Poor nutritional status is a common problem in patients waiting for liver transplantation and it is a risk factor for post-transplant morbidity and mortality. Nutritional status can worsen rapidly in the postoperative period due to preoperative malnutrition, the stress of the surgical procedure, immunosuppressive therapy, and in some patients liver or kidney dysfunction or sepsis. Nutritional interventions for people on a waiting list for liver transplantation include nutritional supplements providing additional protein, fat, and carbohydrates as well as liver-adapted formulas also containing branched-chain amino acids. Nutritional interventions after liver transplantation consist of parenteral or enteral nutrition and oral nutritional supplementation during the postoperative phase.
This systematic review of 13 randomised clinical trials found that there is no convincing evidence for beneficial effects of nutritional interventions for liver-transplanted patients. Accordingly, we could not recommend any specific intervention. More research is needed to identify effective nutritional interventions for patients before and after liver transplantation.
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.
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.
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.
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).
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.
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.
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).