Differential Diagnosis

A detailed history and physical examination along with imaging studies are essential for accurately diagnosing BCS. Chronic BCS should be considered in the differential diagnosis of idiopathic processes including cirrhosis and portal hypertension in the setting of preserved liver function. Patients with BCS generally are young and in good overall health.12  

The fulminant and acute forms of BCS may mimic other causes of acute liver injury, such as ischemic, toxic, or viral hepatitis; malignancy; infiltrative liver diseases; and hepatic veno-occlusive disease. The subacute and chronic forms of BCS share many clinical features with any cause of cirrhosis or portal hypertension. Right-sided heart failure, right atrial myxoma, and constrictive pericarditis may present in a similar fashion but are distinguishable from BCS on physical examination.13 

In patients with symptoms suggestive of BCS, several diagnostic modalities can be performed.  Noninvasive assessment with Doppler ultrasonography, CT, or magnetic resonance imaging (MRI) is effective for initial evaluation. Evidence for thrombosis is rarely obtained with liver biopsy.10 Biopsy usually provides nonspecific evidence for impaired blood outflow, such as congestion, coagulative necrosis, or fibrosis.3 


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Although abnormal liver function tests are an important feature of BCS, completely normal tests do not preclude the presence of BCS. In acute and fulminant BCS, levels of serum aspartate aminotransferase and alanine aminotransferase (ALT) may be more than 5 times the upper limit of normal.2 Levels of serum albumin and bilirubin, as well as prothrombin time can be normal or abnormal.9 Vascular congestion results in ischemic hepatocellular damage, elevating serum ALT.10 ALT concentrations can range from initial values of 100 to 200 U/L to >600 U/L (normal, 10-40 U/L). In acute BCS, serum alkaline phosphatase (ALP) often is in the range of 300 to 400 U/L (normal, 20-140 U/L). Serum bilirubin levels usually are <7 mg/dL at the time of presentation but may increase sharply.10  In subacute or chronic BCS cases, normal or mild to moderate elevations of serum ALT, ALP, and serum bilirubin are evident.7 Serum creatinine should be included in the initial assessment due to the frequency of coexisting renal impairment in patients with BCS.10 

In patients presenting with ascites, diagnostic paracentesis is recommended.2,10  Ascitic fluid in patients with BCS has a high serum-to-ascites protein gradient (>1.1), reflecting elevated portal pressure.6 The protein concentration is variable (ranging from 1.5 to 4.9 g/dL) and is directly related to serum protein and inversely related to portal pressure. Patients with subacute or chronic BCS may have hypoalbuminemia.10 Protein content >3.0 g/dL in ascitic fluid is indicative of BCS or cardiac/pericardial disease.9 

Treatment

A step-wise approach has been suggested for managing BCS14 to achieve the following goals: prevent propagation of any clot, restore patency of thrombosed veins, decompress the congested liver, and manage any complications. Initial steps include correction of underlying disorders, initiation of anticoagulation, and treatment of complications of portal hypertension.15 Angioplasty or stenting are helpful treatment options that may be advisable to restore venous patency.

If initial treatment options fail, a transjugular intrahepatic portosystemic shunt (TIPS) may be placed to decompress the liver.16 Patients with acute liver failure may need transplantation and should be referred to a liver transplantation center for specialized treatment.16 

Patients with chronic BCS should be managed for complications of portal hypertension, hepatocellular carcinoma, and transformation of any underlying MPS. Nutritional status should be evaluated and improved if malnutrition develops.15 

The patient in this case underwent successful TIPS placement for portal hypertension. She was listed as status 1A for liver transplantation and underwent orthotopic liver transplant. Excellent allograft function was observed. Lifelong anticoagulation was started with low-molecular-weight heparin. The patient’s renal function continued to deteriorate, requiring living donor kidney transplantation a few months later. She recovered well from her second organ transplant.

One year after the kidney transplant, hematologic experts diagnosed that patient as having primary myelofibrosis based on a bone marrow biopsy. The patient was found to be positive for the JAK2 mutation at the time of her BCS diagnosis but was able to return to vigorous activity as a personal fitness trainer, exercising several hours each day. Her hepatic and renal function have remained stable for 48 months.  

Conclusion

The overall prognosis from treated BCS is favorable, with 5-year survival rates at 90%.2 Asymptomatic cases have a good prognosis,3 but symptomatic patients have a high mortality rate that exceeds 90% if not treated.7

Long-term outcome data show the potential for transformation of underlying hematologic disorders and the risk of hepatocellular carcinoma.9 In a study that included 25 individuals who underwent liver transplantation for BCS, the overall mortality rate after liver transplantation was similar among patients with (n=18) and without (n=7) an MPS (16.7% vs 14.3%, respectively).1 In patients with an MPS, the recurrent thrombosis rate was 22.2% compared with 14.3% in those without a neoplasm. Follow-up over 4.9 years showed no progression of a known MPS into acute leukemia. After 10 years, the risk of myelofibrosis and acute leukemia does increase. The long-term rate of blastic transformation of underlying MPS occurs in 10% at 15 years and 25% at 25 years. Therefore, clinical surveillance by detailed laboratory assessment is mandatory after liver transplantation throughout a patient’s lifetime.1

The long-term effect of immunosuppression on progression of MPS is uncertain, but evidence for rapid progression of MPS after liver transplantation is scant. BCS patients with and without myeloproliferative neoplasms had similar long-term survival after liver transplantation. Patients who developed leukemia or primary myelofibrosis during long-term follow-up have been identified. However, based on these data, immunosuppression has not heightened risk for progression of MPS.16

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Mary-Kate Hunnicutt, PA-C, is a physician assistant, Alicia Elam, PharmD, is associate professor, and Michael Felz, MD, is clinical associate professor in the Department of Physical Assistant at the Augusta University.

References

  1. Oldakowska-Jedynak U, Ziarkiewicz M, Ziarkiewicz-Wróblewska B, et al.  Myeloproliferative neoplasms and recurrent thrombotic events in patients undergoing liver transplantation for Budd-Chiari syndrome: a single-center experience. Ann Transplant. 2014;19:591-597.
  2. Goel RM, Johnston EL, Patel KV, Wong T. Budd-Chiari syndrome: investigation, treatment and outcomes. Postgrad Med J. 2015;91(1082):692-697.
  3. Valla DC. Primary Budd-Chiari syndrome. J Hepatol. 2009;50(1):195-203.
  4. DeLeve LD, Valla DC, Garcia-Tsao G; American Association for the Study Liver Diseases. Vascular disorders of the liver. Hepatology. 2009;49(5):1729-1764.
  5. De Stefano V, Teofili L, Leone G, Michiels JJ. Spontaneous erythroid colony formation as the clue to an underlying myeloproliferative disorder in patients with Budd-Chiari syndrome or portal vein thrombosis. Semin Thromb Hemost. 1997;23(5):411-418.
  6. Mitchell MC, Boitnott JK, Kaufman S, Cameron JL, Maddrey WC. Budd-Chiari syndrome: etiology, diagnosis and management. Medicine (Baltimore). 1982;61(4):199-218.
  7. Lai M. Etiology of the Budd-Chiari syndrome. UpToDate website. https://www.uptodate.com/contents/etiology-of-the-budd-chiari-syndrome?search=budd%20chiari%20syndrome%20etiology&source=search_result&selectedTitle=1~126&usage_type=default&display_rank=1. October 31, 2018. Accessed February 13, 2020. 
  8. Darwish Murad S, Plessier A, Hernandez-Guerra M, et al.  Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Intern Med. 2009;151(3):167-175.
  9. Plessier A, Valla DC. Budd-Chiari syndrome. Semin Liver Dis. 2008;28(3):259-269.  
  10. Lai M. Budd-Chiari syndrome: epidemiology, clinical manifestations, and diagnosis. https://www.uptodate.com/contents/budd-chiari-syndrome-epidemiology-clinical-manifestations-and-diagnosis?search=budd%20chiari%20syndrome%20etiology&source=search_result&selectedTitle=2~126&usage_type=default&display_rank=2. Updated April 1, 2019. Accessed February 14, 2020.
  11. Darwish Murad S, Valla DC, de Groen PC, et al. Determinants of survival and the effect of portosystemic shunting in patients with Budd-Chiari syndrome. Hepatology 2004;39(2):500-508.  
  12. Lin M, Zhang F, Wang Y, et al.  Liver cirrhosis caused by chronic Budd-Chiari syndrome. Medicine (Baltimore). 2017;96(34):e7425.  
  13.  Cura M, Haskal Z, Lopera J. Diagnostic and interventional radiology for Budd-Chiari syndrome. Radiographics. 2009;29(3):669-681.
  14. Pavri TM, Herbst A, Reddy R, Forde KA. Budd-Chiari syndrome: a single-center experience. World J Gastroenterol. 2014;20(43):16236-16244  
  15. Lai M. Budd-Chiari syndrome: management. UpToDate website. https://www.uptodate.com/contents/budd-chiari-syndrome-management?search=budd%20chiarisyndrome&source=search_result&selectedTitle=2~126&usage_type=default&display_rank=2. Updated November 15, 2018. Accessed February 13, 2020.
  16. Potthoff A, Attia D, Pischke S, et al. Long-term outcome of liver transplant patients with Budd-Chiari syndrome secondary to myeloproliferative neoplasms. Liver Int. 2015;35(8):2042-2049.