Table 16–3.Liver biochemical tests: normal values and changes in hepatocellular and obstructive jaundice. ||Download (.pdf) Table 16–3. Liver biochemical tests: normal values and changes in hepatocellular and obstructive jaundice.
|Tests ||Normal Values ||Hepatocellular Jaundice ||Obstructive Jaundice |
0.1–0.3 mg/dL (1.71–5.13 mcmol/L)
0.2–0.7 mg/dL (3.42–11.97 mcmol/L)
|Urine bilirubin ||None ||Increased ||Increased |
|Serum albumin ||3.5–5.5 g/dL (35–55 g/L) ||Decreased ||Generally unchanged |
|Alkaline phosphatase ||30–115 units/L (0.6–2.3 mkat/L) ||Mildly increased (+) ||Markedly increased (++++) |
|Prothrombin time ||INR of 1.0–1.4. After vitamin K, 10% decrease in 24 hours ||Prolonged if damage is severe; does not respond to parenteral vitamin K ||Prolonged if obstruction is marked; generally responds to parenteral vitamin K |
|ALT, AST ||ALT, ≤ 30 units/L (0.6 mkat/L) (men), ≤ 19 units/L (0.38 mkat/L) (women); AST, 5–40 units/L (0.1–0.8 mkat/L) ||Increased, as in viral hepatitis ||Minimally increased |
Table 16–4.Causes of serum aminotransferase elevations.1 ||Download (.pdf) Table 16–4. Causes of serum aminotransferase elevations.1
|Mild Elevations (< 5 × normal) ||Severe Elevations (> 15 × normal) |
Chronic hepatitis B, C, and D
Acute viral hepatitis (A-E, EBV, CMV)
Alpha-1-antitrypsin (alpha-1-antiprotease) deficiency
Alcohol-related liver injury (AST:ALT > 2:1)
Acute viral hepatitis (A–E, herpes)
Acute bile duct obstruction
Acute Budd-Chiari syndrome
Hepatic artery ligation
Elevated serum alanine and aspartate aminotransferase (ALT and AST) levels reflect hepatocellular injury. Normal reference values for ALT and AST are lower than generally reported when persons with risk factors for fatty liver are excluded. The upper limit of normal for ALT is 29–33 units/L in men and 19–25 units/L in women. Levels decrease with age and correlate with body mass index and mortality from liver disease and inversely with caffeine consumption and physical activity. There is controversy about whether a persistently elevated ALT level is associated with a low or high vitamin D level and, in the general population, with mortality from coronary artery disease, cancer, diabetes mellitus, and all causes; elevated AST levels have been reported to be associated with shorter life expectancy. Truncal fat and early-onset paternal obesity are risk factors for increased ALT levels. Levels are mildly elevated in more than 25% of persons with untreated celiac disease and in type 1 diabetic patients with so-called glycogenic hepatopathy and often rise transiently in healthy persons who begin taking 4 g of acetaminophen per day or experience rapid weight gain on a fast-food diet. Levels may rise strikingly but transiently in patients with acute biliary obstruction from choledocholithiasis. Nonalcoholic fatty liver disease is by far the most common cause of persistent mildly to moderately elevated aminotransferase levels. Elevated ALT and AST levels, often greater than 1000 units/L (20 mckat/L), are the hallmark of hepatocellular necrosis or inflammation. Elevated alkaline phosphatase levels are seen in cholestasis or infiltrative liver disease (such as tumor, granulomatous disease, or amyloidosis). Isolated alkaline phosphatase elevations of hepatic rather than bone, intestinal, or placental origin are confirmed by concomitant elevation of gamma-glutamyl transpeptidase or 5′-nucleotidase levels. Serum gamma-glutamyl transpeptidase levels appear to correlate with the risk of mortality and disability in the general population. The differential diagnosis of any liver test elevation always includes toxicity caused by drugs, herbal and dietary supplements, and toxins.
Demonstration of dilated bile ducts by ultrasonography (eFigure 16–7) or CT indicates biliary obstruction (90–95% sensitivity). Ultrasonography, CT (eFigure 16–8), and MRI may also demonstrate hepatomegaly, intrahepatic tumors, and portal hypertension. Use of color Doppler ultrasonography or contrast agents that produce microbubbles increases the sensitivity of transcutaneous ultrasonography for detecting small neoplasms. MRI is the most accurate technique for identifying isolated liver lesions such as hemangiomas, focal nodular hyperplasia, or focal fatty infiltration and for detecting hepatic iron overload. The most sensitive techniques for detection of individual small hepatic metastases in patients eligible for resection are multiphasic helical or multislice CT; MRI with use of gadolinium or ferumoxides as contrast agents; CT arterial portography, in which imaging follows intravenous contrast infusion via a catheter placed in the superior mesenteric artery; and intraoperative ultrasonography. Dynamic gadolinium-enhanced MRI and MRI following administration of superparamagnetic iron oxide show promise in visualizing hepatic fibrosis. Because of its much lower cost, ultrasonography is preferable to CT (∼six times more expensive) or MRI (∼seven times more expensive) as a screening test. Positron emission tomography (PET) can be used to detect small pancreatic tumors and metastases. Ultrasonography can detect gallstones with a sensitivity of 95%.
Choledocholithiasis. Sagittal scan demonstrates the dilated bile duct (D) and an echogenic structure (arrowhead) in the distal duct with acoustic shadowing. (Reproduced, with permission, from Krebs CA, Giyanani VL, Eisenberg RL. Ultrasound Atlas of Disease Processes. Originally published by Appleton & Lange. Copyright © 1993 by The McGraw-Hill Companies, Inc.)
Dilated bile ducts. A: CT shows a dilated distal bile duct (arrowhead). L, liver; k, kidney. B: CT demonstrates dilated intrahepatic bile ducts (arrow) and a liver mass (M). (Reproduced, with permission, from Barth KH. Percutaneous biliary drainage for high obstruction. Radiol Clin North Am. 1990;28:1226.)
Magnetic resonance cholangiopancreatography (MRCP) is a sensitive, noninvasive method of detecting bile duct stones, strictures, and dilatation; however, it is less reliable than endoscopic retrograde cholangiopancreatography (ERCP; eFigure 16–9) for distinguishing malignant from benign strictures. ERCP requires a skilled endoscopist and may be used to demonstrate pancreatic or ampullary causes of jaundice, carry out sphincterotomy and stone extraction, insert a stent through an obstructing lesion, or facilitate direct cholangiopancreatoscopy. Complications of ERCP include pancreatitis (5% or less) and, less commonly, cholangitis, bleeding, or duodenal perforation after sphincterotomy. Risk factors for post-ERCP pancreatitis include female sex, pregnancy, prior post-ERCP pancreatitis, suspected sphincter of Oddi dysfunction, and a difficult or failed cannulation. Percutaneous transhepatic cholangiography (PTC) is an alternative approach to evaluating the anatomy of the biliary tract (eFigure 16–10). Serious complications of PTC occur in 3% and include fever, bacteremia, bile peritonitis, and intraperitoneal hemorrhage. Endoscopic ultrasonography (EUS) is the most sensitive test for detecting small lesions of the ampulla or pancreatic head and for detecting portal vein invasion by pancreatic cancer. It is also accurate for detecting or excluding bile duct stones.
Endoscopic retrograde cholangiopancreatography (ERCP). A: Line drawing of bile duct stone. G.B., gallbladder; BD, bile duct. B: ERCP film shows a stone as an intraluminal filling defect (arrow) in the distal portion of the dilated bile duct (D). (Reproduced, with permission, from Krebs CA, Giyanani VL, Eisenberg RL. Ultrasound Atlas of Disease Processes. Originally published by Appleton & Lange. Copyright © 1993 by The McGraw-Hill Companies, Inc.)
Percutaneous transhepatic cholangiography. (Reproduced, with permission, from American Gastroenterological Association, Bethesda, Maryland.)
Percutaneous liver biopsy is considered the definitive study for determining the cause and histologic severity of hepatocellular dysfunction or infiltrative liver disease, although it is subject to sampling error and subjective interpretation. It is generally performed under ultrasound or, in some patients with suspected metastatic disease or a hepatic mass, CT guidance. A transjugular route can be used in patients with coagulopathy or ascites, and in selected cases endoscopic ultrasound-guided liver biopsy has proved advantageous. The risk of bleeding after a percutaneous liver biopsy is approximately 0.6% and is increased in persons with a platelet count of 60,000/mcL (60 × 109/mcL) or less. The risk of death is up to 0.1%. Panels of blood tests (eg, FibroSure, nonalcoholic fatty liver disease [NAFLD] fibrosis score, enhanced liver fibrosis score) and elastography (vibration-controlled transient, shear wave, acoustic radiation force impulse, or magnetic resonance elastography) to measure liver stiffness are used for estimating the stage of liver fibrosis and degree of portal hypertension without the need for liver biopsy; they are most accurate for excluding advanced fibrosis.