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Reuters Health Information (2013-03-15): Do nutritional supplements improve cirrhosis outcomes?


Do nutritional supplements improve cirrhosis outcomes?

Last Updated: 2013-03-15 9:30:30 -0400 (Reuters Health)

NEW YORK (Reuters Health) - A new meta-analysis couldn't prove that oral or enteral nutritional supplements help patients with cirrhosis, but the Canadian researchers remain hopeful.

They had data from only six trials involving 470 patients. "Recognizing the limitations of conclusions drawn from subgroup analysis of a small number of low-quality trials, we are cautiously optimistic that the studies of oral supplementation demonstrated a signal for clinical benefit without an increase in adverse events," Dr. Puneeta Tandon from University of Alberta in Edmonton told Reuters Health by email. "Further studies are needed in this very important area."

Dr. Tandon and colleagues sought to provide an up-to-date systematic review and meta-analysis of randomized controlled trials of non-branched chain amino acid (BCAA) oro-enteral nutritional supplementation on nutritional and clinical outcomes in patients with cirrhosis.

Four of the six studies evaluated oral nutritional supplementation; the other two evaluated enteral supplements.

In a paper online February 20th in Alimentary Pharmacology & Therapeutics, the authors say results from the six combined studies showed no significant reduction in mortality and no significant differences in the secondary outcome measures (change in liver function, nutritional outcomes, complications of cirrhosis) between the supplementation and control groups.

In the subgroup analyses, oral nutritional supplementation was associated with a significant 60% reduction in mortality (p=0.03), but the effect of enteral nutritional supplementation on mortality was not significant.

The authors did not have enough data to perform subgroup analyses according to the severity of liver dysfunction, the etiology of cirrhosis, or the total daily intake of calories.

Longer studies were no more effective than shorter studies in demonstrating a survival advantage for nutritional supplementation.

"Given the quality of the available data, it is impossible to conclude with certainty that oro-enteral nutritional supplementation has no impact on mortality," Dr. Tandon said. "Future studies will help to clarify the impact of nutritional supplementation on morbidity and mortality and to determine predictors of response and non-response to therapy."

"The results of this meta-analysis are in line with my expectations," Dr. Luciano D'Agostino from Federico II University of Naples II, Italy, who has studied nutrition in cirrhosis but wasn't involved in this research, told Reuters Health by email. "When we planned our study, we decided to limit the nutritional intervention to Child Pugh A and B HCV-related patients and obtained good results in correcting their protein malnutrition and clinical outcome."

"I believe that nutrition cannot work well in more compromised patients and, therefore, a modification in mortality is hardly obtainable in the late stages of cirrhosis," Dr. D'Agostino said.

Dr. Maitreyi Raman from Canada's University of Calgary told Reuters Health, also by email, "Physicians should understand that this is an evolving area of research, and that larger, well-conducted trials with appropriate duration, and total calories received are necessary before final conclusions can be made. With the current body of evidence, there is a signal that oral/enteral nutrition may be of benefit in reducing mortality. In the absence of major complications, oral/enteral nutrition should be maximized in this patient cohort."

Dr. Raman, who was also not involved in the new analysis, added, "Assessing malnutrition is very challenging in this patient population due to confounding factors that affect weight and BMI, in addition to visceral proteins. Therefore, every attempt should be made by practitioners to assess nutritional status through objective measures including mid-arm circumference, food diaries, and emerging tools, such as hand grip strength if available."

Dr. Lindsay Plank from The University of Auckland, New Zealand agreed with the other experts, adding, "There is no question that malnutrition is a highly prevalent feature of cirrhosis, evident even in early stage disease, with progressive muscle loss as the disease worsens. In decompensated patients (CP-C) the complications that characterize these patients are generally life threatening and the impact of nutritional supplementation on survival is likely to be minimal by comparison."

"That is not to say that such treatment may not be beneficial, as it may help to maintain muscle mass and improve quality of life," Dr. Plank said. "I am not therefore too surprised by the findings especially given that the patients in the studies assessed were at the more severe end of the spectrum."

"What we do know is that these patients enter a 'starvation mode' at an accelerated rate compared with healthy individuals," Dr. Plank explained. "This means that after a typical overnight fasting period of if they go without meals for say six hours or more, they will start breaking down muscle tissue to provide adequate glucose to keep the brain and CNS happy. These increased rates of gluconeogenesis are likely due to the limited glycogen storage capacity of the cirrhotic liver."

Dr. Plank concluded, "It is important then that these patients have frequent meals and ideally a midnight (or late evening) energy dense snack. Our own work would suggest they can gain muscle mass with a nocturnal feed; it has not been shown as yet that this is accompanied by improved quality of life or delayed onset of major complications."


Aliment Pharmacol Ther 2013.

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