Editorial: Lymphocyte-To-Monocyte Ratio and Recompensation in PBC—A New Piece in an Incomplete Puzzle?

The concept of recompensation has emerged as a meaningful outcome in patients with decompensated cirrhosis, reflecting the potential for clinical and biochemical improvement in selected patients [1]. Although patients with decompensated cirrhosis may improve from symptom-directed therapies, such as diuretics and lactulose, successful clearance or suppression of the aetiology of liver disease is considered a prerequisite for long-term recovery of liver function. In primary biliary cholangitis (PBC), a rare chronic cholestatic liver disease that remains incurable short of liver transplantation, predictors of recompensation remain poorly defined and understudied.

Therefore, as presented in this issue of Alimentary Pharmacology & Therapeutics, Lin and colleagues report an interesting study assessing the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in 401 patients with decompensated PBC-related cirrhosis [2]. The most common initial decompensating event was ascites (62.3%), followed by variceal bleeding (24.4%) and hepatic encephalopathy (HE) (13.2%). Recompensation was defined using adapted Baveno VII criteria: UDCA response (ALP < 1.67 × ULN after ≥ 12 months of therapy), resolution of decompensating events, and improved liver function (albumin > 35 g/L, INR < 1.5, bilirubin < 34 μmol/L). In total, 105 patients (26.2%) achieved recompensation. Higher baseline LMR was linearly associated with increased likelihood of recompensation (HR: 1.45; 95% CI: 1.26–1.58), independent from other factors, with stable estimates in case of repeated measurements over time.

These findings underscore the potential of LMR as a simple, readily available, non-invasive biomarker that may reflect the immune-inflammatory milieu in PBC. Biologically, a higher LMR could suggest a more favourable immunologic profile, consistent with the understanding of immune dysregulation in PBC, where monocyte-driven inflammation and lymphocyte imbalances (e.g., Th1/Th17 predominance) are thought to contribute to progressive bile duct injury and fibrosis [3-5]. However, LMR is influenced by a wide range of non-hepatic factors, including infections, comorbid autoimmune conditions, medications (e.g., corticosteroids), lifestyle exposures, and aging. Many of these are difficult to fully account for in retrospective analyses and clinical practice. As such, while LMR may be sensitive to shifts in immune tone, it lacks specificity, and its use as a solitary predictive marker warrants cautious interpretation.

Thus, while promising, several limitations of the presented study warrant consideration. The retrospective, single-centre design limits generalisability, as recompensation remains a subjective endpoint; it requires trials of diuretics and/or HE withdrawal. Variability in supportive management may also affect outcomes. Moreover, while the authors applied adapted Baveno VII criteria, etiological control remains undefined in decompensated PBC-related cirrhosis (ALP loses predictive power in more advanced disease), unlike in viral or alcohol-related cirrhosis where structured frameworks exist [1, 6]. Nonetheless, the observed associations between recompensation and significantly improved transplant-free survival highlight the clinical relevance of the selected endpoint and underscore the importance of efforts to better characterise it in this population.

Looking ahead, LMR could be incorporated into composite tools to stratify decompensated PBC patients by likelihood of recompensation. Its clinical application requires validation in prospective, multicentre cohorts and evaluation of whether longitudinal changes align with treatment response or shifting immune states. Mechanistic studies linking peripheral LMR to intrahepatic immune signatures may further clarify its biological relevance [7]. Translational studies should focus on the clinical implications of LMR, including the thresholds to guide clinical decision-making.

Lin et al. nonetheless provide an important step toward broadening our prognostic armamentarium in PBC, particularly at the end-stage of disease, which remains a reality despite more effective anticholestatic treatments. Whether LMR can inform future prognostic tools for decompensated PBC will depend on its reproducibility, specificity, and clinical actionability. Still, this study helps reinvigorate a critical conversation—how best to identify those who may regain compensation and avoid transplant in a disease long thought to be relentlessly progressive.

Adrielly Martins: writing – original draft, writing – review and editing, conceptualization, supervision. Adriaan J. van der Meer: conceptualization, supervision, writing – original draft, writing – review and editing.

This article is linked to Lin et al. paper. To view this article, visit https://doi.org/10.1111/apt.70233.