Книги по МРТ КТ на английском языке / Advanced Imaging of the Abdomen - Jovitas Skucas

of an unexplained fatty liver. Acute fatty liver in pregnancy is discussed in a separate section.

Mild hepatic iron overload develops in some patients with nonalcoholic steatohepatitis, possibly due to the concomitant presence of the hemochromatosis gene mutation; homozygous or heterozygous mutations of this gene are common in patients with nonalcoholic steatohepatitis.

A minority of patients receiving intraperitoneal insulin during peritoneal dialysis develop subcapsular steatosis, seen with CT as subcapsular hypodense nodules or rindlike regions (33).

Steatosis generally improves once a known inciting agent is removed.

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to their cancellation. Thus on opposed-phase images normal liver parenchyma has an isointense signal and fat appears hypointense and these sequences are useful to detect liver fat. In-phase and opposed-phase GRE sequences provide complementary diagnostic information in the liver; in a fatty liver some focal lesions are obscured if only opposed-phase sequences are used, and for full assessment both are necessary. Fat detection is a complex MR topic, and both fat-suppressed and water-suppressed MRI have certain advantages in specific instances.

Postcontrast, simple fat deposition enhances in a similar pattern to normal liver parenchyma. Fat within abnormal tumors, on the other hand, tends to follow the underlying tumor enhancement pattern.

Diffuse Steatosis

Both CT and US provide qualitative rather than quantitative evidence of liver fat. Precontrast CT suggests steatosis if liver attenuation is less than the spleen; typical criteria for steatosis consist of liver attenuation 10 HU less than spleen or a liver-to-spleen ratio of <0.9. Postcontrast, the spleen is not an accurate reference standard; muscle tissue is an adequate standard only if fatty infiltration is pronounced. Contrastenhanced CT in fatty infiltration reveals normal vessels coursing through fat, rather than being displaced as is often the case with a neoplasm.

Ultrasonography of diffuse fatty infiltration reveals a hyperechoic pattern throughout the liver, to the point of masking the normally hyperechoic portal vein wall. Kidneys have been used as a standard to establish liver echogenicity. The hepatorenal echo intensity difference is greater in fatty livers than in normal livers; a hepatorenal difference of >7dB is a sensitive indicator of a fatty liver.

Because a normal pancreas is slightly more hyperechoic than a normal liver, it too is a useful landmark to detect increases in liver echogenicity.

Magnetic resonance spectroscopy measures the lipid volume fraction in liver steatosis. Spinecho (SE) sequences are relatively insensitive in detecting fatty infiltration. Chemical shift imaging using in-phase and opposed-phase SGE sequences distinguishes proton signals from water and fat. Imaging with fat and water protons in-phase results in their signals being additive, while opposed-phase imaging leads

Focal Fatty Infiltration

Pathogenesis of focal fatty infiltration is not clear. Focal infiltration has a predilection for sites close to the falciform ligament and adjacent to gallbladder fossa. An anomalous portal venous supply, such as aberrant gastric venous drainage, is associated with focal fatty infiltrations. The importance of different insulin levels in an aberrant portal vessel as an inductor of steatosis is conjecture.

Focal fatty infiltration is segmental and often wedge-shaped in appearance; it should not be spherical in outline. As the term suggests, fat infiltrates and should not displace vessels. Rarely, focal involvement appears as multiple small lesions mimicking metastases or abscesses. Some focal infarcts have a similar appearance.

Ultrasonography of focal fatty infiltration shows a normal liver parenchyma containing fatty hyperechoic regions.

The MRI typically reveals a wedge-shaped region, hyperintense on T1-weighted images and extending to the periphery. Magnetic resonance imaging appearance is not pathognomonic; an intrahepatic cholangiocarcinoma can have a similar appearance. Post-ferumoxides, fatty infiltration is relatively high in intensity in all on T1-weighted images, with these regions ranging from hyperto isointense on T2weighted images (34).

Kupffer cells tend to be present in fatty infiltration, evidenced by Tc-99m–sulfur colloid uptake. A minority of focal fatty infiltrations,

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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.

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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.

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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.

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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-

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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

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Figure 7.14. Primary biliary cirrhosis. Only limited intrahepatic bile ducts are filled in spite of a vigorous contrast injection.

of cirrhosis, except for a higher prevalence of diffuse liver enlargement.

A MR periportal halo sign is helpful in identifying this entity (Fig. 7.15). This sign, consisting of a hypointense focus centered around a portal vein branch and identified either on T1or T2-weighted images, was found in 43% of patients with primary biliary cirrhosis awaiting transplantation but in no other cirrhotic patients (48).

Figure 7.15. Primary biliary cirrhosis. Transverse T1-weighted MRI reveals round, hypointense lesions surrounding portal veins (arrows), a finding termed the periportal halo sign. (Courtesy of Jeffrey Wenzel, M.D., Southwest Imaging, Dallas, Texas.)

Computed tomography identifies lymphadenopathy in about 90% of patients with primary biliary cirrhosis requiring orthotopic liver transplantation (49). Adenopathy usually involves periportal and hepatoduodenal ligament nodes, and such adenopathy must be differentiated from that seen with neoplasms. A rough correlation exists between the size of the hepatoduodenal ligament lymph nodes and the degree of hepatocellular damage.

Therapy

The most common causes of death in patients with primary biliary cirrhosis are hepatic failure and gastrointestinal bleeding from varices. Currently no definitive therapy is available aside from liver transplantation. Transplantation has had a significant impact on patient survival. Nevertheless,the histologic features suggestive of recurrence develop in some transplant patients, with the recurrence rate apparently influenced by the type of immunosuppression used. During follow-up after orthotopic liver transplantation, 4% of patients developed recurrence (49).

Secondary Biliary Cirrhosis

Chronic biliary obstruction does evolve into cirrhosis. The overall appearance is similar to that seen in primary biliary cirrhosis, except for increased bile stasis and a lack of duct degeneration.

Liver involvement is uncommon in children with cystic fibrosis, but increasing survival of these patients has led to an increased number presenting with liver disease. These older children and young adults develop focal biliary cirrhosis, which eventually evolves into portal hypertension (Fig. 7.16). Some cystic fibrosis patients have undergone liver transplantation. Whether screening is useful in cystic fibrosis patients with chronic liver disease prior to developing cirrhosis remains to be established.

Fibrosis

Fibrosis is a response to a number of chronic liver insults. In some disorders fibrosis predominates with few or no parenchymal abnormalities identified.

Figure 7.16. A cirrhotic liver in a 24-year-old man with cystic fibrosis and hepatic failure. The liver has a nodular outline. Splenomegaly and vascular congestion (arrowheads) are secondary to portal hypertension. (Courtesy of Douglas S. Katz, M.D., Winthrop University Hospital, Mineola, New York.)

Ultrasonography typically reveals a hyperechoic pattern throughout a fibrotic liver. The hyperechoic changes with periportal fibrosis are seen mostly around the portal vein branches, separated from the adjacent liver parenchyma by a hypoechoic region. The underlying portal vein branches tend to be deformed.

The MRI changes of fibrosis are rather characteristic and familiar to most radiologists. SPIO-enhanced MR imaging identifies fibrosis by decreasing signal intensity from nonfibrotic regions containing Kupffer cells (50). Problems exist when fibrosis is only one part of a complex entity.

Vanishing Bile Duct Syndrome

An occasional patient with cholestasis has narrowed or small intrahepatic bile ducts (ductopenia) with no underlying disease being identified. This condition, termed vanishing bile duct syndrome, probably represents an immunologic or hypersensitive hepatotoxic reaction. Numerous drugs are associated with this condition. Pathologically, it should be suspected if absent interlobar bile ducts are found in over 50% of portal triads. Progressive cholestasis and loss of intrahepatic bile ducts in some of these patients develop to the point that a liver transplant is necessary.

Superficially, the imaging appearance of vanishing bile duct syndrome resembles diffuse intrahepatic sclerosing cholangitis.

Progressive cholestasis and the loss of intrahepatic bile ducts in some of these patients develop to the point that a liver transplant is necessary.

Iron Overload

Clinical

As a rough guide, a normal adult body contains about 4 to 5g of iron, of which 80% is in hemoglobin, myoglobin, and iron-containing enzymes and 1g of iron is stored. Ingested and absorbed iron is bound to transferrin and deposited in bone marrow, hepatocytes, muscle, and other tissues, but not reticuloendothelial cells; the latter derive their iron mostly from phagocytosed red blood cells. Of importance from an imaging viewpoint is that disorders associated with too much ingested iron then store the excess iron in the liver (hepatocytes) and pancreas, while iron from excess blood transfusions is stored in the liver (reticuloendothelial cells), spleen, and bone marrow. Disorders associated with excess hemolysis also lead to renal iron accumulation. Hemorrhage into tissues results in focal iron accumulation.

Iron is a hepatotoxin. Excess iron deposition in body tissues without organ damage is known as hemosiderosis. Hemochromatosis is an ironoverload disorder with structural and functional impairment of involved organs. Primary (hereditary or genetic) hemochromatosis is an inherited abnormality characterized by increased iron absorption from the gastrointestinal tract and resultant tissue iron overload. It is the most common inherited single gene disorder in those of northern European descent (51). Two point mutations in the hemochromatosis candidate gene HFE are known as C282Y and H63D. A diagnostic genotypic test for the C282Y mutation is available. Although this genetic test identifies most hemochromatosis patients, both iron-overload patients without this mutation and homozygous patients without iron overload also exist. In some patients both genetic and acquired factors play a role.

During the early latent stage of compensated hereditary hemochromatosis, aside from iron overload, only minimal hepatocyte damage is evident, but iron overload beyond a critical level

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results in hepatocytic and sinusoidal cell siderosis and intracellular damage and necrosis.

Classic findings of hereditary hemochromatosis consist of bronze diabetes and an underlying cirrhosis, although currently a diagnosis is more often made at an earlier stage. Ideally, the quantity of liver iron overload is determined from a liver biopsy, but the diagnosis is often based mostly on an elevated fasting transferrin saturation level.

Hepatic iron deposition is common in thalassemia and chronic hepatitis, making differentiation between chronic hepatitis and hereditary hemochromatosis difficult. At times these disorders coexist; thus hepatitis C and hereditary hemochromatosis have led to endstage liver disease in children. Secondary hemochromatosis develops most often in patients requiring long-term blood transfusions and those ingesting large amounts of iron. Multiple transfusions eventually lead to extensive iron overload in reticuloendothelial cells, and liver fibrosis is not a prominent feature. Bantu siderosis patients ingest large amounts of iron, which is stored mostly in reticuloendothelial cells and, to some degree, in hepatocytes.

Thalassemia patients also have increased oral iron absorption, driven not by genetic factors directly as in hereditary hemochromatosis but by increased erythroid hyperplasia. These patients initially develop liver findings similar to hereditary hemochromatosis, but additional iron overload due to transfusions modifies this appearance.

Sideroblastic anemia and erythropoiesis also result in secondary hemochromatosis, somewhat similar to transfusion overload. Hemosiderin accumulates in sideroblasts and hepatocytes, but not splenic reticuloendothelial cells. As a result, these patients have a hypointense liver and bone marrow but a close to normal appearing spleen on T1-weighted MR images. Nevertheless, some of these patients receive blood transfusions and the MR appearance can be confusing.

Untreated, patients with hereditary hemochromatosis progress to cirrhosis, congestive heart failure, and various endocrine abnormalities, including diabetes mellitus. Disease progression is gradual,findings are nonspecific,and the true cause is thus often overlooked, especially during the early phase. These patients are at increased risk of developing a hepatocellular

carcinoma. A rare cholangiocarcinoma has developed in hemochromatosis, but whether this is fortuitous or not is speculation.

Imaging

A linear relationship exists between CT attenuation and liver iron content. Computed tomography sensitivity is improved by using 80kVp instead of the usually used 120kVp. Nevertheless, CT sensitivity in measuring liver iron is rather low, and most current research is centered on MR. When hemochromatosis is well established, the intrahepatic vessels are at a lower density than liver parenchyma; this finding is not pathognomonic, and high parenchymal attenuation is found in patients being treated with drugs such as amiodarone (amiodarone and its metabolites contain iodine and are concentrated in hepatocytes), gold therapy,prior thorium dioxide (Thorotrast) use, and occasionally in Wilson’s disease.

Liver US is normal in most patients with early hemochromatosis.

Being a paramagnetic substance, iron becomes magnetized within a magnetic field, adjacent water photons lose phase coherence, and the overall effect is a hypointense MR signal. Magnetic resonance imaging in hereditary hemochromatosis reveals a decrease in liver and pancreas signal intensity on T2weighted sequences. No such decrease in signal intensity is found in the spleen because no significant iron is deposited in the reticuloendothelial system. In iron overload due to transfusion, on the other hand, iron is deposited mostly in the reticuloendothelial cells of the spleen and liver, with relative sparing of liver hepatocytes and pancreas; as a result, a decreased signal intensity is evident on T2weighted images of both the liver and spleen (Fig. 7.17). Initially in iron overload, signal intensity on T1-weighted images is normal but with more severe involvement a hypointense signal also becomes evident. An inverse linear relationship exists between iron concentration and signal intensity liver-to-muscle ratio. Overall, MRI detects relatively low levels of iron overload. A mathematic model is available to estimate iron concentrations from MR imaging data (52), but stringent calibration is required. Among other variables, MR field strength influences the effect of liver iron. A correlation