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An intelligent liver function test platform (iLFT) successfully integrated into one Scottish primary care system reduced unnecessary specialist referrals over a 5-year period, and improved triage for those with fibrosis, according to a descriptive analysis.

Since August 2018, the iLFT pathway has generated 20,895 etiologic and descriptive outcomes of liver disease and abnormalities in the U.K.'s National Health Services (NHS) Tayside primary care system, reported Damien Leith, MBBS, of Ninewells Hospital and Medical School at the University of Dundee in Scotland, at the European Association for the Study of the Liver annual conference in Milan.

The iLFT cascading algorithm indicated that approximately 70% of people with an initial abnormal liver function test (LFT) could be safely managed in primary care. Also, the introduction of the Enhanced Liver Fibrosis (ELF) test into the algorithm reduced fibrosis referrals by 34%, but at the same time improved triage for those at risk of decompensated liver disease.

"Chronic liver disease prevalence is increasing globally with an associated increase in global mortality, such that it's now the second leading cause of working age death in Europe," Leith told attendees. "So there's really a challenge in identifying the people with chronic liver disease and ensuring those people are appropriately referred on to secondary care."

The problem is further compounded by the fact that many abnormal LFTs don't actually represent chronic liver disease, Leith pointed out, but those that do often don't trigger a referral.

How iLFT Works

The iLFT pathway was first piloted in 2015-2016, and then introduced in NHS Tayside in Scotland in 2018, with a population of approximately 400,000. The platform was using a combined dataset of patient information, clinical details, and lab test results synthesized into an algorithm. The algorithm was then coded into the laboratory information management system, Leith explained.

"The primary care clinician requests an iLFT in the same way they would normally request an LFT, but they provide a little bit of extra information," said Leith.

That extra information includes a patient's BMI, maximum weekly alcohol intake in the previous 6 months (>14 units or ≤14 units) and presence or absence of features of metabolic syndrome or type 2 diabetes. The initial LFT panel is then performed and includes laboratory tests for albumin, alanine aminotransferase (ALT), bilirubin, alkaline phosphatase, and gamma-glutamyl transferase. If results from these tests are within the platform's reference range, no further cascade of additional diagnostic tests is triggered.

If one or more tests are outside the reference range, additional tests are automatically cascaded as abnormalities are detected. An etiologic outcome and diagnosis are generated in the presence of abnormal lab tests. In the absence of positive etiological laboratory data, a descriptive outcome of the abnormal liver function is returned. The likelihood of fibrosis -- based on the Fibrosis-4 (FIB-4) Index, the non-alcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS), and ELF tests -- is also reported. The report also includes further recommended testing and management, and a referral recommendation.

Outcomes

From August 2018 to July 2023, a total of 26,459 unique iLFTs were performed at NHS Tayside. Of these, 31.7% required no further testing. A full cascade was triggered in 60.9% and a partial cascade for further testing occurred in 7.4%.

Among 20,895 generated outcomes, about 48% were etiological outcomes and 52% were descriptive outcomes. The most common diagnosis was isolated elevated ALT with no fibrosis (19%). "On local audit, we found the majority of those were probably metabolic dysfunction-associated steatotic liver disease [MASLD] cases where the GP [general practitioner] hadn't identified metabolic syndrome when they were requesting the test," Leith commented.

Alcohol-related liver disease with or without fibrosis accounted for 12% of the outcomes and MASLD with or without fibrosis accounted for about 9%. Other etiological diagnoses identified at smaller percentages included Gilbert's syndrome, viral hepatitis, , hereditary hemochromatosis, and autoimmune liver diseases.

Of iLFTs performed, 20% found biochemical evidence of fibrosis (i.e., FIB-4 >3.25, NFS >0.675, ELF >9.8). Leith detailed how use of iLFT was able to reduce referrals related to indeterminate fibrosis scores by 34% by incorporating ELF testing into the algorithm as a second-line test. An ELF score of >9.8 was used to trigger a referral and an ELF score of >13 triggered an urgent referral.

"Do you have a feel for how [iLFT] is received and acted on in primary care?" queried conference attendee Richard Parker, MBChB, PhD, of the Leeds Teaching Hospitals NHS Trust in England, during a Q&A session.

Leith answered that because iLFT is now well established at his center, "I think the GPs do act on it. I think that the ones where the fibrosis tests are positive, the GPs will always refer them through," but that there is a small risk that the iLFT pathway may fail to identify some patients who should be referred.

Use of the iLFT pathway changed over time. After launching iLFT in 2018, requests peaked right before the COVID-19 pandemic and then fell sharply during the pandemic. However, use of iLFT has now stabilized to 860 requests per month, with 48% of tests cascading over the last 12 months, Leith said.

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