Background. Small-for-size syndrome (SFSS) occurs in the presence of insufficient liver mass to maintain normal function after liver transplantation. Murine mortality following 85% hepatectomy can be reduced by the use of soluble receptor for advanced glycation end products (sRAGE) to scavenge damage-associated molecular patterns and prevent their engagement with membrane-bound RAGE. Aims. To explore serum levels of sRAGE, high-mobility group box-1 (HMGB1) protein, and other soluble inflammatory mediators in a fatal case of SFSS. Methods. Serum levels of HMGB1, sRAGE, IL-18, and other inflammatory mediators were measured by ELISA in a case of SFSS, and the results were compared with 8 patients with paracetamol-induced acute liver failure (ALF) and 6 healthy controls (HC). Results. HMGB1 levels were markedly higher in the SFSS patient (92.1？ng/mL) compared with the ALF patients (median (IQR) 11.4 (3.7–14.8)？ng/mL) and HC (1.42 (1.38–1.56)？ng/mL). In contrast, sRAGE levels were lower in the SFSS patient (1.88？ng/mL) compared with the ALF patients (3.53 (2.66–12.37)？ng/mL) and were similar to HC levels (1.40 (1.23–1.89)？ng/mL). Conclusion. These results suggest an imbalance between pro- and anti-inflammatory innate immune pathways in SFSS. Modulation of the HMGB1-RAGE axis may represent a future therapeutic avenue in this condition. 1. Introduction The capacity for liver regeneration is finite, placing a restriction upon the minimum mass of liver tissue required to maintain hepatic function following split liver transplantation (LT) or liver resection. Small-for-size syndrome (SFSS) occurs in the presence of insufficient liver mass to maintain normal function and is characterised by severe graft dysfunction and increased ascites output [1]. The pathophysiology of SFSS is multifactorial, involving insufficient graft volume, poor graft quality, and excessive portal inflow [2]. Amplification of proinflammatory mediators in the remnant tissue is also recognised to play an important role in limiting liver regeneration [3]. Recent murine studies have suggested that a key pathway in this process involves the receptor for advanced glycation end products (RAGE), a cell-surface multiligand pattern recognition receptor linked with amplification of the innate inflammatory response to cell death. Engagement of membrane-bound RAGE with ligands such as high-mobility group box 1 (HMGB1) protein sustains inflammatory responses and promotes apoptosis in the hepatic remnant following massive hepatectomy [4]. Soluble RAGE (sRAGE), the truncated extracellular domain of RAGE,
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