BUDD CHIARI SYNDROME : Interventional Therapy ROCHAN PANT, SUNDEEP J PUNAMIYA Department of Vascular and Interventional Radiology, Bombay

Hospital, Mumbai. INTRODUCTION Budd Chiari syndrome (BCS) is caused by an obstruction to the venous outflow tract of the liver. It was first described by Budd in 1845 as hepatic vein thrombosis following abscess-induced phlebitis, and expounded by Chiari in 1899, who described similar obliterative phlebitis in the large hepatic veins.[1] In BCS, the obstruction of the hepatic venous outflow usually occurs at the level of the inferior vena cava, hepatic vein or hepatic venule. (Figs. 1,2) Depending on the level and extent of venous occlusion, and its rate of development, the clinical presentation can vary from ascites, abdominal pain and hepatomegaly to more serious problems such as hepatic failure and encephalopathy. Diagnosis is based on clinical evaluat ion and findings on imaging studies such as ultrasonography (US) with colour Doppler imaging (CDI), computed tomography (CT) and magnetic resonance imaging (MR). Medical management is not preferred, as palliation of symptoms is not entirely successful, and progression of liver disease is not halted. Different surgical procedures have been described to improve the portal venous pressure, such as mesocaval and mesoatrial shunts, membranotomy of the IVC web. Recently liver transplantation has been advocated in the treatment of severe BCS. Of late, several percutaneous radiological procedures have been introduced for the effective treatment of BCS, and these have now become the procedures of choice, replacing surgical and medical therapy of BCS.

Fig.1: Diagrammatic representation Fig. 2: Diagrammatic representation of IVC obstruction above insertion of hepatic vein obstruction at its of hepatic vein. ostium.

CLINICAL BACKGROUND BCS can be divided into three groups that differ in aetiopathogenesis and clinical presentation : 1. Hepatic vein thrombosis (HVT) or "classical" BCS is caused by occlusion of the hepatic veins and is commonly due to hypercoagulable states (Table 1). HVT is commoner in the Western countries, and

commonly due to hypercoagulable states (Table 1). HVT is commoner in the Western countries, and presents more often with an acute or hyperacute illness. Occurrence of heptocellular carcinoma (HCC) as a complication is not a notable feature of this type of BCS.

TABLE 1 Hypercoagulable states associated with BCS Myelodysplastic Syndromes Protein C deficiency Protein S Deficiency Paroxysmal Nocturnal Haemoglobinuria Factor V Leiden Antiphospholipid antibodies (Hughes) syndrome G20210A prothombin gene mutation C677T MTHFR gene mutation Antithrombin III deficiency Polycythaemia primary or acquired Behcet's disease Coeliac Disease Ulcerative Colitis Nephrotic syndrome Oral Contraceptive usage Pregnancy 2. BCS due to obstruction of the IVC in its hepatic portion, with or without occlusion of the hepatic vein ostia, is frequently idiopathic in origin, referred to as "obliterative hepatocavopathy". Modern imaging and histological studies have revealed that the so-called "membrane" that occludes the IVC in some of these cases is a sequel of thrombosis. Most patients do not show any evidence of a hypercoagulable state. A milder clinical presentation is the norm, with features of IVC obstruction and dilated collateral veins over the back. 3. There is a third group of patients who have BCS secondary to a mass lesion that obstructs the hepatic venous outflow. Hepatic neoplastic and infective masses like hepatocellular carcinoma, cholangiocarcinoma, amoebic and pyogenic liver abscesses have been known to cause BCS. IVC obstruction caused by renal malignancies or primary leiomyosarcoma of the IVC have also resulted in BCS. Whatever be its cause, obstruction of hepatic venous outflow in BCS leads to a venous congestion and reduced portal inflow, with resultant ischaemia and centrilobular necrosis. When the necrosis is extensive and rapidly developing, acute liver failure may ensue. In the milder and more chronic form, there is a sequence of liver damage, regeneration and fibrosis that progresses to cirrhosis at a later stage. An increased occurrence of malignancy in this background has also been reported, particularly from Korea, Japan and South Africa.[3] The clinical presentation of BCS can thus be varied. The patients may present with one or more of the following: 1.Acute Liver Failure : Patients with rapidly developing and extensive hepatic vein thrombosis present with acute liver failure.

2.Portal Hypertension : Patients with less extensive venous occlusion present with features of portal hypertension and/or cirrhosis. These include refractory ascites, hepatomegaly, splenomegaly. Varices can occur and sometimes bleed. 3. IVC obstruction : Symptoms of pedal oedema and dilated veins on the back and abdomen may be a presenting feature. 4.Asymptomatic : A small group of patients with chronic obstruction can be asymptomatic due to excellent collateralisation.[4] Patients may present with a mixture of features of IVC occlusion, portal hypertension, or liver dysfunction in varying combinations. Primary pathology responsible for the venous occlusion may also influence the clinical picture to a varying extent. TABLE 2 Aetiology of Budd Chiari Syndrome in India Percentage Cause (number) Membranous Obstruction of the IVC 30% (9) Hepatocellular Carcinoma 20% (6) Idiopathic stricture of the IVC 20% (6) Cholangiocarcinoma 3.3% (1) Renal Cell Carcinoma 3.3% (1) Chronic Pancreatitis 3.3% (1) Hydatid Cyst 3.3% (1) Oral Contraceptive usage 3.3% (1) Protein S Deficiency 3.3% (1) Nephrotic syndrome 3.3% (1) withAntiThrombin III deficiency Polycythaemia Rubra Vera 3.3% (1) Chronic Lymphocytic Leukaemia 3.3% (1)

BCS in India Radiological investigations are aimed at establishing abnormalities of hepatic and caval venous flow, presence of abnormal collateral flow in the liver or the retroperitoneum and evaluating the portal system for portal hypertension and portal venous patency. US Doppler is usually the primary investigation, being non-invasive, easily available and affordable, and with a high degree of sensitivity and specificity. CT or MRI can be used when US is inadequate due to technical limitations. Although hepatic veins and IVC can be seen on CT, contrast injection is mandatory and up to 50% of cases may be technically inadequate or false positive for thrombosis.[3] Additional information about obstructing mass lesions may be offered by CT, significantly affecting management. MRI, with or without contrast injection, is rapidly being considered as a better modality for evaluation of suspected BCS. The multiplanar imaging capability and exceptional imaging of blood vessels provided by MR is making it one of the procedures of choice in evaluating BCS. However, unlike US, MR availability is limited and the procedure is expensive. Direct contrast studies (venography and angiography) are used to confirm the imaging findings and to delineate the anatomy accurately for therapeutic interventions. It is vital to clearly define the status of the IVC, hepatic veins and the portal veins, as the treatment options would be dependent on their findings. Angiographic findings

Angiographic findings 1.Inferior vena cava : The IVC may be occluded or stenosed, at or above the level of the hepatic vein insertion. IVC stenosis should be considered as contributing to or causing hepatic venous outflow obstruction if it lies above or across the hepatic venous ostia, has a significant pressure gradient across, and/or is causing development of dilated venous collaterals (Fig. 3). It is relevant to emphasize that compression by an enlarged caudate lobe may cause narrowing of the IVC in the anteroposterior view. This should not be mistaken for a stenosis; a lateral view and a pressure gradient measurement will clarify the situation (Fig. 4).

Fig. 3: Angiogram revealing Fig. 4: Narrowing of the IVC membranous obstruction of the from caudate lobe enlargement. suprahepatic IVC. 2.Hepatic Veins: Anatomic definition of the hepatic veins requires catheterisation of the vein, and should be attempted in all cases. This can be achieved with a transvenous (transjugularor transfemoral) catheter placement into the hepatic vein (Fig. 5). If the ostia of the hepatic veins are occluded, direct puncture hepatogram may be performed, in which the liver is accessed by needle puncture and contrast is injected into the liver parenchyma. The contrast usually breaks into the proximal hepatic venules and fills the intrahepatic veins and collateral channels8 (Fig. 6). The hepatic venogram may either show a short segment stenosis or obstruction at its insertion in the IVC, or extensive thrombosis of intrahepatic veins (Figs. 5-7). Due to hepatic vein obstruction, collateral channels develop within the liver, and these are depicted as a "spider web" pattern (Fig. 8).

Fig. 5: Hepatic venogram obtained following

Fig. 6: Transhepatic venogram showing

transvenous catheterization of the right hepatic vein, revealing short segment obstruction of the hepatic vein.

Fig. 6: Transhepatic venogram showing obstruction of the hepatic vein, close to its insertion into the IVC.

Fig. 7: Hepatic venogram revealing irregular, attenuated hepatic veins throughout the liver.

Fig. 8: "Spider-web" appearance of the intra hepatic collateral venous channels, pathognomonic of BCS.

3.Portal venous system : It may be necessary in some cases to demonstrate patency of the portal venous system by arterioportography, before planning surgical intervention. Renal function abnormality may be a relative contraindication for the use of iodinated contrast media in these patients, and coagulation abnormalities must be looked for and corrected prior to any invasive investigations. Transhepatic punctures can be difficult in the presence of gross ascites; paracentesis is to be done wherever indicated. Use of thrombolytic therapy is another consideration that may impact on the decision to perform invasive procedures. Prognosis The natural history of BCS is variable. Cases with severe affliction and rapidly developing hepatic dysfunction have a poor prognosis unless treated aggressively. Other cases with slower progression and well-developed collaterals may have a prolonged life expectancy. The common presentation in chronic cases is development of ascites and cirrhosis. Gastrointestinal bleeds occur in a few, and maybe responsible for mortality. Earlier literature paints a very dismal picture in cases of BCS. Survival rates between 1971-80 with fibrinolysis and surgery including a few liver transplants was around 59% at 1 year.[9] An improvement in survival statistics in recent times has been seen, attributed to better medical management, improved surgical practice and incorporation of radiological interventions in therapy. A 10year survival of 75% has now been reported.[3] Principles of Management The management of BCS should be aimed at restoring the blood circulation in the liver to physiological direction wherever possible. This not only alleviates symptoms, but also can halt the progression to cirrhosis when carried out in the early stages. Where restoration of normal hepatic outflow is not possible, the aim should be to alleviate symptoms and improve quality of life for the patient. This involves procedures that provide alternative outflow channels, usually the portal vein, to decrease hepatic congestion.

Another important component is the treatment of the underlying condition where possible. Any patient with hypercoagulable state should be placed on anticoagulation as required. Liver transplant is a definitive therapy where liver damage is severe and uncompensated. This option is unfortunately not yet practicable in India. Decision as to which of the available options is ideal for a particular patient is made with an analysis of (1) the site and extent of the venous outflow obstruction, (2) the aetiology of the obstruction and (3) the stage of liver damage and dysfunction. INTERVENTIONAL RADIOLOGY IN THE MANAGEMENT OF BCS Interventional radiology (IR) has a central role to play in the management of BCS, valuable in all types of clinical presentations. Acute or Hyperacute BCS is uncommonly seen in our country, and is usually due to extensive thrombosis. The first line of therapy is thrombolysis, to lyse the obstructing clots. Locoregional thrombolysis using catheter techniques to direct the lytic agent into the thrombus, along with mechanical and hydrodynamic techniques for removal of obstructing thrombus can be used. There is limited data on thrombolytic management; sporadic cases have been reported of successful recanalisation using these procedures.10,11 If thrombolysis is unsuccessful in improving hepatic function, an emergency shunt procedure can provide venous outflow critical for decompressing the liver. The traditional shunt used has been a surgical portocaval shunt. The transjugular intrahepatic portosystemic shunt (TIPS) has proved to be a viable alternative. The TIPS functions like a surgical portocaval shunt, with far less morbidity and mortality as compared to surgical shunts. To date, there have been only small case series and anecdotal reports about usage of TIPS in acute, severe BCS. In 1995, Blum et al reported 7 cases with acute or hyperacute BCS, that had TIPS creation. Procedure was technically successful in all cases, and there were 2 deaths, attributed to septicaemia and liver failure.12 Surgical interventions in cases of acute BCS have shown much higher mortality. Chronic BCS is much more commonly reported in India. The management of these patients presents a challenge in view of the frequently debilitated condition and prolonged obstruction that is difficult to recanalise. The exact intervention in these cases is dependent upon the site and extent of obstruction. These cases can be divided into four groups on this basis: - Type A : IVC obstruction - Type B : Pure hepatic vein obstruction with short segment stenosis - Type C : Combined short segment hepatic vein and IVC occlusion - Type D : Extensive intrahepatic occlusion of hepatic veins with no identifiable main hepatic vein. These can be differentiated on the basis of cross sectional imaging and catheter angiography. Type A (IVC Obstruction) : (Fig. 9) These cases are usually secondary to a membranous occlusion of the vena cava (MOVC) in our country,6 and angioplasty and stenting is the procedure of choice for management of these lesions. A transfemoral approach is employed, with a guidewire being used to cross the obstruction or stenosis. At times a puncture has to be made across a tough, chronic membrane using a long needle, like the Brockenbrough's transseptal needle or a Rosch -Uchida needle. A balloon catheter is then used to dilate the narrowed or occluded part. This procedure is followed by insertion of a metallic stent to increase long-term patency, as pure

part. This procedure is followed by insertion of a metallic stent to increase long-term patency, as pure angioplasty has been associated with limited patency in chronic occlusive lesions. Restenosis is known to occur, but can be tackled by a repeat venous puncture and balloon dilatation. Successful angioplasty and stenting results in rapid resolution of symptoms.[13]

Fig.9a,b,c: Type A obstruction: (a) Angiogram showing short segment obstruction of the IVC, with retrograde filling of the right hepatic vein (b) Needle guided across the obstruction in the suprahepatic IVC, (c) Angiogram following stent placement, showing good flow across the IVC and restoration of normal hepatic outflow.

Type B (Short segment hepatic vein obstruction) : (Fig. 10)

Cases with short segment stenosis or occlusion of the hepatic veins should undergo recanalisation procedure. This can be a complex interventional procedure requiring transvenous and/or transhepatic access. The occluded or stenosed portion of the hepatic vein is crossed using needles, guidewires and catheters, and balloon angioplasty of the stenotic portion is carried out. Earlier cases used simple angioplasty, with stents being reserved for failure of angioplasty. A high incidence of restenosis with angioplasty has led to the primary use of stents to improve long-term patency. Reopening of even one of the three hepatic veins is sufficient for excellent clinical response as intrahepatic collaterals are generally extensive. Hepatic venous stenting have been shown to have results that are better than those of surgical portocaval shunting in terms of procedural mortality and at least as good as in terms of secondary patency in the long term.[14] In addition, unlike surgical portosystemic shunts, normal physiological flow is preserved, thereby obviating shunt-related problems, such as encephalopathy. Cases where attempts at recanalisation are unsuccessful can be treated like type D cases.

Fig. 10a,b,c: Type B obstruction: (a) Angiogram showing obstruction of the hepatic vein at its ostium, (b) The lesion was recanalised and balloon-expandable stent deployed, (c) Angiogram showing excellent flow from the hepatic vein into the IVC. Type C (Combined IVC and short segment hepatic vein occlusion) : (Fig. 11)

Combined IVC and hepatic vein obstruction is also ideally tackled by interventional means. The procedure involves recanalisation of IVC and at least one hepatic vein, with placement of stents in both vessels. The procedure is a combination of procedures used to treat type A and type B cases. Another method that can be utilized is to use a combined radiological-surgical approach, whereby the IVC is recanalised with a stent, followed by a surgical mesocaval shunt. We have abandoned this technique in favour of combined HV and IVC recanalisation, that maintains normal physiological blood flow and avoids surgical complications.

Fig. 11a,b,c: (a) Angiography demonstrating IVC obstruction, (b) Transhepatic Venography showing concomitant hepatic vein obstruction at its ostium, (c) Angiogram after stent

showing concomitant hepatic vein obstruction at its ostium, (c) Angiogram after stent placement into both occluded vessels, revealing good flow. Type D (Extensive intrahepatic venous occlusion) : (Fig. 12) Extensive occlusion of intrahepatic venous channels implies that no usable veins exist for attempts at revascularisation. In this event, the only option is a shunt procedure to improve venous outflow, best achieved by TIPS. The TIPS procedure is carried out through a transjugular venous puncture. A long curved needle is inserted into the stump of the hepatic vein, and passed across the hepatic parenchyma into an intrahepatic main branch of the portal vein. A guide wire is passed through the needle, and the parenchymal tract is dilated with a balloon angioplasty catheter. A stent is then placed in the tract to maintain its patency. This procedure has been described in more detail elsewhere in this issue. A technical challenge in the performance of TIPS in cases of BCS is the absence of normal hepatic vein. Hepatic vein stump is used where one exists, alternatively a direct IVC to portal vein shunt is created (Direct Intrahepatic Portosystemic Shunt, DIPS).[15] The TIPS procedure lowers the venous congestion and excellent symptomatic relief is obtained in most cases of intractable ascites.[16] The main concern with the TIPS procedure has been the long-term patency of the shunt. Ingrowth of the cells lining the stent leads to eventual occlusion and dysfunction of the shunt. A newly developed stentgraft endoprosthesis has shown promise in providing good long-term patency in recent trials.[17] Furthermore, stenosed shunts can easily be subjected to repeat balloon dilatation, a simple outpatient procedure. This is distinct contrast to a surgical shunt, whose revision is very difficult and morbid. Patients with additional thrombosis of the portal vein carry a poor prognosis and is a contraindication to TIPS, though successful TIPS has been carried out in cases where portal vein was acutely thrombosed.[18,19]

Fig. 12a,b,c,d: Type D obstruction: (a) Transhepatic venogram showing diffusely diseased intrahepatic veins, (b) The IVC is patent, but the hepatic veins are occluded from their ostia, (c) The hepatic vein stump was punctured with a long needle, which was traversed across the liver into the portal vein, and portogram obtained, (d) TIPS created between the portal vein and IVC, showing good portal flow diversion into the IVC. Interventional radiology has been successful in treating majority of cases of BCS, and has now become the method of choice for management of this disease (Table 3). We suggest an algorithm for management of BCS (Fig. 13).

Fig. 13: Algorithm for management of BCS.

Reference Fisher et al[14]

Wu et al[20] Baijal et al [21] Chunqing et al [22]

Perello et al[16]

Punamiya et al*

TABLE 3 Interventional treatment in BCS : Literature Review No. of Early Clinical Result Procedure patients deaths Hepatic 18 3 Follow up 1- 9 y. Vein Symptom recurrence in 6. Successful reintervention in 5 Stenting Death after surgery in 1 case. IVC Angioplasty 42 Nil All symptom free at 32 12 m and stenting IVC 9 1 Follow up 3- 31 m Angioplasty 8 survivors symptom free and stenting Hepatic 23 Nil Follow up 1- 43 m vein 1 patient did not have relief of symptoms Others symptom free stenting Purely US guided proceudres TIPS 13 Nil Follow up 4 3 years 1death (Acute liver failure) 1 liver transplant ( 2y). 11 Patients alive and free of ascites. 2 patients underwent successful reintervention for symptomatic TIPS dysfunction. Nil 1 recurrence, rest symptom free 6 IVC 9 Nil 8 symptom free Stenting 1 asymptomatic restenosis, Hepatic refused Rx Vein Both symptom free stenting 5 2 2 patients alive, symptom free 1 early death from stroke

IVC + Hepatic V stenting TIPS *Unpublished data CONCLUSION

Budd-Chiari syndrome should be diagnosed and treated aggressively, as it is one of the few potentially reversible chronic liver diseases. Diagnosis depends on clinical suspicion and imaging studies. Interventional radiological techniques are rapidly being considered as the treatment of choice in the management of acute and chronic cases refractory to medical management. Recanalisation of the hepatic vein and/or inferior vena cava provides excellent long-term restoration of physiological circulation through the liver. If a portosystemic shunt is to be offered, TIPS offers a far lower morbidity and mortality than surgical mesocaval and mesoatrial shunts. However, durability of the TIPS is a concern, and much work is currently being carried out to increase the long-term patency of the TIPS. The TIPS stent-graft devices are very promising in that aspect. In the more severe cases that would require liver transplantation, absence of an established liver transplant programme in India makes it lucrative to attempt the low-morbid interventional radiological procedures for palliation and treatment of this condition.

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17.Saxon RR, Timmermans HA, Uchida BT, et al. Stent-Grafts for revision of TIPS stenoses and occlusions: a clinical pilot study. J Vasc Interv Radiol 1997; 8 : 539-548. 18.Watanabe H, Shinzawa H, Saito T, et al. Successful emergency treatment with a transjugular intrahepatic portosystemic shunt for life-threatening Budd-Chiari syndrome with portal thrombotic obstruction. Hepatogastroenterology 2000; 47 : 839-841. 19.Mahmoud AE, Helmy AS, Billingham L, Elias E. Poor prognosis and limited therapeutic options in patients with Budd-Chiari syndrome and portal venous system thrombosis. Eur J Gastroenterol Hepatol 1997; 9 : 485-489. 20.Wu T, Wang L, Xiao Q, et al. Percutaneous balloon angioplasty of inferior vena cava in Budd-Chiari syndrome. Int J Cardiol 2002; 83 : 175-178. 21.Baijal SS, Roy S, Phadke RV, et al. Management of idiopathic Budd-Chiari syndrome with primary stent placement: early results. J Vasc Interv Radiol 1996; 7 : 545-753. 22.Z Chunqing, F Lina, Z Guoquan, et al. Ultrasonically guided percutaneous transhepatic hepatic vein stent placement for Budd-Chiari syndrome. J Vasc Interv Radiol 1999; 10 : 933-940.

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