The BALLETS Study: Birmingham and Lambeth Liver Evaluation Testing Strategies
Study Overview
The BALLETS study was a landmark prospective cohort study that evaluated the optimal testing strategies for abnormal liver blood tests in primary care patients without pre-existing or self-evident liver disease. 1
The study enrolled 1,290 adults from primary care settings in Birmingham and Lambeth, UK, who were fully characterized and followed for 2 years. 1 This research fundamentally shaped current guidelines on which liver blood tests should be ordered and how to investigate abnormal results. 1
Key Findings on Liver Test Panel Composition
Optimal Initial Testing Strategy
- ALT and ALP identified the vast majority of adults with liver disease, making them the cornerstone tests. 1
- Adding GGT to the panel increased sensitivity marginally but at the cost of decreased specificity and higher false-positive rates, raising the proportion of patients with abnormal results from approximately 15% to 30%. 1
- Routine addition of AST to the initial panel did not improve detection of specific liver diseases. 1
Important Caveats
The BALLETS analysis did not include adults with NAFLD or alcohol-related liver disease (ARLD), which account for 90% of liver mortality. 1 In these populations, GGT and AST would likely improve sensitivity for detection. 1 This limitation explains why current guidelines still recommend including GGT in the initial panel despite its lower specificity. 1
Prevalence of Specific Liver Diseases
Low Yield of Specific Diagnoses
- Less than 5% of people with abnormal liver blood tests had a specific disease affecting the liver. 1
- Only 1.3% had a specific liver disease requiring immediate treatment: 13 patients with viral hepatitis and 4 with genetic hemochromatosis. 1
- Country of origin (not ethnic group) was the strongest predictor of viral hepatitis. 1
High Prevalence of Fatty Liver
- Nearly 40% of adults had fatty liver on ultrasound. 1
- Abnormal ALT concentration was the strongest laboratory predictor of fatty liver on imaging. 1
- Obesity was more strongly associated with fatty liver than alcohol excess, but one-quarter of adults with fatty liver were neither overweight nor excessive alcohol drinkers. 1
Impact on Clinical Guidelines
Streamlined Testing Approach
The BALLETS data supported a strategy of using a streamlined panel with high sensitivity without generating excessive false positives, which would lead to greater patient anxiety, over-investigation, and increased costs. 1
Current guidelines now recommend initial investigation include: bilirubin, albumin, ALT, ALP, and GGT, together with a full blood count if not performed within the previous 12 months. 1
AST:ALT Ratio for Fibrosis Assessment
While AST is not recommended in the initial panel, the BALLETS study informed the recommendation for subsequent AST testing to calculate the AST:ALT ratio. 1 An AST:ALT ratio >1 indicates advanced fibrosis/cirrhosis, and this ratio remains useful even when both values are within normal reference intervals. 1
Reflex Testing Strategy
The study suggested that reflex testing (automatically performing AST on the same sample when ALT or GGT is abnormal) would be more cost-effective than routine dual testing, though definitive cost-effectiveness data were still awaited at the time of guideline publication. 1
Viral Hepatitis Testing Strategy
A subsequent cost-minimization analysis of the BALLETS cohort examined strategies for detecting chronic viral hepatitis in patients with abnormal liver tests. 2
Testing all patients for viral hepatitis without repeating liver function tests was more efficient than the strategy of repeating LFTs before viral testing. 2 The most efficient approach was testing patients born in countries where viral hepatitis is prevalent, which provided high efficiency with minimal loss of sensitivity. 2