From the Guidelines
When working up the etiology of cirrhosis, you should order a comprehensive panel of laboratory tests to identify the underlying cause, starting with liver function tests including ALT, AST, alkaline phosphatase, bilirubin, albumin, and prothrombin time/INR, as recommended by the most recent guidelines 1. The initial assessment of hepatic function involves liver function testing including measurement of serum levels of bilirubin, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, measurement of prothrombin time expressed as international normalized ratio, albumin, and platelet count (surrogate for portal hypertension) 1. Other recommended tests include:
- Complete blood count to evaluate for cytopenias related to portal hypertension
- Blood urea nitrogen and creatinine to assess kidney function, with creatinine being an established prognostic marker in patients with liver disease 1
- Viral hepatitis serologies, including hepatitis A, B, and C, to rule out viral causes
- Autoimmune markers, such as antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver kidney microsomal antibody (anti-LKM), and immunoglobulin levels (IgG, IgM, IgA), to evaluate for autoimmune hepatitis or primary biliary cholangitis
- Iron studies, including serum iron, ferritin, and transferrin saturation, and genetic testing for HFE mutations, if hemochromatosis is suspected
- Ceruloplasmin and 24-hour urinary copper, if Wilson's disease is a consideration, particularly in younger patients
- Alpha-1 antitrypsin levels to rule out alpha-1 antitrypsin deficiency
- Lipid panel and fasting glucose or HbA1c to assess for metabolic syndrome associated with non-alcoholic fatty liver disease These tests provide a comprehensive evaluation that can identify the most common causes of cirrhosis and guide appropriate management strategies. Further assessment of hepatic functional reserve may be performed with tools such as US and MRI elastography, non-focal liver biopsy, and transjugular liver biopsy with pressure measurements, as needed 1. The Child-Pugh classification can be used to assess hepatic functional reserve, incorporating laboratory measurements and clinical assessments of encephalopathy and ascites 1. It is essential to prioritize the most recent and highest-quality study, which in this case is the 2021 guideline from the Journal of the National Comprehensive Cancer Network 1.
From the Research
Initial Workup for Cirrhosis
The initial workup for cirrhosis includes:
- Viral hepatitis serologies
- Ferritin
- Transferrin saturation
- Abdominal ultrasonography
- Complete blood count
- Liver function tests
- Prothrombin time/international normalized ratio, if not already ordered 2
Additional Testing
Additional testing is based on demographics and risk factors, and may include:
- Aspartate transaminase to platelet ratio index score
- Fibrosis 4 score
- FibroTest/FibroSure
- Nonalcoholic fatty liver fibrosis score
- Standard ultrasonography
- Transient elastography 2, 3, 4
Laboratory Tests
Commonly available laboratory tests for assessing liver function include:
- Serum bilirubin
- Liver enzymes (alanine [ALT] and aspartate aminotransferase [AST], serum alkaline phosphatase [ALP], gamma glutamyl transpeptidase [GGT])
- Serum albumin
- Prothrombin time 3
- Quantitative liver function tests like indocyanine clearance tests [ICG-K] and methacetin breath test [MBT] may also be used, but have limitations and availability 3
Imaging-Based Assessment
Imaging-based assessment of liver function may include:
- Transient elastography
- MRI-based 99mTc-coupled asialoglycoprotein mebrofenin scan
- Hepatic venous pressure gradient (invasive and not available in all centers) 3
Scoring Systems
Scoring systems, such as:
- Fibrosis score of 4 [FIB-4]
- Lok index
- Model for end-stage liver disease (MELD)
- Child-Turcotte-Pugh score, may be used to assess liver function in clinical practice 3