Elevated body mass index as a prognostic marker in acute liver failure: Implications from a two-decade cohort

Abstract

The prognostic impact of obesity in acute liver failure (ALF) remains underexplored in recent United States cohorts despite the global rise in obesity prevalence. The aim of this letter is to appraise and contextualize the findings of Krishnan et al, who examined the association between body mass index (BMI) and ALF outcomes in a large, retrospective United States cohort. Krishnan et al analyzed 196 ALF patients over two decades, demonstrating that both overweight and obesity independently doubled the risk of death or need for liver transplantation after adjustment for confounders. Elevated BMI was also associated with higher grades of hepatic encephalopathy and renal dysfunction; two major contributors to ALF mortality. Future research should consider additional markers of metabolic health beyond BMI to refine prognostication. This study provides timely, robust evidence linking elevated BMI to adverse ALF outcomes and highlights the need for targeted clinical strategies in this vulnerable subgroup.

Key Words: Body mass index; Acute liver failure; Renal dysfunction; Hepatic encephalopathy; Obesity

Core Tip: The association between elevated body mass index (BMI) and poor outcomes in acute liver failure (ALF) has been underexplored in recent literature. Krishnan et al present a large, two-decade United States cohort showing that overweight and obese patients face a twofold higher risk of death or need for liver transplantation, along with greater prevalence of severe hepatic encephalopathy and renal dysfunction. These findings highlight BMI as an important prognostic marker in ALF and support its integration into risk assessment frameworks. Targeted monitoring and early interventions in this population may help mitigate adverse outcomes.

TO THE EDITOR

We read with great interest the article by Krishnan et al[1], which offers valuable insight into the interplay between obesity and prognosis in acute liver failure (ALF). The authors present a robust retrospective cohort analysis over two decades from a major tertiary center, demonstrating that both overweight and obesity independently confer a twofold increased risk of death or need for liver transplantation (LT) in ALF patients. This work is timely, clinically relevant, and fills a notable gap in the literature.

Obesity has been recognized as a chronic pro-inflammatory state with immune dysregulation, contributing to worse outcomes in acute illnesses[2,3]. However, as the authors point out, there has been a paucity of recent large-scale United States data exploring the impact of elevated body mass index (BMI) in ALF, a syndrome in which systemic inflammation, cerebral edema, and multi-organ dysfunction drive mortality[4,5]. Earlier work by Rutherford et al[6] from the ALF Study Group suggested a modest association between obesity and adverse ALF outcomes, but was limited by missing BMI data in over a quarter of cases[6]. The present study builds on this foundation with meticulous data collection, stratification by BMI category, and multivariable adjustment for key confounders, strengthening the validity of the findings.

The authors’ observation that overweight patients had slightly worse adjusted outcomes than obese patients is intriguing and reminiscent of the “obesity paradox” described in other critical care settings[7]. While the mechanisms remain speculative, factors such as metabolic reserves, differential inflammatory profiles, or selection bias in LT candidacy may play a role[8,9]. Importantly, the consistent association of higher BMI with severe hepatic encephalopathy and renal dysfunction in this cohort highlights the need for intensified neurologic and renal monitoring in this high-risk population[10].

From a clinical standpoint, these results support the incorporation of BMI into ALF risk stratification frameworks. Given the rising prevalence of obesity worldwide[11], the identification of elevated BMI as a modifiable prognostic factor highlights an avenue for earlier intervention, tailored supportive care, and possibly prioritization in transplant evaluation. Furthermore, as BMI alone may not fully capture metabolic health[12], future research could benefit from integrating waist circumference, sarcopenia assessment, and inflammatory biomarkers to refine risk prediction. Inflammatory biomarkers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha reflect chronic low-grade systemic inflammation, which is closely linked to insulin resistance, endothelial dysfunction, and atherogenesis. Incorporating these biomarkers could help distinguish metabolically unhealthy phenotypes among individuals with similar BMI or body composition, thereby improving the identification of those at heightened cardiometabolic and mortality risk.

In summary, Krishnan et al[1] provide compelling evidence that overweight and obesity adversely influence ALF outcomes, reinforcing the importance of early recognition and targeted management in this subgroup. Their study not only advances our understanding of prognostic determinants in ALF but also sets the stage for prospective multicenter studies to validate and expand upon these important findings.