Viral Hepatitis and Liver Disease Website Course

Evaluating Liver Test Abnormalities

Understanding the Pathophysiology of Liver Disease

for Health Care Providers

Chronic Hepatocellular Injury

Abnormal liver test > Hepatocellular pattern > Chronic > Chronic Hepatocellular injury differential


The differential diagnosis of chronic hepatocellular injury is extensive. It is neither economical nor clinically helpful to perform extensive testing. Initial evaluation of chronic hepatocellular injury should be directed at the more common causes. Further investigation can proceed according to the results of the initial evaluation.

Any chronic liver injury may progress to cirrhosis. Therefore, in addition to determining a possible cause of chronic hepatocellular injury, it is essential to assess whether cirrhosis is present.


Initial questions should be directed at determining risk factors for common etiologies of chronic hepatocellular injury:

To investigate chronic viral hepatitis:

History of blood transfusion, intravenous drug use, unsafe sexual practice

To investigate drug-induced liver injury:

Detailed medication history including over-the-counter medication, herbal remedies and health food supplements.

To investigate alcohol-induced liver injury:

Detailed alcohol ingestion history

To investigate non-alcoholic fatty liver disease:

  • Weight history (correlate with abnormalities in liver tests)
  • History of metabolic syndrome (hyperlipidemia, diabetes, hypertension)

To investigate hereditary liver diseases:

Family history of liver disease

In addition to history directed at determining a possible etiology of chronic hepatocellular injury (below), history should include questions directed at determining the presence of cirrhosis (ascites, gastrointestinal hemorrhage, encephalopathy).

Physical examination

In general, there are no specific findings for chronic hepatocellular injury. Stigmata of chronic liver disease may be present, such as palmar erythema, vascular spiders and muscle hypotrophy, particularly if cirrhosis is present. Some diseases may have specific findings that are detailed in the disease-specific corresponding sections.

Laboratory Investigation

Initial investigation should be directed at determining common etiologies of chronic hepatocellular injury.

Liver biopsy is rarely used in clinical practice today and non-invasive methodologies are now recommended including:

  • Fib 4, APRI score
  • Proprietary tests i.e. Fibrosure, Fibrotest
  • Elastography for liver stiffness/fibrosis
  • Fibroscan
  • Sheer-wave elastography
  • MR based elastography

To investigate chronic viral hepatitis:

  • Hepatitis B surface antigen (HBsAg)
  • Hepatitis B viral load
  • Hepatitis C PCR Quant or Qual (viral load)

To investigate non-alcoholic liver disease:

  • Fasting lipid profile (cholesterol, HDL, LDL, triglycerides)

To investigate autoimmune hepatitis:

  • Antinuclear antibodies (ANA)
  • Anti-smooth muscle antibodies (ASMA)

To investigate hereditary diseases:

  • Iron, iron saturation (for hemochromatosis)
  • Ceruloplasmin levels (for Wilson's disease)
  • Alpha-1 antitripsin levels and/or SPEP


In addition to laboratory investigations directed at determining a possible etiology of chronic hepatocellular injury, platelets, albumin and prothrombin time/INR should be obtained. The presence of the followings is suggestive of cirrhosis:

  • Thrombocytopenia, hypoalbuminemia, or prolonged prothrombin time/INR