A 25-year-old man with very high alkaline phosphatase
AFTER ULTRASONOGRAPHY, WHAT IS THE NEXT STEP?
2. Which of the following is the next most appropriate diagnostic test for our patient?
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Magnetic resonance cholangiopancreatography (MRCP)
- Liver biopsy
- CT of the abdomen
Figure 1 shows a proposed algorithm for evaluating increased alkaline phosphatase levels.
If there is no biliary duct dilation on ultrasonography, then abnormal levels of alkaline phosphatase most likely represent an intrahepatic pattern of cholestatic liver injury. Therefore, additional imaging with CT or magnetic resonance imaging is of limited diagnostic value. ERCP is used today for therapy rather than diagnosis, so its use is limited to patients known to have dilated biliary ducts on imaging. Liver biopsy, however, can provide useful findings.
Case continued: He undergoes biopsy
Our patient underwent transjugular liver biopsy. During the procedure, transjugular venography showed stenosis in the right, middle, and left hepatic veins and the hepatic portion of the inferior vena cava, consistent with Budd-Chiari syndrome.
The liver biopsy specimen was positive for extensive deposition of slight eosinophilic and amorphous material in a sinusoidal pattern in the liver parenchyma, as well as in the portal tracts, with markedly atrophic hepatocytes. Congo red birefringence confirmed the diagnosis of amyloidosis. The immunohistochemical phenotype was positive for kappa light chains, which is diagnostic for primary-type amyloidosis, also called amyloidosis of light chain composition, or AL.
Bone marrow aspiration and bone marrow biopsy were performed and showed 22% plasma cells, well above the normal range (0–2%), consistent with the diagnosis of multiple myeloma.
BUDD-CHIARI SYNDROME: A CHALLENGING DIAGNOSIS
Budd-Chiari syndrome is a rare condition characterized by obstruction of venous outflow from the liver at a site that may vary from the small hepatic veins up to the inferior vena cava or even the right atrium.5,6 Obstruction of hepatic venous outflow leads to sinusoidal congestion and hypoxic damage of the hepatocytes.7 Hypoxia and necrosis of the hepatocytes result in the release of free radicals. Cirrhosis can eventually occur secondary to ischemic necrosis of hepatocytes and hepatic fibrosis.8
The estimated incidence of this syndrome is 1 in 2.5 million persons per year.7 It is more prevalent in women and young adults.8
Heterogeneous in its causes and manifestations
Budd-Chiari syndrome is also heterogeneous in its manifestations, which depend on the extent of the occlusion, on the acuteness of the obstruction, and on whether venous collateral circulation has developed to decompress the liver sinusoids.9,12,13 Therefore, on the basis of its clinical manifestations, it can be classified as fulminant, acute, subacute, or chronic.12–16
The fulminant form presents with hepatic encephalopathy within 8 weeks after the development of jaundice. The subacute form, which is the most common, has a more insidious onset in which hepatic sinusoids are decompressed by portal and hepatic venous collateral circulation. The patient usually presents with abdominal pain, ascites, hepatomegaly, nausea, vomiting, and mild jaundice. Finally the chronic form presents as complications of cirrhosis.12–16
Imaging plays an important role in diagnosing Budd-Chiari syndrome
Imaging plays an important role in detecting and classifying Budd-Chiari syndrome.
Duplex ultrasonography is useful for detecting this syndrome and has a sensitivity and specificity of 85%.9
CT and magnetic resonance imaging can also help in the diagnosis by showing thrombosis, obstruction, or occlusion in the hepatic vein or the inferior vena cava.5
Venography is the gold standard for diagnosis. However, it should be performed only if noninvasive tests are negative or nondiagnostic and there is a high clinical suspicion of this disease.17 Budd-Chiari syndrome has a characteristic pattern on venography known as “spider web,” which is due to the formation of venous collaterals to bypass the occluded hepatic veins.9
Liver biopsy is not necessarily required to confirm the diagnosis of Budd-Chiari syndrome, but it can help in diagnosing the acute or subacute forms and also in ruling out other causes. Histologic findings can include centrizonal congestion, loss of hepatocytes, hemorrhage, and fibrosis.18,19 Regenerative nodules are found in about 25% of patients.19
