Editorial: Cholestasis Is an Important Marker for Evaluating Clinical Outcomes and Prognosis in Severe Burns and Critically Ill Patients

Recognising organ dysfunction is vital in the management and prognostication of critically ill patients [1]. In severe thermal injury, inflammation and hypermetabolism are pronounced, with the liver playing a central role in the systemic response [2]. Given the liver modulates metabolic, inflammatory, immune, and circulatory pathways in the post-burn response [3], a simple but accurate biomarker to identify hepatic stress and dysfunction would prove valuable for prognostication. In Semmler et al. [4] ‘burn-associated cholestasis’ (BAC) (Table 1), first proposed by de Tymowski et al. [5] as well as markers of cholestasis (bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)) were evaluated with regards to association with mortality. This study describes 532 patients admitted to a burns intensive care unit (ICU) over a 10-year period, of which 118 (22%) met BAC criteria. Several key points are highlighted that validate findings from the de Tymowski study. BAC incidence is higher after more severe burns and occurs without known liver disease. Increased severity scores and greater burden of ICU requirement such as mechanical ventilation, ketamine use, and parenteral nutrition are additional risk factors for cholestasis. BAC does not occur immediately, with median time to onset of BAC reported between 9 and 11 days. BAC is associated with in-hospital mortality (HR 2.37, 1.53–3.67), and in multivariate analysis, bilirubin elevation (aHR 1.55, 139–1.73) and BAC types B and C (aHR 3.34, 2.21–5.05) were independently associated with in-hospital mortality. ALP and GGT elevation without hyperbilirubinaemia were not associated with mortality and may be predictive of survival [5]. These findings raise important insights and questions with regards to the mechanism and impact of cholestasis in severe thermal injury and more broadly, critically ill patients. Firstly, bilirubin, which is routinely performed, can serve as a reliable biomarker for hepatic dysfunction during organ failure assessments for ICU patients. Care must be taken to exclude the influence of biliary obstruction, sepsis, haemolysis, and drugs, particularly antibiotics and ketamine [6, 7]. Secondly, there appear to be distinct subgroups of burn patients that sustain hyperbilirubinaemia and thus have poorer prognosis. The factors for this are not clear and further studies are required; however, the severity of burn seems to be related. In de Tymowski et al. BAC type C was associated with higher rates of cirrhosis and higher peak AST levels which suggest underlying liver reserve and the presence of hepatic hypoperfusion-ischaemic injury may influence outcomes in BAC [5]. It would be of interest to see if peak ALT/AST levels were different amongst the BAC subtypes in the Semmler et al. population. Finally, the long-term impact of BAC and critical-illness cholestasis remains a topic of interest. Increased mortality risk was seen to 90 days, and secondary sclerosing cholangitis has been reported in post-burn patients which may be of interest in this study's population follow-up [8, 9]. BAC likely lies within the hypoperfusion-ischaemic, inflammatory-necrosis continuum of hepatic injury [4] and further research is required to identify those at risk of poor prognosis. This study highlights the key risk factors for cholestatic injury and the utility of monitoring cholestasis as a marker of hepatic dysfunction in critically ill burns patients. Andrew T. Roberts: conceptualization, writing – original draft. Deepak Joshi: writing – review and editing. The authors have nothing to report. This article is linked to Semmler et al. papers. To view this article, visit https://doi.org/10.1111/apt.70505. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.