CHAPTER 12 Liver
The liver is a biochemically complex organ, performing important metabolic and synthetic functions in the body. Therefore, it is not surprising that more basic laboratory tests are available to assess liver function than are available for any other organ in the abdomen and pelvis. In isolation, many of these tests are nonspecific. However, familiarity with these tests may add specificity to an imaging examination, direct the search for abnormalities, or aid the radiologist in recommending the appropriate next imaging examination to the referring physician. For these reasons, we provide a brief (alphabetical) summary of common laboratory tests relevant to liver imaging.
Albumin is synthesized in the liver and is a measure of hepatic synthetic function. Low levels of serum albumin can be caused by impaired hepatic synthesis, urinary or enteric losses, or extravascular distribution (e.g., in ascites). Because the half-life of serum albumin is approximately 20 days, serum albumin levels are often normal in patients with acute liver abnormalities.
An increased level of the liver isoenzyme alkaline phosphatase (ALP) implies the presence of cholestasis but does not indicate the level of obstruction. Hepatobiliary origin of ALP can be suggested when γ-glutamyl transpeptidase (GGT) level is also increased. Disproportionately increased ALP levels can be seen with infiltrative malignancy.
The α-fetoprotein (AFP) level is commonly used to screen for or confirm the presence of hepatocellular carcinoma (HCC). The normal serum level of AFP is less than 10 ng/ml. For screening purposes, a level greater than 20 ng/ml may be considered abnormal, but this cutoff has a low positive predictive value because minor increases of AFP are common in patients with chronic liver disease. Increasing AFP levels over time should be considered suspicious, and a level exceeding 400 ng/ml is often considered diagnostic of HCC when correlated with typical imaging findings. Unfortunately, many HCCs, particularly small tumors, are not associated with an AFP level this high, and as many as 20% to 40% of patients with HCC have a normal serum AFP level. AFP levels can also be increased in patients with germ cell tumors and rarely with some gastrointestinal (GI) malignancies.
Alaninaminotransferase (ALT) and aspartate aminotransferase (AST) are sensitive indicators of hepatocellular injury (necrosis or inflammation). Levels of 500 to 1500 IU are common in acute viral or drug-induced hepatitis. Mild increase of ALT and AST concentrations can be seen with alcoholic hepatitis and biliary obstruction. Passage of a common bile duct stone can result in a transient severe increase in aminotransferase levels. An AST/ALT ratio greater than 1.5 to 2 may suggest alcoholic liver disease.
The serum bilirubin level is often increased in cases of hepatocellular disease and biliary obstruction. Contrary to popular belief, the ratio of conjugated to unconjugated bilirubin may be an unreliable indicator of biliary obstruction. It can be more helpful to correlate bilirubin levels with other indicators of cholestasis, such as ALP or 5′ nucleotidase, when biliary obstruction is suspected.
Diffuse increase of immunoglobulin (Ig) levels can be seen in patients with chronic liver disease of various causes. Specific increase of IgG can be present in patients with autoimmune hepatitis. IgM levels may be increased in the setting of primary biliary cirrhosis, and IgA may be disproportionately increased in alcoholic liver disease.
A measurement of prothrombin time represents an assessment of fibrinogen (factor I), prothrombin (factor II), and clotting factors V, VII, and X. These factors are produced by the liver and have a relatively short half-life. Therefore, acute hepatocellular injury can result in an increased prothrombin time, and prothrombin time correlates with the severity of liver damage. Vitamin K deficiency and coumarin-like medications also affect prothrombin time. An increased prothrombin time in association with a normal serum albumin level (another indicator of hepatic synthetic function with a significantly longer half-life) implies acute, rather than chronic, hepatic dysfunction.
Knowledge of segmental anatomy of the liver is critical because the hepatic segments represent discrete regions that can be surgically isolated and removed. Localization of an abnormality to the correct segment is a necessary part of surgical planning. Several systems are currently in use describing the anatomic segments of the liver (Table 12-1). The Couinaud–Bismuth system is currently the most often used nomenclature, although many surgeons are transitioning to the Brisbane terminology. According to the Brisbane 2000 Terminology of Liver Anatomy, the liver is divided into a right hemiliver (commonly referred to as the right lobe) and a left hemiliver (commonly referred to as the left lobe) by a vertical plane along the course of the middle hepatic vein that intersects the gallbladder fossa. The right hemiliver is divided into anterior and posterior sections (also known as segments under the terminology of Goldsmith and Woodburne) by a vertical plane along the right hepatic vein. The medial and lateral sections of the left hemiliver are divided by the fissure for the ligamentum teres, which contains the falciform ligament. The caudate lobe (segment I) protrudes from the right hemiliver between the portal vein and inferior vena cava (IVC).
|Brisbane||Couinaud–Bismuth||Goldsmith and Woodburne|
|Right Hemiliver||Right Lobe||Right Lobe|
|Anterior Section||Anterior Segment|
|Segment VIII (upper)||Segment VIII (upper*)|
|Segment V (lower)||Segment V (lower*)|
|Posterior Section||Posterior Segment|
|Segment VII (upper)||Segment VII (upper)|
|Segment VI (lower)||Segment VI (lower)|
|Left Hemiliver||Left Lobe||Left Lobe|
|Medial Section||Medial Segment|
|Segment IVa (upper)||Segment IVa (upper)|
|Segment IVb (lower)||Segment IVb (lower)|
|Lateral Section||Lateral Segment|
|Segment II (upper)||Segment II (upper)|
|Segment III (lower)||Segment III (lower)|
|Caudate||Segment I||Segment I|
The liver is further divided into segments by a transverse plane (scissura) along the right and left portal vein branches. Each segment has its own blood supply and biliary drainage. These segments are illustrated for multidetector computed tomography (CT) in Figure 12-1. For purposes of this textbook, we refer to the right and left lobes of the liver and use predominately the Couinaud–Bismuth terminology for segments, because this terminology is most familiar to radiologists. However, it is important to be familiar with systems of nomenclature in common use at one’s own institution to facilitate accurate communication.
The right, middle, and left hepatic veins converge at the hepatic venous confluence and drain blood from the liver into the IVC just below the right atrium. The hepatic venous confluence has a variety of configurations, but most commonly, the middle and left hepatic veins share a common trunk before entering the IVC (Fig. 12-2). Segment I (caudate lobe) has a separate venous drainage directly to the IVC.
The middle hepatic vein is of particular importance to hepatic surgeons. In patients undergoing right hepatic resection or right hemiliver donation, the surgeon typically bisects the liver approximately 1 cm to the right of the middle hepatic vein. When such surgery is contemplated, this line serves as a landmark for determining the relative volumes of the right and left lobes. When living liver donation is being considered, it is important to note large tributaries of the middle hepatic vein that drain the right lobe (e.g., segments V and VIII), because these will be transected in the case of right hemiliver transplantation and may require reimplantation in the recipient.
Many individuals have accessory hepatic veins that drain the inferior right hepatic lobe directly into the IVC. In some patients, more than one inferior accessory vein is present. These have a similar relevance to hepatic transplant surgery as large tributaries of the middle hepatic vein. In general, tributaries and accessory hepatic veins in the range of 5 to 10 mm in diameter that cross a transection plane are considered significant. Inferior accessory hepatic veins can also serve as a collateral pathway to circumvent intrahepatic vena cava obstruction (Fig. 12-3).
The portal vein forms from the confluence of the splenic and superior mesenteric veins, and normally contributes a substantial portion of the hepatic blood flow (at least 75%). The main portal vein travels within the hepatoduodenal ligament as it enters the liver hilum. The portal vein typically bifurcates into right and left branches, each of which subsequently branches into anterior and posterior branches (right portal vein) or medial and lateral branches (left portal vein) (Fig. 12-4). These major branches further bifurcate to supply their respective hepatic segments. The portal vein branch to the caudate lobe can originate from either the left or the right portal vein.
The branching pattern of the portal vein may have important implications for the liver surgeon. It is important to recognize portal vein branching variants in patients scheduled for liver resection or donor hemihepatectomy to prevent inadvertent interruption of the portal blood supply to the remaining liver. A variety of portal vein branching variations have been described. Portal trifurcation refers to simultaneous branching of the main portal vein into right posterior segment, right anterior segment, and left portal vein branches (Fig. 12-5). Additional variants are possible involving the lack of a common trunk for the right posterior and anterior segment branches, including origin of the right posterior segment branch from the main portal vein and origin of the right anterior segment branch from the left portal vein (Figs. 12-6 and 12-7). Other, less frequent anomalous portal branching patterns are possible. Some studies have demonstrated a somewhat weak concordance between anomalous portal vein branching and variant bile duct anatomy. However, bile duct anomalies can be present in the absence of variant portal venous branching, and the presence of a normal/classic portal vein branching pattern does not preclude anomalous biliary anatomy. Anomalous branching of the portal vein has also been associated with malposition of the gallbladder. Additional congenital variants of the portal vein include prepancreatic portal vein (often associated with situs inversus), double portal vein, and agenesis of the main portal vein or one of its major branches.
The hepatic artery travels in the hepatoduodenal ligament anterior to the portal vein and supplies the liver with oxygen-rich arterial blood and approximately 25% of the total hepatic blood flow. The common hepatic artery typically originates from the celiac axis together with the splenic and left gastric arteries. After giving off the gastroduodenal artery, the proper hepatic artery bifurcates into the right and left hepatic arteries, which further branch to supply the hepatic segments. The caudate lobe can receive its blood supply from branches of either the right or left hepatic artery.
Correctly mapping out the hepatic arterial anatomy is important before liver and biliary surgery, hepatic chemoembolization, or placement of a chemoinfusion pump. Hepatic artery variants are extremely common. The term replaced is used when the entire right hepatic artery, entire left hepatic artery, or entire common hepatic artery arises from an atypical location. The terms accessory or partially replaced are used when only part of the arterial blood supply to the right or left lobe arises from an atypical location.
Fortunately, most replaced or accessory arteries can be identified by looking in only two locations. The replaced or accessory left hepatic artery arising from the left gastric artery can be found traveling in the fissure for the ligamentum venosum (Fig. 12-8). The replaced or accessory right hepatic artery can usually be identified in the portocaval space (Fig. 12-9). The most common hepatic artery variants are the left hepatic artery (or a portion thereof) arising from the left gastric artery and the right hepatic artery (or a portion thereof) originating from the superior mesenteric artery. Other variants include origin of the hepatic artery directly from the aorta; origin of one of the hepatic arteries before the origin of the gastroduodenal artery; trifurcation of the hepatic artery into left, right, and gastroduodenal arteries; and origin of the left hepatic artery from the celiac axis.
Figure 12-8 Enhanced axial computed tomographic image through the liver of a patient with hereditary hemorrhagic telangiectasia demonstrating the typical location of an accessory or replaced left hepatic artery arising from the left gastric artery. The artery is enlarged because of intrahepatic arteriovenous shunting.
The artery supplying segment IV of the liver is often overlooked but is important to identify in patients who may be undergoing hemihepatectomy (including living hemiliver donors) (Fig. 12-10). In particular, it is important to note whether the segment IV artery arises from the left or right hepatic artery. When arising from the right hepatic artery, additional steps are needed to preserve the segment IV artery during right hepatectomy. A segment IV artery arising from the right hepatic artery has occasionally been referred to as a middle hepatic artery. The posterior part of segment IV can also receive blood supply from caudate artery branches.
Every practicing radiologist is familiar with the dual blood supply to the liver via the hepatic artery and portal vein. However, relatively little attention has been paid in Western radiology training to venous structures other than the main portal vein that drain from extrahepatic sites into the liver. Although these vessels contribute relatively little in the way of critical blood supply to the liver, they are a common source of vexing imaging findings that can generate unnecessary additional tests or invasive procedures.
Four major groups of veins drain into the liver aside from the main portal vein: paraumbilical, cholecystic, gastric, and parabiliary. Most radiologists associate the paraumbilical veins (also referred to as the superior and inferior veins of Sappey) with portal hypertension; in which case, they serve to divert portal blood flow to the systemic circulation. However, the paraumbilical veins normally drain toward the liver and into the hepatic parenchyma along the falciform ligament. These veins may be responsible for fatty infiltration or perfusionrelated pseudolesions in this location (Fig. 12-11). Paraumbilical veins communicate with the epigastric veins and can serve as a collateral pathway in the setting of superior vena cava or IVC obstruction. This helps explain the occasional finding of focal enhancement in the region of the falciform ligament on early-phase CT or magnetic resonance imaging (MRI) in patients with caval obstruction (Fig. 12-12). Hepatic inflow via the cystic (or cholecystic) vein may result in a perfusion-related pseudolesion in the region of the gallbladder fossa during enhanced CT and MRI, or may manifest as areas of focal fatty sparing adjacent to the gallbladder fossa in the setting of hepatic steatosis (Fig. 12-13). Gastric veins that drain into the liver are another potential source of perfusion-related pseudolesions, focal fatty infiltration, or focal fatty sparing involving segments II, III, and IV (Fig. 12-14). The last major group of systemic inflow veins is the parabiliary veins, better known for their role in bypassing portal vein occlusion (cavernous transformation of the portal vein). These veins drain the region of the pancreatic head and duodenum, course along the common bile duct in the hepatoduodenal ligament, and enter the liver at the hilum. They are responsible for perfusion-related pseudolesions and focal fatty infiltration or sparing adjacent to the liver hilum in the caudate and left hepatic lobes (Fig. 12-15).
Figure 12-11 Axial portal-phase gadolinium-enhanced (A), in-phase (B), and opposed-phase (C) T1-weighted magnetic resonance (MR) images through the liver in a young woman with segment IV perfusion anomaly. B, C, Images were obtained 2 years after (A).
Figure 12-12 Axial contrast-enhanced computed tomographic scan through the abdomen (A) and chest (B) shows hyperenhancement in region of segment IV adjacent to falciform ligament in a patient with superior vena cava (SVC) obstruction by lymphoma.
Figure 12-14 Enhanced axial computed tomographic scan showing a gastric vein entering the liver. This vein could be seen draining into segment IV on other images (not shown), although it was initially confused with an accessory left hepatic artery.
It is not entirely predictable when small veins entering the liver will result in an area of enhanced perfusion during the arterial phase, a perfusion defect during the portal phase, an area of focal fatty infiltration, or an area of fatty sparing. The incidence of hepatic pseudolesions will likely increase as quicker CT scanners and rapid bolus injection of intravenous contrast result in better temporal discrimination of vascular phases. Knowledge of the presence and typical locations of inflow vessels may prevent an errant diagnosis of tumor when such imaging findings are encountered.
With sonography, normal hepatic parenchyma is of moderate, homogeneous echogenicity. The liver is normally slightly more echogenic than normal renal cortex and less echogenic than pancreas. Increased periportal echogenicity helps distinguish portal veins from the hepatic veins. The intrahepatic bile ducts are of smaller caliber than the portal veins, lack flow with color Doppler imaging, and are normally relatively inconspicuous.
With CT, normal hepatic parenchyma is of homogeneous density, with attenuation values in the range of 45 to 65 HU. The normal liver is typically 5 to 10 HU denser than the normal spleen on an unenhanced CT image. The normal liver can vary considerably in shape between individuals. Typical liver volumes as determined by CT are approximately 1700 and 1400 ml for male and female individuals, respectively, although this also varies considerably between individuals. The degree of parenchymal enhancement after administration of intravenous contrast material varies with injection rate, injected volume, and the timing of image acquisition after contrast administration. Peak liver enhancement increases with contrast volume and concentration, and decreases with increasing body weight. Peak hepatic parenchymal enhancement lags behind that of the renal cortex and pancreas. Table 12-2 presents the timing of the various phases of a dynamic contrastenhanced CT examination in a typical patient.
|Early arterial (for computed tomography angiographic studies)||20-25 seconds|
|Late arterial||30-40 seconds|
|Portal venous||60-90 seconds|
These estimates vary depending on type of scanner and injection protocol.
The appearance of the normal liver on an MRI examination depends on the pulse sequence applied. On T1-weighted images, the normal liver is of higher signal intensity than the normal spleen but of lower signal intensity than the normal pancreas. On T2-weighted images, the liver is of lower signal intensity than the spleen. The relative signal intensity of the normal liver should not vary significantly between in-phase and opposed-phase gradient-echo images in the absence of abnormal iron or fat deposition. On a T1-weighted sequence after intravenous gadolinium chelate administration, the liver increases in relative signal intensity. Notably, there is no standard MR unit of signal intensity comparable with the Hounsfield unit.
Diffuse hepatic abnormalities may manifest on imaging examinations as altered echogenicity (ultrasound [US]), attenuation (CT), signal intensity (MRI), enhancement, architecture, or size of the liver. When a diffuse process results in homogeneous alteration in the imaging appearance of the liver, it may become apparent only after direct comparison of the hepatic parenchyma to some internal (e.g., the vessels) or external (e.g., the spleen) reference.
|Echogenicity (US)||Hepatitis, tumor||Steatosis, fibrosis, tumor|
|Attenuation (CT)||Steatosis, hepatitis, tumor||Iron, glycogen, amiodarone (Fig. 12-16), iodine|
|T1W SI (in-phase MRI)||Iron,* edema||Steatosis, gadolinium, manganese|
|T1W SI (opposed-phase MRI)||Steatosis, iron*||Gadolinium, manganese|
|T2W SI (MRI)†||Iron||Edema, fibrosis, fat|
CT, Computed tomography; MRI, magnetic resonance imaging; SI, signal intensity; T1W, T1-weighted; T2W, T2-weighted; US, ultrasound.
Figure 12-17 Transverse right upper quadrant ultrasound (A) and coronal T2-weighted magnetic resonance (B) images obtained in a patient with increased liver function tests and unsuspected diffuse hepatic metastases. MRI, Magnetic resonance imaging.
|Condition||Enhancement Pattern and Associated Findings|
|Hepatic congestion (Fig. 12-18)||Heterogeneous, mosaic-like pattern of enhancement associated with enlargement of the inferior vena cava (IVC) and hepatic veins. Reflux of contrast into the IVC and hepatic veins can be present, although this finding alone is not specific for cardiac dysfunction. Doppler ultrasound can demonstrate pulsatility of the portal vein (Fig. 12-19).|
|Budd–Chiari syndrome||Decreased early peripheral enhancement and increased enhancement of the central portions of the liver, particularly the caudate lobe. Nonenhancing hepatic vein or IVC thrombus may be present.|
|Main portal vein occlusion (Fig. 12-20)||Preferential early enhancement of the liver periphery with diminished central and caudate lobe enhancement. This pattern approximates the opposite of that seen with Budd–Chiari syndrome.|
|Right or left portal vein occlusion (Fig. 12-21)||Increased enhancement of liver on side of occlusion during arterial phase with straight border along middle hepatic vein. Steatosis involving one lobe of liver may develop over time (Fig. 12-22).|
|Hereditary hemorrhagic telangiectasia (Fig. 12-23)||Multiple intrahepatic vascular malformations and arteriovenous shunts can result in a bizarre, diffusely heterogeneous early enhancement pattern. Marked enlargement of the hepatic artery is often present.|
Figure 12-20 Early-phase enhanced axial computed tomographic scan of a patient with acute main and intrahepatic portal vein thrombosis demonstrating the typical early enhancement pattern. On portal-phase images (not shown), liver enhancement was homogeneous.
Figure 12-21 Early-phase enhanced axial computed tomographic scan through the abdomen of a patient with acute thrombosis of the left portal vein. Note pseudocyst along greater curvature of stomach (arrow) caused by pancreatitis.
More commonly referred to as fatty liver, hepatic steatosis is often dismissed as a clinically insignificant radiologic finding. However, diffuse fatty infiltration of the liver can be associated with increased liver function tests, and if left unchecked, some types of steatosis can progress to steatohepatitis (manifesting as diffuse fatty infiltration, abnormal liver function tests, and hepatomegaly) and cirrhosis. For this reason, steatosis is a finding worthy of reporting. Hepatic steatosis results from a variety of hepatic insults in addition to dietary indiscretion (Box 12-1).
Sonography is the least specific cross-sectional imaging modality for the diagnosis of hepatic steatosis. The diagnosis may be suggested when the hepatic parenchyma demonstrates increased echogenicity associated with sound attenuation, resulting in poor depth of penetration and poor visualization of the hepatic veins, portal triads, and diaphragm (Fig. 12-24).
CT is more specific for the diagnosis of steatosis, which is suggested when the hepatic parenchyma is at least 10 HU lower in attenuation than the spleen on an unenhanced scan or 25 HU lower on a portal-phase contrast-enhanced CT scan. A liver attenuation of less than 40 HU on an unenhanced CT scan is also suggestive of steatosis. Steatosis can be subjectively diagnosed when hepatic vessels stand out as hyperdense against the low-attenuation background of fatty liver parenchyma (Fig. 12-25). This degree of steatosis may create the appearance of an enhanced scan.
Chemical-shift MRI is highly specific for the diagnosis of hepatic steatosis. Areas of fatty infiltration will lose signal intensity on opposed-phase gradient-echo images relative to in-phase images (Fig. 12-26). Chemical-shift imaging is much more sensitive to the presence of steatosis than fat saturation or short tau inversion recovery MRI, because the latter techniques do not suppress the signal from water protons. MR spectroscopy has been used to further quantify the degree of fatty infiltration of the liver.
Steatosis may manifest in a variety of patterns and distributions (Box 12-2) (Fig. 12-27). Regardless of the pattern or imaging modality used to image the patient with hepatic steatosis, areas of uncomplicated fatty infiltration should not cause mass effect or displace vessels. One additional feature of hepatic steatosis is its capacity to change or fluctuate significantly over a relatively short period (<1 month) given changes in patient behavior or exposure. Resolution can occur in response to correction of the underlying metabolic abnormality or removal of the responsible hepatic toxin, whereas progression can result from continued exposure.
BOX 12-2 Patterns of Hepatic Steatosis
Figure 12-27 A, Unenhanced axial computed tomographic and in-phase (B) and opposed-phase (C) magnetic resonance (MR) images through the liver of a patient with heterogeneously distributed hepatic steatosis. MR imaging was performed to ensure findings on computed tomography (CT) represented fatty infiltration rather than tumor. T1W, T1-weighted.
Diffusely infiltrating lymphoma can mimic hepatic steatosis but can be distinguished with chemical-shift MRI. Acute hepatitis from causes other than steatosis may cause a relatively low-attenuation liver on CT, but such a liver may be decreased or normal in echogenicity with sonography and often will be associated with periportal edema and gallbladder wall thickening. Table 12-5 summarizes imaging findings that suggest hepatic steatosis.
CT, Computed tomography; MRI, magnetic resonance imaging; US, ultrasound.
Iron may be deposited in the liver in two general ways. Deposition of iron directly into the hepatocytes occurs with primary or hereditary hemochromatosis, an autosomal recessive disorder resulting in abnormally increased intestinal absorption of iron. Hereditary hemochromatosis affects the liver, pancreas, heart, joints, endocrine glands, and skin. The spleen is typically unaffected by hereditary hemochromatosis. The presence of excess iron causes organ damage, resulting in cirrhosis, diabetes, heart failure, and arthralgias. These patients are also at increased risk for HCC (Fig. 12-28).
Figure 12-28 Axial portal-phase contrast-enhanced computed tomographic scan through the liver of a patient with cirrhosis and focus of hepatocellular carcinoma (HCC) secondary to primary hemochromatosis.
Iron may also be taken up by the reticuloendothelial system (RES). RES iron deposition is commonly seen in patients with hemolytic anemia or those who require multiple blood transfusions. Iron deposition related to anemia or blood transfusions typically affects the spleen and bone marrow in addition to the liver. Once the RES system becomes saturated with iron, iron can be deposited in the parenchymal cells of various organs as with primary hemochromatosis. Therefore, although the presence of iron within organs such as the pancreas is a helpful differentiating feature between hereditary hemochromatosis and other iron deposition disorders, it is not an entirely specific finding. Increased hepatic iron can also be present in patients with paroxysmal nocturnal hemoglobinuria (PNH) or hemolytic anemia (e.g., sickle cell disease, prosthetic heart valve). With these disorders, excessive iron may be detected within the renal cortex in addition to the RES of the spleen and liver. Patients with PNH are prone to vascular thrombosis; therefore, if PNH is suspected, one should be sure to look for evidence of hepatic vein or portal vein thrombosis.
Iron deposition within the liver is not easily detected with ultrasonography, although the secondary effects (cirrhosis, HCC) may be evident. Unenhanced CT of patients with increased hepatic iron may demonstrate a dense liver (>70 HU) (Fig. 12-29). However, increased liver attenuation on unenhanced CT is not specific for the presence of iron, because patients receiving amiodarone therapy, patients exposed to a prior intravenous iodine dose, and some patients with glycogen storage disease may also have increased attenuation of their liver on CT (see Fig. 12-16).
MRI is more specific for iron deposition, demonstrating signal loss on all pulse sequences because of the ferromagnetic properties of iron (Figs. 12-30 and 12-31). T2*-weighted images (gradient-echo images obtained with a relatively long TE) are highly sensitive to the presence of iron and may be used to quantify the amount of iron present. We frequently consult the in-phase and opposed-phase gradient-echo images routinely obtained as part of our liver protocol to confirm the presence of iron, because the liver will appear to lose signal on the longer TE images in such cases.
MRI can also demonstrate excess iron within the pancreas and heart in patients with hereditary hemochromatosis (see Fig. 12-30). As with the liver, these organs will demonstrate a decrease in signal intensity on most imaging sequences, most noticeable on T2*-weighted images. Once the diagnosis of hereditary hemochromatosis has been established, it is important to assess the liver for evidence of organ damage (cirrhosis) and the presence of HCC (see Fig. 12-28). Nodules or masses within the liver that demonstrate increased signal intensity on T2-weighted images or nodular enhancement after administration of intravenous gadolinium chelate should be viewed with suspicion. Table 12-6 summarizes the imaging findings of hepatic iron deposition disorders.
CT, Computed tomography; MRI, magnetic resonance imaging; US, ultrasound.
A variety of disorders may result in abnormal deposition of substances other than fat or iron within the liver. However, most deposition disorders have nonspecific manifestations on imaging studies. Patients with hepatolenticular degeneration (Wilson disease) have abnormal accumulation of copper within the liver, as well as the brain and cornea. Because of the high atomic number of copper, patients with this disorder may demonstrate a hyperdense liver with CT, although this is uncommon. With all modalities, none of the imaging findings of Wilson disease is specific. More commonly, patients with Wilson disease manifest nonspecific evidence of chronic liver disease such as steatosis and cirrhosis.
Patients with amyloidosis have deposition of protein-mucopolysaccharide complexes in various organs, including the liver. Hepatic amyloidosis may manifest as hepatomegaly or areas of low attenuation on CT. However, no specific findings exist that allow a definitive imaging diagnosis of amyloidosis.
Although glycogen deposited within the liver as a result of glycogen storage disease may appear hyperattenuating on CT images, a low-density liver resulting from associated hepatic steatosis is more common. As with other storage diseases, hepatomegaly may be present. Patients with glycogen storage disease type I (von Gierke) or type III are at risk for development of hepatic adenomas.
Cirrhosis is characterized by fibrosis and nodular regeneration of the liver. These pathologic changes of cirrhosis are nonspecific, representing the end result of a variety of hepatic insults. Although alcohol is responsible for many cases of cirrhosis in the United States, the prevalence of viral hepatitis has been increasing. In addition to leading to impaired hepatic function, cirrhosis significantly increases a patient’s risk for HCC. The typical practicing radiologist can expect to see many cases of cirrhosis and its complications during his/her career. Unfortunately, the combination of fibrosis, liver regeneration, architectural distortion, and altered hepatic hemodynamics makes the imaging assessment of the cirrhotic liver challenging.
Cirrhosis is a nonspecific diagnosis that is the end result of a variety of hepatic insults leading to hepatocellular injury. Most cases of cirrhosis apparent on imaging studies are due to alcohol abuse or viral hepatitis. Table 12-7 lists various categories of causes of cirrhosis.
|General Category||Common Examples|
|Drugs and toxins||Alcohol, methotrexate|
|Biliary abnormalities||Primary sclerosing cholangitis, primary biliary cirrhosis|
|Metabolic disorders||Hereditary hemochromatosis|
|Cardiovascular disorders||Congestive heart failure, Budd–Chiari syndrome|
Cirrhosis is usually preceded by hepatitis. This inflammatory process of the liver may be caused by toxic, metabolic, immune, infectious, or other types of insult. In the acute phase, hepatitis may be characterized clinically by some combination of fever, right upper quadrant pain, malaise, jaundice, elevated liver function tests, and hepatomegaly. Acute hepatitis uncommonly manifests sonographically as hepatomegaly with decreased echogenicity of the hepatic parenchyma and relatively increased echogenicity of the portal vein walls (sometimes referred to as the “starry-sky” appearance), although some studies show this is a nonspecific finding. Periportal edema manifests as periportal sonolucency. Thickening (edema) of the gallbladder wall may be noted. With CT, the periportal edema appears as fluid attenuation tracking along the portal vessels in the place of periportal fat (Fig. 12-32). Alcoholic and nonalcoholic steatohepatitis may be associated with low-attenuation hepatic parenchyma caused by fatty infiltration. Chronic active (viral) hepatitis is frequently associated with lymphadenopathy in the hepatoduodenal ligament (Fig. 12-33). With MRI, the periportal edema present in acute hepatitis manifests as high periportal signal intensity on T2-weighted images. The liver may also demonstrate mildly increased signal intensity on T2-weighted and decreased signal intensity on T1-weighted images, although these changes are likely to be subtle. Associated steatosis will be most evident with in- and opposed-phase MRI.
Figure 12-34 illustrates some typical morphologic changes of cirrhosis that may be present on imaging studies. Not all findings will be present in all cases of cirrhosis, and early in its course, morphologic changes of cirrhosis may be undetectable with imaging. It is also important to emphasize that not all cirrhotic livers will be reduced in volume. Some cirrhotic livers will appear normal in size or enlarged (Fig. 12-35). A quantitative approach to diagnosing cirrhosis has been advocated by some. In our experience, however, calculation of such ratios as the caudate-right lobe ratio is rarely necessary to suggest the diagnosis of cirrhosis because other morphologic findings are usually sufficient. For readers who prefer objective criteria, we include an illustration of the modified caudate-right lobe ratio (Fig. 12-36). A modified caudate-right lobe ratio of at least 0.9 has been shown to have an accuracy rate of almost 75% for the diagnosis of cirrhosis when applied to MR images and should be expected to work equally well for CT. Examination of the left lateral segment (lateral section) of the liver with a high-frequency linear US transducer may identify subtle nodularity of the liver or rounding of the contour of the left lateral segment that may aid in suggesting a diagnosis of cirrhosis (Fig. 12-37).
A cirrhotic liver consists of regenerative nodules with intervening fibrosis, regardless of cause. As a result, significant overlap of imaging findings exists between the various causes of cirrhosis. Despite this overlap, certain imaging appearances are more commonly associated with a particular causative factor. For example, enlargement of the caudate lobe and a right posterior hepatic notch are more common with alcoholic cirrhosis than with viral-induced cirrhosis, although this combination of findings is not specific. Unfortunately, a specific imaging diagnosis is not possible in the majority of cases of cirrhosis, and multiple contributing causes may be present in any given patient (e.g., alcohol and viral hepatitis). Therefore, imaging findings should always be correlated with clinical data before rendering a specific diagnosis. Table 12-8 lists imaging findings that can suggest the cause of cirrhosis.
|Causative Factors||Imaging Findings|
|Primary sclerosing cholangitis (Fig. 12-38)|
|Primary biliary cirrhosis (Fig. 12-39)|
|Hereditary hemochromatosis (see Figs. 12-28 and 12-30)|
|Congenital hepatic fibrosis (considered distinct from cirrhosis)|
When imaging findings suggest the diagnosis of cirrhosis, one should be sure to look for the host of extrahepatic findings that may be present. Stigmata of portal hypertension include splenomegaly, ascites, and varices (Fig. 12-40). Table 12-9 outlines some of the more common venous collateral pathways encountered in patients with portal hypertension. Enlarged lymph nodes are commonly seen in the hepatoduodenal ligament and elsewhere in the setting of cirrhosis. Siderotic deposits within the spleen (Gamna–Gandy bodies) may be noted on MRI (Fig. 12-41). These lesions are most conspicuous on long TE gradient-echo images and appear as small, very-low-signal intensity foci scattered throughout the spleen. Patients with advanced cirrhosis may manifest bowel wall thickening. Edematous thickening of the ascending colon is particularly characteristic, although other segments of large or small bowel may be involved. Colon thickening related to cirrhosis and portal hypertension should not be confused with inflammatory or neoplastic processes. Thickening related to cirrhosis can be seen along the dependent wall of the colon or involving the haustrations. Air-distended nondependent portions of the colon often maintain a thin wall in the setting of portal hypertension (Fig. 12-42).
Figure 12-40 Axial maximum intensity projection image of portal-phase gadolinium-enhanced magnetic resonance imaging through the upper abdomen of a patient with cirrhosis and portal hypertension resulting in large paraumbilical varices.
|Esophageal and paraesophageal||Left gastric (coronary) vein||Predominately (but not exclusively) drain* to azygous/hemiazygous system|
|Gastric||Left gastric vein and short gastric veins||Isolated gastric varices and enlarged gastroepiploic veins suggest splenic vein occlusion|
|Left renal vein shunts||Gastric (gastrorenal shunt) and splenic (splenorenal shunt) veins|
|Paraumbilical||Left portal vein||Drain cephalad to the internal thoracic veins or caudally to the superior epigastric veins (and eventually inferior epigastric and external iliac veins)|
|Extraperitoneal||Mesenteric veins||Drain to gonadal, paravertebral, and other extraperitoneal veins|
One should be aware of entities that may simulate some of the morphologic features of cirrhosis. Patients with liver metastases who have been treated with chemotherapy may occasionally develop morphologic changes in the liver that simulate cirrhosis (Fig. 12-43). This has most frequently been described with breast carcinoma, although other tumors may behave similarly. Some chemotherapy agents can also directly cause hepatotoxicity. Diffuse metastatic disease replacing normal hepatic parenchyma can simulate cirrhosis by creating a nodular architecture that may be associated with stigmata of portal hypertension. The liver contour may appear irregular in patients with pseudomyxoma peritonei, and mucin may simulate simple ascites in such patients, potentially creating confusion with cirrhosis (Fig. 12-44). An appearance of cirrhotic liver morphology may also be created after partial hepatectomy or in the setting of congenital segmental atrophy, although there should be no nodularity or fibrosis of such a liver in the absence of true cirrhosis. Areas of scarring and liver regeneration after fulminant hepatitis and nodular regenerative hyperplasia (regenerative nodules that occur in the absence of fibrosis) may likewise simulate cirrhosis. Granulomatous diseases such as sarcoidosis can mimic cirrhosis early in their course (because of innumerable nodules throughout the liver) or progress to cirrhosis over time (Fig. 12-45).
Figure 12-43 Axial enhanced computed tomographic images through the liver in a patient with breast cancer metastases before treatment (A) and several years after treatment (B). Note that the liver has developed a cirrhotic appearance after therapy (B).
The cirrhotic hepatic architecture is typically heterogeneous and hyperechoic with grayscale US. Unenhanced CT and MRI may show heterogeneity because of areas of fibrosis, fatty infiltration, or iron deposition (Fig. 12-46). Contrast-enhanced CT and MRI often reveal heterogeneous enhancement because of hemodynamic alterations, as well as differential enhancement of cirrhotic nodules and fibrosis.