Primary Budd-Chiari syndrome is characterized by a blocked hepatic venous outflow tract at various levels from small hepatic veins to inferior vena cava, resulting from thrombosis or its fibrous sequellae. This rare disease affects mainly young adults. Multiple risk factors have been identified and are often combined in the same patient. Myeloproliferative diseases of atypical presentation account for nearly 50% of patients; their diagnosis can be made by showing the V617F mutation in Janus tyrosine kinase-2 gene of peripheral blood granulocytes and, should this mutation be absent, by showing clusters of dystrophic megacaryocytes at bone marrow biopsy. Presentation and manifestations are extremely varied, so that the diagnosis must be considered in any patient with acute or chronic liver disease. Doppler-ultrasound, computed tomography or magnetic resonance imaging of hepatic veins and inferior vena cava are usually successful in demonstrating non-invasively the obstacle or its consequences, the collaterals to hepatic veins or inferior vena cava. The disease is considered to be spontaneously lethal within 3 years of first symptoms. A therapeutic strategy has been proposed where anticoagulation, correction of risk factors, diuretics and prophylaxis for portal hypertension are used first; then angioplasty for short-length venous stenoses; then TIPS; and ultimately liver transplantation. Treatment progression is dictated by the response to previous therapy. This strategy has achieved 5-year survival rates approaching 90%. Medium-term prognosis depends on the severity of liver disease. Long-term outcome might be jeopardized by transformation of underlying conditions and hepatocellular carcinoma.
Keywords
1. Introduction
Budd-Chiari syndrome is characterized by an obstruction of the hepatic venous outflow tract in the absence of right heart failure or constrictive pericarditis [
[1]
]. By convention, hepatic veno-occlusive disease (recently renamed sinusoidal obstruction syndrome) occurring in the setting of an exposure to toxic plants or therapeutic agents is also excluded. The obstacle causing BCS can thus be located at the level of the small or large hepatic veins, or on the suprahepatic portion of inferior vena cava (IVC). When the blockage is caused by invasion or compression by a tumour, BCS is considered secondary, an entity which will not be discussed here. Otherwise, it is related to thrombosis and considered primary.Recent years have witnessed significant advances in several areas. The purpose of this article is to provide an update oriented towards the practical management of this disease.
2. Epidemiology
Primary BCS is a rare disease. In the late 1980s, in Japan and in France, incidence estimates derived from questionnaire surveys were about 0.2 per million inhabitants per year, while the prevalence estimate were about 2 per million inhabitants [
2
, 3
]. However, in Nepal, the disease appeared to be at least 10 times more common, and represented the leading cause for hospital admission in a liver unit [4
, 3
]. Current estimates are lacking. There were differences between Asian and Western individuals with BCS: terminal IVC was frequently obstructed in Asians, and usually patent in Western patients. However, this pattern has changed over time in India, where obstruction of terminal IVC now accounts for a lesser proportion of cases [5
, 6
]. Most affected Western patients have been young females whereas in Asia, middle-aged patients of either sex were predominantly affected. Recent data from a European cohort however indicate a change in demographics as the male to female ratio is closer to 1 and mean age is about 45 years [[7]
].3. Pathogenesis of venous lesions
At the time of presentation, venous involvement may take the aspect of a fresh thrombus, superimposed on a previous stenosis, or of a mere stenosis. The latter may involve the entire length of a hepatic vein or of IVC; or be localized to a short portion of it, even taking the aspect of a membrane or ‘web’. In all instances, the primary lesion is a thrombus, later evolving toward a fibrous sequellae [
[8]
]. Short length stenoses are particularly visible in the cephalad segment of inferior vena cava or major hepatic veins [[9]
].Rarely, venous involvement occurs simultaneously in all hepatic veins. Usually, there is an asynchronous and progressive involvement which progresses at a variable speed. The obstruction is followed by the development of a collateral circulation by-passing the obstacle by connecting blocked territories to contiguous territories that have remained well-drained. The collaterals can run an intra- or extra-hepatic course.
4. Etiology
This is an important aspect of Budd-Chiari syndrome, a disease best understood as the hepatic expression of underlying prothrombotic conditions, particularly blood diseases. As improved outcome of BCS as a liver disease has resulted from advances in management, the importance of underlying conditions for therapy and long-term outcome has been revealed.
4.1 Multifactorial etiology
Recent data from several centres have consistently shown that primary BCS must be regarded as a multifactorial disease where several prothrombotic disorders must concur for the development of thrombosis at this uncommon location. A combination of several prothrombotic conditions has been observed in at least 35% of patients, which is several times higher than expected in the general population [
10
, 11
, - Janssen H.L.
- Meinardi J.R.
- Vleggaar F.P.
- van Uum S.H.
- Haagsma E.B.
- van Der Meer F.J.
- et al.
Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study.
Blood. 2000; 96: 2364-2368
12
]. It is of note, however, that a local (non-tumorous) factor is seldom identified, which contrasts with thrombosis in other venous territories. This multifactorial paradigm explains first the rarity of the disease by the uncommon concurrence of factors which, individually, might not be very uncommon. Second, the differing features among various areas or populations mentioned above can be explained by different combinations of various causes, depending on their background prevalence in the specific area or population (e.g. oral contraceptives in the West, extreme poverty in Asia and South Africa, as outlined below). The impact of this multifactorial paradigm for clinical practice is that identification of one causal factor should not halt the search for other factors. Table 1 summarizes the prevalence of the major causal factors reported in patients with primary BCS. Table 2 presents a summary of the diagnostic work-up for etiology of Budd-Chiari syndrome. Individual risk factors are discussed below.Table 1Approximate prevalence of major risk factors in patients with primary BCS
| Prevalence (%) | |
|---|---|
| Inherited conditions | |
| Antithrombin deficiency | 5 |
| Protein C deficiency | 20 |
| Protein S deficiency | 7 |
| Heterozygous Factor V Leiden | 20 |
| Heterozygous G20210A prothrombin | 7 |
| Acquired conditions | |
| V617F JAK2 positive MPD | 40 |
| V617F JAK2 negative MPD | 10 |
| Antiphospholipid syndrome | 10 |
| Behcet’s disease | 5 |
| PNH | 2 |
| Other general condition | 5 |
| External factors | |
| Oral contraceptives in women | 50 |
| Multiple factors including local factors | 35 |
| No factor | 5 |
Data are averages from reports reviewed elsewhere
[54]
and from more recent reports 12
, 17
, 20
, 55
, 56
.a May be over-diagnosed due to liver dysfunction.
Table 2Proposed work-up for investing underlying risk factors of Budd-Chiari syndrome
| A. In all patients |
|
B. In patients with no marked liver dysfunction (normal prothrombin level)
|
| C- In patients with familial or personal history of recurrent spontaneous deep vein thrombosis: refer to blood coagulation specialist for a detailed study |
4.2 Myeloproliferative diseases (MPDs)
MPDs account for about 50% of BCS patients, an enormous proportion compared to the background prevalence which might be in the order of 0.2% [
[13]
]. A recent, crucial, advance in the field of chronic MPD has been the identification of a particular somatic mutation (V617F) in the Janus tyrosine kinase-2 (JAK2) gene in myeloid cells [[14]
]. JAK2 is coupled to the growth factor receptor on the cells of the myeloid lineage. Activation by the ligand (erythropoietin, thrombopoietin or other growth factors) elicits the signal for proliferation and differentiation of the myeloid precursors into mature cells through JAK2 phosphorylation. V617F JAK2 mutation produces constitutive activation of signal transduction resulting in independence from, or hypersensitivity to, growth factors. This single somatic mutation can be detected in granulocytes or other blood cells of the myeloid lineage. V617F JAK2 has been found in about 80% and 50% of patients with polycythemia vera, and essential thrombocythemia or idiopathic myelofibrosis, respectively [[15]
]. In patients with primary BCS, the mutation has been detected in 37–45% of patients [12
, 16
, 17
, 18
, 19
, 20
]. Other somatic mutations of the JAK2 gene or other genes have been identified in MPD, but they appear to account for only a minor proportion of the cases [[17]
]. Also clusters of dystrophic megacaryocytes at bone marrow biopsy proved recently to be a specific feature for MPD [[21]
]. About 80% of BCS patients with a MPD harbour V617F JAK2 mutation [12
, 17
]. In the remaining patients, evidence for the underlying MPD is derived from bone marrow biopsy findings. Testing for JAK2 mutation and bone marrow biopsy have replaced formerly used tests using cultures of erythroid progenitors to demonstrate endogenous colonies.Peripheral blood cell counts remain within normal values in most patients with MPD when BCS is present, due to hypersplenism, hemodilution and iron deficiency. In the past, this lack of typical changes in peripheral blood has represented a major limitation to the recognition of MPD. In practical terms, this means that all BCS patients, whatever the results of their blood cell counts, should be tested for V617F JAK2 in peripheral granulocytes, followed by bone marrow biopsy in those patients that test negative for the mutation. At present, uncertainties remain as to which of these patients with an essentially normal blood cell count should receive cytoreductive therapies. Advances are expected from the possibility to quantify the mutated cells.
4.3 Other acquired conditions
Behcet’s disease usually causes BCS through its well-known involvement of the IVC. However, cases of pure hepatic vein involvement have also been reported [
22
, 23
]. In areas where Behcet’s disease is prevalent, it represents the leading cause for BCS.Paroxysmal nocturnal hemoglobinuria is an extremely rare disease with a frequently devastating course. The cumulative incidence of hepatic vein thrombosis is extraordinarily high in this disease (about 35%). Features of blood disease are varied so that tests for paroxysmal nocturnal hemoglobinuria should be obtained routinely in all BCS patients. Flow-cytometry on peripheral blood for detection of the CD55 and CD59 deficient clone is the current standard for diagnosis. Recently, a specific treatment with eculizumab has been shown to reduce the incidence of haemolytic as well as thrombotic episodes [
24
, 25
]. Bone marrow transplantation has been successfully performed in some patients with BCS.The prevalence of antiphospholipid syndrome cannot be clearly ascertained as anticardiolipin antibodies are commonly found in patients with a chronic liver disease, whatever its origin [
[26]
]. Using stringent criteria, the prevalence of antiphospholipid syndrome has been estimated to be about 15% among BCS patients. Finding lupus anticoagulant is stronger evidence for antiphospholipid syndrome than anti beta2 glycoprotein-1 antibodies. Anticardiolipin antibodies appear to be the least specific features unless they are repeatedly detected at high titers. There is no specific therapy yet available for this condition.As plasma homocysteine levels are increased in patients with liver disease [
[27]
], the role of hyperhomocysteinemia as a cause for BCS is similarly difficult to evaluate. However, the assessment of vitamin deficiencies is certainly worth while in patients with thrombosis.Oral contraceptive use has long been known as a risk factor for BCS, particularly the form with pure hepatic vein involvement. Pregnancy also appears to be a triggering factor for hepatic vein thrombosis. However, in both instances, an underlying condition is usually present [
11
, - Janssen H.L.
- Meinardi J.R.
- Vleggaar F.P.
- van Uum S.H.
- Haagsma E.B.
- van Der Meer F.J.
- et al.
Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study.
Blood. 2000; 96: 2364-2368
28
].Last, pure IVC obstruction has been associated to a very poor standard of living in a case control study, although the mechanism by which this occurs has not been clarified yet [
[4]
]. This association conveniently explains the predominance of IVC obstruction among BCS patients from some areas of the world [6
, 29
].4.4 Inherited conditions
Identification of Factor V Leiden as a risk factor for venous thrombosis has been another major advance for the understanding of BCS pathogenesis. Factor V Leiden accounts for 7–25% of patients with primary BCS, a proportion similar to that found in patients with deep venous thrombosis of the lower limbs [
5
, 10
, 11
, - Janssen H.L.
- Meinardi J.R.
- Vleggaar F.P.
- van Uum S.H.
- Haagsma E.B.
- van Der Meer F.J.
- et al.
Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study.
Blood. 2000; 96: 2364-2368
30
]. In most BCS patients, factor V Leiden is associated with other risk factors for thrombosis, as expected from its relatively weak thrombotic potential [[30]
].By contrast, G20210A prothrombin gene mutation, another recently discovered inherited prothrombotic disorder, appears to be less over-represented among BCS patients than the former prothrombotic conditions [
10
, 11
, - Janssen H.L.
- Meinardi J.R.
- Vleggaar F.P.
- van Uum S.H.
- Haagsma E.B.
- van Der Meer F.J.
- et al.
Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study.
Blood. 2000; 96: 2364-2368
12
].The prevalence of primary deficiencies in protein C, protein S or antithrombin among BCS patients is difficult to estimate for the following reasons: (a) these coagulation inhibitors are synthesized by the liver; (b) the diagnosis of primary deficiencies is based on the determination of the plasma level (most mutations are private which makes a diagnosis by molecular biology alone difficult); (c) liver dysfunction related to BCS induces a non-specific decrease in plasma levels of these inhibitors; and (d) complete family screening is usually impossible. In most cases, the issue of a possible primary deficiency will thus remain unanswered [
[31]
].A number of systemic diseases have been incriminated (sarcoidosis, cryptogenic bowel disease, hypereosinophilic syndrome, etc.). Collectively, these diseases account for only a minority of the cases.
Other recently identified inherited risk factors [
[32]
] have not been extensively studied in BCS patients. In any case, it is obvious that not all inherited risk factors for thrombosis have been identified yet [[33]
].In practical terms, in a patient with decreased coagulation factor levels or marked liver dysfunction, and without a family history of idiopathic thrombosis, it would seem futile to test for diagnostic purpose, plasminogen, protein C, protein S, or antithrombin deficiency, serum homocysteine and plasma factor VIII levels.
4.5 Site-specificity for thrombosis
The increasing amount of available data lends support to the concept of site-specificity for thrombosis according to the underlying prothrombotic disorder [
10
, 16
, 19
]. MPD is clearly more common among BCS patients than among patients with portal vein thrombosis, and even more so than among patients with venous thrombosis at other sites. Factor V Leiden is more strongly associated with BCS than with portal vein thrombosis, whereas the converse appears to apply to G20210A prothrombin. Further site-specificity might be present also within the hepatic venous outflow tract itself. Indeed, factor V Leiden appears to be particularly common in patients with IVC obstruction [[30]
]. Furthermore, oral contraceptives and pregnancy have been specifically associated with hepatic vein involvement [[3]
].Although these considerations are of little practical significance at present, in the future they may help in the understanding of an important observation: the usual lack of a local – mechanical or inflammatory – factor explaining why thrombosis develops at such an unusual site in the context of a general prothrombotic condition [
[10]
].5. Clinical and laboratory features
Various forms of presentation and course have been described, ranging from fulminant to chronic, the latter being the most frequent one. Asymptomatic forms appear to account for about 15% of patients [
[34]
]. These asymptomatic forms are characteristically associated preservation of some hepatic veins and IVC, or with large intrahepatic or extrahepatic collaterals.The clinical manifestations of BCS have been well characterized [
6
, 34
, 35
]. Abdominal pain, ascites, liver and spleen enlargement, and portal hypertension are important features, as well as a prominent dilation of subcutaneous veins of the trunk in those patients with long standing IVC obstruction. Each or all of these features may, however, be lacking. Liver function tests are altered to a various extent according to patients.Presentation bears little relationship with the actual duration of the disease. Most patients presenting with acute manifestations have extensive fibrosis or cirrhosis. Less than 10% of patients presenting with an acute illness actually have a recent disease [
6
, 36
].In BCS patients, HCC appears to be as significant as a long-term complication as it is in other chronic liver diseases. HCC developed in 11 of 97 patients of a recent cohort followed-up for a mean of 5 years [
[37]
]. Serum α foetoprotein appeared to be more specific for a diagnosis of HCC in patients with BCS than with other liver diseases. Patients with long-standing IVC obstruction carried a risk of developing HCC that was 70-fold higher than those with pure hepatic vein involvement. Multivariate analyses in larger cohorts, as well as molecular studies are further needed to clarify HCC pathophysiology in this non-inflammatory disease of the liver.6. Pathophysiology
The marked clinical and pathological heterogeneity among BCS patients partly stems from the diversity of location of the obstruction (IVC or major hepatic veins), but also from the variable number of obstructed hepatic veins [
[38]
], and likely from the various speed of the obstructive process. In addition, a deleterious role of a loss of intrahepatic portal perfusion has been demonstrated in patients undergoing liver transplantation [[39]
]. In these patients with end-stage liver disease, there was a close relationship between deprivation of portal blood supply, and liver cell loss in the corresponding areas. Portal venous deprivation can result either from intrahepatic portal vein thrombosis, or from focally retrograde portal blood flow. Thus, maintenance of portal blood supply might be crucial for preventing progression of liver disease. Regenerative macronodules, occasionally mimicking focal nodular hyperplasia, are found in arterialized liver, in those areas that are deprived of portal perfusion but apparently well-drained by hepatic venous collaterals [[39]
]. Nodular regenerative hyperplasia is commonplace in these arterialised livers [[39]
].Extrahepatic portal vein thrombosis is superimposed on BCS in about 15% of patients [
[40]
]. As compared with patients having a patent portal vein, manifestations at diagnosis were not more severe and, although survival tended to be decreased, the difference was not statistically significant [[40]
]. Therefore, it might be that superimposed extrahepatic portal vein thrombosis is mainly a consequence of portal vein blood stasis, in a context of multiple prothrombotic factors. According to this view, superimposed extrahepatic portal vein thrombosis might be a reflection of severe liver disease rather than a factor for its aggravation.The asynchronous involvement of the hepatic veins, and the mechanisms of atrophy-hypertrophy which result, explain that a markedly dysmorphic liver is common. The hypertrophy of the central parts of the liver (mainly the caudate lobe) is related in part to the maintenance of an adequate venous drainage through the numerous small caudate lobe veins that reach the IVC directly; and for another part, to a better preservation of portal perfusion than in the peripheral areas.
BCS-related hepatic fibrosis differs from that related to alcoholic or viral liver disease, by its predominant, although not exclusive, centrilobular distribution. In addition, the RNA expression of fibrogenic and angiogenic factors differs from that of chronic liver disease related to alcohol or viral hepatitis [
[41]
].7. Diagnosis
A diagnosis of BCS should be considered in any patient with acute or chronic liver disease. Obviously, the diagnosis is more likely when there is no other, more common, cause of liver disease; or when there is a known underlying prothrombotic condition.
Diagnosis is based on the demonstration of an obstructed hepatic venous outflow tract [
[42]
]. For that purpose, modern, non-invasive imaging means are most efficient, provided two conditions are fulfilled. The examiner should (a) be experienced and (b), be aware of the clinical diagnostic suspicion. The arguments for an obstruction comprise a dilatation of the vein upstream to an obstacle; the presence of a solid endoluminal material; the transformation of the veins into a cord devoid of flow signal; and venous collaterals, seen as abnormal circulating structures branching to or from the hepatic veins or IVC. Doppler-ultrasound, triphasic CT scan or MRI is usually sufficient to show these diagnostic features. Patchy enhancement of hepatic parenchyma is only suggestive of a perfusion defect, which can be seen in many other vascular disorders of the liver. At present, there is almost no place for direct or retrograde venography, for the sole purpose of making a diagnosis of BCS [[1]
].Liver biopsy is of diagnostic interest only in the rare forms of the disease where thrombosis is limited to the small intrahepatic veins, i.e. with a normal appearance of the large veins at non-invasive imaging [
[1]
]. Biospy usually brings non-specific evidence for an impaired blood outflow, including congestion, coagulative necrosis or simple loss of hepatocytes without inflammatory infiltrates, and/or fibrosis, all features predominating in the centrilobular area. Such features of outflow obstruction are encountered in patients with BCS, veno-occlusive disease, or cardiac or pericardial disease. Thrombosis of the hepatic veins is an uncommon finding in needle biopsy specimens. In clinical practice, the most challenging differential diagnosis is constrictive pericarditis.8. Natural course and prognosis
Fortuitously recognized, asymptomatic forms carry a good prognosis [
[34]
]. Symptomatic forms have a poor spontaneous course as it has been estimated that 90% of untreated patients will die within 3 years [[43]
]. Death can be related to refractory ascites leading to emaciation, hepatic failure, gastrointestinal bleeding, or a combination thereof.Contrasting with a high degree of heterogeneity in causes, presentation, and level of hepatic venous outflow block, it is remarkable that all the prognostic information appears to be accounted for by the components of the Child-Pugh score or the MELD score [
[7]
]. However, it should be kept in mind that these markers are poor predictors of the outcome in an individual patient. Therefore, they are of no help in the practical management. The major interest of the disease-specific prognostic scores is for clinical studies adjusting the outcome of patient groups on their baseline characteristics.9. Treatment
Randomized clinical trials of treatment options are still lacking. International expert panel conferences have permitted a consensual elaboration of recommendations based on comprehensive reviews of evidence, and on the confrontation of experience in referral centres [
1
, 44
]. Recent studies have generally supported these recommendations.9.1 Underlying disease
Logically, prompt recognition and treatment of underlying diseases has been recommended. However, data on these aspects are largely lacking. Specific therapy for the underlying causes, if any, should be applied early. This important aspect is beyond the scope of this article. There is hope that recent advances in the understanding of MPD and newly available agents for paroxysmal nocturnal haemoglobinuria will result in a clinical benefit for BCS patients affected with these diseases. For many conditions, particularly antiphospholipid syndrome and hereditary thrombophilias, anticoagulation therapy remains the only available therapeutic means. Recombinant antithrombin is available for deficient patients but only for use over a limited period of time [
[45]
].9.2 Anticoagualtion therapy
Early initiation of anticoagulation therapy is recommended for all patients regardless of whether an underlying prothrombotic disorder has been identified or not [
1
, 44
]. Although anticoagulation has not been evaluated in randomized clinical trials, there is much circumstantial evidence for a favourable benefit/risk ratio in BCS patients [[1]
]. Immediate anticoagulation is therefore recommended [[44]
]. This treatment will be sufficient in controlling the liver disease in 10% of patients, mainly those with a mild disease [[45]
]. A surprisingly high incidence of heparin induced thrombocytopenia has been reported with unfractionated heparin [[45]
] and, more recently, with low-molecular weight heparins [[46]
]. These findings have remained unexplained. However, it is safe to recommend that unfractionated heparin,be avoided as it can be replaced by low molecular weight heparin for initiation of anticoagulation. There is no evidence that the efficacy of vitamin K antagonists differs from that of heparin. At present, therefore, the choice for the type of anticoagulation should be dictated by pharmacokinetic considerations and by context, i.e. a need for rapid and short acting anticoagulation therapy, or long-term treatment.9.3 Percutaneous angioplasty
About a third of patients harbour short length stenosis either of the hepatic veins or of the IVC. Such patients are candidates for percutaneous transluminal angioplasty. The efficacy and the inocuity of this procedure (with or without stenting) have been confirmed, at least when a retrograde, transjugular or transfemoral route is used [
45
, 47
]. Therefore, active search for such short-length stenoses, and when found, an appropriate percutaneous intervention, have been recommended in patients with symptomatic BCS. In asymptomatic patients, the benefit-risk ratio of this therapeutic option is still debated. Available data suggest significant procedure-related morbidity with the transhepatic approach to hepatic vein angioplasty, which is considered when a transvenous approach has failed.Taken together, anticoagulation and angioplasty appear to succeed in controlling BCS in only 20–30% of patients, at least in a Western series where pure hepatic vein involvement predominates [
[45]
].9.4 Transjugular intrahepatic portosystemic shunt
Consistent data indicate that in patients where the disease is not fully controlled by the preceding options, the next step should be TIPS insertion. Indeed, in experienced hands, the transcaval approach is technically and clinically successful in most patients [
47
, 48
, 49
]. Furthermore, the advent of covered stents has allowed maintained patency for prolonged periods [[48]
]. Increased difficulties and morbidity of the procedure in BCS patients as compared with the usual cirrhotic patients should not be underestimated. Improved survival in TIPS treated patients is most obvious among those with the most severe disease at baseline. In that subset of patients, 5-year survival rose from 45% in a reference cohort – where TIPS was only marginally used – [[50]
], to 71% in a series of TIPS treated patients [[51]
]. Overall, 60% of current Western patients may require, and be satisfactorily treated with, a covered-stent TIPS.9.5 Liver transplantation
In the remaining 10–20% of patients, anticoagulation, percutaneous angioplasty and TIPS fail either due to technical failure or to poor clinical results of a technically successful procedure. In such patients, liver transplantation is the remaining option. Two recent retrospective analyses of the outcome in large series of transplanted patients have shown 5-year survival rates reaching 80% [
52
, 53
]. The true impact of liver transplantation is difficult to assess based on these two studies, as their data do not allow for a comparison with patients of similar severity given less demanding treatments. Most recent reports suggest that previous attempt at TIPS or percutaneous stenting of the outflow tract did not compromise the results of liver transplantation [[53]
].Patients with blocked portal vein are poor candidates to TIPS or liver transplantation, although each of these procedures has been reported to be successful in a few patients [
[40]
]. Therefore, maintenance of a patent portal vein clearly stands as a major therapeutic target. However, it should be remembered that after adjustment for severity at diagnosis of BCS, prognosis was not influenced by the presence of portal vein obstruction [40
, 50
]. This means that compensated patients with preserved liver function despite extensive blockade of the splanchnic veins usually have prolonged survival when treated only with anticoagulation, and percutaneous angioplasty of the outflow tract when possible.The implementation of these treatment procedures requires experienced operators. Furthermore, patients should be managed in close cooperation with a transplantation center, as an emergency transplantation may happen to be indicated. Indications for percutaneous manoeuvres are based on imaging and haemodynamic data obtained at IVC and hepatic vein catheterization. Thus, while venograpy has little place among diagnostic procedures, it occupies a central place in the elaboration of therapy.
The above strategy is summarized in Table 3. This strategy aiming at minimal invasiveness is based on response to previous therapy rather than on the actual severity of the patient. It has allowed to achieve 5-year survival rates in the order of 90% [
7
, 45
, 47
]. This considerable improvement in survival expectancy has been obtained together with an excellent quality of life due to complete resolution of clinical signs and symptoms, and quasi-normalization of liver function tests [[45]
].Table 3Proposed treatment strategy for Budd-Chiari syndrome
| A. In all patients |
|
| B. In patients not improving or deteriorating with the above measures, proceed to angioplasty with or without stenting, if appropriate. Indication can be broad when the risk of the procedure is deemed minimal |
| C. Proceed to insertion of a covered TIPS when the patient is not responding to the above treatments whether angioplasty has been technically successful or not. Revise TIPS as needed based on clinical, Doppler-ultrasound and hemodynamic assessment |
| D. Consider liver transplantation when the patient is not responding to the above treatments unless TIPS dysfunction can be corrected |
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Published online: October 27, 2008
Associate Editor: M. ColomboFootnotes
☆The author declares that he does not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.
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© 2008 European Association for the Study of the Liver. Published by Elsevier Inc.
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