Budd-Chiari Syndrome Michael A. Zimmerman, MD, Andrew M. Cameron, MD, PhD, R. Mark Ghobrial, MD, PhD * Division of Liver and Pancreas Transplantation, Department of Surgery, The Pfleger Liver Institute, The Dumont-UCLA Transplant Center, The David Geffen School of Medicine at the University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA Budd-Chiari syndrome (BCS) represents a spectrum of disease states re- sulting in hepatic venous outflow occlusion. Obstruction can occur at any level from the hepatic venules to the right atrium of the heart. Anatomic ab- normalities including vascular webs or strictures may be present and possi- bly pre dis pos e to venous thrombosis. Hyp erc oag ulable states often are present, and the incidence of concomitant disorders is increasing ( Box 1) [1]. Untreated, BCS has a mortality rate close to 80% [2]. The most common causes of BCS in the Western world are myeloproliferative disorders, includ- ing polycythemia vera and essential thrombocytosis [3]. Pregnancy, use oforal contraceptives, and cancer are also documented causes. An evolving pathologic concept advocates the presence of a genetic mutation in one or more genes leading to a hypercoagulable predisposition. Coupled with an acq uir ed thr omb oge nic sti mul us (ie , cancer ), the res ult is hep ati c venous thr ombosis and outflow occ lus ion. Spontaneous resolution has bee n re- ported [4], and up to 25% of patients remain asymptomatic [5]. Most pa- ti ents, ho we ver, requ ire an aggres si ve mu lt id isci pl in ary approa ch, including invasive radiologic procedures and surgery, to control symptoms and prevent disease progression. Liver transplantation recently has emerged as the preferred therapy for patients who have fulminant liver failure or cir- rhosis [6]. Al though the cadave ri c organ pool is li mi ted, portos yst emic shunts remain a therapeutic alternative in patients who have preserved liver function. This article outlines the approach to clinical diagnosis and sup- portive medical therapy in patients who have BCS and reviews the clinical * Corre spondi ng author. The Dumont -UCLA Tra nsplan t Cen ter , 77-120 CHS, Box 957054, 10833 Le Conte Avenue, Los Angeles, CA 90095. E-mail address: [email protected](R.M. Ghobrial). 1089-3261/06/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. Clin Liver Dis 10 (2006) 259–273
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successful. Primarily, the thrombus must be recent and incompletely occlu-
sive. Total occlusion of the vessel portends a worse prognosis. To achieve
high concentrations of thrombolytic agent, the drug must be delivered eitherimmediately proximal or within the thrombus. They suggest that tissue plas-
minogen activator is the preferred agent because it has a very short half-life
(5 minutes), and that systemic therapy is of little value.
Balloon angioplasty and stent placement in the IVC and hepatic veins are
useful adjuncts to medical therapy. Stent placement is recommended be-
cause reocclusion occurs frequently after angioplasty [37]. A recent series
of 115 patients who had BCS reported successful stent placement in the
IVC and hepatic veins of 94% and 87%, respectively [38]. Stent patency
with a mean follow-up of more than 45 months was greater than 90%. Clin-ically, almost all patients who had patent stents improved symptomatically.
Seventeen patients had combined IVC and hepatic vein occlusion. Angio-
plasty and stent placement were undertaken first in the IVC, with the hepatic
vein stent placed 1 week later. During long-term follow-up only one patient
developed hepatic vein occlusion (possibly reocclusion), and all IVC stents
were open. A caveat of this report is that all patients who had hepatic
vein occlusion had obstruction of all three veins. Only one vein was stented
in each case, with a universally successful result. Thus, the entire liver can be
decompressed by intrahepatic venous collaterals.Although thrombolytic therapy, angioplasty, and stent placement can be
effective in the acute setting, most patients present weeks to months after he-
patic vein occlusion. Thus, formation of an intrahepatic shunt between the
hepatic veins and main branch of the portal vein, transjugular intrahepatic
portosystemic shunt (TIPS), is an extremely effective method of splanchnic
decompression [39]. Indications for the TIPS procedure have been extended
to select patients who have BCS in both elective and emergent situations
[40,41]. Several authors have documented rapid improvement in symptoms
and liver function after successful shunt placement [42,43]. Similar to angio-plasty and stenting, TIPS does not require surgical exploration and can be
applied in high-risk patients. TIPS also can be employed to manage patients
who have concomitant hepatic outflow obstruction and portal vein throm-
bosis [44].
Few large series exist documenting TIPS placement in patients who have
BCS. Attwell and colleagues [45] at the University of Colorado recently re-
ported their experience in 17 patients who had BCS and undergoing TIPS
placement. With 100% success with stent placement, 82% of patients expe-
rienced improved symptoms or liver function in the short term. Unfortu-nately, at 3-years follow-up only 47% of patients were clinically well.
Twenty-nine percent of the patients in this series ultimately required liver
transplantation. Because three of these patients presented with fulminant
hepatic failure and were acutely stabilized using TIPS, the authors conclude
that TIPS may serve as a bridge to definitive therapy. Almost one in four
patients experienced a complication, however. Overall, seven patients
constructed between the superior mesenteric vein and the right atrium. Portal
pressures were reduced by 20 cm H2O. A recent surgical experience in more
than 1300 patients, including both mesocaval and mesoatrial shunts, reports
an overall complication rate of 15% and a mortality rate of only 3% [58].Orloff and colleagues [60] recently reported a prospective series of 60 pa-
tients who had BCS over a 27-year period, treated with a portosystemic
shunt or liver transplantation. Overall, 50 patients underwent a shunt oper-
ation, and 10 were referred for liver transplantation. The authors make sev-
eral important observations. This is the single largest reported series of
patients who had BCS with isolated hepatic vein occlusion treated by
a side-to-side portacaval shunt (n ¼ 32). With a mean follow-up of almost
14 years, 30-day and overall survival rates are 97% and 94%, respectively.
Only 3% of patients in this group have developed ascites or hepatic enceph-alopathy or have required diuretics in this time interval. Additionally, only
10% of these patients have abnormal liver function tests. Ninety-seven per-
cent had no evidence of parenchymal congestion or hepatocellular necrosis
on biopsy.
A second group of patients had combined hepatic vein obstruction and
IVC occlusion/stenosis (Fig. 3). Over the course of this study the treatment
Table 1
Surgical therapy for Budd-Chiari syndrome: portosystemic shunt versus orthotopic liver
transplantation
Author
[Reference] # in Study Shunt (#)
Liver
Transplant (#) Comments
Ringe [59] 50 12 43 10-year survival after transplant was
69%. Success rate in shunt group
was only 29%.
Mahmoud [4] 44 16 10 37% of shunt patients died within
strategy for IVC occlusion changed dramatically. Eight patients were
treated with a mesoatrial shunt (Fig. 4). Unfortunately, five of these patientsdeveloped shunt thrombosis and died. With a 5-year survival of 38%, mes-
oatrial shunting was abandoned in favor of a side-to-side portacaval shunt
combined with a cavoatrial Gore-Tex stent graft. Ten patients treated with
the combined approach have 30-day and overall survival rates of 100% with
mean follow-up of 9 years. Finally, the side-to-side portacaval shunt had an
overall thrombosis rate of 0.2%. The authors conclude that, once the diag-
nosis of BCS is made, there is no reason to delay portal decompression in
the absence of end-stage liver disease. When performed early, portacaval
shunting can stop or reverse ongoing parenchymal injury.
Orthotopic liver transplantation
Liver transplantation is the preferred treatment for patients who have
BCS and acute fulminant failure or cirrhosis and decompensated disease.
Since the first successful transplantation in a patient who had BCS was
Fig. 2. Mesocaval shunt. Synthetic Gore-Tex H-graft shunt between the superior mesenteric
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