Assessment of Liver Dysfunction
As you have learned, the liver is responsible for many essential functions. Because of these activities, it is exposed to a wide variety of insults and is therefore one of the most frequently injured organs in the body. The impairment of these vital functions by hepatic disease leads to clinical manifestations that are often similar, regardless of the specific cause. This section first explores the numerous causes of liver disease and then describes the signs and symptoms of hepatic dysfunction.
Liver biopsy is a safe and important diagnostic tool for liver disease. As mentioned previously, measurement of hepatic copper and iron stores in biopsy specimens is the most sensitive method for diagnosing metabolic disorders such as Wilson’s disease and hemochromatosis. Often, laboratory studies do not clarify the specific cause of disease, but microscopic examination of a biopsy specimen can reveal disease-specific patterns. In addition, laboratory blood tests may inaccurately stage the disease or estimate the extent of damage, but histological examination of hepatic architecture may provide this important information. Finally, sequential liver biopsies can be useful in assessing the response to medical therapies, such as alpha interferon treatment for viral hepatitis B or C infection.
1. Procedure. Liver biopsies are generally performed as outpatient procedures with a 3- to 6-hour post-biopsy observation period unless patients are considered at high risk (high-risk patients are observed overnight). Prior to biopsy, the physician will check the PT (clotting time) to minimize the risk of excessive bleeding. The presence of tense (severe) ascites usually contraindicates a biopsy.
Patients are placed on their back, and the needle entry site is determined by percussing (tapping with one’s fingers) the liver span; the entry site is usually located between the 8th and 9th ribs on an imaginary line extending down from the armpit. The skin area around the proposed needle entry site is then sterilized, and a local anesthetic, such as lidocaine, is injected into the skin. With the patient holding his/her breath, a 1.4 mm (large diameter) needle is quickly thrust into and out of the liver, obtaining a core of liver tissue by aspiration.
The following are potential complications of liver biopsy, in relative order of frequency.
Pain occurs at the biopsy site or in the right shoulder (“referred pain” from pressure on the liver capsule) in about 1 out of 4 to 5 patients. This is usually temporary and not severe.
There is always mild bleeding at the biopsy site and within the liver, forming a hematoma (collection of blood) that usually resolves by itself. However, in fewer than 1% of patients, more severe bleeding may occur within the liver itself, into the biliary tree (hemobilia), or into the abdominal cavity. This complication requires hospitalization and observation, and may necessitate blood transfusions.
Puncture of other organs, such as the lung, gallbladder, gut, and kidney is rare (one in about 10,000). However, this is a serious complication that may require surgery.
Infection at the site is extremely rare, since the skin is cleaned and the procedure is sterile.
Allergic reaction to the anesthetic is also extremely rare.
2. Histologic Assessment. A very thin “slice” of the liver biopsy specimen is examined under a microscope. Histologic examination is useful to identify specific disease patterns, guide patient management, and follow the response to therapy.
a. Terminology. When examining liver tissue, the pathologist looks for various changes in cellular appearance that are signs of ongoing inflammation, necrosis, and/or fibrosis.
· piecemeal necrosis: cell death (as a result of inflammation) that extends beyond the limiting plate, giving a characteristic irregular appearance of the periportal zone
· bridging necrosis: bands of dead hepatocytes that stretch between adjacent portal triads, between adjacent central veins, and between portal tracts and central veins
· multilobular necrosis: two or more adjacent lobules with panlobular (throughout the lobule) necrosis
· acidophilic bodies: necrotic (dead) hepatocytes that appear as small, dense, dark pink cells when the specimen is stained with eosin (also called eosinophilic bodies)
· ballooning degeneration: hepatocytes that appear enlarged or swollen due to accumulation of excess water inside the cell
· cirrhosis: loss of normal hepatic lobular architecture, with fibrous bands separating and surrounding nodules of regenerating cells
b. Histologic classification. Classically, chronic hepatitis has been divided into two categories, based on histologic findings: chronic persistent hepatitis (CPH) and chronic active hepatitis (CAH). Characteristically, specimens identified as CPH show inflammation confined to the portal triad (does not penetrate the limiting plate). Specimens identified as CAH show inflammation that penetrates the limiting plate, extending to the surrounding individual hepatocytes and yielding piecemeal necrosis. Under this schema, CAH eventually reaches a point where lobular architecture is destroyed, and bands of necrosis (bridging necrosis) are replaced by scar tissue (bridging fibrosis), resulting in the characteristic features of cirrhosis.
As previously noted, the designations of CPH and CAH were originally based on specimens from patients with idiopathic autoimmune chronic active hepatitis (IACAH). It is now recognized that the histologic classifications of CPH and CAH do not accurately predict the prognosis for chronic viral hepatitis. Disease progression in patients with chronic viral hepatitis probably depends more on the presence and replicative status of the virus than on the initial histologic appearance of the biopsy. Therefore, while CPH and CAH are useful terms when describing the histologic appearance of a biopsy, they do not accurately predict disease progression in chronic viral hepatitis, nor should they be used to determine which patients should be treated.
c. Knodell scoring. Given this confusion in the language used to describe liver biopsy specimens, it is easy to understand why a numerical scoring system was developed to objectively classify hepatitis based on histologic examination. Knodell’s scoring system, also called the Hepatitis Activity Index, classifies specimens based on scores in four categories of histologic features:
I. Periportal and/or bridging necrosis
II. Intralobular degeneration and focal necrosis
III. Portal inflammation
The higher the score, the more severe the liver tissue damage. It is important to realize, however, that these scores are still not correlated with clinical prognosis.
A thorough history and physical examination can help identify and diagnose liver disease. In particular, a patient’s history may indicate risk factors (such as needlestick or sexual contact with an infected person) or symptoms (fatigue, jaundice) that the physician can investigate to confirm suspected liver disease. A careful physical examination may reveal signs of hepatic dysfunction (liver enlargement, spider angiomas) in an asymptomatic patient or may further direct the physician in making a diagnosis of liver disease.
Laboratory tests of liver function (such as albumin levels or prothrombin time) can confirm hepatic dysfunction, and certain tests can suggest possible causes of the disorder (such as relative levels of aminotransferases, alkaline phosphatase, and bilirubin). Blood tests for specific antibodies or antigens can confirm infection or autoimmune disease. Certain metabolic disorders can also be indicated by specific blood tests.
Liver biopsy is an important tool for the physician. In many cases, specific histologic patterns can verify the cause of the disease; they can also be used to stage certain types of liver disease or to assess the response to therapy. A number of terms describe the histologic appearance of chronic hepatitis specimens, and they have classically been grouped into two patterns: chronic persistent hepatitis (CPH) and chronic active hepatitis (CAH). In the past, these patterns have been used to predict disease progression and prognosis. However, histologic appearance does not correlate with clinical prognosis in chronic viral hepatitis, since progression in this case is more closely related to viral activity.
This module discussed the basic structure and function of the liver and the manifestations of those diseases afflicting the liver. Anatomically, the liver is able to act as a “purification filter” of systemic and gut-derived blood. It is a resilient organ, able to regenerate after partial removal or subtotal damage, but this capacity can be exceeded, resulting in irreversible scarring. Essential functions of the liver include: synthesis of glucose, proteins, cholesterol, and bile; storage of glycogen, vitamins, and minerals; and metabolism and clearance of hormones, drugs, toxins, and ammonia.
Liver disease of any kind can adversely affect these functions. Hepatitis is a broad term that describes liver inflammation from a variety of causes; its course can be acute, chronic, or fulminant. Hepatitis viruses, bacteria, fungi, and protozoa can all infect the liver. The liver is also very susceptible to toxic insult from drugs and environmental or industrial chemicals. Autoimmune, metabolic, and systemic diseases can involve the liver as well.
Such diseases damage the liver, decreasing its ability to filter blood (resulting in portal hypertension and ascites) and altering its functional capacity (leading to severe jaundice, bleeding, and hepatic encephalopathy). Cirrhosis, defined pathologically as irreversible scarring of the liver, is a common endpoint for many hepatic diseases, such as chronic viral hepatitis and alcoholism. In most instances, cirrhosis increases the risk of hepatocellular carcinoma, a deadly cancer usually diagnosed late in its course.
An astute history helps assess liver dysfunction, by detecting familial diseases, risks for viral infection, or exposure to toxins. Physical examination and the pattern of liver test results can confirm liver disease and may suggest the cause and/or mechanism involved. In addition, liver biopsy can be an asset in deriving a diagnosis, staging a disease, and monitoring therapy.
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