Budd–Chiari syndrome

Budd-Chiari syndrome
Classification and external resources
Posterior abdominal wall, after removal of the peritoneum, showing kidneys, suprarenal capsules, and great vessels. (Hepatic veins labeled at center top.)
ICD-10	I82.0
ICD-9	453.0
OMIM	600880
DiseasesDB	1735
eMedicine	med/2694 ped/296 radio/121
MeSH	D006502

In medicine (gastroenterology and hepatology), Budd–Chiari syndrome is the clinical picture caused by occlusion of the hepatic veins. It presents with the classical triad of abdominal pain, ascites and hepatomegaly. Examples of occlusion include thrombosis of hepatic veins. The syndrome can be fulminant, acute, chronic, or asymptomatic. It occurs in 1 out of a million individuals ^[1] and is more common in females. Some 10-20% also have obstruction of the portal vein.

Signs and symptoms

The acute syndrome presents with rapidly progressive: severe upper abdominal pain, jaundice, hepatomegaly (enlarged liver), ascites, elevated liver enzymes, and eventually encephalopathy. The fulminant syndrome presents early with encephalopathy and ascites. Severe hepatic necrosis and lactic acidosis may be present as well. Caudate lobe hypertrophy is often present. The majority of patients have a slower-onset form of Budd–Chiari syndrome. This can be painless. A system of venous collaterals may form around the occlusion which may be seen on imaging as a "spider's web." Patients may progress to cirrhosis and show the signs of liver failure.

An asymptomatic form may be totally silent and discovered only incidentally. It is generally not concerning.

Causes

• The cause cannot be found in about half of the patients
• Primary (75%): thrombosis of the hepatic vein
• Secondary (25%): compression of the hepatic vein by an outside structure (e.g. a tumor)
• Hepatic vein thrombosis is associated with the following in decreasing order of frequency:
  (A)Polycythemia vera
  (B)pregnancy
  (C)post partum state
  (D)use of oral contraceptive
  (E)paroxysmal nocturnal hemoglobinuria
  (F)Hepatocellular carcinoma
• Infection such as TB
• Congenital venous webs
• Occasionally inferior vena caval stenosis

Often, the patient is known to have a tendency towards thrombosis, although Budd–Chiari syndrome can also be the first symptom of such a tendency. Examples of genetic tendencies include Protein C deficiency, Protein S deficiency, the Factor V Leiden mutation, and Prothrombin Mutation G20210A.^[2] An important non-genetic risk factor is the use of estrogen-containing (combined) forms of hormonal contraception. Other risk factors include the antiphospholipid syndrome, aspergillosis, Behçet's disease, dacarbazine, pregnancy, and trauma.

Many patients have Budd–Chiari syndrome as a complication of polycythemia vera (myeloproliferative disease of red blood cells).^[3] Patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) appear to be especially at risk for Budd–Chiari syndrome, more than other forms of thrombophilia: up to 39% develop venous thromboses ^[4] and 12% may acquire Budd-Chiari.^[5]

A related condition is veno-occlusive disease, which occurs in recipients of bone marrow transplants as a complication of their medication. Although its mechanism is similar, it is not considered a form of Budd–Chiari syndrome.

Other toxicologic causes of veno-occlusive disease include plant & herbal sources of pyrrolizidine alkaloids such as Borage, Boneset, Coltsfoot, T'u-san-chi, Comfrey, Heliotrope (sunflower seeds), Gordolobo, Germander, and Chaparral.

Pathophysiology

Any obstruction of the venous vasculature of the liver is referred to as Budd–Chiari syndrome, from the venules to the right atrium. This leads to increased portal vein and hepatic sinusoid pressures as the blood flow stagnates. The increased portal pressure causes: 1) increased filtration of vascular fluid with the formation of protein-rich ascites in the abdomen; and 2) collateral venous flow through alternative veins leading to oesophageal, gastric and rectal varices. Obstruction also causes centrilobular necrosis and peripheral lobule fatty change due to ischemia. If this condition persists chronically what is known as Nutmeg liver will develop. Renal failure may occur, perhaps due to the body sensing an "underfill" state and subsequent activation of the renin-angiotensin pathways and excess sodium retention.

Diagnosis

When Budd–Chiari syndrome is suspected, measurements are made of liver enzyme levels and other organ markers (creatinine, urea, electrolytes, LDH).

Budd–Chiari syndrome is most commonly diagnosed using ultrasound studies of the abdomen and retrograde angiography. Ultrasound may show obliteration of hepatic veins, thrombosis or stenosis, spiderweb vessels, large collateral vessels, or a hyperechoic cord replacing a normal vein. Computed tomography (CT) or magnetic resonance imaging (MRI) is sometimes employed although these methods are generally not as sensitive. Liver biopsy is nonspecific but sometimes necessary to differentiate between Budd–Chiari syndrome and other causes of hepatomegaly and ascites, such as galactosemia or Reye's syndrome.

Treatment

A minority of patient s can be treated medically with sodium restriction, diuretics to control ascites, anticoagulants such as heparin and warfarin, and general symptomatic management. The majority of patients require further intervention. Milder forms of Budd-Chiari may be treated with surgical shunts to divert blood flow around the obstruction or the liver itself. Shunts must be placed early after diagnosis for best results.^[6] The transjugular intrahepatic portosystemic shunt (TIPS) is similar to a surgical shunt. It accomplishes the same goal but has a lower procedure-related mortality, which has led to a growth in its popularity. Patients with stenosis or vena caval obstruction may benefit from angioplasty.^[7] Limited studies on thrombolysis with direct infusion of urokinase and tissue plasminogen activator (tPA) into the obstructed vein have shown moderate success in treating Budd–Chiari syndrome; however, it is not routinely attempted.

Liver transplantation is an effective treatment for Budd-Chiari. It is generally reserved for patients with fulminant hepatic failure, failure of shunts, or progression of cirrhosis that reduces the life expectancy to 1 year.^[8] Long-term survival after transplantation ranges from 69-87%. The most common complications of transplant include rejection, arterial or venous thromboses, and bleeding due to anticoagulation. Up to 10% of patients may have a recurrence of Budd–Chiari syndrome after the transplant.

Prognosis

Several studies have attempted to predict the survival of patients with Budd–Chiari syndrome. In general, nearly 2/3 of patients with Budd-Chiari are alive at 10 years. ^[6] Important negative prognostic indicators include ascites, encephalopathy, elevated Child-Pugh scores, elevated prothrombin time, and altered serum levels of various substances (sodium, creatinine, albumin, and bilirubin). Survival is also highly dependent on the underlying cause of the Budd–Chiari syndrome. For example, patients with myeloproliferative disorders may progress to acute leukemia independent of Budd–Chiari syndrome.

Eponym

It is named after George Budd^[9][10] and Hans Chiari.^[11]

See also

• Chronic venous insufficiency

External links

• Budd-Chiari Syndrome at Merck Manual of Diagnosis and Therapy Home Edition

References

1. ^ Rajani R, Melin T, Björnsson E, Broomé U, Sangfelt P, Danielsson A, Gustavsson A, Grip O, Svensson H, Lööf L, Wallerstedt S, Almer SH. (Feb 2009). "Budd-Chiari syndrome in Sweden: epidemiology, clinical characteristics and survival - an 18-year experience". Liver International 29 (2): 253–9. doi:10.1111/j.1478-3231.2008.01838.x. PMID 18694401. http://www3.interscience.wiley.com/journal/121372822/abstract. 
2. ^ Podnos YD, Cooke J, Ginther G, Ping J, Chapman D, Newman RS, Imagawa DK (Aug 2003). "Prothrombin Mutation G20210A as a Cause of Budd-Chiari Syndrome". Hospital Physician 39 (8): 41–4. http://www.turner-white.com/pdf/hp_aug03_budd.pdf. 
3. ^ Patel RK, Lea NC, Heneghan MA, et al. (Jun 2006). "Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome". Gastroenterology 130 (7): 2031–8. doi:10.1053/j.gastro.2006.04.008. PMID 16762626. 
4. ^ Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV (Nov 1995). "Natural history of paroxysmal nocturnal hemoglobinuria". N Engl J Med. 333 (19): 1253–8. doi:10.1056/NEJM199511093331904. PMID 7566002. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=7566002&promo=ONFLNS19. 
5. ^ Socié G, Mary JY, de Gramont A, et al. (Aug 1996). "Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology". Lancet 348 (9027): 573–7. doi:10.1016/S0140-6736(95)12360-1. PMID 8774569. http://linkinghub.elsevier.com/retrieve/pii/S0140673695123601. 
6. ^ ^{a b} Murad SD, Valla DC, de Groen PC, et al. (Feb 2004). "Determinants of survival and the effect of portosystemic shunting in patients with Budd-Chiari syndrome". Hepatology (Baltimore, Md.) 39 (2): 500–8. doi:10.1002/hep.20064. PMID 14768004. 
7. ^ Fisher NC, McCafferty I, Dolapci M, et al. (Apr 1999). "Managing Budd-Chiari syndrome: a retrospective review of percutaneous hepatic vein angioplasty and surgical shunting". Gut 44 (4): 568–74. doi:10.1136/gut.44.4.568. PMC 1727471. PMID 10075967. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=10075967. 
8. ^ Orloff MJ, Daily PO, Orloff SL, Girard B, Orloff MS (Sep 2000). "A 27-year experience with surgical treatment of Budd-Chiari syndrome". Ann Surg. 232 (3): 340–52. doi:10.1097/00000658-200009000-00006. PMC 1421148. PMID 10973384. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0003-4932&volume=232&issue=3&spage=340. 
9. ^ Budd-Chiari syndrome at Who Named It?
10. ^ Budd G (1845). On diseases of the liver. London: John Churchill. pp. 135. Brit Lib. 000518193. 
11. ^ Chiari H (1898). "Erfahrungen über Infarktbildungen in der Leber des Menschen". Zeitschrift für Heilkunde, Prague 19: 475–512.