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

J Hepatol. 2021 Nov;75(5):1017-1025. doi: 10.1016/j.jhep.2021.05.037. Epub 2021 Jun 10.


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.

Keywords: Alcoholic liver disease; Decompensation; Liver stiffness; Mortality; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alcohol Drinking / adverse effects*
  • Alcohol Drinking / epidemiology
  • Alcohol Drinking / physiopathology
  • Biomarkers / analysis*
  • Biopsy / methods
  • Biopsy / standards*
  • Biopsy / statistics & numerical data
  • Cohort Studies
  • Denmark / epidemiology
  • Elasticity Imaging Techniques / methods
  • Elasticity Imaging Techniques / statistics & numerical data
  • Female
  • Humans
  • Liver / pathology
  • Liver Diseases / diagnosis*
  • Liver Diseases / epidemiology
  • Male
  • Middle Aged
  • Predictive Value of Tests*
  • Prognosis
  • Prospective Studies
  • Risk Factors


  • Biomarkers