Persistently Increased Resting Energy Expenditure Predicts Short-Term Mortality in Patients with Acute-on-Chronic Liver Failure

Abstract

Objective: Hypermetabolism based on measurements of resting energy expenditure (REE) is suggested to be a potential biomarker for predicting the clinical outcomes of some diseases. We aimed to evaluate the potential value of hypermetabolism for predicting the short-term (28-day) mortality of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods: A total of 105 HBV-ACLF patients, 30 chronic hepatitis B (CHB) patients and 30 healthy controls (HCs) were included in this study. The REE was measured using indirect calorimetry in the morning after 8–10 h of fasting. The predicted REE (REEHB) was determined using Harris-Benedict equation. Persistent hypermetabolism was defined as the REE:REEHB ratio > 1.20 at day 1 and day 7 after admission. The severity of liver disease was estimated using the Model for End-Stage Liver Disease (MELD). Clinical and biochemical variables were determined using blood samples ordered upon admission. These variables were compared between nonsurviving and surviving patients who were classified according to the 28-day mortality. Results: The frequency of hypermetabolism at baseline was significantly higher in ACLF patients than that in HCs and CHB patients. Forty-six (43.8%) ACLF patients died within follow-up of 28 days. Persistent hypermetabolism (OR 2.10; 95% CI 1.15–3.69; p = 0.002) and MELD score (OR 1.93; 95% CI 1.47–3.51; p = 0.012) were independent predictive indicators of 28-day mortality. Furthermore, the performance of the 2 variables (persistent hypermetabolism and MELD) together with the area under the receiver operating curve (AUROC: 0.819) was significantly better than that of MELD alone ­(AUROC: 0.694) for prediction of short-term mortality (p = 0.014). Conclusion: These findings indicate that persistent hypermetabolism is predictive of short-term mortality in this small population.

Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging

“…In two other cohorts, elevated BMR also predicted earlier mortality over the subsequent 20–25 years ( Jumpertz et al, 2011 ; Ruggiero et al, 2008 ). Similarly, in patients with various illnesses (hepatitis B, amyotrophic lateral sclerosis, type 2 diabetes, and cancers), hypermetabolism predicts worse prognosis and mortality ( Sampath, 2019 ; Vazeille et al, 2017 ; Steyn et al, 2018 ; Yao et al, 2018 ). Thus, we propose a model where hypermetabolism reflects the magnitude of allostatic load – i.e., how much energy cells and organisms are expending to maintain stable physiology.…”

The energetic cost of allostasis and allostatic load

“…Higher resting heart rate – which generally scales linearly with metabolic rate ( Green, 2011 ) – also was associated with a 80–90 % increased risk of death over a 12-year follow up ( Nauman et al, 2011 ). In clinical populations with equivalent diagnoses (e.g., cancer, diabetes, and renal disease) patients with hypermetabolism also are more likely to die than those with normal resting metabolic rate ( Steyn et al, 2018 ; Vazeille et al, 2017 ; Yao et al, 2018 ). Thus, physiological states that chronically elevate energy expenditure – which we propose is a consequence of allostatic load and overload – induces a more “mouse-like” state that predicts earlier mortality.…”

Cellular Allostatic Load is linked to Increased Energy Expenditure and Accelerated Biological Aging

“…Among healthy individuals, independently of well-recognized risk factors such as age, body mass index, smoking, white blood cell count, and diabetes, hypermetabolism is associated with poor health in older individuals 89 , and predicts earlier mortality over the subsequent 20-25 years 90,91 . Similarly, in patients with various illnesses (hepatitis B, amyotrophic lateral sclerosis, type 2 diabetes, and cancers), hypermetabolism also predicts worse prognosis and mortality [92][93][94][95] . Thus, we propose a model where hypermetabolism reflects the magnitude of allostatic load i.e., how much energy cells and organisms are expending to maintain stable physiology which subsequently drives the severity of allostatic load that contribute to accelerated aging and early mortality.…”

“…In two other cohorts, elevated BMR also predicted earlier mortality over the subsequent 20-25 years( 97, 98 ). Similarly, in patients with various illnesses (hepatitis B, amyotrophic lateral sclerosis, type 2 diabetes, and cancers), hypermetabolism predicts worse prognosis and mortality( 99–102 ). Thus, we propose a model where hypermetabolism reflects the magnitude of allostatic load - i.e., how much energy cells and organisms are expending to maintain stable physiology.…”