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Research Article
The Enhanced Liver Fibrosis test maintains its diagnostic and prognostic performance in alcohol-related liver disease: A cohort study.
William Rosenberg
Institute for Liver and Digestive Health, University College London
Corresponding Author
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Background
Alcohol is the main cause of chronic liver disease. The Enhanced Liver Fibrosis (ELF) test is a serological biomarker for fibrosis staging in chronic liver disease, however its utility in alcohol-related liver disease warrants further validation. We assessed the diagnostic and prognostic performance of ELF in alcohol-related liver disease.
Methods
Observational cohort study assessing paired ELF and histology from 786 tertiary care patients with alcohol-related liver disease due to alcohol (n = 81) and non-alcohol aetiologies (n = 705). Prognostic data were available for 64 alcohol patients for a median of 6.4 years. Multiple ELF cut-offs were assessed to determine diagnostic utility in moderate fibrosis and cirrhosis. Survival data were assessed to determine the ability of ELF to predict liver related events and all-cause mortality.
Results
ELF identified cirrhosis and moderate fibrosis in alcohol-related liver disease independently of aminotransferase levels with areas under receiver operating characteristic curves of 0.895 (95% CI:0.823–0.968) and 0.923 (95% CI:0.866–0.981) respectively, which were non-inferior to non-alcohol aetiologies. The overall performance of ELF was assessed using the Obuchowski method: in alcohol = 0.934 (95% CI:0.908–0.960); non-alcohol = 0.907 (95% CI:0.895–0.919). Using ELF < 9.8 to exclude and ≧ 10.5 to diagnose cirrhosis, 87.7% of alcohol cases could have avoided biopsy, with sensitivity of 91% and specificity of 85%. A one-unit increase in ELF was associated with a 2.6 (95% CI:1.55–4.31, p < 0.001) fold greater odds of cirrhosis at baseline and 2.0-fold greater risk of a liver related event within 6 years (95% CI:1.39–2.99, p < 0.001).
Conclusions
ELF accurately stages liver fibrosis independently of transaminase elevations as a marker of inflammation and has superior prognostic performance to biopsy in alcohol-related liver disease.
Keywords
Serum biomarker panel, liver fibrosis, alcohol-related liver disease, non-invasive testing, cirrhosis, diagnosis, prognosis
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
- AdditionalFile1V2.docx
A more in depth explanation of a less common statistical method used to calculate the overall performance of the Enhanced Liver Fibrosis test.
- AdditionalFile2V2.docx
A suggested pathway for improved identification and stratification of patients with excess alcohol consumption using multiple cut-offs of ELF.
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CURRENT STATUS: Under Review
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On 29 Dec, 2020
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On 29 Dec, 2020
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Subject Areas
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This preprint is under consideration at BMC Gastroenterology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
The Enhanced Liver Fibrosis test maintains its diagnostic and prognostic performance in alcohol-related liver disease: A cohort study.
William Rosenberg
Institute for Liver and Digestive Health, University College London
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 31 Dec, 2020
No community comments so far
Reviewer #2 agreed
On 16 Jan, 2021
Reviewer #1 agreed
On 16 Jan, 2021
Reviewers invited
Invitations sent on 30 Dec, 2020
Editor assigned
On 29 Dec, 2020
Editor invited
On 29 Dec, 2020
Submission checks complete
On 29 Dec, 2020
First submitted
On 16 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Gastroenterology & Hepatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Alcohol is the main cause of chronic liver disease. The Enhanced Liver Fibrosis (ELF) test is a serological biomarker for fibrosis staging in chronic liver disease, however its utility in alcohol-related liver disease warrants further validation. We assessed the diagnostic and prognostic performance of ELF in alcohol-related liver disease.
Methods
Observational cohort study assessing paired ELF and histology from 786 tertiary care patients with alcohol-related liver disease due to alcohol (n = 81) and non-alcohol aetiologies (n = 705). Prognostic data were available for 64 alcohol patients for a median of 6.4 years. Multiple ELF cut-offs were assessed to determine diagnostic utility in moderate fibrosis and cirrhosis. Survival data were assessed to determine the ability of ELF to predict liver related events and all-cause mortality.
Results
ELF identified cirrhosis and moderate fibrosis in alcohol-related liver disease independently of aminotransferase levels with areas under receiver operating characteristic curves of 0.895 (95% CI:0.823–0.968) and 0.923 (95% CI:0.866–0.981) respectively, which were non-inferior to non-alcohol aetiologies. The overall performance of ELF was assessed using the Obuchowski method: in alcohol = 0.934 (95% CI:0.908–0.960); non-alcohol = 0.907 (95% CI:0.895–0.919). Using ELF < 9.8 to exclude and ≧ 10.5 to diagnose cirrhosis, 87.7% of alcohol cases could have avoided biopsy, with sensitivity of 91% and specificity of 85%. A one-unit increase in ELF was associated with a 2.6 (95% CI:1.55–4.31, p < 0.001) fold greater odds of cirrhosis at baseline and 2.0-fold greater risk of a liver related event within 6 years (95% CI:1.39–2.99, p < 0.001).
Conclusions
ELF accurately stages liver fibrosis independently of transaminase elevations as a marker of inflammation and has superior prognostic performance to biopsy in alcohol-related liver disease.
Figure 1
Figure 2
Figure 3