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Proteomic Profile of EPS-Urine through FASP Digestion and Data-Independent Analysis
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Proteomic Profile of EPS-Urine through FASP Digestion and Data-Independent Analysis

Published on: May 8, 2021

Urine Proteomic Profiling at Admission Reveals Complement Biomarkers Linked to Alcohol-Associated Liver Disease

Luan Prado1, Ryan Musich1, Moyinoluwa Taiwo1

  • 1Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, Ohio, USA.

Alcohol, Clinical & Experimental Research
|June 26, 2026
PubMed

Insights

Urinary complement proteins show potential as biomarkers for distinguishing severe alcoholic hepatitis (sAH) from alcohol cirrhosis (AC) and predicting mortality in sAH patients. These findings offer insights into liver-kidney interactions in alcohol-associated liver disease (ALD).

Area of Science:

  • Immunology
  • Nephrology
  • Hepatology

Background:

  • Circulating complement activation is linked to alcohol-associated hepatitis (AH) and alcohol cirrhosis (AC).
  • Complement activation plays a role in kidney injury within alcohol-associated liver disease (ALD).
  • The interplay between liver and kidney complement in ALD pathogenesis remains poorly understood.

Purpose of the Study:

  • To investigate urinary complement as potential biomarkers for ALD.
  • To explore liver-kidney cross-talk mechanisms in ALD pathogenesis.
  • To assess the diagnostic and prognostic value of urinary complement in distinguishing AH from AC and predicting mortality.

Main Methods:

  • Collected plasma and urine samples from patients with severe alcoholic hepatitis (sAH), alcohol cirrhosis (AC), healthy controls (HC), and heavy drinkers (HD).
  • Utilized unbiased proteomics for urine analysis and multiplex/ELISA assays for plasma complement assessment.
  • Tracked 30- and 90-day mortality in sAH patients.

Main Results:

  • All three complement activation pathways were altered in the plasma and urine of sAH and AC patients.
  • Urinary complement pathway components correlated with mortality in sAH patients.
  • A panel of four urinary complement proteins differentiated sAH from AC with an AUC of 0.78, comparable to MELD score (AUC 0.65).
  • No correlation was observed between plasma and urinary complement levels, suggesting independent effects on liver and kidney.

Conclusions:

  • Urinary proteomic analysis identified complement protein signatures associated with sAH and AC.
  • Urinary complement shows promise as a biomarker for ALD.
  • These findings provide insights into the mechanisms of liver-kidney cross-talk in ALD pathogenesis.
Abstract

Keywords:
ALDalcohol cirrhosisalcohol‐associated hepatitiscomplement

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