Viral Hepatitis and Liver Disease Website Course

Evaluating Liver Test Abnormalities

Understanding the Pathophysiology of Liver Disease

for Health Care Providers

Acute Mild to Moderate Aminotransferase Elevation (ALT/AST < 15 times upper limit of normal)

Abnormal liver test > Hepatocellular pattern > Acute > Mild to moderate ALT/AST elevation


Unlike the limited differential diagnosis for marked elevations of AST and ALT, the potential etiologies of mild to moderate acute aminotransferase elevations is extensive, and include all causes of marked AST/ALT elevation. If the elevation is mild (less than twice the upper limit of normal), liver tests should be repeated prior to embarking on an extensive workup. If the abnormality persists, the initial evaluation is the same as the workup for marked ALT/AST elevations and the following etiologies may be considered:.

  • Acute viral hepatitis
  • Drug-induced liver injury (DILI)
  • Toxin-induced liver injury
  • Ischemic hepatitis
  • Autoimmune hepatitis
  • Acute Budd-Chiari syndrome
  • Acute bile duct obstruction

In addition, the following etiologies may be considered if suggested by history and physical examination:

  • Acute alcoholic hepatitis
  • Wilson disease

Though more commonly associated with marked elevation of ALT/AST, fulminant hepatic failure may occur with any type of acute hepatocellular injury. In addition to determining the possible etiology, it is essential to determine the presence of hepatic dysfunction, as evidenced by encephalopathy (confusion, asterixis) and coagulopathy (prolonged INR).


Initial questions aimed at determining the possible etiology of acute hepatocellular injury are:

To investigate acute viral hepatitis:

History of blood transfusion, intravenous drug use, unsafe sexual practices, and ingestion of raw shellfish within the last six months.

To investigate drug-induced liver injury:

Detailed medication history including over-the-counter medication, herbal remedies and health food supplements, particularly regarding recently prescribed medications

To investigate toxin-induced liver injury:

Detailed diet/environmental/occupational history, as well as illicit drug use (particularly cocaine)

To investigate ischemic liver injury

Recent (within a day or so) symptoms or conditions associated with a low perfusion state such as pre-syncopal or syncopal episodes, hypotension, arrhythmias, low cardiac ejection fraction.

To investigate autoimmune hepatitis

Family or personal history of autoimmune disorders such as thyroiditis, hyper or hypothyroidism, lupus, rheumatoid arthritis, vitiligo

To investigate acute Budd-Chiari syndrome:

Presence of abdominal distension (ascites) with or without peripheral edema and right upper quadrant pain.

To investigate acute bile duct obstruction:

Compatible clinical picture with epigastric or right upper quadrant pain, a history of biliary surgery and/or gallstones.

Physical examination

In general, there are no specific findings for acute hepatocellular injury. Jaundice may be present. Viral causes may be accompanied by common findings associated with viral syndrome (fever, rash, lymphadenopathy).

It is however essential to check for signs of hepatic encephalopathy (confusion, asterixis). Patients with confusion and/or asterixis should be urgently referred to a liver specialist or a transplant center.

Laboratory Investigation

Initial investigation should be directed at evaluating the presence of hepatic dysfunction and investigating the etiology of the acute hepatitis.

Liver biopsy is generally not indicated in acute hepatocellular injury as it will show hepatic necrosis but will not be specific for its etiology.

To evaluate hepatic function:

  • Prothrombin time (PT) and INR
    Patients with abnormal prothrombin time or INR should be urgently referred to a liver specialist or a transplant center.

To investigate acute viral hepatitis:

  • Hepatitis A antibody of the IgM type (IgM anti-HAV)
  • Hepatitis B core antibody of the IgM type (IgM anti-HBc)
  • Hepatitis B surface antigen (HBsAg)
  • Hepatitis C antibody (anti-HCV)
  • Consider HBV-DNA titer* and HCV-RNA titer*
  • Serologies and/or PCR for CMV, EBV and HSV (if the tests above are non-revealing)

*In the very early course of acute hepatitis B or C or in the immunocompromised patient, viral serologies may be negative. PCR testing should be obtained if suspicion for recent infection is high (for example, history of IV drug use or unsafe sexual contact within the last six months) or in the immunocompromised patient.

To investigate autoimmune hepatitis:

  • Antinuclear antibodies (ANA)
  • Anti-smooth muscle antibody (ASMA)
  • Serum protein electrophoresis (SPEP)

To investigate toxic damage:

  • Toxicology screen

To investigate acute alcoholic hepatitis:

  • AST/ALT ratio usually greater than 2

To investigate Wilson's disease (WD):

  • Ceruloplasmin levels
  • Alkaline phosphatase (frequently low in WD)
  • Alkaline phosphatase/bilirubin ratio lower than 2