They were presented to the Budd-Chiari Study Group of Ain Shams University Hospital. BCS was confirmed using abdominal Doppler US. Abdominal magnetic resonance imaging (MRI), MR venography and/or multislice computed tomography (CT) were performed to confirm all diagnoses and to assess vascular anatomy. Hepatic focal lesions detected during the study period (2005-2011) were evaluated using serum alpha foetoprotein (AFP) level, imaging features and histopathological examination. RESULTS: Diagnosis of HCC was confirmed in 15/348 patients (4.3%). Imaging studies showed that 60% had multiple hepatic focal lesions ranging from 2 to 6.3 cm in size. The median level of serum AFP in BCS with HCC was 300 ng/mL vs 11 ng/mL in those without HCC (P<.001). A cut-off level >24.5 ng/mL for serum AFP showed sensitivity 80%, specificity 97.9%, positive predictive value 93.18% and negative predictive value 99.1% for detection of HCC in BCS patients. Male gender, older age, cigarette smoking, serum AFP (>24.5 ng/mL) and shrunken liver by ultrasonography were independent factors associated with HCC development. CONCLUSION: Male gender, older age and cigarette smoking are independent risk factors for development of HCC in BCS. Serum AFP is a good screening test in BCS.

Number and function of circulating endothelial progenitor cells in patients with primary Budd-Chiari syndrome.

BACKGROUND AND AIM: Primary Budd-Chiari syndrome (BCS) is associated with vascular endothelial injury. Circulating endothelial progenitor cells (EPCs) provide an endogenous mechanism to repair endothelial injury. This study investigated the levels and functionality of EPCs in patients with primary BCS. METHODS: EPCs (CD34+/CD133+/KDR+) were quantified in 82 patients with primary BCS (inferior vena cava type: n=19; hepatic vein type: n=22; and mixed type: n=41), 10 cirrhosis controls (CC group) and 10 age-matched healthy controls (HC group), using flow cytometry. EPCs proliferation was detected by MTT assay, adhesion by adhesion activity assay, and migration capacity by Transwell assay. RESULTS: EPCs levels were significantly lower in the BCS group (0.020±0.005%) than in the CC and HC groups (0.260±0.201%, 0.038±0.007%; P<0.001 for each). EPCs cultured in vitro from BCS and CC groups had, respectively, lower proliferation activity (0.20±0.04, 0.23±0.06 vs 0.58±0.07, each P<0.001), adhesion activity (15.8±1.7, 18.2±4.3 vs 35.0±2.5 cells/random microscopic field (RMF), each P<0.001) and migration activity (16.1±1.5, 16.7±3.0 vs 23.9±2.0 cells/RMF, each P<0.001) than in the HC group. EPCs functionality did not significantly differ between the BCS and CC groups. The numbers and functions of EPCs did not significantly differ among patients with inferior vena cava type, hepatic vein type and mixed type of BCS. CONCLUSION: Patients with primary BCS had lower EPCs levels, with less proliferation, adhesion and migration activities. These findings suggest that lower levels of less functional EPCs may be associated with venous occlusion in primary BCS patients.

Review article: the aetiology of primary Budd-Chiari syndrome - differences between the West and China.

BACKGROUND: China may have the largest number of Budd-Chiari syndrome (BCS) cases in the world (at least 1914 original papers were published, and at least 20 191 BCS patients were reported). Considering the discrepancy in the clinical profiles and preferred treatment selection of primary BCS between the West and China, understanding its aetiology in these two different regions is very important. AIM: To review the data from large cohort studies and meta-analyses to illustrate the epidemiology of risk factors for BCS in the West and China. METHODS: Relevant papers were identified by major English- and Chinese-language databases, conference abstracts, and by manual search. RESULTS: Risk factors reviewed include myeloproliferative neoplasms (MPNs) and their related gene mutations, anti-phospholipid syndrome, paroxysmal nocturnal haemoglobinuria (PNH), hyperhomocysteinaemia and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation, factor V Leiden (FVL) and prothrombin G20210A mutations, inherited anti-thrombin, protein C and protein S deficiencies, pregnancy and puerperium, poverty, and family history. CONCLUSIONS: We examined the differences in the aetiological distribution of BCS between the West and China. Several recommendations should be considered in Chinese BCS patients: (i) screening for hyperhomocysteinaemia and MTHFR mutation should be regularly performed; (ii) screening for MPNs, PNH, and anti-phospholipid syndrome should be selectively performed; (iii) inherited anti-thrombin, protein C, and protein S deficiencies should be actively explored; (iv) screening for FVL and prothrombin G20210A mutations may be unnecessary; and (v) the clinical significance of pregnancy and puerperium, poverty with bacterial infections and unsanitary environments, and family history as possible risk factors should never be neglected.

[Experience in treating portal thromboses in patients with chronic myeloproliferative diseases].

Patients with myeloproliferative diseases (MPD) are noted to be at high risk for portal thromboses. This problem gives rise to disability if it is untimely treated or resistant to therapy. The paper gives the experience of the Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation, in using antithrombin III in MPD patients (3 patients with primary myelofibrosis, 3 with essential thrombocythemia) and acute and subacute portal vein thromboses resistant to therapy with direct anticoagulants. In all 5 cases, the use of antithrombin III in combination with low-molecular-weight heparin showed a positive clinical effect as rapid relief of pain syndrome and comparatively early (3-week to 1.5-2-month) recanalization of thrombosed vessels. Three clinical cases are described in detail.

Increased prevalence of heparin-induced thrombocytopenia in patients with Budd-Chiari syndrome: a retrospective analysis.

BACKGROUND: Budd-Chiari syndrome (BCS) is a rare, potentially fatal disease characterized by hepatic venous outflow tract obstruction. Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin therapy, with mortality approaching 10%. The reported prevalence of HIT in adults is 0.2-5.2%. Expert consensus through case reports is the only existing evidence of HIT in BCS. To our knowledge, this is the first study to formalize this anecdotal evidence. METHODS: A retrospective analysis was carried out of patients presenting at a tertiary liver centre with acute liver failure because of BCS or BCS as the primary indication for liver transplantation between 2000 and 2013. The prevalence of HIT in the study group was compared with the highest reported prevalence in adult medical patients receiving heparin (5.2%). Mortality, length of stay and liver transplantation rates were also studied. RESULTS: Of 32 BCS patients, 9 (28.1%) developed HIT, significantly higher than the previously reported prevalence of HIT in medical patients (5.2%) (P<0.0001). There was no difference in mortality (P=0.66), length of stay (P=0.58) and liver transplantation rate (P=0.39) between HIT-positive and HIT-negative patients. CONCLUSION: The prevalence of HIT (28.1%) in our cohort of BCS patients is significantly higher than that in the general population (0.2-5.2%). Although this study was not powered to detect outcome differences, as heparin is the mainstay of acute BCS treatment, this represents a significant risk. We recommend a high index of suspicion for HIT in patients with BCS and thrombocytopenia, an appropriate HIT-testing strategy and consideration of direct thrombin inhibitors.

Diagnosis, etiology and management of the Budd-Chiari Syndrome: a bloodcoagulation and hepatological study on the course of the disease treated with TIPS.

BACKGROUND: Budd-Chiari Syndrome (BCS) is characterized by obstruction of blood flow in hepatic veins. The aim of the study was to analyze diagnosis, etiology and management of BCS. METHODS: We analyzed 44 patients (32 females, 12 males, the mean age <35y of age) treated with TIPS. Ascites was found in 35 patients as the most frequent symptom. The median of total follow-up was 52 months. Non-covered (bare) or covered stent was inserted to all patients. Diagnosis of myeloproliferative neoplasm (MPN) was based on WHO criteria. Other inherited or acquired thrombophilia were assessed as well. Therapy of BCS was with regard to the etiology. RESULTS: The etiology of BCS was identified in 38 cases. Ph- MPN was found as the most common risk factor (50%, N.=22), especially polycythemia vera. JAK2V617F mutation was detected in the most of 22 MPN cases (82.5%). The second most common etiologic factor was inherited thrombophilia (18%, N.=8). In the non-covered (bare) stent group, a primary patency rates 52.9% in 1 year and 20% in 5 years after TIPS (Portasystemic Shunt, Transjugular Intrahepatic) creation. In the covered stent group the 1-year and 5-year primary patency rates were was 80% and 33.3% respectively. The average 5-year re-intervention rate per patient was 1.65 procedures in the bare stent group and 0.67 in the covered stent group. Re-interventions were more frequent in MPN patients. All patients were anticoagulated with heparin at the beginning, switched to vitamin K antagonist. On top of TIPS, anticoagulant and a vigorous therapy of underlying disorder are necessary. CONCLUSION: BCS is a serious and life-threatening disorder in MPD is a major cause of morbidity and mortality. Therapy requires a multidisciplinary approach. Insertion of TIPS dedicated covered stent is a very effective treatment in cases resistant to conservative approach with lower dysfunction rate and the number of re-interventions.

Serum Iodine Is Increased in Subjects Having Budd-Chiari Syndrome.

This study was performed to investigate the status of serum iodine concentration among the Budd-Chiari syndrome (BCS) patients and its effect on thyroid hormone. The study group serum specimens were collected from 233 BCS patients and 60 healthy people. Serum iodine was analyzed with the Sandell-Kolthoff method, and the ELISA method was used to detect thyroid function: TSH, T3, T4, FT3, and FT4. The serum iodine level of patients with BCS was 316.7 ± 256.8 µg/L, greatly higher than 76.3 ± 25.7 µg/L of serum iodine for control group (p < 0.001), but with no significant difference among different types of BCS. There were no statistically significant differences in thyroid hormone levels (TSH, T3, T4, FT3, and FT4) between people with BCS and control group, although the TSH level of BCS group is slightly higher than that of normal control group. This study demonstrates that iodine may be related to the pathogenesis of BCS and needs to be paid more attention.