What is the laboratory workup for determining the cause of chronic liver disease (CLD)?

From the Guidelines

The initial laboratory workup for chronic liver disease should include a comprehensive panel of tests to identify the underlying cause, starting with liver function tests, viral hepatitis serologies, autoimmune markers, and metabolic cause evaluations, as supported by the most recent evidence 1. The laboratory workup should begin with liver function tests (ALT, AST, alkaline phosphatase, GGT, bilirubin, albumin, and prothrombin time) to assess liver damage and synthetic function. Viral hepatitis serologies should be ordered, including hepatitis A, B, and C antibodies and antigens (HBsAg, anti-HBc, anti-HBs, anti-HAV IgM, anti-HCV), as recommended by 1. Autoimmune markers are essential, including antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-mitochondrial antibody (AMA), and immunoglobulin levels. For metabolic causes, check iron studies (ferritin, transferrin saturation), ceruloplasmin for Wilson's disease, and alpha-1 antitrypsin levels, as suggested by 1 and 1. A complete blood count, metabolic panel, and lipid profile should be included to assess for comorbidities and complications. Imaging studies such as ultrasound, FibroScan, or other elastography methods help evaluate liver structure and fibrosis, as noted in 1. These tests are crucial for diagnosis as chronic liver disease can result from various etiologies including viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, primary biliary cholangitis, hemochromatosis, and Wilson's disease. Early identification of the cause allows for targeted treatment and potentially prevents progression to cirrhosis and liver failure, highlighting the importance of a thorough initial workup 1.

Some key points to consider in the workup include:

• Systematically investigating other causes of chronic liver disease, as recommended by 1 and 1
• Assessing for co-morbidities, including alcoholism, autoimmunity, genetic or metabolic liver diseases, and the possibility of drug-induced hepatotoxicity, as suggested by 1 and 1
• Evaluating liver disease severity prior to therapy, with non-invasive methods initially, and reserving liver biopsy for cases where there is uncertainty or potential additional aetiologies, as recommended by 1
• Considering the role of serum-based biomarker panels for the assessment of hepatic fibrosis, as discussed in 1

From the Research

Lab Workup for Chronic Liver Disease

The lab workup for chronic liver disease involves a series of tests to determine the underlying cause of the disease.

• The initial tests include serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin levels 2.
• Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels, while cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 2.
• The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 2.

Autoantibodies in Chronic Liver Disease

Autoantibodies play a significant role in the diagnosis of chronic liver disease, particularly in autoimmune hepatitis.

• The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1), and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis 3.
• Autoantibodies are commonly detected in chronic hepatitis C (HCV) but their significance remains uncertain 4.
• The presence of autoantibodies, and specifically SMA, was associated with an increase in interface hepatitis score amongst men, but no difference in other necroinflammatory measures, liver function tests, or immunoglobulins (Ig) 4.

Diagnostic Approach

The diagnostic approach for chronic liver disease involves a combination of laboratory tests, imaging studies, and liver biopsy.

• A liver biopsy may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2.
• The detection of characteristic autoantibodies is essential for the accurate diagnosis and classification of autoimmune hepatitis (AIH) 5.
• Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionize the field if properly standardized and when used in combination with classical immunofluorescence 5.