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Serum conjugated primary bile acids accumulate in alcohol-related hepatitis (AH), distinguishing it from decompensated cirrhosis. Elevated hepatocyte growth factor (HGF) may worsen the bile acid profile in AH.

Keywords:
alcohol‐associated hepatitisalcohol‐related hepatitisbile acidsfibroblast growth factor 19hepatocyte growth factor

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Area of Science:

  • Hepatology
  • Gastroenterology
  • Metabolomics

Background:

  • Alcohol-related hepatitis (AH) is a severe liver condition characterized by cholestasis and dysfunction.
  • Understanding the specific metabolic alterations in AH is crucial for diagnosis and treatment.

Purpose of the Study:

  • To define and compare the bile acid (BA) profile in patients with AH, decompensated alcohol-related cirrhosis (DC), and healthy controls (HC).
  • To investigate the role of hepatocyte growth factor (HGF) and bile acid transporters in AH.

Main Methods:

  • Serum and fecal bile acids were quantified using UHPLC-MS.
  • FGF19 levels were measured by ELISA.
  • RNA-sequencing and multiplex immunoassays were used to analyze liver tissue and serum cytokines/growth factors.
  • HGF effects on primary human hepatocytes (PHH) and bile acid transporter expression were assessed.

Main Results:

  • Total serum bile acids were significantly higher in AH compared to DC and HC, primarily due to elevated conjugated primary BAs.
  • Serum bile acid profiles effectively differentiated AH from DC.
  • Fecal bile acids were reduced in AH, while serum FGF19 was elevated.
  • Elevated HGF was observed in AH, and HGF treatment reduced BSEP expression in PHH.

Conclusions:

  • Serum conjugated primary bile acids accumulate in AH, contributing to a distinct metabolic profile.
  • Elevated HGF in AH may impair adaptive changes in bile acid transporters (NTCP and BSEP), potentially exacerbating liver injury.