What is the approach to evaluate for non-alcoholic liver disease (NALD)?

From the Guidelines

The evaluation of non-alcoholic liver disease (NALD) should begin with a comprehensive clinical assessment, including detailed history, physical examination, and laboratory testing, followed by a stepwise approach using non-invasive tests such as the fibrosis-4 index (FIB-4) and imaging techniques like transient elastography, as recommended by the EASL-EASD-EASO clinical practice guidelines 1. The initial laboratory workup should include liver function tests (ALT, AST, alkaline phosphatase, GGT, bilirubin), complete blood count, lipid profile, fasting glucose, and HbA1c to assess for metabolic risk factors. Some key points to consider in the evaluation of NALD include:

• Imaging studies are essential, with ultrasound being the first-line modality due to its accessibility and ability to detect steatosis when fat content exceeds 20-30% 1.
• More advanced imaging options include FibroScan (transient elastography) to assess liver stiffness as a surrogate for fibrosis, and MRI-based techniques like MRI-PDFF for precise fat quantification 1.
• Liver biopsy remains the gold standard for definitive diagnosis and staging, though it's typically reserved for cases with diagnostic uncertainty, suspected advanced disease, or before initiating specific pharmacotherapy 1.
• Risk stratification tools like the NAFLD Fibrosis Score, FIB-4 index, and Enhanced Liver Fibrosis (ELF) test can help identify patients at higher risk of advanced fibrosis who may benefit from specialist referral 1.
• The evaluation should also include screening for common comorbidities such as diabetes, cardiovascular disease, and obstructive sleep apnea, as these conditions frequently coexist with NALD and impact management decisions 1. It is also important to note that the term non-alcoholic fatty liver disease (NAFLD) is being replaced by metabolic dysfunction-associated steatotic liver disease (MASLD) to identify steatotic liver disease in the presence of at least one cardiometabolic risk factor associated with insulin resistance 1.

From the Research

Evaluation Approach for Non-Alcoholic Liver Disease (NALD)

To evaluate for non-alcoholic liver disease (NALD), the following steps can be taken:

• Identify patients with risk factors for NALD, such as diabetes and/or metabolic syndrome, and consider screening for its presence with biomarkers, such as the fatty liver index (FLI) 2.
• Exclude other causes of chronic liver disease and steatosis, especially heavy alcohol consumption and viral hepatitis, particularly HCV genotype 3 2.
• Evaluate family and personal history of components of the metabolic syndrome and assess liver tests, fasting blood glucose, triglycerides, and HDL levels 2.
• Consider the use of imaging techniques, such as ultrasound (US) and MRI-based techniques, to confirm the diagnosis of NALD and quantify steatosis, although these are not in routine use outside clinical trials 2.
• Use non-invasive tests, such as the NAFLD fibrosis score, fibrosis-4, and the enhanced liver fibrosis test, to diagnose the presence of stage 3 or 4 fibrosis, although these are not reliable for the diagnosis of non-alcoholic steatohepatitis (NASH) 2.

Diagnostic Modalities

The diagnostic modalities for NALD include:

• Biochemical biomarkers, such as liver function tests and tests for metabolic syndrome 3.
• Imaging modalities, such as US, computed tomography, and magnetic resonance imaging, to assess hepatic fat, measure liver and spleen size, and exclude other diseases 4.
• Multi-omics approaches, which have been developed and evaluated for the diagnosis of NALD 3.
• Liver biopsy, which remains the gold standard for the diagnosis of NASH and staging of NALD, although it is invasive and not practical for routine use 5, 3, 4.

Non-Invasive Diagnostic Tools

Non-invasive diagnostic tools, such as:

• Innovative hepatic imaging techniques, including ultrasound techniques, have been developed to attempt to overcome the need for biopsy, both in diagnosis and staging of NAFLD, and in possible use in the follow-up of the disease 5.
• Biochemical markers and algorithms that combine anthropometric and laboratory parameters have been developed to diagnose and stage NALD 5.
• Elastography, which has received the most attention and is being used in routine clinical practice, although it is not sufficiently accurate to replace liver biopsy for clinical trials as yet or are cost-effective for use in routine clinical settings 2.