Diffuse benign liver disease.

After completing this article, the reader should be able to:

* Explain the liver's functions.

* Describe the differences and connections between cirrhosis, fatty liver and vascular abnormalities of the liver.

* List and describe laboratory tests used to evaluate liver function.

* Discuss the advantages and disadvantages of various imaging techniques with regard to evaluating liver disease.

* Describe how and why liver biopsies are performed.

* Explain treatment options for benign liver disease, including lifestyle changes and transplantation.

Liver diseases afflict millions of people throughout the world, and more than 43 000 Americans die from them yearly, (1,2) with an average loss of 16 to 23 years of life. (2,3) The occurrence of these diseases appears to be rising due to increasing contact with chemicals and environmental pollutants and increasing use of medications. (1) The spectrum of liver diseases ranges from mild, reversible illness to more advanced stages with rising possibilities for complications and morbidity. Many of these diseases are astonishingly common, while others are noted only rarely. Chronic liver disease is a slow process that results in progressive destruction of the organ. Research and accurate diagnosis are crucial in the battle for progress in treating and preventing these diseases. It is estimated that current knowledge about liver diseases, including cirrhosis, fatty liver and resulting vascular pathologies, could help reduce their occurrence by half. (1)

Anatomy and Physiology Of the Liver

The liver, a part of the digestive system, is a powerful organ that has been associated with bravery, courage and strength since ancient times. Augurs once used animal organs to foretell the future, and a deep-red, healthy liver was considered a sign that all would be well. (4) Today the liver still is viewed as a measure of vitality because of its unique and essential role in sustaining life. It is the largest of all the internal organs, weighing slightly more than 3 lbs in the average adult, or about 2% of total body weight. In infants the liver accounts for about 5.5% of total body weight. (5) It usually lies in the upper right side of the abdomen and is situated mainly behind the lower ribs, immediately below the diaphragm and above the right kidney, stomach, pancreas and intestines. (6) The top of the liver is roughly at the level of the nipples.

Traditionally, the liver has been divided into 4 lobes: left, right, caudate and quadrate (see Figure 1). The right lobe is 6 times larger than the left, and these 2 lobes are separated by the falciform ligament. The Glisson capsule, a network of various connective tissues, covers the entire organ and extends into the parenchyma, along with blood vessels and the bile ducts. (6)

[FIGURE 1 OMITTED]

Viewing this gland through a microscope reveals that it is made up of 50 000 to 100 000 functional units called lobules. These lobules are minute, cylindrical structures of hepatic tissue positioned around a central vein. (7) They are located within the parenchyma and constitute the basic functional units of the liver. Each lobule consists of cellular plates that radiate from a vein. Small bile canaliculi are located between the cells in these plates and empty into terminal bile ducts (see Figure 2). These ducts combine with 2 larger ones (the hepatic duct and the cystic duct), which then join to form the common bile duct upon leaving the liver. (6)

[FIGURE 2 OMITTED]

Blood entering the liver circulates around it via smaller vessels until it reaches the surface of the liver. It then becomes exposed to the liver cells, known as hepatocytes, whose task is to treat and filter the blood. (7) The liver also has a large lymphatic supply; consequently, it is often the site for metastatic cancer. (8)

Some of the liver's many functions include:

* Producing bile, blood proteins, clotting factors and various enzymes.

* Storing energy (glycogen) to fuel muscles.

* Controlling the production and excretion of cholesterol.

* Detoxifying drugs and poisons, including alcohol, from the body.

* Regulating several hormones.

* Maintaining normal blood glucose concentration. (9)

Because of its many functions as the body's "warehouse," the liver is essential to life. It is linked to almost all of the body's biochemical processes. And although it is an unusually resilient organ, illness or disease involving the liver can cause widespread disruption of bodily functions. Many diseases and disorders can cause the liver to function improperly or stop functioning altogether.

Cirrhosis

Definition and Causes

One of the most important and prevalent liver diseases is cirrhosis, which is a term applied to various degenerative, chronic liver diseases in which normal liver cells are damaged and then replaced by scar tissue, resulting in loss of normal liver tissue. (5) Scarring alters the liver's function and structure, compromising its ability to manufacture proteins and process hormones, nutrients, medications and poisons. (10) Blood and lymph flow become increasingly inefficient, leading to the eventual failure of the liver.

Cirrhosis-related deaths occur each year in more than 26 000 Americans, making cirrhosis the seventh leading cause of death in the United States.(1,2,3) Cirrhosis occurs twice as often in men as in women and is the fourth leading disease-related cause of death overall in people aged 25 to 44 years. (1,9,10) The following types and percentages of cirrhosis have been noted clinically: (1,4-6)

* Portal, nutritional or alcoholic cirrhosis occurs in 30% to 50% of cirrhotic patients, about 90% of whom have a history of alcoholism.

* Biliary cirrhosis affects 15% to 20% of patients with cirrhosis and results from bile duct diseases that suppress blood flow.

* Postnecrotic (posthepatic) cirrhosis affects 10% to 30% of patients with cirrhosis and originates from various types of hepatitis.

* Pigment cirrhosis affects 5% to 10% of patients with cirrhosis and stems from disorders such as hemochromatosis.

* Cardiac cirrhosis is a rare type of liver damage caused by right-sided heart failure.

* Idiopathic cirrhosis affects approximately 10% of patients with cirrhosis and has no known cause.

Long-term alcoholism is the main cause of cirrhosis, and alcoholic cirrhosis is the tenth leading cause of death in the United States. (10) Men and women respond differently to alcohol consumption. Individual tolerances vary, but those who drink more frequently and in greater volumes have a higher risk of developing cirrhosis. Although most men can safely consume 2 to 5 drinks a day, 1 or 2 drinks can cause liver damage in women. Even as little as 1 drink per day can lead to liver scarring. (10) A drink is defined as approximately I can (12 oz) of beer or ale, 1 glass (6 oz) of wine or a single shot (1.5 oz) of distilled 90-proof spirits. The type of alcohol consumed is not a factor; all alcohol is toxic. (4)

Even though cirrhosis is most often associated with alcohol abuse, it can result from many causes, including severe liver injury and almost any chronic liver disease. (8) (See Table 1.)

Signs and Symptoms

Because it mirrors many other diseases and conditions, cirrhosis often is not suspected until it has reached an advanced stage. Often, people with cirrhosis eventually experience loss of appetite, nausea, vomiting, weight loss and a lack of interest in sex. Any of these signs or symptoms can be combined with a dull abdominal ache, constipation or diarrhea. (1,4,5) Stools can become black or bloody, urine can be dark brown or bright yellow and the patient can develop continuously elevated blood pressure (ie, portal hypertension). (4)

Symptoms of cirrhosis often are the result of high blood pressure in the portal vein system. Blood flow from the intestinal area to the liver becomes compromised because of cirrhosis, which leads to increased pressure. (11) Hypertension combines with hormonal, metabolic and renal abnormalities to cause fluid accumulation in the abdomen (ascites) and in peripheral tissues (edema). (8) The fluids seep into the abdominal cavity and accumulate, pressing against the diaphragm and interfering with breathing. This ascites fluid, which comes from both the liver and the intestines, exceeds the amount that the body's lymphatic system can remove. Further complications can result if the fluid becomes infected with bacteria normally found in the gut. (1,4)

Spontaneous intra-abdominal infections and internal hemorrhage tend to occur in correlation with the other symptoms. (12) In advanced cases, the liver can appear either enlarged and firm or shrunken. Additional signs and symptoms include an enlarged spleen, "spider veins" on the easily bruised skin of the upper body, loss of hair from the chest and pubic area, diminished testes and tingling sensations in the hands and feet. (1,11,13) Reduced kidney function and, ultimately, kidney failure also have been documented. (8) However, many patients remain asymptomatic and only are found to have cirrhosis upon physical examination, laboratory tests or other testing for an unrelated illness.

Although cirrhosis is perhaps the most noteworthy cause of liver damage related to chronic alcoholism, fatty liver is also a leading cause of alcohol-related liver damage.

Fatty Liver

Definition and Causes