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. 2012 Aug 15;2012(8):CD007605.
doi: 10.1002/14651858.CD007605.pub2.

Nutritional interventions for liver-transplanted patients

Gero Langer  1 , Katja Großmann, Steffen Fleischer, Almuth Berg, Dirk Grothues, Andreas Wienke, Johann Behrens, Astrid Fink
Affiliations

Nutritional interventions for liver-transplanted patients

Gero Langer et al. Cochrane Database Syst Rev. .

Abstract

Background: Malnutrition is a common problem for patients waiting for orthotopic liver transplantation and a risk factor for post-transplant morbidity. The decision to initiate enteral or parenteral nutrition, to which patients and at which time, is still debated. The effects of nutritional supplements given before or after liver transplantation, or both, still remains unclear.

Objectives: The aim of this review was to assess the beneficial and harmful effects of enteral and parenteral nutrition as well as oral nutritional supplements administered to patients before and after liver transplantation.

Search methods: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (March 2012), the Cochrane Central Register of Controlled Trials (Issue 2 of 12, 2012) in The Cochrane Library, MEDLINE (January 1946 to March 2012), EMBASE (January 1974 to March 2012), Science Citation Index Expanded (January 1900 to March 2012), Social Science Citation Index (January 1961 to October 2010), and reference lists of articles. Manufacturers and experts in the field have also been contacted and relevant journals and conference proceedings were handsearched (from 1997 to October 2010).

Selection criteria: Randomised clinical trials of parallel or cross-over design evaluating the beneficial or harmful effects of enteral or parenteral nutrition or oral nutritional supplements for patients before and after liver transplantation were eligible for inclusion.

Data collection and analysis: Two authors independently assessed the risk of bias of the trials and extracted data. Dichotomous data were reported as odds ratios (OR) and continuous data as mean differences (MD) along with their corresponding 95% confidence intervals (CI). Meta-analysis was not possible due to clinical heterogeneity of included interventions.

Main results: Thirteen trials met the inclusion criteria. Four publications did not report outcomes pre-defined in the review protocol, or other clinically relevant outcomes and additional data could not be obtained. Nine trials could provide data for the review. Most of the 13 included trials were small and at high risk of bias. Meta-analyses were not possible due to clinical heterogeneity of the interventions.No interventions that were likely to be beneficial were identified.For interventions of unknown effectiveness,postoperative enteral nutrition compared with postoperative parenteral nutrition seemed to have no beneficial or harmful effects on clinical outcomes. Parenteral nutrition containing protein, fat, carbohydrates, and branched-chain amino acids with or without alanyl-glutamine seemed to have no beneficial effect on the outcomes of one and three years survival when compared with a solution of 5% dextrose and normal saline. Enteral immunonutrition with Supportan® seemed to have no effect on occurrence of immunological rejection when compared with enteral nutrition with Fresubin®.There is weak evidence that, compared with standard dietary advice, adding a nutritional supplement to usual diet for patients during the waiting time for liver transplantation had an effect on clinical outcomes after liver transplantation. The combination of enteral nutrition plus parenteral nutrition plus glutamine-dipeptide seemed to be beneficial in reducing length of hospital stay after liver transplantation compared with standard parenteral nutrition (mean difference (MD) -12.20 days; 95% CI -20.20 to -4.00). There is weak evidence that the use of parenteral nutrition plus branched-chain amino acids had an effect on clinical outcomes compared with standard parenteral nutrition, but each was beneficial in reducing length of stay in intensive care unit compared to a standard glucose solution (MD -2.40; 95% CI -4.29 to -0.51 and MD -2.20 days; 95% CI -3.79 to -0.61). There is weak evidence that adding omega-3 fish oil to parenteral nutrition reduced the length of hospital stay after liver transplantation (mean difference -7.1 days; 95% CI -13.02 to -1.18) and the length of stay in intensive care unit after liver transplantation (MD -1.9 days; 95% CI -1.9 to -0.22).For interventions unlikely to be beneficial, there is a significant increased risk in acute rejections in malnourished patients with a history of encephalopathy and treated with the nutritional supplement Ensure® compared with usual diet only (MD 0.70 events per patient; 95% CI 0.08 to 1.32).

Authors' conclusions: We were unable to identify nutritional interventions for liver transplanted patients that seemed to offer convincing benefits. Further randomised clinical trials with low risk of bias and powerful sample sizes are needed.

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Conflict of interest statement

None known

Figures

1
1
Methodological quality summary: review authors' judgments about each methodological quality item for each included study.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Study flow diagram.
1.1
1.1. Analysis
Comparison 1 Hepatic product (HepaticAid®) versus diet (without supplement), Outcome 1 Re‐hospitalisation after liver transplantation [event per patient].
1.2
1.2. Analysis
Comparison 1 Hepatic product (HepaticAid®) versus diet (without supplement), Outcome 2 Infections [event per patient].
1.3
1.3. Analysis
Comparison 1 Hepatic product (HepaticAid®) versus diet (without supplement), Outcome 3 Acute rejection [event per patient].
1.4
1.4. Analysis
Comparison 1 Hepatic product (HepaticAid®) versus diet (without supplement), Outcome 4 New onset of diabetes.
1.5
1.5. Analysis
Comparison 1 Hepatic product (HepaticAid®) versus diet (without supplement), Outcome 5 Hepatic encephalopathy related hospitalisation [events per patient].
1.6
1.6. Analysis
Comparison 1 Hepatic product (HepaticAid®) versus diet (without supplement), Outcome 6 changes in grade of hepatic encephalopathy [grade 0‐4].
2.1
2.1. Analysis
Comparison 2 Standard casein product (Ensure®) versus diet only (without supplement), Outcome 1 Re‐hospitalisation after liver transplantation [event per patient].
2.2
2.2. Analysis
Comparison 2 Standard casein product (Ensure®) versus diet only (without supplement), Outcome 2 Infections [event per patient].
2.3
2.3. Analysis
Comparison 2 Standard casein product (Ensure®) versus diet only (without supplement), Outcome 3 Acute rejection [events per patient].
2.4
2.4. Analysis
Comparison 2 Standard casein product (Ensure®) versus diet only (without supplement), Outcome 4 New onset of diabetes.
2.5
2.5. Analysis
Comparison 2 Standard casein product (Ensure®) versus diet only (without supplement), Outcome 5 Hepatic encephalopathy related hospitalisation [events per patient].
2.6
2.6. Analysis
Comparison 2 Standard casein product (Ensure®) versus diet only (without supplement), Outcome 6 Changes in grade of hepatic encephalopathy [grade 0‐4].
3.1
3.1. Analysis
Comparison 3 Nutritional supplement (500 ml) and standard diet versus standard diet alone, Outcome 1 Mortality during time on waiting list (ITT).
3.2
3.2. Analysis
Comparison 3 Nutritional supplement (500 ml) and standard diet versus standard diet alone, Outcome 2 6 months mortality after liver transplantation (ITT).
3.3
3.3. Analysis
Comparison 3 Nutritional supplement (500 ml) and standard diet versus standard diet alone, Outcome 3 Mild acute rejection episodes (within 6 months after liver transplantation).
3.4
3.4. Analysis
Comparison 3 Nutritional supplement (500 ml) and standard diet versus standard diet alone, Outcome 4 Severe acute rejection episodes (within 6 months after liver transplantation).
4.1
4.1. Analysis
Comparison 4 Enteral immunonutrition with Supportan® versus enteral nutrition with Fresubin®, Outcome 1 Rejection.
5.1
5.1. Analysis
Comparison 5 Postoperative feeding via nasojejunal tube versus postoperative parenteral nutrition (conventional i.v. electrolyte solution), Outcome 1 Days in hospital after liver transplantation.
5.2
5.2. Analysis
Comparison 5 Postoperative feeding via nasojejunal tube versus postoperative parenteral nutrition (conventional i.v. electrolyte solution), Outcome 2 Re‐hospitalisation [events per patient].
5.3
5.3. Analysis
Comparison 5 Postoperative feeding via nasojejunal tube versus postoperative parenteral nutrition (conventional i.v. electrolyte solution), Outcome 3 Infections (overall).
5.4
5.4. Analysis
Comparison 5 Postoperative feeding via nasojejunal tube versus postoperative parenteral nutrition (conventional i.v. electrolyte solution), Outcome 4 Infections (bacterial).
5.5
5.5. Analysis
Comparison 5 Postoperative feeding via nasojejunal tube versus postoperative parenteral nutrition (conventional i.v. electrolyte solution), Outcome 5 Infections (viral).
5.6
5.6. Analysis
Comparison 5 Postoperative feeding via nasojejunal tube versus postoperative parenteral nutrition (conventional i.v. electrolyte solution), Outcome 6 Intensive care unit length of stay after liver transplantation [hours].
5.7
5.7. Analysis
Comparison 5 Postoperative feeding via nasojejunal tube versus postoperative parenteral nutrition (conventional i.v. electrolyte solution), Outcome 7 Time on ventilator [hours until initial extubation].
6.1
6.1. Analysis
Comparison 6 Postperetative enteral nutrition (Osmolite®) via nasojejunal tube versus postoperative parenteral nutrition, Outcome 1 Length of hospital stay after liver transplantation [days].
6.2
6.2. Analysis
Comparison 6 Postperetative enteral nutrition (Osmolite®) via nasojejunal tube versus postoperative parenteral nutrition, Outcome 2 Days on ventilator.
6.3
6.3. Analysis
Comparison 6 Postperetative enteral nutrition (Osmolite®) via nasojejunal tube versus postoperative parenteral nutrition, Outcome 3 Mortality.
6.4
6.4. Analysis
Comparison 6 Postperetative enteral nutrition (Osmolite®) via nasojejunal tube versus postoperative parenteral nutrition, Outcome 4 Side effects (vomiting, diarrhoea).
6.5
6.5. Analysis
Comparison 6 Postperetative enteral nutrition (Osmolite®) via nasojejunal tube versus postoperative parenteral nutrition, Outcome 5 Infection (overall).
7.1
7.1. Analysis
Comparison 7 Enteral nutrition via nasojejunal tube plus intravenous glutamine‐dipeptide supplementation versus standard parenteral nutrition, Outcome 1 Death (during length of initial hospital stay; ITT).
7.2
7.2. Analysis
Comparison 7 Enteral nutrition via nasojejunal tube plus intravenous glutamine‐dipeptide supplementation versus standard parenteral nutrition, Outcome 2 Infection (ITT).
7.3
7.3. Analysis
Comparison 7 Enteral nutrition via nasojejunal tube plus intravenous glutamine‐dipeptide supplementation versus standard parenteral nutrition, Outcome 3 Acute rejection (ITT).
7.4
7.4. Analysis
Comparison 7 Enteral nutrition via nasojejunal tube plus intravenous glutamine‐dipeptide supplementation versus standard parenteral nutrition, Outcome 4 Length of hospital stay after liver transplantation [days] (ITT).
7.5
7.5. Analysis
Comparison 7 Enteral nutrition via nasojejunal tube plus intravenous glutamine‐dipeptide supplementation versus standard parenteral nutrition, Outcome 5 Intensive care unit length of stay after liver transplantation [days] (ITT).
7.6
7.6. Analysis
Comparison 7 Enteral nutrition via nasojejunal tube plus intravenous glutamine‐dipeptide supplementation versus standard parenteral nutrition, Outcome 6 Days on ventilator (ITT).
7.7
7.7. Analysis
Comparison 7 Enteral nutrition via nasojejunal tube plus intravenous glutamine‐dipeptide supplementation versus standard parenteral nutrition, Outcome 7 Costs of postoperative hospitalisation [USD].
8.1
8.1. Analysis
Comparison 8 Parenteral nutrition with protein, fat, carbohydrates, branched‐chain amino acids versus 5% dextrose and normal saline, Outcome 1 One‐year survival.
8.2
8.2. Analysis
Comparison 8 Parenteral nutrition with protein, fat, carbohydrates, branched‐chain amino acids versus 5% dextrose and normal saline, Outcome 2 Three‐year survival.
9.1
9.1. Analysis
Comparison 9 Parenteral nutrition with alanyl‐glutamine, protein, fat, carbohydrates, and branched‐chain amino acids versus 5% dextrose and normal saline, Outcome 1 One‐year survival.
9.2
9.2. Analysis
Comparison 9 Parenteral nutrition with alanyl‐glutamine, protein, fat, carbohydrates, and branched‐chain amino acids versus 5% dextrose and normal saline, Outcome 2 Three‐year survival.
10.1
10.1. Analysis
Comparison 10 Parenteral nutrition plus branched‐chain amino acid‐enriched formula versus standard isotonic intravenous glucose solution, Outcome 1 Length of hospital stay after liver transplantation [days].
10.2
10.2. Analysis
Comparison 10 Parenteral nutrition plus branched‐chain amino acid‐enriched formula versus standard isotonic intravenous glucose solution, Outcome 2 Length of stay in intensive care unit after liver transplantation [days].
10.3
10.3. Analysis
Comparison 10 Parenteral nutrition plus branched‐chain amino acid‐enriched formula versus standard isotonic intravenous glucose solution, Outcome 3 Days on ventilator.
10.4
10.4. Analysis
Comparison 10 Parenteral nutrition plus branched‐chain amino acid‐enriched formula versus standard isotonic intravenous glucose solution, Outcome 4 Mortality (within first 10 weeks after liver transplantation).
11.1
11.1. Analysis
Comparison 11 Standard parenteral nutrition versus standard isotonic intravenous glucose solution, Outcome 1 Length of hospital stay after liver transplantation [days].
11.2
11.2. Analysis
Comparison 11 Standard parenteral nutrition versus standard isotonic intravenous glucose solution, Outcome 2 Days on ventilator.
11.3
11.3. Analysis
Comparison 11 Standard parenteral nutrition versus standard isotonic intravenous glucose solution, Outcome 3 Length of stay in intensive care unit after liver transplantation [days].
11.4
11.4. Analysis
Comparison 11 Standard parenteral nutrition versus standard isotonic intravenous glucose solution, Outcome 4 Mortality (within first 10 weeks after liver transplantation).
12.1
12.1. Analysis
Comparison 12 Parenteral nutrition with omega‐3 fish oil compared with standard parenteral nutrition, Outcome 1 Length of hospital stay after liver transplantation.
12.2
12.2. Analysis
Comparison 12 Parenteral nutrition with omega‐3 fish oil compared with standard parenteral nutrition, Outcome 2 Length of stay in intensive care unit after liver transplantation.
12.3
12.3. Analysis
Comparison 12 Parenteral nutrition with omega‐3 fish oil compared with standard parenteral nutrition, Outcome 3 Acute rejection.
12.4
12.4. Analysis
Comparison 12 Parenteral nutrition with omega‐3 fish oil compared with standard parenteral nutrition, Outcome 4 Mortality.
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