Diffuse Liver Disease

Felicia Toreno and Kathryn Kuntz

Objectives

• Define the processes that cause and affect diffuse liver disease.

• Define and describe hepatocellular diseases and their sonographic findings.

• Compare and contrast the various diffuse liver diseases and their sonographic appearances.

• Understand and describe the changes in laboratory values associated with diffuse liver diseases.

• Describe the changes in portal venous circulation that accompany diffuse liver diseases.

• Define and describe the sonographic findings associated with conditions caused by diffuse liver diseases.

CLINICAL SCENARIO

A 51-year-old man undergoes an abdominal sonogram. He has elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and increasing abdominal girth. No previous films are available for comparison. The abdominal sonogram reveals a small, dense liver (Fig. 3-1) with increased echogenicity, surrounding ascites, and an irregular liver surface. A hyperechoic mass is noted anterior to the right portal vein (Fig. 3-2). The hepatic vasculature is difficult to visualize, but no flow within the portal vein is noted (Fig. 3-3; see Color Plate 1). What are the possible diagnoses for this patient?

FIGURE 3-1 Transverse image of small, dense liver.

Diffuse Liver Disease

Diseases that affect the functional cells of the liver, the hepatocytes, are referred to as diffuse liver diseases. These diseases are treated medically rather than surgically. Diffuse disease occurs as the hepatocytes are damaged and liver function decreases. Disease processes that affect the liver diffusely include infections, fatty infiltration, and liver fibrosis. The sonographic appearance of the liver varies depending on the cause. The sonographic appearance of the liver changes as diffuse disease progresses from the acute phase to long-standing chronic illness.

Patients with diffuse liver diseases often have altered laboratory values for enzymes and proteins essential to liver function. Elevated liver enzyme levels, especially aspartate aminotransferase (AST) and alanine aminotransferase (ALT), elevate as cellular function decreases as a result of the diffuse changes to the hepatocytes. Although both ALT and AST levels are sensitive to liver diseases, AST levels may also elevate in patients with diseases of the skeletal or muscular systems.

Laboratory values for proteins such as γ-glutamyl transpeptidase (GGT) and albumin may be helpful in determining the nature of liver disease. These protein levels are likely to increase in cases of long-standing hepatic cellular damage, although acute damage to liver cells may lead to a decrease in albumin levels. Prothrombin is a blood-clotting protein manufactured in the liver. Prothrombin time (PT) is used to measure how long it takes the prothrombin in blood to merge and form a clot. PT can be impaired by diffuse liver disease.

Bilirubin is produced by the breakdown of hemoglobin; the process begins in the spleen and continues in the liver. The terms “direct” and “indirect” reflect the way the two types of bilirubin chemically react. Bilirubin that has been absorbed by the hepatocytes is referred to as direct, or conjugated, bilirubin. Levels of direct bilirubin are likely to increase in cases of biliary obstruction and liver cellular diseases. Indirect, or unconjugated, bilirubin levels may increase in cases of anemia or other diseases that lead to increased breakdown of red blood cells. When there is an excess of bilirubin circulating in the blood (hyperbilirubinemia), it may leak out into surrounding tissues causing jaundice, a yellowish tinge to the skin and sclera (the white part of the eye).

Because many laboratory values are likely to be altered by a wide variety of diseases, other laboratory values in addition to liver function values should be considered in determining a definitive diagnosis. For example, increased white blood cell (WBC) levels may indicate infection or abscess in the liver. When diffuse liver disease is suspected, it is imperative that a good clinical history and laboratory values accompany a thorough assessment with sonography. Table 3-1 provides a guide to laboratory values related to diffuse liver disease.

TABLE 3-1

Liver-Related Laboratory Values

Test	Significance of Change
Alkaline phosphatase	↑ in liver disease
Ammonia	↑ in liver disease and diabetes mellitus
Bile and bilirubin	↑ during obstruction of bile ducts
Glucose	↑ in diabetes mellitus and liver disease
Hematocrit	↓ in cirrhosis of liver
Hemoglobin	↓ in cirrhosis of liver
Iron	↑ in liver disease
Lactic dehydrogenase	↑ in liver disease
Cholesterol	↑ in chronic hepatitis
	↓ in acute hepatitis
Platelet count	↑ in cirrhosis of liver
Transaminase	↑ in liver disease
Urea	↑ in some liver diseases
	↓ during obstruction of bile ducts

Hepatocellular Disease

The liver may be enlarged especially in acute stages of hepatocellular disease. In some diseases, such as hepatitis, sonographic findings in the acute stage may be subtle and difficult to detect. The liver often becomes atrophied as pathologic changes become chronic, and the hepatocytes are replaced either by fat cells or by fibrous tissue (Fig. 3-4). Over time, replacement of the hepatocytes by fat and fibrous components leads to decreased liver function and an increase in liver enzymes. Liver cells regenerate, and this process may be accompanied by the development of regenerating liver nodules. The presence of these nodules further complicates the sonographic evaluation of the liver parenchyma and sonographic assessment of the liver for possible masses.

As damage to the hepatocytes increases, liver function decreases, which affects the liver’s ability to conjugate bilirubin and to receive blood from the portal venous system. Damage to the liver can lead to jaundice when bilirubin accumulates in the interstitial fluids as it leaks from the damaged hepatocytes. The type of bilirubin, along with patterns of elevated levels, can help determine which disease is present. For example, direct or conjugated bilirubin levels become elevated as the hepatocytes become damaged. Direct bilirubin levels also increase in cases of biliary obstruction. Damage to the hepatocytes can lead to an increase in both direct and indirect bilirubin levels.

The hepatocytes become unable to perform their normal functions because of fibrous and fatty replacement; this can eventually lead to high blood pressure in the portal vein and its tributaries, which is known as portal hypertension. The increased pressure within the portal vein causes it to become enlarged and tortuous. The spleen enlarges as it is forced to store the excess blood that the liver is unable to receive. As this process worsens, varices or collateral channels form to provide a means of bypassing the high pressure in the portal vein.

Ascites, the accumulation of free fluid within the abdominal cavity, may develop as pressure within the liver increases, and serous fluids leak from the hepatocytes into the surrounding peritoneal cavity. This condition may be due to low levels of albumin (hypoalbuminemia) or severe portal hypertension. The increased pressure within the liver causes the fluids to leak from the liver sinuses into the hepatic lymphatics. When the pressure is high enough, some fluids leak directly into the peritoneal cavity (Fig. 3-5).

FIGURE 3-5 Ascites surrounding the liver as a result of severe hepatocyte damage and liver failure.

The increasing pressure within the portal venous system may prevent blood from flowing in its normal direction, hepatopetal, which is toward the liver. Patients with suspected diffuse liver disease should undergo evaluation with color or spectral Doppler, which may detect hepatofugal, or reverse, blood flow in the portal-splenic circulatory system (Fig. 3-6; see Color Plate 2). These patients may develop vascular collateral channels to supply the liver with blood. Patients with impaired blood flow may undergo surgical placement of shunts or transjugular intrahepatic portosystemic shunt (TIPS) placement to help return portal blood to the systemic circulation.

FIGURE 3-6 **(A),** Hepatopetal (normal) flow in the main portal vein. **(B),** Hepatofugal (reversed) flow in the main portal vein.

Fatty Liver Disease

Fatty liver disease is an acquired, reversible disorder that results from the accumulation of triglycerides (fats) within the hepatocytes. Alcoholism, obesity, and diabetes are the most common causes of fatty liver disease. In most instances, liver function is not permanently impaired. Nonalcoholic steatohepatitis (NASH) is a form of fatty liver that occurs in a few patients with fatty liver. NASH may impair the ability of the liver to function and lead to complications.

The appearance of diffuse fatty infiltration of the liver varies from mild to severe. The fatty replaced liver has increased echogenicity because of increased attenuation of the sound beam, as seen in Figure 3-4. As fatty replacement becomes more severe, the liver is difficult to penetrate, and the vascular structures are poorly visualized, especially the hepatic veins (Fig. 3-7). In some instances, the entire liver is not affected, and areas of the liver may be spared from fatty infiltration. These fat-spared areas appear as localized regions of decreased echogenicity within the fatty echogenic liver (Fig. 3-8). This fat sparing is often seen anterior to the gallbladder and the right portal vein, or within the left lobe.

FIGURE 3-7 Transverse image of fatty replaced liver with increased echogenicity. Vascular structures are difficult to visualize.

Because fat increases the attenuation of the liver parenchyma, use of a lower frequency transducer may be helpful in imaging of the liver anatomy. The sonographer must keep in mind the loss of resolution that accompanies a lower frequency transducer. Harmonic imaging, if available, can be another useful tool in evaluation of the dense liver. The frame rate of the image may become degraded on certain machines when using this option.

Hepatitis

The multiple variations of hepatitis (hepatitis A to G) vary in severity and sonographic findings (Table 3-2). The most common forms of hepatitis are A, B, and C. Hepatitis A is a contagious liver disease that results from infection with the hepatitis A virus. It can range in severity from a mild illness lasting a few weeks to a severe illness lasting several months. Hepatitis A is usually spread when a person ingests fecal matter (even in microscopic amounts) from contact with objects, food, or drinks contaminated by the feces or stool of an infected person.

TABLE 3-2

Types of Hepatitis

	Hepatitis A	Hepatitis B	Hepatitis C	Hepatitis D	Hepatitis E	Hepatitis F	Hepatitis G
Facts and findings		Increased risk for development of cirrhosis and HCC	Increased risk for development of cirrhosis and HCC; leading cause of liver failure and transplantation	Occurs only in patients with hepatitis B infection	Mostly found in Asia and South America	Similar to hepatitis C; uncertain whether it is a separate virus	Similar to hepatitis C
Acute vs. chronic	Mostly acute and resolves	Acute and chronic forms; acute can become chronic	Acute and chronic forms; acute converts to chronic in most infected people	See hepatitis B; severity of infection worsens with coinfection	Mostly acute and resolves within 6 mo	Similar to hepatitis C; uncertain whether it is a separate virus	Similar to hepatitis C
Mechanisms of contraction	Infected food or drinking water	Blood and body fluid contact	Blood and body fluid contact	Blood and body fluid contact	Infected food or drinking water	Blood and body fluid contact	Blood and body fluid contact
Vaccine available	Yes	Yes	No	See hepatitis B	Being developed	No	No

Hepatitis B is usually spread when blood, semen, or another body fluid from a person infected with the hepatitis B virus enters the body of someone who is not infected. This can happen through sexual contact with an infected person or sharing needles, syringes, or other drug-injection equipment. Hepatitis B can also be passed from an infected mother to her infant at birth. Acute infection can, but does not always, lead to chronic infection. Chronic hepatitis B is a serious disease that can result in long-term health problems and death.

Hepatitis C is usually spread when blood from a person infected with the hepatitis C virus enters the body of someone who is not infected. Hepatitis C is a rapidly growing concern to health care workers. Hepatitis C can be either acute or chronic. Acute hepatitis C is a short-term illness that occurs within the first 6 months after someone is exposed to the hepatitis C virus. For most people, acute infection leads to chronic infection. Chronic hepatitis C is a serious disease that can result in long-term health problems or death and is now the leading indication for liver transplantation in the United States.

Damage to the liver from hepatitis may vary from mild to severe. Liver cells are damaged, healed by the reticuloendothelial system, and then regenerated. Patients develop flulike symptoms, including nausea, vomiting, and fatigue, and progression to liver failure can occur depending on the patients’ immune response. The liver is often slightly enlarged, and splenomegaly may be present. AST and ALT levels are usually markedly elevated.

Sonographic Findings

The liver may be enlarged and may show decreased echogenicity (Fig. 3-9), although it often appears normal in echo texture. Because of an accumulation of fluid within the hepatocytes, the walls of the gallbladder may thicken and appear prominent. Periportal cuffing, or thickening of the portal vein walls, may be noted, and the walls of the portal veins may appear more hyperechoic than normal, which is referred to as the “starry sky” appearance.