Budd-Chiari syndrome and extensive inferior vena cava thrombosis treated with sequential interventional radiology and transjugular intrahepatic portosystemic shunting: A case report from Kenya

Abstract

Budd-Chiari syndrome is a rare disease characterized by the obstruction of hepatic venous outflow. Stepwise treatment options aimed to relieve obstruction and prevent complications of Budd-Chiari syndrome are medical therapy, interventional recanalization, and surgery. Aggressive interventions for complicated Budd-Chiari syndrome are placement of a transjugular intrahepatic portosystemic shunt, surgical shunting, or liver transplantation. Although literature suggests differences in the presentation and management between Europe and Asia, cases documenting successful use of stepwise management of Budd-Chiari syndrome in Sub-Saharan Africa are scarce. A 47-year-old male on treatment for chronic hepatitis B presented with abdominal pain and distension for 2 weeks and findings of gross ascites without stigmata of chronic liver disease. Laboratory investigations performed showed anemia, elevated transaminases, coagulopathy, and renal dysfunction. Abdominal ultrasound and computed tomography abdominal scan revealed filling defects in intrahepatic veins and inferior vena cava extending to bilateral renal and external iliac veins. Extensive workup for thrombophilia and myeloproliferative disorders was negative. The diagnosis was hepatic dysfunction secondary to inferior vena cava obstruction due to a thrombus in the setting of extensive inferior vena cava thrombosis, and heparin was initiated. However, due to lack of recanalization with anticoagulation, we performed aspiration thrombectomy, balloon angioplasty, and local thrombolysis. Transjugular intrahepatic portosystemic shunt procedure was subsequently done due to hepatic venous congestion and refractory ascites. He was discharged on oral anticoagulation. Imaging exams performed 4 months later showed patent inferior vena cava and transjugular intrahepatic portosystemic shunt, good flows in the portal vein and resolution of ascites.

Introduction

Budd-Chiari syndrome (BCS) refers to a constellation of conditions characterized by the obstruction of venous outflow at any level from the hepatic veins to the confluence of the inferior vena cava (IVC) and the right atrium. ¹ The obstruction can result in hepatic venous congestion and sinusoidal hepatocyte necrosis, which can progress to cirrhosis and its associated complications, including portal hypertension. ²

BCS is a rare disease whose prevalence has a huge variability of 1.4 to 5.2 per million persons from studies done in European and Asian countries. ³ The etiology of BCS is classified as primary, mainly due to venous thrombosis and secondary to extrinsic compression from tumors or other masses. In the Western world, up to 75% of patients with thrombosis have an identified underlying thrombophilia disorder.^2,4 However, in Asian countries, endoluminal obstruction due to webs or stenosis accounts for more cases than thrombi.^5,6 Studies done in Egypt revealed thrombophilia as the most common etiology of BCS.^7,8 The prevalence or etiological pattern of BCS in other African countries is unknown.

Differences in the presentation and management between Western and Asian patients have been reported in literature. However, data on the African population is scarce. In addition, few case reports from Sub-Saharan African have documented successful use of stepwise management of BCS. Here, we report a case of an African male who had acute presentation of BCS, concurrent extensive IVC thrombi and IVC stenosis in the setting of chronic hepatitis B and was treated with thrombectomy, thrombolysis, angioplasty, and transjugular intrahepatic portosystemic shunt (TIPS) resulting in recanalization and resolution of presenting symptoms and liver decompensation.

Case report

A 47-year-old male presented with abdominal pain and distension for 2 weeks. His medical history was significant for chronic hepatitis B infection, chronic kidney disease (stage 2), and hypertension. His regular medications consisted of tenofovir 300 mg once daily, amlodipine 5 mg once daily, lactulose 20 gm once daily and carvedilol 12.5 mg twice daily. His recent hepatitis B viral load was 385 IU/mL. He had a negative family history of thrombophilia or malignancies. He neither took alcohol, nor use any herbal or over-the-counter medications.

On examination, he was hemodynamically stable, pale, and jaundiced. The neurological examination revealed an alert and oriented middle-aged male with no asterixis. Abdominal examination was positive for features of ascites evidenced by gross distension, flank dullness on percussion, and positive fluid thrill. He did not exhibit any other stigmata of chronic liver disease.

Laboratory investigations revealed anemia, elevated transaminases, coagulopathy, and renal dysfunction (hemoglobin 11.80 g/dL, AST 914 IU, ALT 535 IU, INR 2.02, total bilirubin 40 µmol/L, ALP 94 IU, GGT 90 IU, albumin 49, Creatinine 525 µmol/L, BUN 25.20 mmol/L). The platelet count and white cells counts were normal at 253 × 10⁹/L and 10.78 × 10⁹/L, respectively. Notably, the results of routine hepatic tests performed 2 weeks prior were normal. Hepatitis A and C antibodies were negative. Ascitic fluid analysis showed polymorphonuclear cell counts of 88 × 10⁶/L, and both cultures and cytology were negative. The serum albumin ascitic gradient was 2.2 g/dL, indicative of portal hypertension as the cause of the ascites.

Computed tomography (CT) abdominal scan showed thrombi in the middle and right intrahepatic veins and in the IVC involving bilateral renal and external iliac veins (Figure 1). Moderate volume ascites was also present (Figure 2).

Figure 1.

Coronal post-contrast CT of the abdomen demonstrating extensive thrombosis of the inferior vena cava (white star), bilateral common iliac, and renal veins along with hepatic congestion.

Figure 2.

Axial post-contrast CT at the level of the liver demonstrating calcification around a narrowed non-enhancing intrahepatic IVC (black arrow) and ascites.

Workup done for thrombophilia included protein C and S activity, factor V Leiden mutation, prothrombin gene mutation G2021A and anti-phospholipid antibodies. The results disclosed reduced activity of factors C and S, at 22% (70%–130%) and 53% (normal range 77%–143%), respectively. The other investigations were negative. Myeloproliferative disorders were ruled out by normal results of complete blood count, peripheral blood film, bone marrow examination, and Janus kinase 2 (JAK2) V617F mutation testing. Screening for paroxysmal nocturnal hemoglobinuria was also negative.

A diagnosis of hepatic dysfunction secondary to IVC obstruction due to a thrombus in the setting of extensive IVC thrombosis was established. The imaging modalities ruled out any masses compressing the vessels.

The initial treatment was unfractionated heparin with monitoring of activated partial thromboplastin time (APTT) levels to achieve values of 1.5 to 2 times the control, diuresis with furosemide and prevention of hepatic encephalopathy with lactulose and rifaximin. He also required intermittent hemodialysis due to oliguria and acidosis. Subsequent liver tests showed improvement with reduction in AST and ALT to 29 and 149, respectively. However, he still had significant ascites despite diuresis and paracentesis. A follow-up CT abdominal scan 1 week after admission demonstrated the previously seen extensive IVC thrombosis and an increase in ascites. The patient was referred to a facility with capability of radiological and surgical interventions for the extensive thrombus.

Ultrasound venography at the referral facility confirmed thrombosis of the IVC and iliac veins. Furthermore, a short segment of significant stenosis of retrohepatic IVC was also revealed. A decision was made for mechanical thrombectomy, angioplasty of the stenosed IVC segment, filter insertion, and local chemical thrombolysis. Access for the interventions were through ultrasound-guided punctures of both the right internal jugular and right common femoral veins and insertion of 10 French (Fr) Cook Flexor (Cook Europe, Bjaeverskov, Denmark) sheaths in both the vessels. Transfemoral aspiration thrombectomy was done using 8 Fr Aspirex^® S (Straub Medical, Wangs, Switzerland) along the IVC and right iliac veins until restoration of flow in these vessels. Transluminal angioplasty of the stenosed segment of the retrohepatic IVC was then done with a Cook balloon (LONV^TM, Bloomington, Indiana, USA) up to 20 mm. Evaluation of patency done via venography showed significant restoration of flow and minimal residual thrombus along the IVC. A Günther Tulip filter (Cook Medical, Bloomington, IN) was then successfully deployed to the infrarenal segment of the IVC. Afterwards, catheter-guided thrombolysis using alteplase (15 mg bolus dose and continuous infusion of 1 mg/h for 24 h) was commenced. Both the internal jugular and femoral catheters were left in position. An APTT-controlled intravenous heparin infusion was then administered.

One week after the initial interventions, the patient still had significant abdominal distension. CT abdominal scan done showed recanalization of the IVC but showed persistent ascites with new features of hepatic venous congestion involving the right lobe of the liver. A decision was made for TIPS and IVC stenting. The patient underwent stenting of the IVC after access through the femoral sheath and deployment of a 22 mm (diameter) by 40 mm (length) uncovered self-expandable metal stent (Wallstent™ Endoprosthesis Stent, Boston Scientific, USA) in the area of narrowed retrohepatic IVC (Figure 3). Subsequently, the shunting procedure consisted of combined percutaneous transhepatic and transjugular techniques for accessing the portal and systemic systems, respectively. The portogram showed evidence of significant portal hypertension with hepatofugal portal venous flow into the inferior mesenteric vein and posterior gastric veins. Transcaval puncture from the internal jugular vein into the right portal vein was achieved. Significant portosystemic pressure gradient of 23 mmHg was noted. A Viatorr^® (Gore, Flagstaff, AZ, USA) polytetrafluoroethylene (PTFE)-covered stent was deployed between the right portal vein and within the IVC stent with achievement of good flows through the TIPS stent into the right atrium and reduction in portosystemic gradient to 9 mmHg (Figure 4).

Figure 3.

Coronal post-contrast CT abdominal scan post-stenting of the inferior vena cava with thrombus within the stent (short arrow). Infrarenal IVC filter is also present (long arrow). Near complete resolution of ascites and reduction in extent of the IVC thrombosis.

Figure 4.

Serial coronal images demonstrating the Viatorr stent uncovered component in the right portal vein (a) extending to the bifurcation of the main portal vein (b) and cranial end landed within an inferior vena cava stent (c). Percutaneous transhepatic access tract into portal vein embolization with coils and gel foam (arrow in Figure 4(a)).

The patient had significant resolution of ascites during the recovery period. He was initiated on oral anticoagulation (rivaroxaban) after discontinuation of heparin infusion and discharged 1 week after the final procedure. He required twice weekly hemodialysis for a month post-discharge, after which his renal functions returned to the baseline state. Subsequent imaging 4 months later demonstrated patent IVC and TIPS, good flows in the portal vein, and resolution of ascites. The liver tests results were AST 68 IU, ALT 58 IU, ALP 119 IU, total bilirubin 45 µmol/L, and albumin 44 g/L.

Discussion

We present a case of an African male patient who presented with acute decompensation of hepatic and renal functions and after being diagnosed with BCS and concomitant extensive IVC thrombosis underwent successful interventional procedures after failed initial medical therapy. In addition to thrombosis, the patient in our case also had stenosis of the IVC.

The common predisposing factor in BCS differs between Western and Asian cohorts. In the former, an underlying thrombotic condition, commonly myeloproliferative disease, was identified in 75%–84% of cases. ⁹ In contrast, these conditions, including polycythemia vera, essential thrombocytosis, and myelofibrosis, are rare causes of BCS in reports from Asian countries. ⁶ In addition, the prevalence of genetic thrombophilia disorders including proteins C and S deficiencies, factor V Leiden mutation and prothrombin G20210A gene mutation also varies between the two groups. The patient in our case underwent workup for both acquired and genetic causes of thrombophilia which revealed reduced activity of proteins C and S, at 22% and 53% of normal activity, respectively. The plasma assays of these proteins involved in thrombin generation can be reduced in the setting of either an acute thrombus or liver dysfunction.^1,9 Our patient presented with extensive IVC thrombi and also had chronic hepatitis B. In such settings, only levels below 10%–20% of normal activity would suggest true deficiencies.^1,2 Screening the family members for these deficiencies can also help in establishing the diagnosis. ¹

A stepwise therapeutic approach to BCS, which utilizes the medical, interventional, and surgical options, has been proposed.^1,9 Anticoagulation is recommended in all patients with BCS for both the initial treatment of thrombosis as well as maintenance of lumen patency after interventions. The options are: (1) unfractionated or low molecular weight heparin, (2) warfarin, and (3) direct acting anticoagulants.^1,10 The other components of medical therapy are systemic thrombolysis and treatment of complications, including portal hypertension, ascites, and concomitant organ dysfunction. In cases where the initial treatment is unsuccessful in resolution of ascites or organ failure, an escalation to interventions including thrombectomy, angioplasty with or without stenting, TIPS, and liver transplantation is advocated.^1,9 Our patient had persistence of ascites and worsening hepatic and renal functions despite 2 weeks of optimal anticoagulation with unfractionated heparin. Furthermore, imaging after the initial treatment demonstrated persistence of the extensive thrombi and stenosis of the IVC.

The main aim of interventions in BCS is to relieve obstruction or provide by pass for hepatic outlet thereby preventing venous congestion and progression to fibrosis or cirrhosis. ¹¹ The status of the IVC determines the procedure required for relief of the obstruction. In cases where the IVC can be accessed by catheters, dilatation may be attempted. In addition, mechanical or chemical thrombolysis may be performed in cases of significant thrombus after angioplasty. Local thrombolysis is then used an adjunctive therapy for partially recanalized vessel after the interventions. ¹¹ Our patient had access to the IVC through both right internal jugular vein and right femoral vein. These enabled the sequential procedures of IVC dilatation, followed by mechanical aspiration along the IVC. Local thrombolysis was then administered via the femoral sheath.

TIPS creates a portocaval shunt through the liver parenchyma and provides an outlet for hepatic veins through the portal system. It was traditionally used in portal hypertension and variceal bleeding, but the efficacy in BCS is now well documented, with reported 93% procedural success and 84% 5-year liver transplant–free survival.^12,13 TIPS in BCS is recommended to prevent hepatic congestion from leading to cirrhosis; in pre-existing liver cirrhosis and portal hypertension; and extensive hepatic vein occlusion. Complications of the procedure include bleeding, stent thrombosis or dysfunction, and hepatic encephalopathy. The rates of stent occlusion or restenosis are lower with use of covered as compared to bare metal stents. ¹⁴ A PTFE-covered stent was deployed for our patient. Similar to our case, ascites is the most frequent indication for treatment escalation from medical therapy to TIPS in patients with BCS.^12,14

Patients with BCS who develop liver cirrhosis should be considered for liver transplantation. Hepatic outflow thrombosis is a rare indication for liver transplantation, accounting for less than 2% of procedures. ¹⁵ The challenges include the extent of thrombosis, huge size of the liver, thrombotic complications, and difficult venous reconstruction. ¹⁶ The latter challenge is compounded in cases of living donor liver transplantation (LDLT), especially with significant IVC involvement in the recipient. In deceased donor liver transplantation (DDLT), the donor IVC replaces the recipient’s IVC, whereas in LDLT, the graft does not contain the retrohepatic IVC. Techniques applicable for LDLT involving recipients with extensive IVC thrombosis include recanalization, venoplasty, resection of thrombosed segment, and direct anastomosis between the hepatic vein and the right atrium or IVC reconstruction using synthetic material or vascular allografts.^15,17

The rarity, multitude of etiologies and heterogeneous presentation of BCS limits head-to-head comparison of the different modes of treatment. We contribute to the scarce literature on BCS presentation and management from the region. Our case highlights successful sequential treatment in an African patient with thrombosis and stenosis of the IVC based on close clinical and radiologic monitoring of response to therapy.

Conclusion

We describe a case of interventional treatment of BCS and IVC thrombosis presenting as liver and renal dysfunction. Stepwise interventional radiological technique is an essential component that should be considered in treatment of BCS associated with organ dysfunction refractory to anticoagulation.