Budd-Chiari syndrome: is TIPS tops?

Budd-Chiari syndrome is a severe disease characterized by occlusion of large hepatic veins leading to death if untreated. Using the classical criteria for the diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF), overt PV was the underlying cause in about 10% of the cases and ET or IMF in only a very few. Using spontaneous endogenous erythroid colony (EEC) formation in vitro and/or bone marrow biopsies, a primary myeloproliferative disorder (PMD) was present in 78% of the patients with apparently idiopathic Budd-Chiari syndrome and in about half of the patients with portal, splenic, and/or mesenteric vein thrombosis. The diagnoses in 40 reported cases with hepatic vein thrombosis and spontaneous EEC were overt PV in 25 and latent unclassified PMD in 15 patients. The diagnoses of 40 reported cases with splanchnic vein thrombosis and spontaneous EEC were overt PV in 12, ET in 2, IMF in 2, and latent unclassified PMD with the presence of EEC in 24 patients. Thrombocytosis as a manifestation of myeloproliferative disease was recorded in 34 of 80 (42.5%) patients with spontaneous EEC and Budd-Chiari syndrome or portal vein thrombosis. Thrombocythemia was present in 15 of 41 patients with a proven and in 19 of 39 patients with a latent myeloproliferative disorder. Patients with hepatic vein or splanchnic vein thrombosis associated with a PMD are predominantly females younger than 45. It is concluded that both spontaneous EEC and histopathology from bone marrow biopsy provide specific information as sensitive clues to the diagnosis of all variants of overt and latent myeloproliferative disorders. The association of hepatic and splanchnic vein thrombosis and PMD is not fully understood. Therapeutic options of Budd-Chiari syndrome include anticoagulation with heparin, fibrinolysis followed by oral anticoagulation, and appropriate treatment of the underlying PMD. In case of failure, invasive options include local procedures such as angioplasty or stenting, venous decompression by portal-systemic shunts, or liver transplantation.

EUS-guided portal pressure gradient measurement: a promising tool in noncirrhotic portal hypertension

Introduction: Portal hypertension (PHT), elevated pressure in the portal venous system, is primarily attributed to cirrhosis. Other pre- and post-hepatic causes of PHT include thrombosis, granulomas, Budd-Chiari syndrome, and congestive heart failure (CHF). There is sparse data on PHT secondary to polycystic kidney (PKD) and liver disease (PLD). Still, advanced cases can cause post-hepatic PHT through hepatic venous outflow obstruction, portal vein obstruction, and/or inferior vena cava syndrome. The prevalence of PHT was estimated at 6% in PLD in a retrospective study of 125 patients but poorly defined in concurrent PKD/PLD. We present a case of PHT in a patient with PKD/PLD and CHF, highlighting unique diagnostic challenges. Case Description/Methods: A 56-year-old man with autosomal dominant PKD, PLD, CHF, and ESRD on hemodialysis (6 days per week due to hypotension) presented to the hospital with recurrent abdominal distention requiring semimonthly paracentesis. Abdominal US revealed ascites and hepatic and renal cysts; Hepatology was consulted and recommended a computed tomography scan that demonstrated compression of the hepatic veins and intrahepatic IVC with dilated main portal vein to 1.5 cm. Serologic workup ruled out other intrinsic liver diseases. Serum-Ascites Albumin gradients (SAAG) was 1.54 g/dL and total protein was 2.8 g/dL, consistent with PHT. Treatment options were discussed with the patient; he was not interested in evaluation for transplant and opted to continue serial paracentesis. Given the diffuse nature of the cysts, aspiration would not have improved symptoms. We discussed Pleurx for ascites, but this was not pursued due to the risk of leaking and infection. Discussion: Mechanical obstruction of portal flow and fluid retention as hepatic cysts expand and exert pressure on vessels may lead to PHT. Ascites is often multifactorial, encompassing cirrhosis, PHT, and other conditions, occurring in 40% of PKD/PLD-associated cases. This patient has multiple potential causes for ascites, including heart failure and ESRD. Elucidating the underlying cause of ascites was essential in forming a treatment plan. A liver biopsy was considered to rule out cirrhosis however, targeting hepatic parenchyma was challenging due to extensive PLD. In cases with a large dominant cyst causing compression, aspiration may ameliorate PHT and ascites. This case contributes to the limited reported instances of PKD/PLD-induced PHT, presenting a diagnostic dilemma and complicated PHT-induced ascites management.

Thrombophilia is an important medical problem that carries a great morbidity and mortality especially in young patients and great laboratory workup is usually needed to detect the underlying etiology. Several factors have been claimed to be responsible for thrombosis, some of them are common and others are not, the acquired causes represent the majority while hereditary causes are the minority. The case is an example for acute thrombosis in hepatic veins and chronic thrombosis in portal vein in a young adult that was addict for tramadol for last three years with excellent response to anticoagulation as regards hepatic vein thrombosis.

Budd-Chiari syndrome represents a rare vascular disorder defined by obstruction of hepatic venous outflow which, without timely intervention, may progress to portal hypertension, cirrhosis, and liver failure. Primary Budd-Chiari syndrome refers to intrinsic venous obstruction, which is most commonly associated with underlying prothrombotic states that predispose individuals to venous thrombosis. Interventional procedures are often required as a therapeutic modality when medical therapy alone is insufficient. Transjugular intrahepatic portosystemic shunt (TIPS) is commonly used to reduce portal hypertension in Budd-Chiari syndrome; however, it may not be feasible in the presence of hepatic vein thrombosis where cannulation of the hepatic vein, and thus, shunt creation may not be possible. In such cases, direct intrahepatic portosystemic shunt (DIPS) may provide an alternative route for portal decompression through the creation of a shunt directly between the inferior vena cava and the portal venous system. We describe a 34-year-old female presenting with autoimmune hepatitis and primary Budd-Chiari syndrome who underwent a successful ultrasound-guided direct intrahepatic portocaval shunt creation between the portal vein and the intrahepatic inferior vena cava, resulting in a significant reduction in portal venous pressure gradient and improved portal venous flow. This case highlights the feasibility of DIPS in a tertiary hospital setting and supports its role as an alternative endovascular approach for managing portal hypertension in Budd-Chiari syndrome.

Splenectomy is indicated after orthotopic liver transplantation (OLT) for various reasons, including left-sided portal hypertension, trauma, and hemorrhage prevention in patients with splenic artery aneurysms. Complications of splenectomy may include infections, bleeding, and portal vein thrombosis (PVT). The incidence of symptomatic postsplenectomy PVT ranges from 0.7% to 2%,1, 2 whereas the incidence of asymptomatic PVT can reach 7% to 10%.3 There is, however, limited literature pertaining to postsplenectomy PVT in recipients of OLT. The sequelae of PVT are particularly serious in OLT recipients. The reduction of the portal vein flow severely compromises allograft and patient survival.4, 5 In patients who have not undergone OLT, acute portal or mesenteric vein thrombosis is usually managed with anticoagulation alone, and this leads to recanalization in more than 90% of patients.6 Alternatively, thrombolysis or thrombectomy is performed, but this has not been widely reported and is not the standard of care.7 There are few studies addressing the management of postsplenectomy PVT in OLT recipients. Here we describe a case of acute postsplenectomy PVT in an OLT recipient who was successfully treated with both mechanical thrombolysis and directed and systemic anticoagulation. The patient was a 54-year-old male who suffered from end-stage liver disease secondary to complications from hepatitis C and alcohol abuse. He underwent OLT on March 5, 2007. The piggyback technique was used with a biliary duct-to-duct anastomosis. The operation and the postoperative course both went well without complications. Approximately 2 years later, he presented with increasing left upper quadrant pain. A computed tomography (CT) scan revealed an enlarged spleen with a calcified cyst that measured 17 cm. Therapeutic options were discussed with the patient, and splenectomy was planned. He received subcutaneous heparin perioperatively as deep venous thrombosis prophylaxis. The operation lasted 2 hours and was performed through an extension of the left subcostal incision from the initial OLT. An Endo GIA stapler was used to divide the hilum. Pathology revealed a 960-g spleen measuring 18.2 cm × 14.3 cm × 10.2 cm with capsular fibrosis indicating perisplenitis. Postoperative laboratory tests revealed a 5-fold rise in transaminase levels. An ultrasound examination of the liver was performed and revealed an absence of flow in the portal vein. Dual-phase CT of the liver showed complete thrombosis of the splenic and portal veins with extension into both right and left portal vein branches. The superior mesenteric vein was spared. An intravenous infusion of heparin was initiated. Complete thrombosis of the intrahepatic portal vein branches precluded percutaneous transhepatic cannulation of the portal system. The patient was taken immediately to the operating room in an attempt to salvage the hepatic allograft. A peripheral mesenteric venous branch was located and cannulated with a 5-Fr Fogarty catheter. An initial portogram confirmed the CT finding and revealed complete thrombosis of the main portal vein with some residual flow within the intrahepatic branches (Fig. 1A). Thrombectomy of the main portal vein was attempted via the catheter. With the assistance of interventional radiology, an infusion catheter was placed. Tissue plasminogen activator (t-PA) was injected through the catheter at a rate of 2.5 mg every 15 minutes. After the administration of a total of 16 mg of t-PA, only partial recanalization of the main portal vein was achieved (Fig. 1B). The catheter was withdrawn, the venotomy was ligated, and the abdomen was closed. The patient was extubated and then monitored in the intensive care unit. A postoperative ultrasound examination demonstrated no flow in the portal system. A follow-up CT scan revealed a filling defect in the portal vein and throughout the splenic vein. Interventional radiology was reconsulted, and the patient was taken to the angiography suite. This time, through a right internal jugular vein puncture, the right hepatic vein was cannulated, and the portal vein was accessed transhepatically. The portogram revealed thrombosis of the splenic vein stump, the main portal vein, and the intrahepatic portal veins extending beyond the bifurcation. The superior mesenteric vein was spared. A Trellis 8 pharmacomechanical thrombolysis device (Bacchus Vascular, Santa Clara, CA) was introduced into the portal vein. A total dose of 10 mg of t-PA was administered over 10 minutes, and mechanical thrombolysis was performed simultaneously from the portal confluence to the portal bifurcation. The device was then repositioned between the portal confluence and the inferior mesenteric vein, and another cycle of thrombolysis was undertaken with an additional 8 mg of t-PA. A subsequent portogram revealed significant improvement of the flow in the portal system, with residual thrombus in the splenic vein stump extending only along the medial wall of the main portal vein (Fig. 2A). A low-rate thrombolytic infusion of t-PA and heparin was administered overnight in an attempt to resolve the residual thrombus (0.5 mg/hour via an infusion catheter extending from the splenic vein stump to the main portal vein and 200 U/hour via a transjugular sheath in the main portal vein). The next day, the patient was taken back to the angiography suite, and a portogram revealed a patent portal vein with minimal residual nonocclusive thrombi in the main and right portal veins (Fig. 2B). A repeat ultrasound examination demonstrated recanalization of the portal venous system. Follow-up ultrasound examinations were performed 1 and 2 weeks after the procedure, and all revealed patent vessels. The transaminasemia returned to normal over a period of 5 days after splenectomy. The patient was maintained on a heparin infusion and was converted to warfarin for a total of 6 months after the procedure. The patient did well in the 3 years following this procedure with good allograft function, and portal vein patency was maintained, as demonstrated by follow-up imaging. This case demonstrates that mechanical and directed thrombolysis via a transjugular, transhepatic approach can be both safe and effective. It may represent another viable option when open thrombectomy is neither feasible nor effective. This is, however, only a single case. In order to determine the best therapeutic measures for this type of complication, multicenter experiences and studies are warranted. Lloyd Brown, M.D.1 Ahmad Abou Abbass, M.D.1 Shunji Nagai, M.D.1 Vrishali Patil, M.D.1 Marwan Abouljoud, M.D.1 Todd Getzen, M.D.2 Atsushi Yoshida, M.D.1 Marwan Kazimi, M.D.1 Dean Y. Kim, M.D.1 Divisions of 1Transplant and Hepatobiliary Surgery and 2Interventional Radiology Henry Ford Hospital Detroit, MI

Several studies have investigated the correlation between the effects of different surgical treatments and laboratory exams for schistosomal portal hypertension, especially concerning portal system thrombosis. The etiopathogenic factors of this thrombosis are not fully understood. In this study, the correlation between surgical treatment for schistosomal portal hypertension and the occurrence of postoperative portal system thrombosis was investigated. A total of 61 patients who underwent surgical treatment for schistosomal portal hypertension were distributed into four groups: Patients in Group 1 (n=12) underwent portal variceal disconnection associated with splenic artery ligation and spleen preservation. Patients in Group 2 (n=20) underwent portal variceal disconnection and total splenectomy. Patients in Group 3 (n=20) underwent portal variceal disconnection with subtotal splenectomy, preserving the upper splenic pole supplied by the splenogastric vessels. Patients in Group 4 (n=9) underwent portal variceal disconnection with total splenectomy and autogenous splenic implants on the greater omentum. Late postoperative portal vein thrombosis was diagnosed using Doppler ultrasound. Over the 10-year follow-up, portal vein thrombosis occurred in 26 operated patients (42.6%), with no significant difference observed among the four surgical groups (p=0.217). Most of the thrombi only partially occluded the portal system veins. All the patients presented with a thrombus inside the portal vein. There was no difference in hematological and biochemical tests between groups with or without portal vein thrombosis. Portal vein thrombosis is often observed in the late postoperative period, irrespective of the surgical treatment employed, and is not associated with patient characteristics or any hematological and biochemical tests.

Non-cirrhotic intrahepatic portal hypertension (NCIPH), also called idiopathic or benign, may lead to life-threatening complications. It is a rare indication for orthotopic liver transplantation (OLTx), although it may remain underdiagnosed. Overt symptoms of portal hypertension, predominantly variceal bleedings, misleadingly suggest that these patients are cirrhotic. Non-cirrhotic intrahepatic portal hypertension can be related to obliteration of portal venous microcirculation as a consequence of ADAMTS13 deficiency, a metalloproteinase which cleaves the ultra-large molecular weight forms of von Willebrand factor (VWF). The physiological role of VWF, secreted from endothelium, is to facilitate platelet adhesion at sites of endothelial damage. Decreased ADAMTS13 activity and persistence of ultra-large VWF at the endothelial surface predisposes to platelet clumping, causing microvascular occlusion. We describe the first OLTx for ADAMTS13 deficiency-related NCIPH in Poland. A 20-year-old, previously healthy male student presented with upper gastrointestinal bleeding. Gastroduodenoscopy revealed active bleeding from oesophageal varices, which was successfully treated with endoscopic banding ligation. Physical examination showed splenomegaly, but was otherwise normal with no signs suggesting chronic liver disease. Laboratory investigations were all normal except thrombocytopenia of 40,000/ml. Viral, metabolic, and autoimmunological markers of liver disease as well as bone marrow examination were normal. Transjugular liver biopsy was performed and was essentially normal. However, the tissue sample size was rather slight and we were not able to measure hepatic venous pressure gradient (HVPG). Percutaneous liver biopsy performed later confirmed these findings. Contrast enhanced magnetic resonance imaging scan excluded portal vein thrombosis and Budd-Chiari syndrome. Laboratory investigations showed undetectable levels of ADAMTS13. The patient has been followed up over a period of 5 years, showing constant progression of his portal hypertension with continuous enlargement of his spleen (Figures 1 and ​and2)2) and frequent oesophageal/gastric variceal treatments. Follow-up liver biopsy showed progression to F2 fibrosis. He underwent OLTx with rapid recovery and remains extremely well 6 months after surgery. The histological changes in the explanted liver are shown in Figures 3 A–C. Figure 1 Magnetic resonance imaging of portal hypertension Figure 2 Computed tomography images of the liver hypotrophy and spleen enlargement Figure 3 Histopathology of the explanted liver: A – Liver fibrosis with inflammatory infiltrates. Neocholangioles, small venules, and lack of correct arterioles. Haematoxylin and eosin stain (H + E). Objective magnification 10×. B – Thick ... Non-cirrhotic intrahepatic portal hypertension secondary to ADAMTS13 deficiency is a progressive condition and in case of uncontrolled symptoms of portal hypertension may require liver transplantation. Non-cirrhotic intrahepatic portal hypertension is also called idiopathic or benign portal hypertension. The latter term is misleading as it was shown that more than half of these patients develop liver failure when observed over a median period of 88 months [1]. Thus NCIPH is considered a rare but clinically important cause of portal hypertension. The underlying problem is related to the obliteration of portal venous microcirculation, secondary to the deficiency of ADAMTS13, a metalloproteinase that cleaves the ultra-large molecular weight forms of VWF to smaller ones [2]. The physiological role of VWF, secreted from endothelium, is to facilitate platelet adhesion at sites of endothelial damage. Mutations of ADAMTS13 are seen in congenital TTP, while antibodies to ADAMTS13 are found in the majority of adult acquired cases. Decreased ADAMTS13 activity and persistence of ultra-large VWF at the endothelial surface is thought to predispose to platelet clumping, causing microvascular occlusion. The imbalance in VWF and ADAMTS13 levels in portal microcirculation, where hepatic arterial blood pressures are superimposed, with upstream relation to hepatic stellate cells, would provide a mechanism for obliteration of terminal portal venules, which is characteristic of NCIPH. In our patient plasma activity of ADAMTS13 was below 1%, and its inhibitor was within the normal ranges. He has been treated with β-blockers and remains clinically stable with appropriate endoscopic surveillance. However, in sequential MRI and computed tomography imagines, atrophy of the right lobe of the liver has been observed, with enlargement of the left lobe, periportal fibrosis, varices, and dilatation of the portal tract veins. Chronic NCIPH leads to hepatic atrophy, although the progression of the disease is usually slow. The disorder can be associated with celiac disease and ulcerative colitis, and sustained deficiency of ADAMTS13 appears characteristic of NCIPH despite preserved liver function [1]. Older age at first presentation, hepatic encephalopathy, and portal vein thrombosis were found to be significant predictors of reduced transplant-free survival with, as already mentioned, progression to decompensated liver disease and the need for liver transplantation in a significant proportion of patients [1].

Revising consensus in portal hypertension: Report of the Baveno V Consensus Workshop on methodology of diagnosis and therapy in Portal Hypertension

Background and Objectives: Budd–Chiari syndrome is a vascular disorder of the liver which can cause fulminant liver injury and lethal portal hypertension-related complications. It is a rare disease and can be primary or secondary. The objective of our work is to detail evolution, treatment of patients with BCS and MPN according to the experience of a Moroccan center. Patients and Methods: This is a retrospective and descriptive study in the university hepato-gastroenterology department including all patients with BCS and MPN with portal hypertension (PH) over a period of 29 years. All our patients benefited from an etiological work-up and morphological explorations. Results: Out of a total 29 patients had BCS, 4 had MPN with a prevalence of 10%. Clinically, the signs of decompensated PH were predominant. Imaging confirmed BCS. The etiological work-up showed that all our patients had essential thrombocytemia. We had also association of other prothrombotic factors in 50 % of cases and a portal thrombosis in 25% of cases. Our patients had received treatment for the causative disease and treatment of thrombosis associated with the treatment of PH complications. The evolution was marked by the death of 2 patients (50%). Conclusion: The strong association between MPN and BCS is well established. The knowledge of the molecular mutations underlying MPN has dramatically improved in the last decade, allowing early diagnosis of MPN in a significant portion of BCS patient.

Paroxysmal nocturnal hemoglobinuria is a rare intravascular hemolytic anemia, and thrombosis is the leading cause of mortality rate. The hepatic veins is the common site where Budd-Chiari syndrome usually occurs. We confronted a patient who simultaneously happened to have portal vein and superior mesenteric vein thrombosis leading to prehepatic portal hypertension and upper gastrointestinal bleeding. Percutaneous thrombolysis is an efficacious treatment.

Although portal and/or splenic vein thrombosis after partial splenic embolization (PSE) is a well-known complication, few reports evaluating risk factors have been published. To investigate risk factors and clinical course of portal and/or splenic vein thrombosis after PSE. Sixteen patients with severe hypersplenism underwent PSE between March 2005 and April 2008. The correlation between portal and/or splenic vein thrombosis after PSE detected on multidetector row CT (MDCT) and various factors were retrospectively reviewed. Further, the clinical course of portal and/or splenic vein thrombosis after PSE was observed on follow-up MDCT. Splenic vein thrombosis was detected in eight patients (50%) on MDCT images taken within 9 days after PSE. In one, the thrombosis also involved the portal vein. The infarct volume was identified as a significant risk factor for portal and/or splenic vein thrombosis (P=0.046). In all but one patient, splenic vein thrombosis resolved completely or improved without anticoagulation therapy. In this patient, both portal and splenic vein thrombosis developed after PSE, and anticoagulation therapy was necessary. It is suggested that a large splenic infarct volume is a risk factor for portal and/or splenic vein thrombosis after PSE. Indications for treatment of thrombosis of the portal vein system after PSE may be limited to patients with portal vein thrombosis.

Background: In adults, portal hypertension is generally caused by hepatic cirrhosis, whereas in children it is more commonly caused by extrahepatic abnormalities with normal liver function. Portal hypertension causes hemodynamic abnormalities. Gastrointestinal bleeding is the most severe clinical manifestation of portal hypertension in both children and adults. Pathogenetically, increased pressure in the portal vein can be caused by increased vascular resistance and increased portal blood flow. The site of obstruction can be prehepatic (portal vein obstruction), intrahepatic (presinusoidal: eg congenital hepatic fibrosis; para sinusoidal: cirrhosis, hepatotoxic drug therapy, vitamin A hepatotoxicity; post sinusoidal: venocclusive disease) and/or post hepatic (Budd-Chiari syndrome, constrictive pericarditis). Case presentation: The study reports the results of observations of a case of a boy, FAA, aged 12 years and 2 months who came to the emergency room at Dr. M. Djamil General Hospital Padang with the main complaint of hematemesis and splenomegaly from physical examination. Non cirrhotic portal fibrosis is a cause that is not uncommon in the population in the early second decade of life. Some children with non-cirrhotic portal fibrosis as adults can end up with end stage liver disease. Conclusion: Patients with noncirrhotic or cirrhotic portal hypertension can be assessed using the Child Pugh instrument as an instrument that is still used to determine the survival rate if patients with portal hypertension.

Hyperkinetic circulatory syndrome in patients with presinusoidal portal hypertension: Effect of propranolol

Simultaneous retrohepatic inferior vena cavoplasty and side-to-side portacaval shunt for recurrent thrombosed mesoatrial shunt in the Budd-Chiari syndrome.