Diagnosis and Management of Chronic Liver Diseases, An Issue of Medical Clinics, E-Book (eBook)

Diagnosis and Management of Chronic Liver Diseases, An Issue of Medical Clinics, E-Book

Anne M. Larson (Autor)

eBook Download: PDF | EPUB

2014 | 1. Auflage
100 Seiten
Elsevier Health Sciences (Verlag)
978-0-323-28713-5 (ISBN)

Infos

Chronic liver diseases progressively destruct liver tissue, leading to fibrosis and cirrhosis. Liver diseases can be caused by viral, autoimmune, or toxic (drugs/alcohol). Most conditions can be managed pharmacologically for indefinite periods of time. The articles in this issue will review best practices for managing and treating patients who present with these chronic problems, like hepatitis, nonalcoholic fatty liver, end stage liver disease, and drug-induced injuries.

Textauszug

Evaluation of Abnormal Liver Tests

Tinsay A. Woreta, MD and Saleh A. Alqahtani, MD∗[e-mail],     Division of Gastroenterology and Hepatology, The Johns Hopkins Hospital, 1830 East Monument Street, Suite 428, Baltimore, MD 21287, USA

∗Corresponding author.

Serum biochemical tests play an important role in the diagnosis and management of acute and chronic liver disease. Their routine use has led to the increased detection of liver enzyme abnormalities in otherwise asymptomatic patients. These tests consist of markers of hepatocellular injury, tests of liver metabolism, and tests of liver synthetic function. Liver injury can be characterized as primarily hepatocellular versus cholestatic based on the degree of elevation of aminotransferases compared with alkaline phosphatase. A comprehensive history, physical examination, and assessment of pattern of liver injury with additional directed laboratory testing establish the cause of hepatobiliary disease in most cases.

Keywords

Aminotransferases

Alkaline phosphatase

Hepatocellular injury

Cholestasis

Bilirubin metabolism

Key points

• Serum aminotransferases are sensitive markers of hepatocellular injury.

• Assessing the pattern and degree of elevation in aminotransferases can help suggest the cause of liver injury.

• Elevation in serum alkaline phosphatase occurs as a result of cholestasis, which may result from intrahepatic causes, extrahepatic obstruction, or infiltrative disorders of the liver.

• Hyperbilirubinemia may occur as the result of both hepatocellular and cholestatic injury.

• Albumin and prothrombin time are true markers of liver synthetic function.

Introduction

The use of serum biochemical tests plays an important role in the diagnosis and management of liver diseases. The routine use of such tests has led to the increased detection of liver diseases in otherwise asymptomatic patients, often providing the first clue of the presence of liver pathology. Such laboratory tests, in addition to a careful history, physical examination, and imaging tests, can help clinicians determine the cause of liver disease in most cases.

The term “liver function tests” is commonly used to refer to a combination of liver biochemical tests, including serum aminotransferases, alkaline phosphatase (AP), and bilirubin. This is a misnomer, because aminotransferases and AP are markers of hepatocyte injury and do not reflect liver synthetic function. Traditionally, liver injury has been characterized as primarily hepatocellular versus cholestatic based on the degree of elevation of aminotransferases compared with AP (Table 1). Although such a distinction can help direct initial evaluation, there is often significant overlap in the presentation of various liver diseases, which often have a mixed pattern.1 It is useful to classify liver biochemical tests into the following categories2: (1) markers of hepatocellular injury (aminotransferases and AP); (2) tests of liver metabolism (total bilirubin); (3) tests of liver synthetic function (serum albumin and prothrombin time [PT]); and (4) tests for fibrosis in the liver (hyaluronate, type IV collagen, procollagen III, laminin, FibroTest [BioPredictive, Paris, France], and FibroScan [Echosens, Paris, France]).

Table 1

Categorization of liver diseases by pattern of elevation of liver enzymes

Liver Disease Category

Aminotransferases

Alkaline Phosphatase

Hepatocellular

↑↑

↑

Cholestatic

↑

↑↑

Furthermore, when evaluating patients with abnormal liver enzyme or function tests, it is helpful to define the liver injury as acute versus chronic. Liver disease is considered chronic if the abnormalities in liver enzyme tests or function persist for more than 6 months.

Markers of hepatocellular injury

The liver contains a multitude of enzymes in high concentration, some of which are present in the serum in very low concentrations. Injury to the hepatocyte membrane leads to leakage of these enzymes into the serum, which results in increased serum concentrations within a few hours after liver injury. Serum enzymes tests can be categorized into two groups2: enzymes whose elevation reflects generalized damage to hepatocytes (aminotransferases); and enzymes whose elevation primarily reflects cholestasis (AP, γ-glutamyltransferase [GGT], 5′ nucleotidase [5′-NT]).

Aminotransferases

The aminotransferases (previously called transaminases) are located in hepatocytes and are sensitive indicators of hepatocyte injury. They are useful in detecting acute hepatocellular diseases, such as hepatitis.2 They consist of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Aminotransferases catalyze the transfer of the α-amino groups from aspartate or alanine to the α-keto group of ketoglutaric acid, forming oxaloacetic acid and pyruvic acid, respectively. The enzymatic reduction of oxaloacetic acid and pyruvic acid to malate and lactate, respectively, is coupled to the oxidation of the reduced form of nicotinamide dinucleotide to nicotinamide dinucleotide. Because only nicotinamide dinucleotide absorbs light at 340 nm, this reaction can be followed spectrophotometrically by the loss of absorptivity at 340 nm, and provides an accurate method to assay aminotransferase activity.3

AST and ALT are present in the serum at low concentrations, usually less than 30 to 40 IU/L.4 The normal range varies among clinical laboratories, based on measurements in specific populations. Several factors have been shown to influence ALT activity, such as gender and obesity.5 Men tend to have a higher serum ALT activity compared with women.

ALT is found in highest concentration in hepatocytes and in very low concentrations in any other tissues. In contrast, AST is found in many other tissues including muscle (cardiac, skeletal, and smooth muscle); kidney; and brain.2 Thus, ALT is a more specific marker for liver injury. A ratio of AST/ALT greater than five, especially if ALT is normal or slightly elevated, is suggestive of injury to extrahepatic tissues, such as skeletal muscle in the case of rhabdomyolysis or strenuous exercise.

AST is present in the cytoplasm and mitochondria, whereas ALT is only present in the cytoplasm (Fig. 1). About 80% of AST activity in the liver is derived from the mitochondrial isoenzyme, whereas most serum AST activity is derived from the cytosolic isoenzyme in healthy persons.2 Processes leading to necrosis of hepatocytes or damage to the hepatocyte cell membrane with increased permeability result in release of AST and ALT into the blood.6

Fig. 1 Location of AST and ALT in hepatocyte. ALT is only present in the cytoplasm, whereas AST is present in both the cytoplasm and mitochondria. Eighty percent of AST activity in the liver is derived from the mitochondrial isoenzyme.

Assessing the pattern and degree of elevation in liver enzymes can help elucidate the cause of liver injury and direct subsequent diagnostic testing and management. Any type of liver cell injury can cause moderate elevations in serum aminotransferase levels. Levels up to 300 IU/L are nonspecific and can be seen in any type of liver disorder.7 Massive elevations with aminotransferase levels greater than 1000 IU/L are almost exclusively seen in disorders associated with extensive hepatocellular injury, most commonly caused by (1) toxin- or drug-induced liver injury, (2) acute ischemic liver injury, or (3) acute viral hepatitis. Severe autoimmune hepatitis or Wilson disease may also cause markedly elevated aminotransferases.

ALT is present in highest concentration in periportal hepatocytes (Zone 1) and in lowest concentration in hepatocytes surrounding the central vein (Zone 3). AST, however, is present in hepatocytes at more constant levels (Fig. 2). Hepatocytes around the central vein have the lowest oxygen concentration and thus are more prone to damage in the setting of acute hepatic ischemia that can occur as the result of acute hypotension or severe cardiac disease. The ensuing centrilobular necrosis results in a rapid rise in aminotransferases, with AST value greater than ALT in the initial days of hepatic injury.

Fig. 2 Concentration of AST and ALT according to location of hepatocytes in portal triad.

After there is no further injury to hepatocytes, the rate of decline of AST and ALT depends on their rate of clearance from the circulation. AST and ALT are catabolized by the liver, primarily by cells in the reticuloendothethlial system. The plasma half-life of AST and ALT are 17 ± 5 hours and 47 ± 10 hours, respectively.2 Thus, AST declines more rapidly than ALT, and ALT may be...

Produkt-Details

• Erscheint lt. Verlag: 7.2.2014
• Sprache: englisch
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Hepatologie
• ISBN-10: 0-323-28713-1 / 0323287131
• ISBN-13: 978-0-323-28713-5 / 9780323287135