Are Predictive Energy Expenditure Equations Accurate in Cirrhosis?

Malnutrition is associated with significant morbidity and mortality in cirrhosis. An accurate nutrition prescription is an essential component of care, often estimated using time-efficient predictive equations. Our aim was to compare resting energy expenditure (REE) estimated using predictive equations (predicted REE, pREE) versus REE measured using gold-standard, indirect calorimetry (IC) (measured REE, mREE). We included full-text English language studies in adults with cirrhosis comparing pREE versus mREE. The mean differences across studies were pooled with RevMan 5.3 software. A total of 17 studies (1883 patients) were analyzed. The pooled cohort was comprised of 65% men with a mean age of 53 ± 7 years. Only 45% of predictive equations estimated energy requirements to within 90⁻110% of mREE using IC. Eighty-three percent of predictive equations underestimated and 28% overestimated energy needs by ±10%. When pooled, the mean difference between the mREE and pREE was lowest for the Harris⁻Benedict equation, with an underestimation of 54 (95% CI: 30⁻137) kcal/d. The pooled analysis was associated with significant heterogeneity (I2 = 94%). In conclusion, predictive equations calculating REE have limited accuracy in patients with cirrhosis, most commonly underestimating energy requirements and are associated with wide variations in individual comparative data.

Predicting Hepatic Encephalopathy-Related Hospitalizations Using a Composite Assessment of Cognitive Impairment and Frailty in 355 Patients With Cirrhosis.

INTRODUCTION: Hepatic encephalopathy (HE) is the most common potentially modifiable reason for admission in patients with cirrhosis. Cognitive and physical components of frailty have pathophysiologic rationale as risk factors for HE. We aimed to assess the utility of a composite score (MoCA-CFS) developed using the Montreal Cognitive Assessment (MoCA) and the Clinical Frailty Scale (CFS) for predicting HE admissions within 6 months. METHODS: Consecutive adult patients with cirrhosis were followed for 6 months or until death/transplant. Patients with overt HE and dementia were excluded. Primary outcome was the prediction of HE-related admissions at 6 months. RESULTS: A total of 355 patients were included; mean age 55.9 ± 9.6; 62.5% male; Hepatitis C and alcohol etiology in 64%. Thirty-six percent of patients had cognitive impairment according to the MoCA (≤24) and 14% were frail on the CFS (>4). The MoCA-CFS independently predicted HE hospitalization within 6 months, a MoCA-CFS score of 1 and 2 respectively increasing the odds of hospitalization by 3.3 (95% CI:1.5-7.7) and 5.7 (95% CI:1.9-17.3). HRQoL decreased with increasing MoCA-CFS. Depression and older age were independent predictors of a low MoCA. CONCLUSIONS: Cognitive and physical frailty are common in patients with cirrhosis. In addition to being an independent predictor of HE admissions within 6 months, the MoCA-CFS composite score predicts impaired HRQoL and all-cause admissions within 6 months. These data support the predictive value of a "multidimensional" frailty tool for the prediction of adverse clinical outcomes and highlight the potential for a multi-faceted approach to therapy targeting cognitive impairment, physical frailty and depression.

A MELD-based model to determine risk of mortality among patients with acute variceal bleeding.

BACKGROUND & AIMS: Patients with cirrhosis with acute variceal bleeding (AVB) have high mortality rates (15%-20%). Previously described models are seldom used to determine prognoses of these patients, partially because they have not been validated externally and because they include subjective variables, such as bleeding during endoscopy and Child-Pugh score, which are evaluated inconsistently. We aimed to improve determination of risk for patients with AVB. METHODS: We analyzed data collected from 178 patients with cirrhosis (Child-Pugh scores of A, B, and C: 15%, 57%, and 28%, respectively) and esophageal AVB who received standard therapy from 2007 through 2010. We tested the performance (discrimination and calibration) of previously described models, including the model for end-stage liver disease (MELD), and developed a new MELD calibration to predict the mortality of patients within 6 weeks of presentation with AVB. MELD-based predictions were validated in cohorts of patients from Canada (n = 240) and Spain (n = 221). RESULTS: Among study subjects, the 6-week mortality rate was 16%. MELD was the best model in terms of discrimination; it was recalibrated to predict the 6-week mortality rate with logistic regression (logit, -5.312 + 0.207 • MELD; bootstrapped R(2), 0.3295). MELD values of 19 or greater predicted 20% or greater mortality, whereas MELD scores less than 11 predicted less than 5% mortality. The model performed well for patients from Canada at all risk levels. In the Spanish validation set, in which all patients were treated with banding ligation, MELD predictions were accurate up to the 20% risk threshold. CONCLUSIONS: We developed a MELD-based model that accurately predicts mortality among patients with AVB, based on objective variables available at admission. This model could be useful to evaluate the efficacy of new therapies and stratify patients in randomized trials.

Transient elastography for the noninvasive assessment of liver fibrosis: a multicentre Canadian study.

BACKGROUND: Liver stiffness measurement (LSM) using transient elastography (TE) is a promising tool for the noninvasive assessment of hepatic fibrosis. OBJECTIVES: To determine the feasibility and performance of TE in a North American cohort of patients with chronic liver disease. METHODS: LSMs were obtained using TE in 260 patients with chronic hepatitis B or C, or nonalcoholic fatty liver disease from four Canadian hepatology centres. The accuracy of TE compared with liver biopsy for the prediction of significant fibrosis (Metavir fibrosis score of F2 or greater), bridging fibrosis (Metavir fibrosis score of F3 or greater) and cirrhosis (Metavir fibrosis score of F4 ) was assessed using area under ROC curves (AUROCs), and compared with the aspartate aminotransferase-to-platelet ratio index. The influence of alanine aminotransferase (ALT) levels and other factors on liver stiffness was determined using linear regression analyses. RESULTS: failure of TE occurred in 2.7% of patients, while liver biopsies were inadequate for staging in 0.8%. Among the remaining 251 patients, the AUROCs of TE for Metavir fibrosis scores of F2 and F3 or greater, and F4 were 0.74 (95% CI 0.68 to 0.80), 0.89 (95% CI 0.84 to 0.94), and 0.94 (95% CI 0.90 to 0.97), respectively. LSM was more accurate than the aminotransferase-to-platelet ratio index for bridging fibrosis (AUROC 0.78) and cirrhosis (AUROC 0.88), but not significant fibrosis (AUROC 0.76). At a cut-off of 11.1 kPa, the sensitivity, specificity, and positive and negative predictive values for cirrhosis (prevalence 11%) were 96%, 81%, 39% and 99%, respectively. For significant fibrosis (prevalence 53%), a cut-off of 7.7 kPa was 68% sensitive and 69% specific, and had a positive predictive value of 70% and a negative predictive value of 65%. Liver stiffness was independently associated with ALT, body mass index and steatosis. The optimal LSM cut-offs for cirrhosis were 11.1 kPa and 11.5 kPa in patients with ALT levels lower than 100 U/L and 100 U/L or greater, respectively. For fibrosis scores of F2 or greater, these figures were 7.0 kPa and 8.6 kPa, respectively. CONCLUSIONS: the major role of TE is the exclusion of bridging fibrosis and cirrhosis. However, TE cannot replace biopsy for the diagnosis of significant fibrosis. Because liver stiffness may be influenced by significant ALT elevation, body mass index and/or steatosis, tailored liver stiffness cut-offs may be necessary to account for these factors.