Ahmed Hammad

Impact of quality as well as quantity of skeletal muscle on outcomes after liver transplantation

Intramuscular fat accumulation has come to be associated with loss of muscle strength and function, one of the components of sarcopenia. However, the impact of preoperative quality of skeletal muscle on outcomes after living donor liver transplantation (LDLT) is unclear. The present study evaluated the intramuscular adipose tissue content (IMAC) and psoas muscle mass index (PMI) in 200 adult patients undergoing LDLT at our institution between January 2008 and October 2013. Correlations of IMAC with other factors, overall survival rates in patients classified according to IMAC or PMI, and risk factors for poor survival after LDLT were analyzed. IMAC was significantly correlated with age (r = 0.229, P = 0.03) and PMI (r = −0.236, P = 0.02) in males and with age (r = 0.349, P < 0.001) and branched‐chain amino acid (BCAA)‐to‐tyrosine ratio (r = −0.250, P = 0.01) in females. The overall survival rates in patients with high IMAC or low PMI were significantly lower than those for patients with normal IMAC or PMI (P < 0.001, P < 0.001, respectively). Multivariate analysis showed that high IMAC [odds ratio (OR) = 3.898, 95% confidence interval (CI) = 2.025‐7.757, P < 0.001] and low PMI (OR = 3.635, 95% CI = 1.896‐7.174, P < 0.001) were independent risk factors for death after LDLT. In conclusion, high IMAC and low PMI were closely involved with posttransplant mortality. Preoperative quality and quantity of skeletal muscle could be incorporated into new selection criteria for LDLT. Perioperative nutritional therapy and rehabilitation could be important for good outcomes after LDLT. Liver Transpl 20:1413‐1419, 2014.

Impact of preoperative quality as well as quantity of skeletal muscle on survival after resection of pancreatic cancer

BACKGROUND Skeletal muscle depletion, referred to as sarcopenia, is predictive of mortality in patients undergoing digestive operations. The impact of muscle quality on outcomes, however, is unclear. This retrospective study investigated the impact of preoperative skeletal muscle quantity and quality on survival in patients undergoing resection of pancreatic cancer. METHODS We investigated 230 patients who underwent resection of pancreatic cancer between 2004 and 2013. The quantity and quality of skeletal muscle, indicated by psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), were measured in preoperative computed tomography images. Overall survival (OS) and recurrence-free survival (RFS) rates were compared according to PMI and IMAC, and prognostic factors after pancreatic resection were assessed. RESULTS The OS and RFS rates in patients with low PMI were lesser than in those with normal/high PMI (P < .001, P < .001), with a mean survival time of 17.7 and 33.2 months, respectively. The OS and RFS rates in patients with high IMAC also were less than in those with normal/low IMAC (P < .001, P = .003) (mean survival time = 21.5 and 56.5 months, respectively). Low PMI (low muscle mass) and high IMAC (low muscle quality) were independent prognostic factors of poor OS (hazard ratio [HR] = 1.999, P < .001; HR = 2.527, P < .001) and RFS (HR = 1.607, P = .007; HR = 1.640, P = .004), respectively. CONCLUSION Preoperative sarcopenia, indicating low quality and quantity of skeletal muscle, is closely related to mortality after resection of pancreatic cancer.

Preoperative intramuscular adipose tissue content is a novel prognostic predictor after hepatectomy for hepatocellular carcinoma

Sarcopenia has been shown to be an independent predictor of lower disease‐free and overall survival in various kinds of diseases. The quality of skeletal muscle has recently attracted much attention as a new parameter of sarcopenia.

Perioperative nutritional therapy in liver transplantation.

Protein-energy malnutrition is frequently seen in patients with end-stage liver disease who undergo liver transplantation. This causes a deterioration of the patients’ clinical condition and affects their post-transplantation survival. Accurate assessment of the nutritional status and adequate intervention are prerequisites for perioperative nutritional treatment. However, the metabolic abnormalities induced by liver failure make the traditional assessment of the nutritional status difficult. The methods that were recently developed for accurately assessing the nutritional status by body bioelectrical impedance may be implemented in pre-transplant management. Because preoperative malnutrition and the loss of skeletal muscle mass, called sarcopenia, have a significant negative impact on the post-transplantation outcome, it is essential to provide adequate nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the necessary caloric intake. We herein discuss both bioelectrical impedance and the latest findings in the current perioperative nutritional interventions in liver transplant patients regarding synbiotics, micronutrients, branched-chain amino acid supplementation, the use of immune system modulating formulas, the fluid balance and the offering of nocturnal meals.

Proposal of Muscle-MELD score, including muscularity, for prediction of mortality after living donor liver transplantation.

Background The Model for End-stage Liver Diseases (MELD) is currently the most widely accepted scoring system for predicting prognosis and for allocation of liver grafts in patients awaiting liver transplantation (LT). However, this system is independent of the severity of recipient nutritional and functional status. Methods The present study retrospectively evaluated the preoperative quality and quantity of skeletal muscle in 231 adult patients undergoing living donor LT (LDLT) between January 2008 and December 2014. Using plain computed tomography imaging at the third lumbar vertebral level, the preoperative muscularity (quantity and quality of skeletal muscle) was evaluated. We included muscularity with the MELD score (Muscle-MELD) and investigated its ability to predict posttransplant mortality. Results Cox regression analysis provided the following equation for Muscle-MELD: Muscle-MELD = MELD score + 27.0 × low muscle quality + 25.2 × low muscle mass. The overall survival rate after LDLT was significantly lower in patients with high Muscle-MELD than in patients with low Muscle-MELD scores (P < 0.001). Muscle-MELD scores more accurately predicted posttransplant mortality than conventional MELD scores (P = 0.038 for 3 months, P = 0.002 for 6 months, P < 0.001 for 12 months, and P = 0.001 for overall mortality). With multivariate analysis, high Muscle-MELD score was an independent predictor of 6-month mortality after LDLT (odds ratio, 6.715; 95% confidence interval, 3.305-14.653; P < 0.001). Conclusions Muscle-MELD score closely correlates with posttransplant mortality. Our results suggest that perioperative nutritional intervention and rehabilitation would affect posttransplant outcomes with improving pretransplant low muscularity.

Impact of sarcopenic overweight on the outcomes after living donor liver transplantation

Background The effect of body composition disturbances has been recently in focus. Sarcopenic obesity, a co-occurrence of low muscle mass and high body fat was reportedly predictive of high mortality in patients with cirrhosis. However, the impact of the interacting sarcopenia and overweight on the outcomes after liver transplantation is still unclear. Methods We evaluated 200 patients undergoing adult-to-adult living donor liver transplantation at our institution between January 2008 and November 2013 classified according to BMI and psoas muscle index (PMI) on admission to transplant into 4 subgroups; sarcopenic overweight (SO), sarcopenic non-overweight (SN), non-sarcopenic overweight and non-sarcopenic non-overweight (NN). Short-term outcomes and overall post-transplant survival were compared among the four subgroups. Results Sarcopenic patients with preoperative low PMI had higher incidence of postoperative bacteremia and major postoperative complications, and poorer overall post-transplant survival than non-sarcopenic patients with normal/high PMI (P<0.001, respectively). Overweight recipients had a significantly higher overall survival (OS) rate than non-overweight patients (P=0.021). SO subgroup (low PMI and BMI ≥25) had statistically indifferent incidence of postoperative bacteremia, major postoperative complications or overall post-transplant survival than other recipients. In contrast, SN subgroup (low PMI and BMI <25) had higher incidence of postoperative bacteremia (P<0.001), major postoperative complications (P<0.001) than the SO subgroup and possessed the poorest OS among the four recipient subgroups (P=0.001). Conclusions In living donor liver transplantation, preoperative SO did not confer added significant morbidity or mortality risks than the stand-alone sarcopenia.

Nutritional Therapy in Liver Transplantation

Protein-energy malnourishment is commonly encountered in patients with end-stage liver disease who undergo liver transplantation. Malnutrition may further increase morbidity, mortality and costs in the post-transplantation setting. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognized. The metabolic abnormalities induced by liver failure render the conventional assessment of nutritional status to be challenging. Preoperative loss of skeletal muscle mass, namely, sarcopenia, has a significant detrimental impact on post-transplant outcomes. It is essential to provide sufficient nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the needed energy intake. Herein, the latest currently employed perioperative nutritional interventions in liver transplant recipients are thoroughly illustrated including synbiotics, micronutrients, branched-chain amino acid supplementation, immunonutrition formulas, fluid and electrolyte balance, the offering of nocturnal meals, dietary counselling, exercise and rehabilitation.

Perioperative changes in nutritional parameters and impact of graft size in patients undergoing adult living donor liver transplantation

In a recent issue of Liver Transplantation, we read the article by Hammad et al. entitled “Perioperative changes in nutritional parameters and impact of graft size in patients undergoing adult living donor liver transplantation.” They aimed to investigate the benefit of liver transplantation with respect to several parameter changes and the impact of the graft-to-recipient weight ratio on such changes. However, we wish to make some comments on prealbumin levels, which the authors thought as one of these markers. Prealbumin, or transthyretin, is a serum transfer protein for retinol and thyroxine. There are several factors that can change serum prealbumin levels. Previous studies suggested that certain diseases such as chronic kidney disease, Alzheimer disease, type 1 diabetes mellitus, acute phase response (infection, inflammation, or trauma), ankylosing spondylitis, rheumatoid arthritis, pneumonia, Helicobacter pylori infection, protein-losing enteropathy, Kawasaki disease, major depression, and thyroid diseases could affect serum prealbumin levels. Hammad et al. did not mention these contributing diseases in their article. Several drugs such as antithyroid drugs, nonsteroidal anti-inflammatory drugs, estrogens, progestational agents, and anabolic steroids could alter serum prealbumin levels. In addition, dietary food supplements such as zinc, omega-3 fatty acids, vitamin A, and vitamin C can affect serum prealbumin concentration also. In this regard, the authors should state whether the participants used these kinds of drugs and dietary supplements in their recent history. A patient’s body position while giving a blood sample is of great importance. It is recommended that blood samples for measuring plasma proteins be taken after approximately 15 to 20 minutes in a sitting position. If not, concentrations have to be evaluated with consideration of the patient’s position. Lower levels are to be expected in bedridden patients. Lastly, Bruguerolle et al. suggested that serum prealbumin levels showed a circadian rhythm. We think, it is essential to define the sampling time for the measurement of serum prealbumin to provide reliable data. Therefore, the interpretation of the findings with its current form seems problematic. In conclusion, we believe that the study of Hammad et al. contributed valuable data to the medical literature. However, clarifying the above concerns will provide a clearer picture to the readers.

Perioperative changes in nutritional parameters and impact of graft size in patients undergoing adult living donor liver transplantation: Peri-transplant nutritional parameters

Derangements of various serum biochemical nutritional/metabolic parameters are common in patients with end‐stage liver disease who undergo liver transplantation (LT). The aim of this study was to explain the benefit of LT with respect to parameter changes and to examine the impact of the graft‐to‐recipient weight ratio (GRWR) on such changes. We investigated each parameters course in 208 adult recipients for 1 year after living donor LT and analyzed changes in the parameters with a GRWR of 0.8% as the cutoff point. Bonferroni corrections were applied to account for multiple testing. Liver disease–induced high pretransplant ammonia and tyrosine levels and low branched‐chain amino acids to tyrosine ratio (BTR) and zinc levels normalized within 2 weeks after transplantation, and the total lymphocyte count (TLC) normalized within 2 months, whereas low pretransplant prealbumin levels took 1 year to normalize. Branched‐chain amino acids (BCAA), zinc, and TLC levels transiently dropped shortly after transplantation and then were corrected later. An accelerated recovery of ammonia and tyrosine levels and the BTR were found with larger grafts, especially early after transplantation, whereas zinc, prealbumin, BCAA, and TLC levels recovered regardless of the graft size. In conclusion, graft size had little effect on the recovery of nutritional/metabolic parameters except for ammonia and tyrosine levels. Liver Transpl 20:1486‐1496, 2014.

Henoch-Schönlein Purpura after Living Donor Liver Transplantation: Report of the First Case

Henoch-Schönlein purpura (HSP) is a systemic vasculitis affecting the small vessels that mainly presents in children and young adults. It is characterized by tissue deposition of immunoglobulin A (IgA) immune complexes with the classic manifestations of purpura, arthritis, arthralgia, and gastrointestinal and renal involvements. We report a case of HSP nephritis that occurred 2 years after living-donor liver transplantation (LDLT). After pulse steroid administration, the patients symptoms disappeared and blood markers normalized. To the best of our knowledge, this is the first HSP case to be reported in a liver transplant recipient.