Clinical presentation and transcriptome analysis of acute alcohol-induced microvesicular steatosis mimicking alcoholic steatohepatitis

Spahr, Laurent;Lanthier, Nicolas;Rubbia-Brandt, Laura;Goossens, Nicolas
(2019) American Association for the Study of the Liver (AASLD): The Liver Meeting 2020 — Location: Boston (8.November.2019)

Files

AASLD2019Spahr.docx
  • Open Access
  • Microsoft Word XML
  • 14.56 KB
Download

Details

Authors
  • Spahr, Laurent
    Author
  • Lanthier, Nicolasorcid-logoUCLouvain
    Author
  • Rubbia-Brandt, Laura
    Author
  • Goossens, Nicolas
    Author
Abstract
Background: Acute microvesicular steatosis (MIC), or “alcoholic foamy degeneration”, may complicated acute alcohol intoxication and may mimic severe alcoholic steatohepatitis (ASH) . However, detailed patients characteristics, natural history and pathophysiology of MIC are unknown. We analyzed the clinical presentation, histological findings and detailed transcriptome analysis of patients presenting with MIC compared with ASH patients. Methods: Heavily drinking patients (>150gr/day) from a prospective cohort with a biopsy performed early after admission were included either in the MIC group (>50% microvesicular steatosis, no inflammation) or in the ASH group (polynuclear infiltration, macrosteatosis, ballooned hepatocytes) . All patients received supportive care plus steroids in severe ASH. In the genomic substudy (MIC: 7 patients, ASH: 17 patients), liver mRNA was extracted from snap-frozen specimens followed by transcriptome profiling (Affymetrix) . Patients FU lasted 3 months. Results: A: clinical study: Compared to ASH (n=24, mean age 49.5 yrs, M/F: 12/12), patients in MIC group (n=12, mean age 47.1 yrs, M/F: 7/5) had lower MELD score (p<0.05), lower HVPG (p<0.01), higher ALT (p<0 .02) and GGT (p<0 .001), higher triglycerides (p<0 .001) and total cholesterol (p<0 .002), but similar serum bilirubin levels (p=0 .23) . Histology revealed the absence of significant fibrosis in 50% of MIC compared with cirrhosis in all patients with ASH . Bilirubinostasis was observed in 75% (MIC) and 66% (ASH) of patients . During FU, death/LT occurred in 11 patients (MIC: n=4, median time 34.5 days [5-55]; ASH: n=7, median time 28.5 days [10-62]). Improvement in MELD was similar between survivors in both groups (MELD: -5). Alcohol relapse rate was 25% and 16% in MIC and ASH, respectively . B: genomic substudy: (see figure) At transcriptome analysis the main pathways differentially expressed in MIC vs ASH are related to cell cycle (upregulated), stellate cell activation/ fibrosis and inflammation (downregulated). Important genes involved in lipid metabolism were identified (ie:THRSP, CD36). Conclusion: MIC is an acute, non-inflammatory, potentially severe liver injury which may mimic ASH, and is associated with marked derangements in lipid metabolism . Multiple genes show significant differential expression in patients with MIC when compared to ASH, involving liver cell repair, lipid metabolism and detoxification. These observations may help clarify the pathogenesis of MIC.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Spahr, L., Lanthier, N., Rubbia-Brandt, L., & Goossens, N. (2019). Clinical presentation and transcriptome analysis of acute alcohol-induced microvesicular steatosis mimicking alcoholic steatohepatitis. Hepatology, 70(1), 174A. https://hdl.handle.net/2078.5/170273 (Original work published 2019)