Budd-Chiari Syndrome: Aetiologi, Diagnosis, and Management

hepatic vein and is commonly not considered as a diagnosis. Such obstruction may happen in all hepatic vein congenital and acquired prothrombotic conditions, myeloproliferative disease, and oral contraceptives use. Advancement in imaging enables most BCS to be diagnosed based on non-invasive imaging tests. Colour Doppler investigation of Budd-Chiari syndrome. Colour Doppler ultrasonography and multi-slice computed tomography diagnosing BCS. Management of BCS starts with the non-invasive to highly invasive procedures, consisting of medical or recanalization therapy to prevent necrosis.


INTRODUCTION
than 5/10000 patients, may become the aetiology of a The common characteristic in most of these disorders is that this disease may cause non-cirrhosis portal hypertension with high morbidity and mortality. The progress in knowledge of liver vascular disorders is impeded by the small number of cases and studies which evaluated the natural disease progressions, pathophysiology or therapy. 1 Currently, Budd-Chiari syndrome (BCS) is known as a disease caused by the obstruction of hepatic vein the opening of inferior vena cava in the right atrium, irrespective of the aetiology. BCS is a rare disease. This syndrome appears in approximately 0.001% of the population and has various aetiologies, including congenital and acquired prothrombotic conditions, myeloproliferative disease, and oral contraceptive use. Improvement in imaging techniques permits most BCS to be diagnosed using non-invasive imaging examinations. Colour Doppler ultrasonography which appropriate technique to initially investigate Budd-Chiari syndrome. Colour Doppler ultrasonogtaphy and 91.3% with a p value > 0.05 between both modalities in diagnosing BCS. Most obstruction in the hepatic particularly hepatic vein and/or inferior vena cava thromboses. This type of BCS is considered as primary BCS, whereas secondary BCS ensues as a result of extraluminal compressions, such as due to tumor, abcess, or cyst. 2 Budd-Chiari syndrome is not commonly considered as a primary diagnosis, and usually the presence of abnormal result in liver function test may be misevaluated as hepatitis. Patient is commonly diagnosed with cholestitis due to the combination of abdominal pain and ultrasonography examination showing the thickening of bile duct wall. Finally, many investigations are commonly performed to may be delayed. Therefore, it is important to consider the diagnosis of Budd-Chiari syndrome in all patients pain, hepatomegaly, and ascites with progressive deterioration; (2) massive ascites with slight changes in liver function test; (3) fulminant liver failure with hepatomegaly and ascites; (4) chronic liver disease with indeterminate causes; (5) liver diseases with thrombogenic disease features. 1,2,3 PATHOGENESIS Hepatic vein obstruction triggers increased sinusoidal pressure, hepatomegaly, upper right abdominal pain and portal hypertension. Severe vein are obstructed, resulting in increased sinusoidal pressure that may decrease perfusion, causing perisinusoidal necrosis which started from zone 3 and may result in liver failure. Necrosis which happens is an ischemic necrosis and may stimulate the oxidative stress process and free radical release. This will further cause the necrosis to expand and become fulminant. In the caudate lobe, the drainage immediately ends in inferior vena cava that may compensate the obstructed vein and cause hypertrophy of the caudate lobe. Collateral is an important clinical feature. Collaterals in the abdominal wall may occur around the umbilicus along the obstructed hepatic vein. The collateral is a acute (26%), chronic (20%), and superimposed acute on chronic (50%). 3,4

AETIOLOGY
Factors which may predispose to the development of Budd-Chiari syndrome include hypercoagulable states, either hereditary or congenital and acquired and other patients. Haematological abnormalities, particularly myeloproliferative disorder, are the most common causes in Budd-Chiari syndrome. Polycytemia vera contributes to 10-40% of all cases in this syndrome, are usually rare. The development of erythroid endogens which can be seen in 87% patient suspected to suffer from idiopathic Budd-Chiari syndrome shows that in majority of patients, where the aetiology of Budd-Chiari syndrome is unclear, actually had myeloproliferative disorder. 5 Other aetiologies of this syndrome are paroxysmal nocturnal haemoglobinuria, antiphospholipid syndrome, and acquired protein C, protein S, and anti-thrombin deficiency. In some patients with associated with myeloproliferative disorder. Low levels of protein C, protein S, and antithrombin III are also linked to the presence of acute thrombus and in patients with liver disease, including Budd-Chiari syndrome. Factor V Leiden mutation, prothrombin gene mutation, and methylentetrahydropholate reductase mutation have also been documented in Budd-Chiari syndrome patients. Although some of these mutations can be found, the presence of only one mutation, might not be a predisposing factor to hepatic vein thrombosis as association to any of them with other predisposing factors may also lead to Budd-Chiari syndrome. 4,5,6

Other Aetiological Factors
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired chronic disorder which is marked by the presence of intravascular haemolysis and haemoglobinuria that usually occurs in patients during sleep at night. It is caused by cellular disorder due to somatic mutation in pluripotent haematopoietic stem cells leading to intrinsic damage in erythrocyte membrane causing it to be more prone to lysis from complement. This may also result in thrombocytopenia, leukopenia, and vein thrombosis emergency PNH has been reported in 9-19% BCS patients. Evaluation of PNH should be performed routinely in patients with BCS. 3,7 Hormonal factors, including the use of oral contraceptives and pregnancy, are considered as risk factors for BCS. Oral contraceptive has been associated with at least 2-fold increased risk of BCS. 3,4,6

DIAGNOSIS OF BUDD-CHIARI SYNDROME
The important step in establishing the diagnosis is to consider the BCS diagnosis in patients who experienced sign or symptoms, such as liver enlargement with excruciating pain or the development of sudden or refractory ascites. The diagnosis of BCS also needs to be considered in acute or chronic liver disease with prothrombotic condition with unknown cause.
can be observed accurately through non-invasive imaging such as Doppler ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI). Doppler ultrasonography is considered as an initial choice of investigation that has high sensitivity [3][4][5][6][7][8] Standard laboratory analysis such as routine blood examination, blood chemistry, liver function test, kidney function test and International normalized ratio (INR), although provide little information in diagnosing BCS, are very helpful in determining the severity of the disease, predicting mortality and response to therapy. Albumin, PT or INR, bilirubin, alanine aminotransferase (ALT) and creatinine levels are important laboratory tests to determine the prognosis index in BCS (Child-Pugh, model for end stage liver disease/MELD, Rotterdam index, New Clichy and BCS-TIPS). Other laboratory examinations are mainly performed to determine the underlying prothrombotic cause.

Sonography Features in Budd-Chiari Syndrome 9-14
The most common imaging modality being used to evaluate BCS consists of ultrasonography (USG), (1) If accompanied with liver injury, protein C, protein S, and antithrombin examination is less meaningful (if observed from the increase of INR value); (2) Anticardiolipin antibody examination is commonly found in chronic liver disease and should be interpreted with caution; (3) In chronic coloured Doppler, and other advanced examinations which are equipped with computed tomography (CT) and magnetic resonance imaging (MRI) examination (Figure 1). BCS has various imaging appearance depending on the form of the disease (acute or chronic). In the acute phase of this disease, the liver is enlarged with simultaneous feature of ascites. Sometimes in and infarct. Thrombus in the hepatic vein has various echogenicity which can be seen in the lumen and in the from chronic occlusion of the inferior vena cana and/ or the presence of intrahepatic collaterals (Figure 2). Intrahepatic collaterals, which are observed as small and Caudate lobe is not frequently enlarged because it has to the inferior vena cava. In monophasic wave Doppler, the hepatic vein occlusion or intrahepatic collateral is observed, compared to the triphasic wave in normal hepatic vein due to the radiation of atrial pulsation. nodule regenerative hyperplasia (NRH), cirrhosis and portal hypertension, which are observed as the rough liver structure echogenicity, with protruded splenoportal axis appearance and splenomegaly. low contrast uptake in acute disease, while in chronic disease, there could be increased and heterogenous contrast uptake with lower increase in liver peripheral area and strong increase in the middle. The arterial phase imaging in the chronic phase of this disease may show very solid nodular lesion or probably showing less developed area due to arterio-portal shunting and of the portal phase may reveal various increase of heterogeneous and spotted pattern which has increased strong uptake in the middle part of the liver which is adjacent to the inferior vena cava and relatively less or none in peripheral area with low contrast uptake is also observed. In the delayed phase, the increasing uptake pattern will become more homogeneous. Nevertheless, the non-opaque shadowing of the hepatic vein does not change in all phases ( Figure 5). This is mainly associated with stasis occurring in the portal vein and sinusoids due to the hepatic vein obstruction and occlusion with or without intrahepatic collaterals. In chronic BCS, changes in liver morphology are also seen. Sometimes, nodular regenerative hyperplasia (NRH) is observed as multiple nodules with various sizes ranging from 0.5 to 4.0 cm. This changes occur vein perfusion. Thus, this lesion is seen as an uptake in arterial phase and is observed more evidently in portal phase. Hepatocelullar carcinoma (HCC) is the main is no increased uptake compared with HCC that may show wash-out contrast in portal phase. In addition, the acute phase MRI showed liver enlargement with low wave uptake intensity in T1 phase (breath hold) and equal increased wave uptake in T2 phase (weighted fast spin echo) and happen in the peripheral area. In the chronic form when liver starts wave capture intensity can be seen. Similar to CT, in MRI with contrast, there is a decreased uptake in acute phase and various features in chronic BCS. NRH is more hyperintensed in T1 and iso-or hypointense in liver parenchyma in T2. CT and MRI imaging may due to caudate lobe hypertrophy and occlusion in inferior vena cava in cases with unclear aetiology or USG appearances (Figure 6).

MANAGEMENT OF BUDD-CHIARI SYNDROME
The management of BCS ranges from non-invasive procedures to highly invasive modalities, consisting of medical and recanalization therapy to prevent necrosis. Angioplasty and stenting aim to rapidly decompress sinusoids, so that the hepatic blood flow can be restored. Percutaneous angioplasty using balloon or Gruntzi catheter through femoral or jugular vein can provide better results. Portosystemic shunting; the purpose of side-to-side portosystemic shunting operation is liver decompression. Yet, due to the high perioperative mortality rates, this procedure had been gradually discontinued. Transjugular intrahepatic portosistemic shunt (TIPS) is usually more preferred.
(PTFE) could yield in better outcomes. [15][16][17] Patients with BCS usually require therapy for ascites and variceal-related conditions. This therapy should be given according to similar management recommendations such as that in ascites and portal hypertension in cirrhosis. [18][19][20] BCS patients must receive a long-term anticoagulant therapy as soon as possible to decrease the risk of obstruction caused by clots and new thrombus development episodes. Based on the recommendation for deep vein thrombosis (DVT), low molecular weight heparin (LMWH) is used at least for 5 to 7 days and oral anticoagulant treatment with vitamin K antagonist (VKA), which aims to achieve Internasional Normalised Ratio (INR) between 2 and 3. LMWH can be discontinued if INR target is not achieved in 2 consecutive measurements. [21][22][23]