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Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease

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  • MicrobLiver consortia
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Background & Aims: Alcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a history of excess drinking. Methods: We performed a prospective cohort study in patients with early, compensated alcohol-related liver disease. At baseline, we obtained a liver biopsy, transient elastography (TE), 2-dimensional shear-wave elastography (2D-SWE), enhanced liver fibrosis test (ELF), FibroTest, fibrosis-4 index (FIB-4), non-alcoholic fatty liver fibrosis score (NFS) and Forns index. We compared C-statistics and time-dependent AUC for prognostication. We used validated cut-off points to create 3 risk groups for each test: low, intermediate and high risk. Results: We followed 462 patients for a median of 49 months (IQR 31–70). Median age was 57 years, 76% were males, 20% had advanced fibrosis. Eighty-four patients (18%) developed a liver-related event after a median of 18 months (7-34). TE had the highest prognostic accuracy, with a C-statistic of 0.876, and time-dependent AUC at 5 years of 0.889, comparable to 2D-SWE and ELF. TE, ELF and 2D-SWE outperformed FibroTest, FIB4, NFS, Forns index and biopsy-verified fibrosis stage. Compared to patients with TE <10 kPa, the hazard ratios for liver-related events for TE 10–15 kPa were 8.1 (3.2–20.4), and 27.9 (13.8–56.8) for TE >15 kPa. Periods of excessive drinking during follow-up increased the risk of progressing to liver-related events, except for patients in the low-risk groups. Conclusion: TE, ELF and 2D-SWE are highly accurate prognostic markers in patients with alcohol-related liver disease. Easy-to-use cut-offs can distinguish between substantially different risk profiles. Lay summary: Alcohol is the leading cause of death and illness due to liver disease. In this study, we assessed the ability of biomarkers to predict the risk of developing symptomatic liver disease in patients with early stages of alcohol-related liver disease. We found that several tests accurately predicted the risk of liver-related events such as ascites, esophageal varices and hepatic encephalopathy during an average follow-up of 4.1 years. Liver stiffness measurements by ultrasound elastography and the enhanced liver fibrosis test performed best. By using them, we were able to stratify patients into 3 groups with significantly different risks.

Original languageEnglish
JournalJournal of Hepatology
Volume75
Issue number5
Pages (from-to)1017-1025
Number of pages9
ISSN0168-8278
DOIs
Publication statusPublished - Nov 2021

Bibliographical note

Funding Information:
This project received funding through the GALAXY project from the European Union's Horizon 2020 Framework Programme for Research and Innovation, Grant Agreement number 668031, through the MicrobLiver project from the Novo Nordic Foundation Challenge Programme, grant number NNF15OC0016692, and from the Research Foundations at University of Southern Denmark, Odense University Hospital and Region of Southern Denmark. Siemens Healthcare A/S (Ballerup, Denmark) provided the assays used for measuring the enhanced liver fibrosis test, and partly funded the salary for collecting outcome data without restrictions. The Toyota Foundation and The AP Moeller Foundation granted funds to purchase the FibroScan and Aixplorer systems. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Funding Information:
This project received funding through the GALAXY project from the European Union’s Horizon 2020 Framework Programme for Research and Innovation , Grant Agreement number 668031 , through the MicrobLiver project from the Novo Nordic Foundation Challenge Programme, grant number NNF15OC0016692 , and from the Research Foundations at University of Southern Denmark , Odense University Hospital and Region of Southern Denmark . Siemens Healthcare A/S (Ballerup, Denmark) provided the assays used for measuring the enhanced liver fibrosis test, and partly funded the salary for collecting outcome data without restrictions. The Toyota Foundation and The AP Moeller Foundation granted funds to purchase the FibroScan and Aixplorer systems. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Publisher Copyright:
© 2021 The Authors

    Research areas

  • Alcoholic liver disease, Decompensation, Liver stiffness, Mortality, Prognosis

ID: 69206392