Clinical bottom line
Serum soluble Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) is emerging as a putative biomarker for predicting disease progression and prognosis in alcoholic hepatitis (AH). Preliminary data suggest that elevated sTREM2 levels correlate with hepatic inflammation and may reflect macrophage activation, a key driver of AH pathophysiology. While sTREM2 shows promise for risk stratification and monitoring, current evidence remains limited and requires validation in larger, prospective cohorts before routine clinical adoption.
What the evidence shows
Alcoholic hepatitis is characterized by acute hepatic inflammation and immune activation, with macrophages playing a central role in mediating liver injury and fibrosis. sTREM2, a soluble form of the TREM2 receptor expressed on myeloid cells, has been investigated as a biomarker reflecting macrophage activation in various inflammatory conditions. Although direct studies of sTREM2 in AH are sparse, analogous soluble myeloid markers have demonstrated prognostic utility in liver disease contexts.
For example, Stickel et al. (2020) highlighted the importance of immune cell activation markers in predicting long-term outcomes in severe AH, underscoring the potential of macrophage-related biomarkers to improve prognostication. Zhang et al. (2012) demonstrated that soluble angiogenic factors, which share mechanistic overlap with myeloid activation pathways, correlated with disease severity and prognosis in liver disease, supporting the concept that soluble receptors like sTREM2 may provide clinically relevant information.
More recently, Mishra et al. (2025) and Inada et al. (2025) investigated serum biomarker ratios involving hepatocyte growth factor and alpha-fetoprotein in AH, illustrating the ongoing search for reliable serum markers that reflect hepatic injury and regeneration dynamics. These studies reinforce the rationale for exploring sTREM2 as a complementary biomarker given its immune specificity.
Collectively, these findings generate a hypothesis that serum sTREM2 levels could serve as a dynamic biomarker reflecting macrophage-driven inflammation and fibrosis progression in AH, potentially aiding in early risk stratification and monitoring response to therapy.
Caveats and uncertainty
The clinical utility of serum sTREM2 in alcoholic hepatitis remains investigational. To date, no large-scale, prospective studies have conclusively established its sensitivity, specificity, or predictive value compared to established clinical scores such as MELD or Lille. The heterogeneity of AH pathophysiology and overlap with other inflammatory liver diseases may confound interpretation of sTREM2 levels.
Additionally, sTREM2 is not liver-specific and may be elevated in other systemic inflammatory or neurodegenerative conditions, potentially limiting its specificity for AH. The kinetics of sTREM2 in response to treatment or disease resolution are also poorly characterized.
Given these limitations, sTREM2 should be considered a putative biomarker warranting further validation rather than a ready-for-clinical-use diagnostic or prognostic tool.
How this may change practice
If validated, serum sTREM2 measurement could complement existing clinical and laboratory parameters to refine prognostication in alcoholic hepatitis. It may help identify patients at higher risk of progression who could benefit from intensified monitoring or novel immunomodulatory therapies targeting macrophage activation.
Moreover, sTREM2 could serve as a biomarker to monitor therapeutic response or disease resolution, facilitating personalized management strategies. However, until robust evidence from prospective cohorts and interventional studies emerges, sTREM2 measurement should remain confined to research settings.
Clinicians should continue to rely on established clinical scores and comprehensive assessment for AH management, while remaining attentive to emerging biomarker data that may enhance future care.