Jaundice

Essentials of Diagnosis

• Results from accumulation of bilirubin in body tissues; the cause may be hepatic or nonhepatic

• Hyperbilirubinemia may be due to abnormalities in the formation, transport, metabolism, or excretion of bilirubin

• Persistent mild elevations of the aminotransferase levels are common in clinical practice and caused most often by nonalcoholic fatty liver disease

• Evaluation of obstructive jaundice begins with ultrasonography and is usually followed by cholangiography

General Considerations

• May be caused by predominantly unconjugated or conjugated bilirubin in the serum (Table 16–1)

• In the absence of liver disease, hemolysis rarely elevates the serum bilirubin level to more than 7 mg/dL (119.7 mcmol/L)

• "Cholestasis" denotes retention of bile in the liver, and "cholestatic jaundice" implies conjugated hyperbilirubinemia from impaired bile flow

• Mediators of pruritus due to cholestasis have been identified to be lysophosphatidic acid (LPA) and autotaxin, the enzyme that forms LPA

Symptoms and Signs

• See Table 16–2

UNCONJUGATED HYPERBILIRUBINEMIA

• Normal stool and urine color—no bilirubin in the urine

• Mild jaundice

• Splenomegaly occurs in hemolytic disorders except in sickle cell disease

CONJUGATED HYPERBILIRUBINEMIA

• Hereditary cholestatic syndromes or intrahepatic cholestasis

  • May be asymptomatic

  • Cholestasis is often accompanied by pruritus, light-colored stools, and jaundice

• Hepatocellular disease

  • Malaise, anorexia, low-grade fever, and right upper quadrant discomfort are frequent

  • Dark urine, jaundice and, in women, amenorrhea occur

  • An enlarged, tender liver; spider telangiectasias; palmar erythema; ascites; gynecomastia; sparse body hair; fetor hepaticus; and asterixis may be present, depending on the cause, severity, and chronicity of liver dysfunction

Biliary obstruction

• Right upper quadrant pain, weight loss (suggesting carcinoma), jaundice, pruritus, dark urine, and light-colored stools

• Symptoms and signs may be intermittent if caused by stone, carcinoma of the ampulla, or cholangiocarcinoma

• Pain may be absent early in pancreatic cancer

• Stool occult blood suggests cancer of the ampulla

• A palpable gallbladder (Courvoisier sign) is characteristic, but neither specific nor sensitive for pancreatic head tumor

• Fever and chills are more common in benign obstruction with associated cholangitis

Differential Diagnosis

• Obstructive hepatobiliary disease

• Hepatitis, eg, viral, alcoholic, toxic

• Hemochromatosis

• Cirrhosis

Laboratory Tests

• Table 16–3

• Elevated serum alanine and aspartate aminotransferase (ALT, AST) levels, often > 1000 units/L (> 20 mckat/L), accompanying jaundice are the hallmark of hepatocellular necrosis or inflammation

• Persistent mildly to moderately elevated aminotransferase levels without jaundice are common in clinical practice and caused most commonly by nonalcoholic fatty liver disease

• ALT and AST levels

  • The upper limit of normal for ALT in men is 29–33 units/L and in women is 19–25 units/L

  • Decrease with age

  • Correlate with body mass index and mortality from liver disease

  • Correlate inversely with caffeine consumption and physical activity

• An isolated elevation of serum ALT may be seen in celiac disease

• Elevated alkaline phosphatase levels are seen in cholestasis or infiltrative liver disease (such as tumor, granulomatous disease, or amyloidosis) (gamma-glutamyl transpeptidase [GGT] also elevated)

• Alkaline phosphatase elevations of hepatic rather than bone, intestinal, or placental origin are confirmed by concomitant elevation of GGT or 5'-nucleotidase levels

Imaging Studies

• Demonstration of dilated bile ducts by ultrasonography or CT indicates biliary obstruction (90–95% sensitivity)

• Ultrasonography, CT, and MRI may also demonstrate hepatomegaly, intrahepatic tumors, and portal hypertension

• The most sensitive techniques for detecting individual small hepatic lesions in patients eligible for resection of metastases

  • 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

  • Intraoperative ultrasonography

• Color Doppler ultrasound or contrast agents that produce microbubbles increase the sensitivity of transcutaneous ultrasound 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

  • Detecting hepatic iron overload

• Positron emission tomography (PET) can be used to detect small pancreatic tumors and metastases

• Because of its much lower cost, ultrasonography is preferable to CT or MRI as a screening test

• Ultrasonography can detect gallstones with a sensitivity of 95%

• Magnetic resonance cholangiopancreatography (MRCP) is a sensitive, noninvasive method for detecting bile duct stones, strictures, and dilatation

• Endoscopic ultrasonography

  • 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 in detecting or excluding bile duct stones

Diagnostic Procedures

• Percutaneous liver biopsy

  • Definitive diagnostic method for determining the etiology and severity of the liver disease

  • Generally performed under ultrasonography

  • In some patients with suspected metastatic disease or a hepatic mass, is done under CT guidance

  • A transjugular route can be used in patients with coagulopathy or ascites

  • In selected cases, endoscopic ultrasound-guided liver biopsy has proved advantageous

• Panels of blood tests (eg, FibroSure, NAFLD fibrosis score, Enhanced liver fibrosis score) and ultrasound (vibration-controlled transient, shear wave, or acoustic radiation force impulse) elastography 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

Therapeutic Procedures

• Treatment of the causative etiology

• Uncomplicated obstructive jaundice responds to parenteral vitamin K

• Use endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC)

  • To demonstrate pancreatic or ampullary causes of jaundice

  • To perform sphincterotomy and stone extraction

  • To insert a stent through an obstructing lesion

Complications

• Complications of ERCP include pancreatitis in ≤ 5% of cases and, less commonly, cholangitis, bleeding, or duodenal perforation after sphincterotomy

• Serious complications of PTC occur in 3% of cases and include fever, bacteremia, bile peritonitis, and intraperitoneal hemorrhage

When to Refer

• Patients with unexplained jaundice should be referred for diagnostic procedures

When to Admit

• Patients with liver failure should be hospitalized