Evaluation of Liver Disease

GENERAL PRINCIPLES

• Liver disease presents as a spectrum of clinical conditions that ranges from asymptomatic disease to end-stage liver disease (ESLD).

• A comprehensive investigation combining thorough history and physical examination with diagnostic tests, liver histology, and imaging can often establish a precise diagnosis.

DIAGNOSIS

Clinical Presentation

HISTORY

History taking should focus on the following:

• History of present illnesses

• Medication history: prescription, herbal medicine, and dietary supplements

• Toxin exposures: alcohol, illicit, and recreational drugs

• Common signs and symptoms of liver disease: icterus, jaundice, ascites and edema, pruritus, encephalopathy, and gastrointestinal (GI) bleeding

• Family history of liver disease

• Comorbid conditions: obesity, diabetes, hyperlipidemia, inflammatory bowel disease (IBD), systemic hypotension, and HIV

• Risk factors for infection: IV/intranasal drug use, body piercings, tattooing, high-risk sexual behavior, travel to foreign countries, and occupation

PHYSICAL EXAMINATION

A detailed physical examination is necessary. Physical stigmata of acute and chronic liver disease may include the following:

• Jaundice and icterus

• Ascites, peripheral edema, and pleural effusions

• Hepatomegaly and splenomegaly

• Gynecomastia and testicular atrophy

• Muscle wasting (temporal and/or proximal)

• Telangiectasias and palmar erythema

• Confusion and asterixis

Diagnostic Testing

LABORATORIES

• Serumenzymes

î Elevations primarily in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) suggest hepatocellular injury; however, AST elevations may be seen with muscle or red blood cell damage, for example, rhabdomyolysis, myocardial infarction, and hemolysis.

î Alkaline phosphatase (ALP) is an enzyme found in a variety of tissues (bone, intestine, kidney, leukocytes, liver, and placenta).

• Excretory products

o Bilirubin is a degradation product of hemoglobin and nonerythroid hemoproteins. Total serum bilirubin is composed of conjugated (direct) and unconjugated (indirect) fractions. Unconjugated hyperbilirubinemia occurs as a result of excessive bilirubin production (hemolysis, hemolytic anemias, ineffective erythropoiesis, and resorption of hematomas), reduced hepatic bilirubin uptake (Gilbert syndrome and drugs such as rifampin and probenecid), or impaired bilirubin conjugation (Gilbert and Crigler-Najjar syndrome). Elevation of conjugated and unconjugated fractions occurs in Dubin-Johnson and Rotor syndromes and in conditions associated with intrahepatic (i.e., hepatocellular, canalicular, or ductular damage) and extrahepatic (i.e., mechanical obstruction) cholestasis.

î #945;-Fetoprotein (AFP) is normally produced by fetal liver cells. Its production falls to normal adult levels of lt;10 ng/mL within the first year of life. AFP is an insensitive and nonspecific biomarker for hepatocellular carcinoma (HCC), with a sensitivity and specificity of 61% and 81%, respectively, at a cutoff of 20 ng/mL and 22% and 100%, respectively, at a cutoff of 200 ng/mL.¹ Levels gt;400 ng/mL or a rapid doubling time are suggestive of HCC. Mild to moderate elevations can be seen in acute and chronic liver inflammation.

IMAGING

• Ultrasonography is a relatively inexpensive, low-risk imaging test that can identify changes in the liver surface and parenchyma, biliary tree, and gallbladder. It is frequently used as a first-line imaging for the evaluation of right-sided abdominal pain, meal-related epigastric discomfort, and abnormal liver function tests (LFTs).

• CT scan with IV contrast is useful to evaluate the liver parenchyma. This test can define space­occupying lesions (e.g., abscess or tumor) and calculate liver volume. Triple-phase CT or quadruple­phase CT is indicated for liver mass evaluation. A delayed phase is useful when HCC is suspected.

• MRI with contrast offers information similar to CT, with the additional advantage of better characterization of liver lesions, fatty infiltration, and iron deposition. It is the modality of choice in patients with an iodinated contrast allergy. However, MRI cannot be used in patients with renal failure (glomerular filtration rate [GFR] lt;30 mL/min/1.73 m²) because of the low risk of gadolinium- associated nephrogenic systemic fibrosis. Of all the cross-sectional imaging techniques, MRI provides the highest tissue contrast. This, in conjunction with various contrast agents, allows for definitive noninvasive characterization of liver lesions.

• Magnetic resonance cholangiopancreatography (MRCP) is a specialized study that provides an alternative noninvasive diagnostic modality to visualize the intrahepatic and extrahepatic bile ducts. MRCP does not require contrast administration into the ductal system.

• Elastography is a method of measuring liver stiffness as a surrogate for fibrosis. Noninvasive tools for fibrosis staging are increasingly used in the evaluation of chronic liver disease, especially in chronic hepatitis C and nonalcoholic steatohepatitis (NASH).

DIAGNOSTIC PROCEDURES

• Percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP) involve injection of contrast into the biliary tree. These invasive procedures are most effectively used to investigate abnormalities detected on ultrasonography, CT, or MRI/MRCP. PTC and ERCP allow for diagnostic and therapeutic maneuvers including biopsy, brushings, stenting, and drain placement.

• Transjugular assessment of portal pressure is an invasive procedure measuring the hepatic venous pressure gradient (HVPG): the difference between the wedged (representing the portal venous pressure) and the free hepatic venous pressures. The normal HVPG pressure is lt;6 mm Hg. HVPG gt;6 mm Hg is consistent with portal hypertension. Complications of portal hypertension, such as ascites and esophageal varices, usually occur with HVPG gt;12 mm Hg.²

• Liver biopsy is an invasive procedure that is typically performed percutaneously. Suspicious liver lesions are usually biopsied with ultrasound or CT guidance, although imaging is not absolutely required. If coagulopathy, thrombocytopenia, and/or ascites are of concern, a transjugular liver biopsy can be performed instead. Finally, surgical laparoscopy is also an alternative way to obtain liver tissue. Bleeding, pain, infection, injury to nearby organs, and (rarely) death are potential complications.

• Additional noninvasive tests to assess fibrosis and cirrhosis are available. These include serum direct and indirect biomarkers of fibrosis, proprietary and nonproprietary serum biomarkers, and other noninvasive imaging tools. They are considered as alternatives to biopsy, although precise guidelines for their use are not defined.