Figure 73.1. Eye findings in Wilson disease; Kayser-Fleischer ring. SOURCE: Image courtesy of Jonathan Kruska, MD, Chair of Radiology, Beth Isreal Deaconess Medical Center.

SERUM FERRITIN

Serum ferritin levels accurately reflect hepatic and total-body iron stores. Serum ferritin levels are low in iron deficiency and elevated in iron overload disorders such as genetic idiopathic hemochromatosis. Occasionally, normal levels of serum ferritin may be found in patients with precirrhotic hemochromatosis. Conversely, a very high level of serum ferritin may be present in patients who turn out not to have hemochromatosis. Serum ferritin levels may be elevated in the absence of iron overload in a variety of conditions (see box 73.7). Measurement of serum iron concentration, percentage transferring saturation, and serum ferritin level is the screening regimen currently recommended for idiopathic genetic hemochromatosis. Of note, cirrhosis is very unlikely in hemochromatosis if the patient is younger than 40 years old, has no hepatomegaly, has normal transaminases, and has a serum ferritin <1000 ng/mL.

Box 73.7 CAUSES OF ELEVATIONS IN SERUM FERRITIN

ANTI–SMOOTH MUSCLE ANTIBODIES

Smooth muscle antibodies are directed against cytoskeletal proteins such as actin, troponin, and tropomyosin. They frequently occur in high titers in association with ANA. They are associated with autoimmune hepatitis and have been shown to occur in advanced liver diseases of other etiologies and in infectious diseases and rheumatic disorders. Although less prevalent than ANA, they are more specific, particularly when present in titers of 1:100 or more. Circulating anti–smooth muscle antibodies are also found in patients with chronic hepatitis C. The mean titer is generally higher in patients with autoimmune hepatitis.

ANTINUCLEAR ANTIBODY

ANAs are an often-utilized serologic marker of autoimmune disease and are present in several disorders (see box 73.8). These antibodies can also provide diagnostic and prognostic data concerning patients who have minimal symptoms or who have clinical features of more than one autoimmune disease. They are the most common circulating autoantibodies in autoimmune hepatitis. They are seen in both type 1 disease and rarely in type 2 disease. In most laboratories a titer of 1:100 or greater is considered positive. ANA may be the only autoantibody present or may occur in conjunction with anti–smooth muscle antibody. In one study the specific immunofluorescence patterns of ANAs did not distinguish clinical features of liver disease, although speckled patterns were associated with a younger age and greater aminotransferase activity, and multiple autoantibodies were frequently associated with each immunofluorescent pattern.

Box 73.8 COMMON DISEASES ASSOCIATED WITH POSITIVE ANA

LACTATE DEHYDROGENASE

Serum lactate dehydrogenase comes from myocardium, liver, skeletal muscle, brain, or kidney tissue and red blood cells. Thus, an elevated serum lactate dehydrogenase value is nonspecific. Hepatic serum lactate dehydrogenase can be verified by isoenzymes. Increased lactate dehydrogenase levels are seen in patients with a variety of hepatobiliary disorders including acute viral or drug hepatitis, congestive heart failure, cirrhosis, and extrahepatic obstruction. Marked elevations in serum lactate dehydrogenase and alkaline phosphatase levels are highly suggestive of metastatic disease to the liver.

ULTRASOUND

Ultrasonography with Doppler flow studies presents a noninvasive, commonly utilized modality that provides valuable information regarding the appearance of the liver and blood flow in the portal and hepatic veins in cirrhosis and several other liver diseases. A study using high-resolution ultrasonography in cirrhotic patients (confirmed by biopsy or laparoscopy) found a sensitivity and specificity for cirrhosis of 91.1% and 93.5%, respectively, and positive and negative predictive values of 93.2% and 91.5%, respectively. Ultrasonography is the least expensive radiology study and does not pose the radiation exposure risks of other studies. Thus, it is appropriately the test of choice in the evaluation of liver and biliary tract disease in children and pregnant women. Ultrasonography also lacks the risk of nephrotoxicity from intravenous contrast seen in CT. Nodularity, irregularity, increased echogenicity, and atrophy are the ultrasonographic hallmarks of cirrhosis. It should be noted, however, that the absence of the above-mentioned features does not rule out cirrhosis.

    Marked obesity and excessive intestinal gas can be limiting factors in obtaining good resolution of the images. Ultrasound examination of the liver will often identify mass lesions 1–2 cm or greater in size in the hepatic parenchyma and do this independently of hepatic function. The nature of defects seen on technetium-99m sulfur colloid scanning—solid or cystic—can readily be ascertained, and ultrasound can thus facilitate guided aspiration of cysts or biopsy specimens of lesions. Ultrasonography is a useful procedure for detecting gallstones and confirming the presence of ascites, keeping in mind that study in the fasting state is important. Ultrasound is often used as the first test in the evaluation of patients with cholestatic jaundice. Dilated bile ducts can be readily seen on ultrasound examination in patients with mechanical extrahepatic biliary tract obstruction. Dilation of the bile ducts may not be evident if the obstruction is incomplete or intermittent or if it has been present for a short duration. Serial ultrasound examinations may provide clues in these circumstances. Note that the common bile duct is frequently dilated following cholecystectomy. Hence, an enlarged duct in this situation does not necessarily signify ongoing biliary tract obstruction.

CT AND MRI

The predominantly used imaging tools other than ultrasonography in imaging the liver are CT and MRI. The goals of imaging patients with liver failure are to evaluate for cirrhosis and portal hypertension, to identify conditions that may complicate or preclude treatment, and to identify and stage tumors within the liver or extrahepatic malignancies. Continuous improvements in these imaging modalities over the past few years have expanded their role and improved their utility. At most centers, CT is the predominant tool in evaluating patients with advanced liver disease, while ultrasonography, MRI, and angiography maintain important screening and problem solving roles (see figures 73.2–73.4).

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