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Journal of Digestive Diseases 2014; 15; 321–326
doi: 10.1111/1751-2980.12141
Original article
Impact of nutritional status of Egyptian patients with end-stage liver disease on their outcomes after living donor liver transplantation Ayman YOSRY,* Dalia OMRAN,* Mohamad SAID,* Waleed FOUAD* & Osama FEKRY† *Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, and †Department of Clinical Nutrition, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
OBJECTIVE: Malnutrition is prevalent among patients with end-stage liver disease (ESLD) awaiting liver transplantation. Our aim was to examine prospectively the impact of patients’ nutritional status on their outcomes after living donor liver transplantation (LDLT). METHODS: In all, 30 patients scheduled for LDLT were subjected to a preoperative nutritional status assessment through subjective global assessment (SGA), nutritional risk screening (NRS 2002) and anthropometric measurements. All patients were followed up for 3 months after LDLT for mortality, graft rejection, number of clinically significant infective episodes, time spent in hospital (ward and intensive care unit [ICU]) and graft failure or dysfunction. RESULTS: All patients were nutritionally compromised (evaluated by SGA and NRS 2002), and were
divided into two groups: moderately and severely malnourished. Compared with moderately malnourished patients, severely malnourished patients showed significant postoperative hyperbilirubinemia, higher number of infective episodes and longer ICU stay. Preoperative triceps skinfold and mid-arm circumference were negatively correlated with the number of infective episodes (r = −0.33, P = 0.03 and r = −0.377, P = 0.04, respectively). Moreover, skeletal muscle mass was negatively correlated with postoperative serum alanine aminotransferase level (r = −0.52, P = 0.003) and the number of postoperative infective episodes (r = −0.3, P = 0.04).
CONCLUSION: Poor nutritional status of Egyptian patients with ESLD negatively affects the patients’ outcomes after LDLT.
KEY WORDS: anthropometry, end stage liver disease, liver transplantation, nutritional risk screening 2002, subjective global assessment.
INTRODUCTION Correspondence to: Dalia OMRAN, Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Hafez Badawey Street, Nasr City, Cairo, Egypt. Email: [email protected] Conflict of interest: None. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
Malnutrition is prevalent among patients with chronic liver disease (CLD),1–3 the severity of which ranges from subclinical status to overt protein-energy malnutrition.4 There are many factors that contribute to malnutrition in patients with CLD, including abnormal nutrient and caloric intake, decreased intestinal absorption, pancreatic insufficiency, cholestasis, portosystemic shunt, metabolic alterations, dietary
321
322
Journal of Digestive Diseases 2014; 15; 321–326
A Yosry et al.
restrictions, frequent lactulose therapy.4–7
paracentesis,
diuresis
and
Protein-energy malnutrition was reported to be associated with increased morbidity and mortality in patients undergoing liver transplantation.8–10 Thus, screening for malnutrition had been proposed as a part of liver transplantation protocols. The nutritional assessment of patients with CLD is complex due to a number of confounding factors. Body weight estimation is unreliable owing to variable degrees of ascites and edema. Serum albumin and other proteins, such as transferrin, prealbumin or retinol-binding proteins, which are commonly used as indicators of nutritional status in patients with normal liver function, are of limited values in patients with end-stage liver disease (ESLD) due to reduced protein synthesis by the liver in addition to increased catabolism caused by protein-calorie malnutrition.11 Although there has been no gold standard for the assessment of malnutrition in patients with CLD, anthropometry and subjective global assessment (SGA) have been considered the most useful indices of nutritional evaluation in such patients.2 Triceps skinfold thickness (TSF) has also been reported to be able to identify muscle and fat depletion.12,13 The aim of our study was to examine, with a prospective design, the influence of the ESLD patients’ nutritional status on the outcome of living donor liver transplantation (LDLT).
Before transplantation, all patients were subjected to a nutritional status assessment (carried out by a single operator): 1. SGA was performed as described by Detsky14 and modified by Hasse et al.15 SGA integrates medical and dietary history, body weight and height, coexisting medical conditions, and physical activity to classify patients into: well-nourished, moderately malnourished, or severely malnourished. 2. Nutritional risk screening 2002 (NRS 2002)16: the degree of malnutrition was recorded according to a grading scale questionnaire ranging from 0 up to 6 points. 3. Anthropometric including
were
taken,
•
body weight (kg)
•
body mass index (BMI, kg/m2)
•
mid-arm circumference (MAC, cm) was measured with a spring tape at a point between the tip of acromion and the ulnar process, with the arm hanging vertically.
•
TSF (mm) was obtained using a Lange Skinfold Caliper (Cambridge Scientific Industries, Cambridge, MD, USA) with a constant pressure of 10 g/mm2 on the contact surface. The measure was taken on the back of the arm, parallel to the longitudinal axis, at the midpoint between the acromion and olecranon about 4 s after placing the caliper tips on the skinfold.
•
mid-leg circumference (MLC, cm). A nonstretchable measuring tape was looped horizontally around the greatest calf circumference while the patient sit on the examination table with the right or left leg hanging freely. The tape was tightened around the calf so that it contacted the skin without indenting or compressing the soft tissue.
PATIENTS AND METHODS Thirty male patients with ESLD scheduled for LDLT at liver transplant centers in Dar-Al Fouad Hospital (21 patients) and El Manial Specialized Hospital, Cairo University (9 patients) were enrolled in our study. In our transplantation program most recipients are men, and women constitute only 4% of the total recipients. All patients who received transplantation during the study period were men, and thus there was no selection bias against women. Nine patients received liver transplantation from their sons, five from their wives and sixteen from matching volunteers. In our protocol, the graft recipient weight ratio was ≥ 1 to avoid small-for-size syndrome. The study was conducted in accordance with the 1975 Helsinki Declaration and was approved by the Institutional Ethics Committee of Cairo University and the National Hepatology and Tropical Medicine Research Institute. Written informed consent was obtained from each patient before the enrollment.
measurements
In each case we used the mean values of three consecutive measurements. •
body composition was evaluated by bioelectrical impedance. Each patient was scanned using Omron HBF-510W (Omron
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2014; 15; 321–326 Healthcare, Inc., Lake Forest, IL, USA). BMI, visceral fat level and percentage of body fat and skeletal muscle were recorded.17 Postoperative immunosuppressive therapy included a first-line therapy of steroid for 3 months and calcineurin inhibitors (CNI) with mycophenolate mofetil. As a second-line therapy, CNI was replaced with everolimus when non-manageable adverse effects occurred. After LDLT, all the patients were followed up for a period of 3 months for mortality, graft rejection, number of clinically significant infective episodes requiring systemic antibiotics or antiviral therapy, length of hospital stay (ward and intensive care unit [ICU]) and graft failure or dysfunction, by using postoperative serum total bilirubin, liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) levels and international normalized ratio (INR). Statistical analysis Statistical analyses were performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA). Quantitative variables were expressed as mean ± standard deviations (SD), and were compared using Student’s t-test and paired t-test, Wilcoxon signed-rank test or ANOVA test, when appropriate. Pearson’s correlation for correlating quantitative variables and regression were used. Qualitative variables were expressed as number (frequency) and percentage. P ≤ 0.05 was considered statistically significant. RESULTS These patients were divided into two groups according to their SGA: moderately malnourished (n = 16) and severely malnourished patients (n = 14). According to their NRS 2002 scores, 11 patients were moderately malnourished (NRS 2002 score < 4) and 19 patients were severely malnourished (NRS 2002 score ≥ 4). There was significant agreement between SGA and NRS (83.3%) in the assessment of nutritional status (κappa = 0.67, P < 0.001). The baseline characteristics of the patients are shown in Table 1. According to the Child–Pugh classification, 13 patients were Child– Pugh A and B and 17 were Child–Pugh C. The effect of Child–Pugh grade on the outcome of LDLT was not significant (Table 2). During the 3-month follow-up after LDLT, there was no reported death of patients or graft rejection. There
Malnutrition and liver transplantation
323
Table 1. Baseline characteristics of the enrolled patients (n = 30) Characteristics Age (years, mean ± SD) Gender (n, male/female) Child–Pugh classification (n, A/B/C) BMI (kg/m2, mean ± SD) Skeletal muscle (%, mean ± SD [recorded by bioelectrical impedance]) TSF (mm, mean ± SD) MAC (cm, mean ± SD) MLC (cm, mean ± SD)
50.3 ± 4.85 30/0 3/10/17 28.40 ± 3.78 33.97 ± 4.03 2.25 ± 0.85 26.56 ± 3.88 35.56 ± 3.88
BMI, body mass index; MAC, mid-arm circumference; MLC, midleg circumference; TSF, triceps skinfold thickness.
Table 2. Effect of Child–Pugh classification on the outcome of living donor liver transplantation Child–Pugh Child–Pugh A and B C P value Time spent in ICU (n)
Journal of Digestive Diseases 2014; 15; 321–326
doi: 10.1111/1751-2980.12141
Original article
Impact of nutritional status of Egyptian patients with end-stage liver disease on their outcomes after living donor liver transplantation Ayman YOSRY,* Dalia OMRAN,* Mohamad SAID,* Waleed FOUAD* & Osama FEKRY† *Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, and †Department of Clinical Nutrition, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
OBJECTIVE: Malnutrition is prevalent among patients with end-stage liver disease (ESLD) awaiting liver transplantation. Our aim was to examine prospectively the impact of patients’ nutritional status on their outcomes after living donor liver transplantation (LDLT). METHODS: In all, 30 patients scheduled for LDLT were subjected to a preoperative nutritional status assessment through subjective global assessment (SGA), nutritional risk screening (NRS 2002) and anthropometric measurements. All patients were followed up for 3 months after LDLT for mortality, graft rejection, number of clinically significant infective episodes, time spent in hospital (ward and intensive care unit [ICU]) and graft failure or dysfunction. RESULTS: All patients were nutritionally compromised (evaluated by SGA and NRS 2002), and were
divided into two groups: moderately and severely malnourished. Compared with moderately malnourished patients, severely malnourished patients showed significant postoperative hyperbilirubinemia, higher number of infective episodes and longer ICU stay. Preoperative triceps skinfold and mid-arm circumference were negatively correlated with the number of infective episodes (r = −0.33, P = 0.03 and r = −0.377, P = 0.04, respectively). Moreover, skeletal muscle mass was negatively correlated with postoperative serum alanine aminotransferase level (r = −0.52, P = 0.003) and the number of postoperative infective episodes (r = −0.3, P = 0.04).
CONCLUSION: Poor nutritional status of Egyptian patients with ESLD negatively affects the patients’ outcomes after LDLT.
KEY WORDS: anthropometry, end stage liver disease, liver transplantation, nutritional risk screening 2002, subjective global assessment.
INTRODUCTION Correspondence to: Dalia OMRAN, Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Hafez Badawey Street, Nasr City, Cairo, Egypt. Email: [email protected] Conflict of interest: None. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
Malnutrition is prevalent among patients with chronic liver disease (CLD),1–3 the severity of which ranges from subclinical status to overt protein-energy malnutrition.4 There are many factors that contribute to malnutrition in patients with CLD, including abnormal nutrient and caloric intake, decreased intestinal absorption, pancreatic insufficiency, cholestasis, portosystemic shunt, metabolic alterations, dietary
321
322
Journal of Digestive Diseases 2014; 15; 321–326
A Yosry et al.
restrictions, frequent lactulose therapy.4–7
paracentesis,
diuresis
and
Protein-energy malnutrition was reported to be associated with increased morbidity and mortality in patients undergoing liver transplantation.8–10 Thus, screening for malnutrition had been proposed as a part of liver transplantation protocols. The nutritional assessment of patients with CLD is complex due to a number of confounding factors. Body weight estimation is unreliable owing to variable degrees of ascites and edema. Serum albumin and other proteins, such as transferrin, prealbumin or retinol-binding proteins, which are commonly used as indicators of nutritional status in patients with normal liver function, are of limited values in patients with end-stage liver disease (ESLD) due to reduced protein synthesis by the liver in addition to increased catabolism caused by protein-calorie malnutrition.11 Although there has been no gold standard for the assessment of malnutrition in patients with CLD, anthropometry and subjective global assessment (SGA) have been considered the most useful indices of nutritional evaluation in such patients.2 Triceps skinfold thickness (TSF) has also been reported to be able to identify muscle and fat depletion.12,13 The aim of our study was to examine, with a prospective design, the influence of the ESLD patients’ nutritional status on the outcome of living donor liver transplantation (LDLT).
Before transplantation, all patients were subjected to a nutritional status assessment (carried out by a single operator): 1. SGA was performed as described by Detsky14 and modified by Hasse et al.15 SGA integrates medical and dietary history, body weight and height, coexisting medical conditions, and physical activity to classify patients into: well-nourished, moderately malnourished, or severely malnourished. 2. Nutritional risk screening 2002 (NRS 2002)16: the degree of malnutrition was recorded according to a grading scale questionnaire ranging from 0 up to 6 points. 3. Anthropometric including
were
taken,
•
body weight (kg)
•
body mass index (BMI, kg/m2)
•
mid-arm circumference (MAC, cm) was measured with a spring tape at a point between the tip of acromion and the ulnar process, with the arm hanging vertically.
•
TSF (mm) was obtained using a Lange Skinfold Caliper (Cambridge Scientific Industries, Cambridge, MD, USA) with a constant pressure of 10 g/mm2 on the contact surface. The measure was taken on the back of the arm, parallel to the longitudinal axis, at the midpoint between the acromion and olecranon about 4 s after placing the caliper tips on the skinfold.
•
mid-leg circumference (MLC, cm). A nonstretchable measuring tape was looped horizontally around the greatest calf circumference while the patient sit on the examination table with the right or left leg hanging freely. The tape was tightened around the calf so that it contacted the skin without indenting or compressing the soft tissue.
PATIENTS AND METHODS Thirty male patients with ESLD scheduled for LDLT at liver transplant centers in Dar-Al Fouad Hospital (21 patients) and El Manial Specialized Hospital, Cairo University (9 patients) were enrolled in our study. In our transplantation program most recipients are men, and women constitute only 4% of the total recipients. All patients who received transplantation during the study period were men, and thus there was no selection bias against women. Nine patients received liver transplantation from their sons, five from their wives and sixteen from matching volunteers. In our protocol, the graft recipient weight ratio was ≥ 1 to avoid small-for-size syndrome. The study was conducted in accordance with the 1975 Helsinki Declaration and was approved by the Institutional Ethics Committee of Cairo University and the National Hepatology and Tropical Medicine Research Institute. Written informed consent was obtained from each patient before the enrollment.
measurements
In each case we used the mean values of three consecutive measurements. •
body composition was evaluated by bioelectrical impedance. Each patient was scanned using Omron HBF-510W (Omron
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2014; 15; 321–326 Healthcare, Inc., Lake Forest, IL, USA). BMI, visceral fat level and percentage of body fat and skeletal muscle were recorded.17 Postoperative immunosuppressive therapy included a first-line therapy of steroid for 3 months and calcineurin inhibitors (CNI) with mycophenolate mofetil. As a second-line therapy, CNI was replaced with everolimus when non-manageable adverse effects occurred. After LDLT, all the patients were followed up for a period of 3 months for mortality, graft rejection, number of clinically significant infective episodes requiring systemic antibiotics or antiviral therapy, length of hospital stay (ward and intensive care unit [ICU]) and graft failure or dysfunction, by using postoperative serum total bilirubin, liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) levels and international normalized ratio (INR). Statistical analysis Statistical analyses were performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA). Quantitative variables were expressed as mean ± standard deviations (SD), and were compared using Student’s t-test and paired t-test, Wilcoxon signed-rank test or ANOVA test, when appropriate. Pearson’s correlation for correlating quantitative variables and regression were used. Qualitative variables were expressed as number (frequency) and percentage. P ≤ 0.05 was considered statistically significant. RESULTS These patients were divided into two groups according to their SGA: moderately malnourished (n = 16) and severely malnourished patients (n = 14). According to their NRS 2002 scores, 11 patients were moderately malnourished (NRS 2002 score < 4) and 19 patients were severely malnourished (NRS 2002 score ≥ 4). There was significant agreement between SGA and NRS (83.3%) in the assessment of nutritional status (κappa = 0.67, P < 0.001). The baseline characteristics of the patients are shown in Table 1. According to the Child–Pugh classification, 13 patients were Child– Pugh A and B and 17 were Child–Pugh C. The effect of Child–Pugh grade on the outcome of LDLT was not significant (Table 2). During the 3-month follow-up after LDLT, there was no reported death of patients or graft rejection. There
Malnutrition and liver transplantation
323
Table 1. Baseline characteristics of the enrolled patients (n = 30) Characteristics Age (years, mean ± SD) Gender (n, male/female) Child–Pugh classification (n, A/B/C) BMI (kg/m2, mean ± SD) Skeletal muscle (%, mean ± SD [recorded by bioelectrical impedance]) TSF (mm, mean ± SD) MAC (cm, mean ± SD) MLC (cm, mean ± SD)
50.3 ± 4.85 30/0 3/10/17 28.40 ± 3.78 33.97 ± 4.03 2.25 ± 0.85 26.56 ± 3.88 35.56 ± 3.88
BMI, body mass index; MAC, mid-arm circumference; MLC, midleg circumference; TSF, triceps skinfold thickness.
Table 2. Effect of Child–Pugh classification on the outcome of living donor liver transplantation Child–Pugh Child–Pugh A and B C P value Time spent in ICU (n)
