Clarifying prognostic and translational aspects of lactate and MAP thresholds in cirrhosis

We read with great interest the article by Smith et al.¹ entitled “Serum lactate and mean arterial pressure thresholds in patients with cirrhosis and septic shock.” The authors demonstrated that a lactate concentration ≥4 mmol/L and a mean arterial pressure (MAP) ≤60 mm Hg were independently associated with mortality, underscoring their prognostic value in patients with cirrhosis and septic shock. These findings advance critical-care hepatology, and we wish to offer several methodological clarifications that may refine their clinical interpretation.

First, the definition of sepsis adopted (SOFA score ≥2 with positive cultures or radiographic pneumonia) may conflate baseline hepatic dysfunction with infection-related organ failure. In advanced cirrhosis, elevated SOFA scores may reflect chronic hyperbilirubinemia or coagulopathy rather than acute sepsis. Clarifying whether diagnostic adjudication followed Sepsis-3—“suspected infection + organ dysfunction” confirmed by clinical context—would improve comparability.² Moreover, only baseline lactate and MAP were analyzed; dynamic trends within 24–48 hours after resuscitation could introduce time-varying confounders. Could the authors clarify whether serial or time-weighted measures were evaluated, or whether single baseline values were modeled as fixed predictors?

Second, thresholds were handled dichotomously (lactate ≥4 mmol/L, MAP ≤60 mm Hg), although physiologic risk likely follows a continuous, nonlinear trajectory. Recent studies in Hepatology Communications indicate that hemodynamic risk is better represented with restricted cubic splines.³ In addition, ROC analysis with the Youden index can empirically verify optimal discriminative cutoffs and avoid arbitrary dichotomization.⁴ If ROC-derived thresholds (with CIs) were estimated, reporting their Youden-optimal cutoffs and AUCs would confirm discriminative validity and generalizability.

Third, clinical translation should consider the unique circulatory physiology of cirrhosis. Patients with portal hypertension often exhibit low systemic vascular resistance and high-output states, which may render a conventional MAP ≥65 mm Hg insufficient for organ perfusion.⁵ Analyses stratified by vasopressor dose, hyperdynamic status, or renal perfusion markers could contextualize optimal resuscitation thresholds. Such subgroup insights may help define individualized therapeutic targets aligned with AASLD critical-care guidance.

In summary, clarifying diagnostic adjudication, ROC-based threshold derivation, and physiologic context would enhance the reproducibility and bedside applicability of this important study. These refinements may provide statistical robustness and actionable hemodynamic guidance for patients with advanced liver disease.

AUTHOR CONTRIBUTIONS

Qing-Bao Jiang and Guo-Ming Zhang conceived and drafted the correspondence, verified all the data interpretations, and approved the final version.

FUNDING INFORMATION

This correspondence received no specific grant from any funding agency, commercial, or not-for-profit sector. The author declares no funding.

CONFLICTS OF INTEREST

The authors have no conflicts to report.