Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography

David J Harman, Stephen D Ryder, Martin W James, Matthew Jelpke, Dominic S Ottey, Emilie A Wilkes, Timothy R Card, Guruprasad P Aithal, Indra Neil Guha, David J Harman, Stephen D Ryder, Martin W James, Matthew Jelpke, Dominic S Ottey, Emilie A Wilkes, Timothy R Card, Guruprasad P Aithal, Indra Neil Guha

Abstract

Objectives: To assess the feasibility of a novel diagnostic algorithm targeting patients with risk factors for chronic liver disease in a community setting.

Design: Prospective cross-sectional study.

Setting: Two primary care practices (adult patient population 10,479) in Nottingham, UK.

Participants: Adult patients (aged 18 years or over) fulfilling one or more selected risk factors for developing chronic liver disease: (1) hazardous alcohol use, (2) type 2 diabetes or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme with negative serology.

Interventions: A serial biomarker algorithm, using a simple blood-based marker (aspartate aminotransferase:ALT ratio for hazardous alcohol users, BARD score for other risk groups) and subsequently liver stiffness measurement using transient elastography (TE).

Main outcome measures: Diagnosis of clinically significant liver disease (defined as liver stiffness ≥8 kPa); definitive diagnosis of liver cirrhosis.

Results: We identified 920 patients with the defined risk factors of whom 504 patients agreed to undergo investigation. A normal blood biomarker was found in 62 patients (12.3%) who required no further investigation. Subsequently, 378 patients agreed to undergo TE, of whom 98 (26.8% of valid scans) had elevated liver stiffness. Importantly, 71/98 (72.4%) patients with elevated liver stiffness had normal liver enzymes and would be missed by traditional investigation algorithms. We identified 11 new patients with definite cirrhosis, representing a 140% increase in the number of diagnosed cases in this population.

Conclusions: A non-invasive liver investigation algorithm based in a community setting is feasible to implement. Targeting risk factors using a non-invasive biomarker approach identified a substantial number of patients with previously undetected cirrhosis.

Trial registration number: The diagnostic algorithm utilised for this study can be found on clinicaltrials.gov (NCT02037867), and is part of a continuing longitudinal cohort study.

Keywords: GENERAL MEDICINE (see Internal Medicine).

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
Diagnostic algorithm and patient flow chart through non-invasive biomarker pathway. ALT, alanine aminotransferase, AST, aspartate aminotransferase; GP, general practitioner; TE, transient elastography.
Figure 2
Figure 2
Distribution of chronic liver disease risk factors for all patients (n=378) undergoing transient elastography examination (ALT, alanine aminotransferase).
Figure 3
Figure 3
Transient elastography results of patients with successful liver stiffness acquisition (n=366) (ALT, alanine aminotransferase).

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