الفهرس 
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Abstract
Nutrition is an integral part of health maintenance. The liver is the largest and most important metabolic organ, playing a pivotal role in integrating several biochemical pathways of carbohydrate, fat, protein, and vitamin metabolism, therefor, malnutrition is a common complication of ESLD.
Liver transplantation revolutionized the management of liver disease, while progressive deterioration of nutritional status has been associated with poor outcome in cirrhotic patients.
There is debate on the use of Many nutrient supplementations as Branched-chain amino acid-enriched nutrients, b-hydroxy-b-methyl butyrate, omega-3 fish oil, Immunonutrients and Glutamine Dipeptide.
Thus, we aim to run this systematic search and meta-analysis on the efficacy of different dietary nutritional supplements for liver recipients’ patients postoperatively by pooling and analysis of the outcomes of reliable published epidemiological studies regarding this issue in the last ten years.
A systematic search was performed at PubMed, Scopus, Cochrane Central Register of Controlled Trials, EKB, Web of Science, Embase, and Science Direct till February 2022 with relevant keywords to find all available clinical comparative studies that assess and compare the clinical outcomes of ICU patients underwent liver transplantation surgery and supplied with dietary supplement three months postoperatively with the outcomes of standard diet group.
The total number was 484 articles, we excluded 29 articles due to duplication. 455 articles underwent title and abstract screening, and 422 were excluded because they did not meet the inclusion criteria. The remaining 33 articles underwent full-text screening. A total of 7 studies were finally included for the final qualitative synthesis and the quantitative analysis.
We analyzed seven studies from 2012 to 2020 , different countries, with a total number of 409 and sample size ranging from 22 to 101. All of the patients were critically ill, admitted to ICU and receiving liver graft for any indication.
The studies also assessed the laboratory assessment of patients postoperatively during ICU admission period. and discussed many nutritional elements as Branched-chain amino acid-enriched nutrients by Yoshida et al., (2012), b-hydroxy-b-methyl butyrate by Kamo et al., (2020) and Lattanzi et al., (2019), omega-3 fish oil by Zhu et al., (2012) and (2013), Immunonutrition by Plank et al., (2015) and Alanyl Glutamine Dipeptide (Ala-Gln) by Qiu et al., (2009)
By using the Cochrane handbook of systematic reviews of interventions 5.1.0 (Green et al., 2011), the overall quality of the included studies was moderate to high quality studies. No high risk of bias in terms of selection bias, attrition bias, reporting bias and other biases. Only performance bias and detection bias were at high risk of bias in Qiu et al. (2009) and Zhu (2012)
We obtained data from text, tables, figures (using graph grabber version 2.0), and supplementary data. We focused on the following outcome measures: Overall Infectious complications (mainly bacteremia), Graft rejection rate, Postoperative hospital stay, Postoperative Mortality rate (up to 1-year mortality), Postoperative ALT, AST, Total bilirubin, direct bilirubin level and Prealbumin level (mg/dL).
Estimates from the seven included studies were pooled for analysis using the RevMan Manager Software 5.4 [Computer program].
A sensitivity analysis was performed (leave one out sensitivity test) by sequentially deleting trials to check the stability of the primary outcomes. , when we applied to leave one-out meta-analysis test excluding Plank et al. from the included studies, The heterogeneity was best resolved by excluding Plank et al and the pooled analysis showed a significant difference between the interventional group and the control group regarding the decrease in infectious complications and the length of hospital stay rates. (Figure 8,10)
The meta-analysis of these study illustrated that a statistically significant difference was found between the interventional group with Branched-chain amino acid-enriched nutrients, B-hydroxy-b-methyl butyrate, omega-3 fish oil and Immunonutrients, Glutamine dipeptide as dietary supplements and the control group with standard isocaloric diet as a reduction of postoperative infectious complication rate and length of hospital stays after exclusion of Plank et al, by leave one sensitivity test, postoperative mortality rate, postoperative ALT, AST and prealbumin level.
However, we found no significant reduction in graft rejection rate, postoperative total and direct bilirubin level in the dietary supplementation group than control group, meaning no favorable effect of nutrition supplementation in post-operative liver transplantation period over the other control groups.
Also a qualitative synthesis was done Regarding grip strength (GS) and muscle strength (as respiratory muscles), some studies report improvement in those outcomes postoperative to immunonutrients and b-hydroxy-b-methyl butyrate (HMB) interventions.
In the study by Plank et al., they reported significant improvements in grip strength (P = 0.044) and respiratory muscle strength (P = 0.037). Voluntary handgrip strength was measured in the dominant hand using a dynamometer and respiratory muscle strength was measured with a bidifferential pressure transducer.
In Kamo et al. their primary outcome was grip strength two months after liver donner liver transplant (LDLT). They reported that GS at one and two months were significantly higher in the b-hydroxy-b-methyl butyrate (HMB) group than in the control group (P < 0.001). These results qualify for the significance of hand grip strength improvement following immunonutrition interventions.
In Lattanzi et al, the administration of β-Hydroxy-β-Methyl-Butyrate in patients after liver transplantation show a statistically significant increase in ASMI at the end of supplementation period (30 days) in HMB patients but not in controls ,muscle strength, assessed by HG test, increased significantly in the HMB group, at the same end point (30 days of supplementation) and at 12 months later , In the control group, the muscle strength evaluated by HG was substantially stable.
This meta-analysis had some limitations, first; small sample size of included studies. Next, there was heterogeneity, which may be caused by different doses, forms, and duration of nutrients used in our study. Finally, it was not feasible to perform the subgroup analysis based on different dosages and treatment time for drug administration.