|Year : 2021 | Volume
| Issue : 4 | Page : 143-147
Dynamic scoring of appetite predicts inpatient survival in patients with acute-on-chronic liver failure
Rajeeb Jaleel1, Anand Sharma1, Vimala Selvaraj2, Rekha Aaron3, Jayaprakash Muliyil3, Balakrishnan Vijayalekshmi3, Kunnisery Ananthsubramanian Balasubramanian3, Balavendra Antonisamy4, Ashish Goel1, Uday George Zachariah1, Chundamannil Eapen Eapen1
1 Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Nursing Services, Christian Medical College, Vellore, Tamil Nadu, India
3 Wellcome Trust Research Laboratory, Division of GI Sciences, Christian Medical College, Vellore, Tamil Nadu, India
4 Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India
|Date of Submission||02-Mar-2021|
|Date of Acceptance||20-Aug-2021|
|Date of Web Publication||24-Sep-2021|
Department of Hepatology, Christian Medical College, Ida Scudder Road, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background and Aim: Decreased appetite is common in patients with liver disease and may be mediated by inflammatory cytokines. Acute-on-chronic liver failure (ACLF) is associated with raised inflammatory cytokines. The aim of this study was to evaluate appetite scoring as a predictor of inhospital survival in patients with ACLF. Methods: In a prospective observational study, consecutive hospitalized patients with ACLF were recruited. Appetite was assessed daily using Simplified Nutritional Appetite Questionnaire (SNAQ). The total SNAQ score ranged from 4 to 20, and a change in SNAQ score ≥1 was considered significant. Patients received standard medical care. Outcome was defined as good when patient was discharged in a stable condition and as poor if patient died or was discharged in terminal state. Results: Seventy-five ACLF patients (mean age 44 years; 66 males) were recruited. The median length of hospital stay was 5 (range: 1–20) days. Outcome was good in 50 and poor in 25 patients. Patients with good outcome had higher Day 1 SNAQ score (median: 12, range: 7–16) than patients with poor outcome (median: 10, range: 5–16) (P < 0.001). The area under receiver operating characteristic curve to predict poor outcome was 0.71 (95% confidence interval [CI]: 0.56–0.86) for Day 1 SNAQ score and 0.90 (95% CI: 0.82–0.98) for SNAQ δ. When divided into tertiles based on Day 1 SNAQ score, the outcome was good for all patients whose appetite improved and poor for all patients whose appetite worsened on Day 3. Conclusion: Appetite (SNAQ) scores on Day 1 and change on Day 3 predict inhospital survival in ACLF patients. SNAQ is a simple bedside tool which may help in guiding therapeutic decisions in ACLF patients. Further larger studies are required to validate these findings.
Keywords: Liver disease, outcome, Simplified Nutritional Assessment Questionnaire score
|How to cite this article:|
Jaleel R, Sharma A, Selvaraj V, Aaron R, Muliyil J, Vijayalekshmi B, Balasubramanian KA, Antonisamy B, Goel A, Zachariah UG, Eapen CE. Dynamic scoring of appetite predicts inpatient survival in patients with acute-on-chronic liver failure. Gastroenterol Hepatol Endosc Pract 2021;1:143-7
|How to cite this URL:|
Jaleel R, Sharma A, Selvaraj V, Aaron R, Muliyil J, Vijayalekshmi B, Balasubramanian KA, Antonisamy B, Goel A, Zachariah UG, Eapen CE. Dynamic scoring of appetite predicts inpatient survival in patients with acute-on-chronic liver failure. Gastroenterol Hepatol Endosc Pract [serial online] 2021 [cited 2021 Oct 24];1:143-7. Available from: http://www.ghepjournal.com/text.asp?2021/1/4/143/326638
| Introduction|| |
Acute-on-chronic liver failure (ACLF) is a syndrome associated with organ failures and high short-term mortality., Identification of prognostic indicators in ACLF patients is needed to guide appropriate treatment. Different prognostic indicators found useful in ACLF patients include scores of liver disease severity,, markers of endothelial activation,, and markers of macrophage activation.
Anorexia is commonly associated with most diseases including cirrhosis. The pathogenesis of reduced appetite is multifactorial and may be secondary to raised inflammatory cytokines including interleukin (IL)-1, IL-6, IL-8, leptin, tumor necrosis factor (TNF)-α, and interferon-gamma. Pro-inflammatory cytokines drive liver injury in ACLF patients.
In many situations, decision-making for managing patients with liver diseases like ACLF is based on qualitative inputs. In such situations, it is the usual practice for the clinical team to look at reports of appropriate tests like serial biochemistry and then assess the patient clinically. Such decision-making may involve assessing fitness for discharge, assessment of prognosis, and need for additional therapeutic interventions.
Wang and Shen assessed appetite in hospitalized patients with cirrhosis using a Simplified Nutritional Assessment Questionnaire (SNAQ) and found a significant correlation with low serum albumin and weight loss, but its correlation with clinical outcome was not evaluated. The SNAQ score consists of four components – present appetite, degree of abdominal fullness and quantity of food intake, taste of the food, and comparison of present food intake with premorbid food intake. Each component is scored from 1 to 5. The total score of SNAQ ranges from 4 to 20.
In this study, we evaluated whether dynamic appetite scores correlate with liver disease severity scores such as the Model for End-Stage Liver Disease (MELD) score and also with survival. We studied the role of appetite in patients with ACLF in relation to inhospital survival using SNAQ as the assessment tool. Low levels of apolipoprotein A1 (Apo A1) predicts the severity of liver failure, complications, and survival in patients with cirrhosis. Hence, we also looked for any correlation between plasma TNF-α and Apo A1 levels in a subset of the study patients.
| Methods|| |
This prospective observational study was conducted in the Department of Hepatology in our institution from January 1, 2016, to February 28, 2017. The primary objective of the study was to correlate SNAQ score on Day 1 of hospital stay and change in SNAQ score between Day 1 and Day 3 with inhospital survival in patients with ACLF. Consecutive inpatients fulfilling criteria for ACLF as per the Asian Pacific Association for the Study of the Liver 2014 (serum bilirubin ≥5 mg/dl and international normalized ratio ≥1.5 complicated within 4 weeks by ascites in a patient with previously diagnosed or undiagnosed chronic liver disease) were recruited for the study. Patients with hepatic encephalopathy, age <18 years, pregnancy, hepatocellular carcinoma, portal vein thrombosis, delirium, and alcohol withdrawal were excluded.
Appetite score was assessed daily by a nurse using SNAQ. The nurse performing SNAQ score was blinded to the disease severity and other laboratory reports of the study patients. The SNAQ questionnaire was translated and administered in the native language of the patient (i.e., Tamil, Telugu, Hindi, Bengali, or English).
Plasma TNF-α levels were measured using Quantikine immunoassay kit (R and D Systems). Plasma Apo A1 levels were measured using EHAPOA1 ELISA kit (from Thermo Scientific), and values were calculated from standard curve using four-parameter logistic curve analysis.
Patient inhospital outcome was classified as good (discharged in stable condition) or poor (discharged in terminal state or died). In patients who were still in hospital on Day 3, appetite (SNAQ) score on Day 1 was divided into tertiles and the resultant categories were named “good appetite,” “intermediate appetite,” and “poor appetite.” The movement of these patients from one category to the other was analyzed. Any change in SNAQ score from Day 1 of admission to Day 3 of admission (henceforth called SNAQ δ) ≥1 was considered significant.
Since there was no similar studies utilizing SNAQ questionnaire in liver disease for assessment of appetite, sample size of our study was arbitrarily chosen as 75 patients diagnosed and admitted with ACLF.
The continuous variables were expressed as median and range. The categorical variables were expressed as numbers and percentage. The patients with good outcome and poor outcome were compared using Mann–Whitney U-test for continuous variables and Chi-square test for categorical variables. Correlation of SNAQ score on Day 1 with disease severity scores (Sequential Organ Failure Assessment [SOFA] and MELD scores) on Day 1 was studied using Spearman's correlation coefficient. Receiver operator characteristic curve (ROC) was used to study the ability of SNAQ score, SOFA, MELD, and Lactate-free AARC ACLF Score (LaFAS) on Day 1 to predict poor outcome. ROC was used to study the ability of SNAQ δ to predict poor outcome.
P < 0.05 was considered statistically significant. Statistical analysis was done using SPSS (IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp).
The study was approved by the Institutional Ethics Committee of the Christian Medical College, Vellore.
| Results|| |
Baseline characteristics of the study population
Seventy-five consecutive inpatients with ACLF were recruited for the study after obtaining informed consent [Table 1]. Most patients were from eastern and southern states of India. Fifty (68%) patients had good outcome and 25 (33%) patients had poor outcome (discharged in terminal state 16 patients; died 9 patients). None of the patients studied underwent liver transplant. The median duration of hospital stay was 5 (range: 1–20) days. The baseline details and disease severity of the study patients are given in [Table 1]. Alcohol was the most common etiology of acute insult in patients with good outcome (36%) and poor outcome (64%). Alcohol was also the single most common etiology of underlying chronic liver disease in patients with good outcome (50%) and poor outcome (72%).
|Table 1: Baseline details and liver disease severity scores in 75 acute-on-chronic liver failure patients with good outcome and poor outcome|
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Daily appetite assessment by Simplified Nutritional Assessment Questionnaire scores in 75 acute-on-chronic liver failure patients
The median SNAQ score on Day 1 in 75 ACLF patients was 11 (range: 9–14). ACLF patients who had good outcome had significantly better appetite scores throughout hospital stay compared to those who had poor outcome [Table 2].
|Table 2: Appetite assessment by Simplified Nutritional Assessment Questionnaire scores on each day of hospital stay in acute-on-chronic liver failure patients who were still admitted on the respective day|
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Correlation with appetite score with disease severity scores on Day 1 of hospital stay in 75 acute-on-chronic liver failure patients
SNAQ score had a moderate negative correlation with MELD score (r = −0.28; P = 0.02) and SOFA score (r = −0.34; P = 0.002) on Day 1 of hospital stay.
Day 1 appetite (Simplified Nutritional Assessment Questionnaire) score and disease severity scores as a predictor of poor outcome in 75 acute-on-chronic liver failure patients
The area under ROC curve (AUROC) to predict poor outcome for SNAQ score, MELD, LaFAS, and SOFA scores on Day 1 in the 75 study patients was 0.71 (95% confidence interval [CI]: 0.56–0.86), 0.70 (95% CI: 0.56–0.84), 0.72 (95% CI: 0.58–0.86), and 0.65 (95% CI: 0.52–0.78), respectively [Figure 1].
|Figure 1: Area under the receiver operator characteristic curve for predicting poor outcome by appetite assessment (Simplified Nutriational Appetite Questionnairre score), model for end-stage liver disease, and lactate-free AARC ACLF Score in 62 patients who were still admitted on Day 3|
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Serial change in appetite on Day 3 of hospital stay in 62 acute-on-chronic liver failure patients
On Day 3 of hospital stay, 62 patients were still in hospital. In these patients, the median SNAQ score on Day 1 and improvement in appetite on Day 3 from Day 1 were significantly higher in patients with good outcome (n = 42). Serial decrease in appetite on Day 3 was more often seen in patients with poor outcome (n = 20). These 62 patients were divided into tertiles based on Day 1 SNAQ scores and categorized as “good appetite,” “intermediate appetite,” and “poor appetite” representing SNAQ score of <9, 9–12, and >12, respectively. Most of the patients belonging to the categories “good appetite” and “poor appetite” on Day 1 stayed in the same category on Day 3. Of the 28 patients belonging to “intermediate appetite” category on Day 1, the outcome was good in all 7 patients who had better appetite on Day 3 (100%) and poor in all 5 patients whose appetite worsened on Day 3 (100%) [Figure 2].
|Figure 2: The categories of patients based on SNAQ score on Day 1, namely “good appetite” (SNAQ >12), “intermediate appetite” (SNAQ 9–12), and “poor appetite” (SNAQ <9), have been depicted by the emotions. The number of patients who change from one appetite category to the other on Day 3 and their respective outcome are shown. SNAQ: Simplified Nutritional Assessment Questionnaire|
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AUROC for SNAQ δ to predict poor outcome was 0.90 (95% CI: 0.82, 0.98) [Figure 1].
Plasma tumor necrosis factor-α and apolipoprotein A1 levels in patients with acute-on-chronic liver failure
Of the 34 patients tested, there was a trend to lower plasma TNF-α values in 19 patients with good outcome (median: 25.7, range: 7.8–264.5) pg/ml than 13 patients with poor outcome (median: 33.7, range: 13.5–45.5 pg/ml) (P = 0.12), which was not statistically significant.
Of the 25 patients tested, plasma Apo A1 levels in 15 patients with good outcome (median: 3.2, range: 0.4–16.3 ng/dl) compared to 10 patients with poor outcome (median: 6.5, range: 0.8–56.3 ng/dl) (P = 0.08) were lower but not statistically significant.
There was no significant correlation of plasma TNF-α and Apo A1 with SNAQ score on Day 1.
| Discussion|| |
In this study of 75 patients with ACLF, we document appetite assessment to have prognostic significance. Appetite was significantly lower (lower SNAQ score) on admission in patients who had a poor outcome compared to patients with good outcome. Improvement of appetite on Day 3 compared to Day 1 was significantly more common in patients who had a good outcome, whereas patients with poor outcome showed significantly reduced appetite on Day 3 compared to Day 1.
The period from onset of liver failure to onset of sepsis and extrahepatic organ failure has been termed as the “golden window,” when appropriate intervention may improve prognosis of the patients. Hence, a score to identify patients with poor prognosis can help intensify the effort in the right direction.
The subjective nature of appetite makes it difficult to quantify. Questionnaires such as Functional Assessment of Anorexia/Cachexia Therapy and Appetite, Hunger, Feelings, and Sensory Perception have not been validated in liver disease patients and are too cumbersome for bedside use. SNAQ has been studied in patients with cirrhosis to predict malnutrition. SNAQ score <14 has been shown to predict weight loss >5% within 6 months with a sensitivity of 81.5% and a specificity of 76.4% and weight loss of >10 with a sensitivity and specificity of 88.2% and 83.5%, respectively. Moreover, the simplicity and ease of administration of the questionnaire makes it a suitable bedside tool for daily assessment of appetite.
In our study, SNAQ score on Day 1 of hospital stay and dynamic change in appetite were good predictors of inhospital survival. Thus, the clinical worsening is reflected by the decrease in appetite over the course of admission in patients with poor outcome. When categorized based on SNAQ scores on Day 1, it was noted that most of the patients belonging to “good appetite” and “poor appetite” categories on Day 1 stayed in the same category on Day 3. In contrast, appetite (SNAQ) scores on Day 3 changed to a different category in 12/28 (43%) of patients who were in “intermediate appetite” category on Day 1 and this change correlated with the outcome [Figure 2]. Thus, appetite assessment can help identify the patients in whom intensification of therapeutic efforts may yield the maximum clinical benefit.
In this study, dynamic appetite scoring correlated with MELD score and with inpatient survival in ACLF patients. It is likely that the disease process affecting liver function is reflected in MELD score as well as in appetite score. We believe our study sets the stage for further studies to assess the utility of appetite scoring to help with clinical decision-making in ACLF patients, wherein the patient management requires qualitative inputs, in addition to objective scores of liver function.
Inflammation plays an important role in pathophysiology of ACLF. Since the decrease in appetite in acute and chronic diseases is mediated by cytokines and other inflammatory mediators, it is plausible that there might be a relationship between appetite and clinical outcomes in ACLF patients. The SNAQ score of ACLF patients in our study was lower than that in the cirrhotic patients from the study by Wang and Shen. This may be a reflection of heightened systemic inflammation in ACLF compared to low-grade systemic inflammation in cirrhosis. On Day 1, lower plasma TNF-α and Apo A1 levels were noted in ACLF patients with good outcome in our study. However, this did not correlate with SNAQ scores or outcome. This may be because they were measured in only a subset of the study population and need to be evaluated in a larger population. We did not analyze other possible causes of reduced appetite such as gastritis and medications.
| Conclusion|| |
Appetite assessment by SNAQ score at baseline and the change in score from Day 1 to Day 3 are good predictors of inhospital survival in ACLF patients. This can be incorporated into clinical practice to help guide therapeutic decisions. Studies with larger number of patients are needed to validate these results.
We would like to thank Dr. George Kurian, Professor and Former Head of Gastroenterology Department, Christian Medical College, Vellore, whose clinical observation sparked this research idea.
Financial support and sponsorship
Funding support from FLUID research funds, Christian Medical College, Vellore, Tamil Nadu, India
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]