Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

LIVER

however, has no colloid uptake and the appearance mimics a metastasis.

Focal Sparing

Focal regions of sparing are found in some patients with generalized fatty infiltration. Diffuse fatty infiltration with focal sparing tends to be segmental, with sparing having a predilection for segment IV and specific sites, such as subcapsular, close to the porta hepatis, and adjacent to the interlobar fissure. Efferent gallbladder blood flow plays a role in focal sparing at the gallbladder fossa. Doppler US reveals blood flow from the gallbladder in many patients with adjacent focal sparing. Thus focal sparing depends to some degree on whether the gallbladder is intact or not. In patients with fatty infiltration, gray-scale US detected focal sparing more often in patients with an intact gallbladder than in those with a prior cholecystectomy. An association exists between sparing along the posterior edge of segment IV and aberrant gastric venous drainage to this segment. A focal decrease in portal blood flow to this segment is the most likely cause of such sparing. Focal sparing of a fatty liver develops in a setting of an arterioportal shunt, presumably due to a decrease in portal blood flow.

Focal sparing is hyperdense both with preand postcontrast CT and appears as a hypoechoic focus with US. Difficulty arises in a fatty liver in differentiating focal sparing from neoplasms.An occasional metastasis can appear as a wedge-shaped hyperdense region on nonenhanced CT, similar to focal sparing in a fatty liver, due to focal intrahepatic portal vein obstruction.

Regions of focal sparing, representing normal liver containing reticuloendothelial cells, take up the SPIO contrast agent ferumoxides. Focal sparing thus reveals a signal loss and has a low intensity on T1and T2-weighted images (34).

Liver metastases appear to be less common in patients with a fatty liver than in a normal liver. When present, their appearance is modified by the underlying fat (Fig. 7.13).

Cirrhosis

Cirrhosis is a reaction by the liver to chronic hepatocyte injury and is often classified morphologically into micronodular and macron-

Figure 7.13. Metastatic breast carcinoma in a fatty liver. Multiple nodules are scattered throughout a heterogeneous, poorly enhancing liver. (Courtesy of Patrick Fultz, M.D., University of Rochester.)

odular.A micronodular pattern predominates in alcohol-induced cirrhosis (also called portal or nutritional cirrhosis), while viral hepatitis generally has more of a macronodular appearance, but such a differentiation is not clear-cut, overlap exists, and with time micronodular cirrhosis tends to evolve into a mixed or macronodular appearance. So-called cardiac cirrhosis develops in some patients with chronic rightsided cardiac failure, especially in patients with constrictive pericarditis; the liver grossly mimics that seen in Laënnec’s cirrhosis, except hepatic vein and sinusoidal congestion are evident. Cirrhosis due to biliary causes is discussed in later sections.

Etiologies of cirrhosis range from infectious, chemical, metabolic, and immunologic, to idiopathic. In children, causes of cirrhosis include Wilson’s disease, primary Budd-Chiari syndrome, and glycogen storage disease. Cirrhosis in children is usually progressive and chronic, with attempts at regeneration resulting in a nodular and irregular liver outline.

In the Western world chronic alcoholism is the most common associated factor for cirrhosis, while in Asia chronic hepatitis predominates. Less common are hemochromatosis, chronic biliary obstruction such as Oriental cholangiohepatitis, chronic congestive failure, reaction to toxic substances such as methotrexate therapy, and idiopathic conditions such as primary biliary cirrhosis.

Table 7.7. Child-Turcotte classification of hepatic reserve

A clinical classification of hepatic reserve is outlined in Table 7.7. In spite of new prognostic models such as the model for end-stage liver disease (MELD), shortand long-term prognostic indices (STPI and LTPI), and the Rockall score and Emory score for assessing prognosis in patients with liver disease, little evidence suggests that the long-used Child-Turcotte classification should be replaced. It is a useful guide in both a setting of portal hypertension and other conditions leading to hepatic failure; it correlates with prognosis.

Preoperative CT in patients with end-stage cirrhosis prior to liver transplantation detects enlarged lymph nodes in about half, mostly located in the porta hepatis and hepatoduodenal regions; adenopathy is most common in a setting of primary biliary cirrhosis and less common in alcohol-related cirrhosis. Histology reveals benign nodal hyperplasia.

Laënnec’s Cirrhosis

The precise etiology of a shrunken liver composed of small grains, elegantly described by Laënnec in 1826, is unknown. A number of congenital and acquired conditions have cirrhosis as their final end point, but the current tendency is to distinguish them from classic Laënnec’s cirrhosis on both clinical and pathologic grounds. Histologically, Laënnec’s cirrhosis consists of hepatocellular necrosis, regenerating nodules, fibrosis, and steatosis, with the specific appearance in any one patient depending on the stage of disease. Superimposed inflammation is often identified. A nodular liver outline is common, with nodularity probably being secondary to both regeneration and distortion produced by fibrosis. From a clinical viewpoint, loss of liver function evolves into portal hypertension and its associated myriad complications.

ADVANCED IMAGING OF THE ABDOMEN

For unknown reasons some patients with Laënnec’s cirrhosis develop primary pulmonary hypertension. An association of cirrhosis, ascites, and pleural effusion is not uncommon. A rare cirrhotic patient develops hydrothorax with little or no evidence of ascites.

Both regenerating nodules and dysplastic nodules develop in livers involved by Laënnec’s cirrhosis. These are discussed in a later section (see Nonneoplastic Tumors) because from an imaging viewpoint they are part of a differential diagnosis for focal liver tumors.

Imaging

Liver US is probably the most common screening examination performed in patients with suspected diffuse liver disease; it is also useful in routine follow-up. Nevertheless, in a setting of diffuse liver disease a strong point can be made for liver-specific contrast-enhanced MRI; if deemed necessary, a single MR study can combine unenhanced and enhanced MR to evaluate liver parenchyma, magnetic resonance cholangiopancreatography (MRCP) for bile duct visualization, and MRA to study liver vasculature.

From an imaging viewpoint, Laënnec’s cirrhosis and most macronodular cirrhoses are generally treated as similar entities; with some exceptions, imaging findings tend to be similar, regardless of the inciting cause. One exception is that the caudate lobe is significantly larger, and the presence of a right posterior hepatic notch is more common in patients with alcoholic cirrhosis than in those with viral-induced cirrhosis (35).

Nevertheless, serial MR follow-up of patients with progressing viral-induced cirrhosis also shows right lobe and medial segment atrophy, correlating with clinical findings (36); in patients with stable disease the caudate lobe and lateral segment continue to increase in size.

Typical temporal findings show that initially the liver enlarges, then the right lobe and medial segment of the left lobe atrophy, and the caudate lobe and lateral segment of the left lobe become prominent, findings described years ago with rectilinear scintigraphy. This change in relative lobe size is rather specific for cirrhosis. A CTbased caudate-to-right lobe ratio of >0.65 is strong presumptive evidence for cirrhosis.

LIVER

Eventually the liver shrinks. These changes are not invariable and about 25% of end-stage cirrhotic livers are normal in size.At times unusual atrophic and hypertrophic combinations lead to a bizarre appearance.

Initially CT detects a mild diffuse increase in attenuation, although more often liver attenuation remains within a normal range. Postcontrast, no significant difference in vascular enhancement and liver enhancement is evident during the arterial phase in patients with and without cirrhosis, but portal venous phase enhancement is significantly lower in cirrhotics. The liver margin varies from smooth, to nodular, to a lobular appearance.

Regeneration, fibrosis, fatty replacement, and vascular shunting lead to an inhomogeneous postcontrast CT appearance. At times thick, fibrotic bands interlace the liver. Peripherally located vessels become attenuated. Some patients develop small peribiliary cysts. More prominent collateral shunts become apparent postcontrast. Although intrahepatic arterioportal shunts are more common with hepatocellular carcinomas, they do occur in cirrhotic livers.

Mesenteric edema is common in cirrhotics; it occurs alone or in combination with omental or extraperitoneal edema. The CT appearance of mesenteric edema varies. About two thirds of patients have gastrointestinal wall thickening, and most often the jejunum and ascending colon are affected, with thickening being multisegmental, concentric, and homogeneous in appearance (37).

The CT appearance of cirrhosis is mimicked in patients undergoing systemic chemotherapy for breast cancer metastatic to the liver.

Liver outline, reflectivity, attenuation, and size are US criteria used to diagnose cirrhosis. Liver surface nodularity is recognized if ascitic fluid is identified adjacent to the liver, keeping in mind that subcapsular metastases also result in a nodular appearance. Fibrosis and fat produce a coarse, heterogeneous hyperechoic appearance. This appearance is also nonspecific and is seen in fatty infiltration and with some neoplasms, such as hepatocellular carcinoma, lymphoma, and metastases. The quadrate lobe transverse diameter (segment IV), measured on oblique subcostal US scans, was 43mm in controls and 28mm in cirrhotics (38). A ratio of caudal lobe width to right lobe width is another

sonographic sign of cirrhosis; a cut-off value of 0.65 provides high specificity but low sensitivity. An increased ratio is also seen in other disorders. In general, the US findings of a normal liver, fatty liver, and chronic liver disease such as cirrhosis overlap somewhat, although differentiation can often be made.

In children, a Doppler US finding of portal vein velocity <20cm/sec identified cirrhosis with a sensitivity of 83% and specificity of 100%, better than that achieved with arterioportal velocity ratios or hepatic artery visualization (39), sensitivity increased to 91% when all three signs were evaluated together.

The MRI findings are similar to those seen with CT. Magnetic resonance imaging identified hilar periportal enlargement in 98% of patients with pathologically proved early cirrhosis who did not have any other imaging findings of cirrhosis, a finding occasionally also seen in normals (40); mean hilar periportal fat thickness was significantly greater in early cirrhotics (16 ± 6mm) than in controls (5 ± 3mm), with the sensitivity and specificity of this finding for diagnosing cirrhosis (using a cutoff value of 10mm) being 93% and 92%, respectively. A widened gallbladder fossa also appears to be a specific MR indicator of cirrhosis.

Fibrosis is hypointense on T1and also hypointense on T2-weighted images, although the presence of fluid varies the T2-weighted appearance. Postcontrast, fibrosis does not enhance during the arterial phase but shows greatest enhancement during hepatic venous phase. Intervening liver parenchyma (or nodules) tends to be hypointense on T1and hyperintense on T2-weighted images. Postcontrast parenchymal enhancement is mild in most patients; in a minority, large, irregular regions of prolonged enhancement mimic the appearance of hepatocellular carcinoma.

A MR scoring system distinguished between clinical Child-Pugh grade A cirrhosis and further severity grades with a sensitivity of 93% and specificity of 82% (41); the scoring system was based on four factors: spleen volume index, volume index of posterior + medial + lateral liver segments, the presence of ascites, and the presence of collateral vessels.

Gadolinium results in greater enhancement in cirrhotic livers than noncirrhotic ones; enhancement varied from homogeneous to heterogeneous.

LIVER

mirrors findings in portal blood flow discussed previously. Whether this finding in cirrhotics is due to vascular or parenchymal factors is unknown.

Complications

Neoplasm

Current knowledge suggests that a hepatocellular carcinoma developing in a setting of cirrhosis evolves from regenerating nodules to dysplastic nodules (both are discussed in a later section). These cancers tend to be insidious, multifocal, and difficult to detect by most imaging modalities. An occasional cancer is identified as a smaller nodule within a larger regenerating nodule.

Although a hepatocellular carcinoma developing in a noncirrhotic liver is often resected or treated locally, in a setting of cirrhosis liver transplantation is a more viable option. Preoperative detection of multiple cancer foci or diffuse liver involvement is generally considered a contraindication to liver transplantation because invariably metastases are present. A number of unsuspected hepatocellular carcinomas are first detected after liver transplantation.

What is the risk of harboring an unsuspected hepatocellular carcinomas in a setting of advanced cirrhosis? Data for this question are available from liver transplantation studies, but the answer varies depending on whether cirrhosis is posthepatitic or Laënnec in etiology. Unsuspected hepatocellular carcinomas were most prevalent with hepatitis B (27%) and hepatitis C (22%), less so with other etiologies of cirrhosis (44); serum a-fetoprotein levels did not suggest most small tumors.

A retrospective orthotopic cirrhotic liver transplantation study found that preoperative CT identified 61% of 18, CT during arterial portography (CTAP) 58% of 12, and MR 62% of 21 malignant tumors (45); most missed tumors were <2cm in diameter.

Extensive fibrosis tends to mimic a neoplasm on unenhanced CT, although postcontrast CT aids in differentiating these two entities. Postcontrast MRI is also useful in differentiating between fibrosis and tumor; hepatocellular carcinomas enhance more during the arterial phase, while fibrosis enhances during the portal phase.

Ultrasonography is used as a screening test to follow patients with cirrhosis. Such a screening program performed every 6 months can lead to earlier detection of smaller, potentially curable hepatocellular carcinomas. A more basic question is whether such screening is cost-effective. For most Western patients with Child-Pugh class A cirrhosis, screening with a-fetoprotein and US every 6 months appears to provide a negligible benefit in increased life expectancy (<3 months), even when the risk of cancer is high (6% per year) (46); for some patients with a predicted cirrhosis-related survival rate above 80% at 5 years, however, screening may increase mean life expectancy by several months.

Some evidence suggests that patients with cirrhosis have an higher prevalence of extrahepatic cancers than would be expected.

Other Complications

Some patients with cirrhosis develop small peribiliary cysts adjacent to portal vein branches (peribiliary cysts are discussed later). Computed tomography reveals small periportal cysts. Ultrasonography shows these cysts as round or tubular anechoic region around major portal tracts. With time, these cysts tend to enlarge, and differentiation from bile ducts is difficult.

In general, the risk of systemic bacterial infection increases with the severity of the cirrhosis. Infection with Vibrio parahaemolyticus is associated with ingestion of raw seafood; in most patients this infection results in gastroenteritis, but in cirrhotic patients it has led to fatal sepsis. Spontaneous Streptococcus bovis bacterial peritonitis should raise suspicion for cirrhosis.

In an autopsy study, 2% of patients with viralinduced cirrhosis or subacute liver atrophy developed clinically unsuspected phlegmonous colitis (47).

Hepatorenal syndrome is a known complication of liver disease. Believed to represent a circulatory dysfunction primarily involving arterial circulation, patients with hepatorenal syndrome do not maintain a normal effective arterial blood volume. Early changes consist of renal vasoconstriction detectable by renal Doppler US. And Doppler US thus identifies cirrhotics potentially at risk for developing hepatorenal syndrome.

Endoscopic retrograde cholangiopancreatography reveals evidence of chronic pancreatitis in a minority of cirrhotics. Most of these findings are in patients with alcoholic cirrhosis.

Cirrhotics have a higher prevalence of peptic ulcer disease than the general population. Helicobacter pylori does not appear to play a role in these patients.

Cirrhotic patients have a significantly lower bone mineral density than controls.

Primary Biliary Cirrhosis

Clinical

Of unknown pathogenesis, primary biliary cirrhosis is probably neither autoimmune nor infectious in origin, although it is associated with autoimmune hepatitis. A strong association exists with antimitochondrial antibodies (AMAs), yet some patients are AMA negative and antinuclear antibody positive; the latter is also called autoimmune cholangitis (or cholangiopathy) rather than primary biliary cirrhosis. Whether patients with so-called autoimmune cholangitis (i.e., those with an absence of antimitochondrial antibodies) should be consigned to a separate disease entity or considered to have a variant of primary biliary cirrhosis is conjecture (autoimmune cholangitis is also discussed in Chapter 8). Few differences are evident in clinical and serologic features in AMA-negative and AMA-positive primary biliary cirrhosis patients.

A relationship exists between primary biliary cirrhosis and Sjögren’s syndrome. In fact, Sjögren’s syndrome is one of the most frequent extrahepatic associations of primary biliary cirrhosis, and some investigators consider that primary biliary cirrhosis is a secondary form of Sjögren’s syndrome. Celiac sprue appears to be more common among patients with primary biliary cirrhosis than the general population. A rare patient also has chronic autoimmune gastritis or idiopathic thrombocytopenic purpura.

No association is believed to exist with inflammatory bowel disease, which distinguishes this condition from sclerosing cholangitis. Pregnancy probably has no effect on disease activity.

Pulmonary alveolar diffusion capacity is often impaired in these patients, although such impairment is usually asymptomatic. An asso-

ADVANCED IMAGING OF THE ABDOMEN

ciation between primary biliary cirrhosis and bronchial asthma has been reported. Severe hypoxemia has developed.

Patients with primary biliary cirrhosis are believed not to be at increased risk for developing hepatocellular carcinoma. Nevertheless, hepatocellular carcinoma and even a cholangiocarcinoma does occur occasionally.

The majority of patients are middle-aged women. Typically an early prodromal stage with mild elevation of liver function tests leads to cholestasis, although some patients are symptomatic even prior to cholestasis.

Sacral insufficiency fractures have developed in women with primary biliary cirrhosis.

Pathology

Progressive destruction of intrahepatic bile ducts, surrounding inflammation, and intrahepatic bile stasis mark primary biliary cirrhosis. Liver granulomas are a characteristic feature. The granulomas are noncaseating and nonnecrotizing, consisting of epithelioid cells and occasional giant cells. These granulomas are not pathognomonic and are found in other disorders, including primary sclerosing cholangitis.

The extrahepatic bile ducts are not involved. The intrahepatic bile ducts attenuate and, with progression, become somewhat tortuous and splayed, presumably due to adjacent regenerating nodules. Histologically, the bile duct wall is not as thickened as in sclerosing cholangitis. Nodular regenerative hyperplasia is common.

Imaging

Imaging differentiation between primary biliary cirrhosis and sclerosing cholangitis is generally straightforward. A cholangiographic “pruned-tree” appearance gradually becomes evident (Fig. 7.14); the exception is in a minority of patients with sclerosing cholangitis who have involvement only of small intrahepatic ducts; a gradual obliteration of these ducts may eventually lead to an appearance mimicking primary biliary sclerosis.

Computed tomography initially detects an enlarged or normal-size liver having a smooth contour; fibrosis and regenerative nodules are evident in about one third. Varices and ascites gradually develop. With advanced disease, CT findings are similar to those seen in other types