J Gastroenterol 1999; 34:634–639

Case report
Aged Budd-Chiari syndrome attributed to chronic deep venous
thrombosis with alcoholic liver cirrhosis
Yujin Hoshida1, Susumu Yamakado1, Kei Shinoki1, Tsukasa Takeuchi1, Toshihiko Nagai1,
Yusuke Hyakuna2, and Yuji Itoh3
1

Division of Gastroenterology, Tokyo Metropolitan Tama Geriatric Hospital, 1-7-1 Aoba-cho, Higashimurayama, Tokyo 189-8511, Japan
Division of Surgery, Tokyo Metropolitan Tama Geriatric Hospital, Tokyo, Japan
3
Division of Pathology, Tokyo Metropolitan Tama Geriatric Hospital, Tokyo, Japan
2

Abstract: Budd-Chiari syndrome is a rare disease, but
there are many known causes. Recent studies showed
that it can be an acquired lesion resulting from thrombosis in some elderly patients. We report a 74-year-old
man with Budd-Chiari syndrome attributed to chronic
deep venous thrombosis and alcoholic liver cirrhosis.
When he was aged 45 years, stasis ulcers of the lower
extremities appeared. Cerebral infarction and left hemiparesis occurred at age 71. Ultrasonography, venacavography, and three-dimensional-magnetic resonance
imaging on admission demonstrated total obstruction of
the inferior vena cava with several massive thrombi and
developed collateral vessels. Although the etiology of
the thrombosis remained obscure, we made some
speculative assumptions that chronic disseminated intravascular coagulation (which is frequently observed in
cirrhosis) or hereditary coagulopathy could be involved,
from his familial history of thrombotic phenomena and
a severe deficiency of clotting inhibitors. Despite the
high mortality of untreated Budd-Chiari syndrome reported in previous studies, this patient had been alive
for about 30 years from the suspected onset.
Key words: Budd-Chiari syndrome, alcoholic liver cirrhosis, deep venous thrombosis, elderly

Introduction
Budd-Chiari syndrome (BCS) is an uncommon disorder
caused by obstruction of hepatic venous outflow.1,2
There are a number of known causes of BCS, such as
tumors, thrombosis, and congenital fibrous diaphragm
or web across the vena cava.2 In Japan, primary membranous obstruction of the inferior vera cava (IVC) was
Reprint requests to: Y. Hoshida
Received: September 14, 1998 / Accepted: April 16, 1999

considered the main cause of BCS. However, in recent
studies, it has been reported that BCS can be an
acquired lesion resulting from thrombosis in some patients.3 In these patients, congenital or acquired coagulation disorders were frequently noted. The prognosis
of untreated BCS is considered to be very poor.4–6 We
report an elderly man with BCS attributed to chronic
deep venous thrombosis (DVT) with alcoholic liver cirrhosis whose survival period from onset was estimated
to be about 30 years.

Case report
A 74-year-old man was admitted to our hospital for
evaluation of sudden disturbance of consciousness in
September, 1996. When he was 35 years old, liver dysfunction was identified, but he refused any medical
follow-up. At age 45, stasis ulcers of the lower extremities appeared. Cerebral infarction and left hemiparesis
occurred at age 71. He had been drinking heavily—
approximately 240 g of ethanol a day from age 20 to
age 60 years, then gradually reducing to 10 g per day
until admission. Physical examination revealed spider
angiomas of the skin, palmar erythema, uprising venous
dilatation on the abdomen, stasis dermatitis of bilateral
crural skin, and clubbed fingers. Laboratory tests gave
the following results: leukocyte count, 8.9 3 103/mm3;
erythrocyte count, 380 3 104/mm3; hemoglobin, 14.0 g/
dl; platelet count, 6.0 3 104/mm3; aspartate aminotransferase (AST), 23 IU/l; alanine aminotransferase
(ALT), 8 IU/l; lactate dehydrogenase (LDH), 228 IU/l;
alkaline phosphatase (ALP), 159 IU/l; γ-glutamyl
transpeptidase (GTP), 52 IU/l; albumin, 3.0 g/dl; total
bilirubin, 3.3 mg/dl; direct bilirubin, 0.7 mg/dl; prothrombin time, 14.1 s (control, 11.5–13.5 s); activated
partial thromboplastin time, 41.1 s (control, 22.9–35.2 s);
fibrinogen, 398 mg/dl (control, 200–400); ammonia,
197 µg/dl; alpha-fetoprotein (AFP), ,10 ng/ml; des-

Y. Hoshida et al.: Aged Budd-Chiari syndrome attributed to chronic deep venous thrombosis

gamma-carboxyl prothrombin (DCP), 13.1 AU/ml; IgG,
2217 mg/dl; IgA, 479 mg/dl; IgM, 211 mg/dl. Serum α1
protease inhibitor and ceruloplasmin levels were
normal. Antinuclear and anti-pyruvate dehydrogenase
(PDH) antibodies were negative. Results of serological
tests for hepatitis A, B, C, and G viruses were all negative. Tests for Epstein-Barr virus and cytomegalovirus
infection were also negative. Electrocardiogram was
normal. Upper gastrointestinal endoscopy revealed
esophageal varices and mild portal hypertensive
gastropathy. Colonoscopy revealed multiple tubulovillous adenomas. On ultrasonography, irregular surface of the liver, hypertrophy of the lateral segment of
the left hepatic lobe, multiple small gallstones in the
gallbladder, and mild splenomegaly were noted. In addition, hepatic veins and the hepatic portion of the IVC
were obscure. At this time, he was diagnosed with
hepatic encephalopathy as a complication of liver cirrhosis, and his condition was improved by intravenous
branched-chain amino acid infusions. However,
asymptomatic cholecystolithiasis was also present.
Physical findings such as crural stasis dermatitis and
uprising venous dilatation on the abdomen, which could
not be explained only by portal hypertension, together
with the findings of ultrasonography, suggested vena
caval involvement. Venocavography demonstrated
total obstruction of the IVC just above the renal veins,
thrombotic occlusion of the right common iliac vein and
left internal iliac vein, and several massive thrombi in
the IVC (Fig. 1). Three-dimensional-magnetic resonance imaging also revealed total obstruction and
kinking of the IVC (Fig. 2). On dynamic helical computed tomography, several collateral circulations were
observed, e.g., bilateral ascending lumbar veins to the
azygos vein, and the great saphenous vein to the superficial epigastric and circumflex iliac veins (Fig. 3).
Transarterial portography via the superior mesenteric
artery showed patent portal venous flow and developed
hepatofugal collaterals such as that to the left gastric
vein. At this time, he was diagnosed with BCS with
DVT. The presence of multiple DVTs suggested the
existence of a coagulation disorder. Additional hemostatic data were then obtained: fibrin split products
(FSPs), 367 ng/ml (normal, ,100); D-dimer, 1177 ng/ml
(normal, ,1000); antithrombin III-antigen, 13.0 mg/dl
(normal, 23–34); antigenic activity, 58% (normal, 79%–
121%); protein C antigen, 27% (normal, 70%–150%);
antigenic activity, 18% (55%–140%); activated protein
C (APC) resistance ratio, 2.60 (normal, ^2); protein S
antigen, 61% (normal, 65%–135%); antigenic activity,
35% (normal, 60%–150%); α2-plasmin inhibitor,
3.4 mg/dl (normal, 4.0–6.0); antigenic activity, 56% (normal, 13%–135%); plasminogen, 4.7 mg/dl (normal, 7.0–
13.0); antigenic activity, 37% (normal, 73%–135%);
α2-plasmin inhibitor-plasmin complex, 3.6 µg/ml (nor-

635

Fig. 1. Venocavography demonstrated total obstruction of
the inferior vena cava, the right common iliac vein, and the left
internal iliac vein. Several massive thrombi were observed

Fig. 2. Three-dimensional magnetic resonance imaging
(maximum intensity projection method) demonstrated total
obstruction and kinking of the inferior vena cava just above
the renal vein

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Y. Hoshida et al.: Aged Budd-Chiari syndrome attributed to chronic deep venous thrombosis

Fig. 4. Cut surface of the liver at autopsy demonstrated
micronodular liver cirrhosis with chronic congestion

Fig. 3. Schematic presentation of venous collateral circulation
reconstructed from the finding of dynamic helical computed
tomography. Shaded areas, thrombus. SVC, superior vena
cava; IVC, inferior vena cava

mal, %0.8); thrombin-antithrombin III complex, 13.1 ng/
ml (normal, ,3.0); factor II, 42% (normal, 62%–127%);
factor V, 45% (normal, 50%–150%); factor VII, 34%
(normal, 65%–135%); factor VIII-related antigen,
^200% (normal, 50%–150%); factor IX, 42% (normal,
60%–140%); factor X, 34% (normal, 23%–34%).
Lupus anticoagulant and anti-cardiolipin antibodies
were negative.
The patient died of acute cholecystitis accompanied
by septic shock in December, 1996. Pathological findings at autopsy demonstrated micronodular liver cirrhosis with the presence of hyaline bodies and chronic
congestion of the liver (Fig. 4), spleen, and kidneys.
Histologically, hepatic congestion, with zone 3 sinusoidal distension arising from occlusion of the entry of
hepatic veins to the IVC, was observed (Fig. 5). The
hepatic portion of the IVC was occluded 6.5 cm in
length, with organized thrombi of varying age (Fig. 6).
Phlebosclerosis with calcification in the IVC and
thrombotic occlusion of the left common iliac vein were
observed. Just below the occluded lesion, localized cal-

Fig. 5. Histological section of the liver showed hepatic congestion with zone 3 sinusoidal distension and pooling. Azan,
38

cification of the IVC was observed. Orifices of hepatic
veins were recognized only as small depressed regions
on the wall of the IVC (type 2 BCS; according to
Sugiura,7 a relatively common pattern in Japan).

Discussion
BCS is a disorder caused by hepatic venous outflow
obstruction (HVOO) and is rarely observed in daily
clinical practice. According to Okuda et al,8 the number
of patients with BCS was estimated to be about 300
(prevalence of 2.4/million), with about 20 new cases
occurring every year in Japan. The average age at the
time of the first medical visit was 36.4 years (range, 10–
72 years) in men and 46.5 years (range, 16–75 years) in
women. The average period from suspected onset was

Y. Hoshida et al.: Aged Budd-Chiari syndrome attributed to chronic deep venous thrombosis

637

Fig. 6A,B. Hepatic portion of the
IVC. A Total obstruction of the
IVC (arrow). B Phlebosclerosis with
calcification in the hepatic portion of
the IVC and total obstruction with
organized thrombus (T). L, liver;
V, inferior vena cava. Elastica van
Gieson, 34

6.6 years.8 In a histopathological study of 17 autopsy
cases by Kage et al.3 the oldest patients were a 66-yearold man, and a 72-year-old woman.
The nature of HVOO is variable9 and there are geographic variations. In the United States and Western
countries, thrombosis with apparent pathogenesis is
the most common cause of HVOO. Previously
reported conditions that predispose to thrombosis are
myeloproliferative disorders such as polycythemia vera
and essential thrombocytosis, including preclinical
stage,10 and abnormal clotting tendencies due to deficiencies of antithrombin III,11 protein C,12,13 or protein
S,14 blood constituents that protect against thrombosis.
Oral contraceptive use,15 the presence of lupus anticoagulant16 and anticardiolipin antibodies,17 paroxysmal
nocturnal hemoglobinuria (PNH),18 and factor V
Leiden mutation19 also predispose to thrombosis. Less
well documented associations were reported, such as
ulcerative colitis,20 Behcet’s disease,21 fat overload syndrome,22 idiopathic granulomatous venulitis,23 and pregnancy. Tumors or caudate hypertrophy due to chronic
HVOO, with caval compression and hepatic abscess or
cyst directly obstructing major hepatic veins were also
reported.1 In Africa and Asia, primary membranous
obstruction of the IVC (MOVC), such as weblike
stenosis or occlusion, is frequently observed and it is
considered endemic.3,24 Although congenital so-called
MOVC was regarded as the major cause of Japanese

BCS,8 only about 10% of the cases have identifiable
etiologies. A recent study by Kage et al.3 suggested that
it was an acquired lesion after thrombosis in some patients with late age onset. Regarding the etiology of
BCS in our patient, chronic DVT was considered to be
the most likely etiology from the findings of X-ray examination and autopsy.
To clarify the etiology of DVT, additional hemostatic
data were obtained, allowing us to make some speculative assumptions. Elevated levels of FSPs and D-dimers,
and normal fibrinogen level suggested a chronic intravascular hypercoagulable condition similar to disseminated intravascular coagulation (DIC), which is
frequently observed in cirrhotic patients. Similarly,
despite low levels of α2-plasmin inhibitor and plasminogen, due to reduced synthesis in the cirrhotic liver, elevated levels of α2-plasmin inhibitor-plasmin complex
and thrombin-antithrombin lll complex were observed,
possibly reflecting the existence of thrombosis and
chronic thrombolysis. Broad depression of plasma clotting factors and inhibitors, except for factor VIII, was
compatible with impaired protein synthesis in the uncompensated cirrhotic liver. However, it is usually
thought that depressed levels of clotting inhibitors in
liver disease are not associated with thrombotic complications,25,26 and the very severe deficiency of clotting
inhibitors, such as protein C, S, and AT III, suggested
the presence of masked hereditary coagulopathy. As for

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Y. Hoshida et al.: Aged Budd-Chiari syndrome attributed to chronic deep venous thrombosis

the patient’s familial history, his older brother died after
a long course of myocardial infarction and cerebral
infarction, and his son suffered cerebral infarction at the
age of 40. However, their sera and the sera of other,
living, siblings could not be investigated, so it was unclear whether this conjecture was right. Factor V Leiden
mutation was ruled out, with the result of a normal APC
ratio. Further, regarding the rare condition of PNH occasionally found in association with venous thrombosis,
diagnostic tests such as the Ham test and sugar water
test were not performed. But there was no clear evidence of abnormal hemolysis, such as abnormal red
cells, hemoglobinuria, hemosiderinuria, and elevated
levels of LDH. So the probability of PNH was thought
to be negligible. According to Chedid et al.,17 anticardiolipin antibodies, which are strongly associated with
thromboembolic phenomena, were present in the
serum of patients with alcoholic liver disease. In our
patient, these antibodies were negative, despite his history of alcohol drinking.
In regard to the etiology of liver cirrhosis, metabolic
diseases such as α1 protease inhibitor deficiency,
hemochromatosis, and Wilson’s disease were ruled out.
There was no evidence of viral hepatitis or autoimmune
disease, such as primary biliary cirrhosis or autoimmune
hepatitis. Thus, alcohol abuse was considered to be the
most likely etiology. Furthermore, chronic liver congestion after the formation of the IVC occlusion could have
contributed to the progression of liver cirrhosis. As for
the reasons to explain why the hepatic portion of the
IVC was obstructed, several possibilities, such as mechanical injury, stasis of blood flow, and infection of the
IVC (perhaps long ago) have already been offered.3
Finally then, it was considered that the long course of
the disease made the mechanism complicated.
Some studies have reported the poor prognosis of
patients with untreated BCS.4–6 In the study of
McCarthy et al.,4 overall mortality of BCS was 57%
(medical treatment, 86%; surgical treatment, such as
side-to-side portacaval shunt, 31%). Reported causes of
death are liver failure, variceal bleeding, and hepatocellular carcinoma.1 In our patient, the diagnosis of BCS
was made almost incidentally and from the history of
physical findings, the occlusion of the IVC was estimated to have begun about 30 years previously. The
reason for this patient having been alive for such a
relatively long period, despite frequent episodes of
thrombotic phenomena, was unclear. But it was considered that the developed venous collaterals decompressed the caval pressure and led to a mild form of
BCS without some major symptoms such as abdominal
pain and ascites.
Acknowledgments. We thank Dr. Y. Suzuki of the Division of
Gastroenterology, Toranomon Hospital, Tokyo, for his kindly
advice and assistance.

References
1. Reynolds TB. Budd-Chiari syndrome. In: Schiff ER, editor. Diseases of the liver. 7th ed. Philadelphia: JB Lippincott; 1993. p.
1091–8.
2. Schwartz ME. Diseases of the hepatic blood vessels. In: Haubrich
WS, editor. Bockus gastroenterology. 5th ed. Philadelphia: WB
Saunders; 1995. p. 2381–92.
3. Kage M, Arakawa M, Kojiro M, Okuda K. Histopathology of
membranous obstruction of the inferior vena cava in the BuddChiari Syndrome. Gastroenterology 1992;102:2081–90.
4. McCarthy PM, van Heerden JA, Adson MA, Schafer LW,
Wiesner RH. The Budd-Chiari syndrome. Medical and surgical
management of 30 patients. Arch Surg 1985;120:657–62.
5. Maddrey WC. Hepatic vein thrombosis (Budd Chiari syndrome).
Hepatology 1984;4:44S–6S.
6. Ishibe R, Maruko M, Tabata D, Toyohira H, Furuzono K,
Nishimura A, et al. Membranous obliteration of the inferior vena
cava in the hepatic portion—postmortem study of a rapidly deteriorated aged case. Nippon Geka Gakkai Zasshi (J Jpn Surg Soc)
1990;91:290–2.
7. Sugiura M. Etiology and symptoms of the portal system. In:
Kimoto S, editor. Current surgery no. 40 (in Japanese). Tokyo:
Nakayama; 1970. p. 72–85.
8. Okuda H, Yamagata H, Obata H, Iwata H, Sasaki R, Imai F, et al.
Epidemiological and clinical features of Budd-Chiari syndrome in
Japan. J Hepatol 1995;22:1–9.
9. Ludwig J, Hashimoto E, McGill DB, van Heerden JA. Classification of hepatic venous outflow obstruction: ambiguous terminology of the Budd-Chiari syndrome. Mayo Clin Proc 1990;65:51–5.
10. Valla D, Casadevall N, Lacombe C, Varet B, Goldwasser E,
Franco D, et al. Primary myeloproliferative disorder and hepatic
vein thrombosis. A prospective study of erythroid colony formation in vitro in 20 patients with Budd-Chiari syndrome. Ann
Intern Med 1985;103:329–34.
11. Das M, Carroll SF. Antithrombin III deficiency. An etiology of
Budd-Chiari syndrome. Surgery 1985;97:242–6.
12. Sugano S, Suzuki T, Makino H, Yanagimoto S, Nishio M,
Onmura H, et al. Budd-Chiari syndrome attributed to protein C
deficiency. Am J Gastroenterol 1996;91:777–9.
13. Bourliere M, Le Treut YP, Aronoux D, Castellani P, Bordigoni L,
Maillot A, et al. Acute Budd-Chiari syndrome with hepatic failure
and obstruction of the inferior vena cava as presenting manifestation of hereditary protein C deficiency. Gut 1990;31:949–52.
14. D’Angelo A, Bigano-D’Angelo S, Esmon CT, Comp PC. Acquired deficiencies of protein S: protein S activity during oral
anticoagulation, in liver disease, and in disseminated intravacular
coagulation. J Clin Invest 1988;81:1445–54.
15. Lewis JH, Tice HL, Zimmermann HJ. Budd-Chiari syndrome
associated with oral contraceptive steroids:review of treatment of
47 cases. Dig Dis Sci 1983;28:673–83.
16. Pomeroy C, Knodell RG, Swaim WR, Arneson P, Mahowald ML.
Budd-Chiari syndrome in a patient with the lupus anticoagulant.
Gastroenterology 1984;86:158–61.
17. Chedid A, Chadalawada KR, Morgan TR, Moritz TE,
Mendenhall CJ, Hammond JB, et al. Phospholipid antibodies in
alcoholic liver disease. Hepatology 1994;20:1465–71.
18. Valla D, Dhumeaux D, Babany G, Hillon P, Rueff B,
Rochant H, et al. Hepatic vein thrombosis in paroxysmal nocturnal hemoglobinuria. A spectrum from asymptomatic occlusion of
hepatic venules to fatal Budd-Chiari syndrome. Gastroenterology
1987;93:569–75.
19. Fickert P, Ramschak H, Kenner L, Hoefler G, Hinterleitner TA,
Petritsch W, et al. Acute Budd-Chiari syndrome with fulminant
hepatic failure in a pregnant woman with factor V leiden mutation. Gastroenterology 1996;111:1670–3.
20. Brinson RR, Curtis WD, Schuman BM, Mills LR. Recovery from
hepatic vein thrombosis (Budd-Chari syndrome) complicating ulcerative colitis. Dig Dis Sci 1988;33:1615–20.

Y. Hoshida et al.: Aged Budd-Chiari syndrome attributed to chronic deep venous thrombosis
21. Bismuth E, Hadenque A, Hammel P, Benhamou JP. Hepatic
vein thrombosis in Behcet’s disease. Hepatology 1990;11:969–
74.
22. Haber LM, Hawkins EP, Seilheimer DK, Saleem A. Fat overload
syndrome. An autopsy study with evaluation of the coagulopathy.
Am J Clin Pathol 1988;90:223–7.
23. Young ID, Clark RN, Manley PN, Groll A, Simon JB. Response
to steroids in Budd-Chiari syndrome caused by idiopathic
granulomatous venulitis. Gastroenterology 1988;94:503–7.

639

24. Simson IW. Membranous obstruction of the inferior vena cava
and hepatocellular carcinoma in South Africa. Gastroenterology
1982;82:171–8.
25. Aurousseau MH, D’Angeli JL, Josso F. Antithrombin III
versus prothrombin in liver cirrhosis. Haemostasis 1981;10:104–
7.
26. Epstein DJ, Berjum PW, Bajaj SP, Rapaport SI. Radioimmunoassays for protein C and factor X: plasma antigen levels in abnormal
hemostatic states. Am J Clin Pathol 1984;82:573–81.