Intelligent test platform improves chronic liver disease diagnosis, management in primary care

The intelligent liver function test (iLFT) platform has made strides in a primary care system in Scotland, facilitating detection of chronic liver disease while reducing unnecessary specialist referrals, as reported in a study.

Five years since the platform’s rollout in NHS Tayside with a population of around 400,000 people, a total of 26,459 iLFTs were performed, of which 31.7 percent required no further testing and 68.3 percent cascaded to an aetiology screen, reported Dr Damien Leith from Ninewells Hospital in Dundee, Scotland. [EASL 2024, abstract OS-007-YI]

Cascaded iLFT generated 20,895 outcomes, which were grouped into categories of descriptive and aetiologic. Of the descriptive outcomes, isolated abnormal alanine transaminase (ALT) without fibrosis was the most common, accounting for 19 percent of all iLFTs performed. Most of these cases were likely to be metabolic dysfunction-associated steatotic liver disease (MASLD), Leith noted.

In terms of iLFT with aetiology-specific outcomes, alcohol-related liver disease with or without fibrosis accounted for 12 percent of iLFTs and MASLD with or without fibrosis accounted for further 9 percent, Leith said. Additionally, iLFT identified Gilbert’s syndrome (3.7 percent), MASLD with increased alcohol intake (MetALD; 2.5 percent), hereditary hemochromatosis (1.8 percent), possible autoimmune liver diseases (0.9 percent), and hepatitis C and B infections (0.37 percent).

Biochemical evidence of significant fibrosis was seen in 20.0 percent of all iLFTs requested. Moreover, 69.9 percent of the cascaded outcomes recommended that patients could be safely managed in primary care.

According to Leith, iLFT was introduced to address the challenge of identifying chronic liver disease in primary care, given the insensitivity of traditional LFTs. Even trickier is the fact that many abnormal LFT results do not represent chronic liver disease, and some that do might be missed without proper follow-up, he pointed out.

Piloted in 2015–2016, the iLFT platform was rolled out fully in August 2018.

The iLFT platform

A novel, algorithm-based testing pathway, iLFT was developed using the minimum information—a combination of patient details and lab test results—required to determine the likely diagnosis and most suitable management pathway. This dataset was then synthesized into an algorithm that was coded into the laboratory information management system, Leith said.

Primary care clinicians request an iLFT in the same way they would request standard LFTs, he continued. However, during an iLFT request, clinicians are prompted to provide additional information, namely the patient’s BMI, maximum weekly alcohol intake in the previous 6 months (> or ≤14 units), and the presence or absence of features of metabolic syndrome.

Blood samples are obtained and processed via the iLFT pathway. If the results are found to be within the iLFT reference range (ALT ≤30 U/L, ALP* ≤130 U/L, bilirubin ≤21 µmol/L, GGT** ≤73 U/L), then no further tests are performed, and clinicians get the report. Otherwise, the lab system will automatically cascade additional tests and generate one of 33 potential, predefined iLFT outcomes. The iLFT report, according to Leith, gives a clear recommendation on the follow-up investigation and whether referral is indicated based on the probable diagnosis and/or the likely presence and severity of liver fibrosis.

During the pandemic, reflexive Enhanced Liver Fibrosis (ELF) testing for individuals with indeterminate FIB-4 or NAFLD Fibrosis Scores was further introduced to the iLFT pathway in response to increasing secondary care hepatology clinic waiting times. This, in turn, reduced referrals to secondary care by 34 percent.

Development of the iLFT is ongoing, with a focus on further refining the algorithm and supporting national rollout, Leith said.

Leith and colleagues believe that iLFT is a well-established example of what ‘intelligent’ laboratory medicine can do in terms of not only providing accurate and reliable test results but also guiding the interpretation and diagnosis of those results.

“Such intelligent platforms should be trialled in and expanded to appropriate new disease areas as a matter of priority—to aid the wider range of healthcare professionals now ordering and interpreting lab results, to increase healthcare efficiency by reducing unnecessary and duplicate testing and, ideally, to provide results directly to patients, alongside patient-appropriate interpretations,” the researchers stated. [Diagnostics 2024;14:960]

“Finally, intelligent lab systems such as iLFT will be integral to providing the comprehensive, patient-centred precision medicine platforms of the future, essential for an increasingly complex, ageing, and multimorbid global population,” they added.

*alkaline phosphatase

**gamma glutamyltransferase