What is the diagnostic workup for Alcoholic Liver Disease (ALD)?

From the Guidelines

The diagnostic workup for alcoholic liver disease (ALD) should begin with a thorough history and physical examination, focusing on alcohol consumption patterns and signs of liver dysfunction, as recommended by the most recent guidelines 1. The diagnostic approach should include laboratory tests such as liver function tests (elevated AST typically higher than ALT with a ratio >2:1), complete blood count, gamma-glutamyl transferase, and markers of synthetic function like albumin, prothrombin time, and INR.

• Additional tests should include hepatitis viral serologies to exclude viral causes, autoimmune markers, iron studies, and ceruloplasmin to rule out other liver diseases.
• Imaging studies are important, with ultrasound being the first-line option to assess liver size, texture, and exclude other pathologies.
• FibroScan (transient elastography) can non-invasively assess liver stiffness and fibrosis.
• In selected cases, liver biopsy remains the gold standard for definitive diagnosis, showing characteristic features like steatosis, hepatocyte ballooning, Mallory-Denk bodies, and neutrophilic infiltration, as described in the guidelines 1. The diagnosis of ALD is usually suspected upon documentation of regular alcohol consumption of >20 g/d in females and >30 g/d in males together with the presence of clinical and/or biological abnormalities suggestive of liver injury 1. Patients should also be assessed for complications of advanced liver disease including ascites, varices, and hepatic encephalopathy. Nutritional status evaluation is important as malnutrition is common. This comprehensive approach allows for accurate diagnosis, staging of disease severity, and guides appropriate management strategies including alcohol cessation, which remains the cornerstone of treatment. The use of non-invasive models, such as the ALD/non-alcoholic fatty liver disease (NAFLD) index, can aid in the differential diagnosis of ALD with NAFLD 1. The Maddrey Discriminant Function and the MELD score are recommended for identifying severe forms of alcoholic hepatitis, with a Maddrey score ≥32 indicating severe disease 1.

From the Research

Diagnostic Workup for Alcoholic Liver Disease

The diagnostic workup for alcoholic liver disease (ALD) involves a combination of clinical evaluation, laboratory tests, and imaging studies.

• The diagnosis of ALD can generally be made based on history, clinical and laboratory findings 2.
• Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase, as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio 2.
• In unclear cases, the diagnosis can be supported by imaging and liver biopsy, with histological features of ALD including hepatic steatosis, inflammation, and Mallory-Denk bodies 2.

Laboratory Tests and Biomarkers

• There is no single laboratory test that confirms the diagnosis of ALD, but a combination of tests and markers can increase diagnostic accuracy 3.
• Routine liver function tests have poor diagnostic accuracy and poor sensitivities for diagnosing significant and advanced alcohol-related liver fibrosis 4.
• Novel biomarkers, scoring systems, and imaging modalities are improving the ability to diagnose and manage ALD, but their adoption is limited due to cost and uncertainty in their performance characteristics 5.

Imaging and Histologic Studies

• Imaging studies, such as transient elastography, can help diagnose significant and advanced alcohol-related liver fibrosis 4.
• Liver biopsy can provide histological features of ALD, including hepatic steatosis, inflammation, and Mallory-Denk bodies, which can ultimately define the diagnosis 2.
• The ELF test, a non-invasive test, can also help diagnose significant and advanced alcohol-related liver fibrosis 4.

Clinical Evaluation and Risk Factors

• The diagnosis of ALD remains founded in an accurate patient history and detailed physical examination 5.
• Risk factors for ALD progression include the amount and duration of alcohol consumption, female sex, obesity, and specific genetic polymorphisms 6.
• Symptomatic alcoholic hepatitis is characterized by rapid onset of jaundice and a 30% risk of mortality 1 year after diagnosis, and severe alcoholic hepatitis is associated with the development of acute-on-chronic liver failure and multiorgan failure 6.