The minor changes are known as minimal hepatic encephalopathy. Overt hepatic encephalopathy refers to the more severe stages with clinically apparent manifestations such as changes in the level of consciousness or neuropsychiatric abnormalities. Many people with cirrhosis lack amino acids which act as building blocks of proteins. The body can make several different amino acids. Essential amino acids are amino acids that the body cannot produce. Some of the essential amino acids have a carbon atom bound to more than two other carbon atoms (a branch). People with cirrhosis often have a low quantity of the three essential branched-chain amino acids (BCAA) leucine, isoleucine, and valine. BCAA also play an important part of the generation muscles and of the signalling chemicals in the brain. These effects may benefit people with hepatic encephalopathy.
Study characteristics
We identified 16 randomised clinical trials (trials where participants are randomly allocated to treatment groups) including 827 participants. The included people had cirrhosis often due to alcoholic liver disease or viral hepatitis (liver infection due to a virus). The trials compared BCAA with placebo (a pretend treatment), no intervention, diets, lactulose (a liquid sugar often used to treat constipation), or neomycin (an antibiotic). The evidence is current to October 2014.
Key results
The analyses found no effect on mortality, but that BCAA had a beneficial effect on symptoms and signs of hepatic encephalopathy. BCAA did not increase the risk of serious adverse events, but was associated with nausea and diarrhoea. When excluding trials on lactulose or neomycin, BCAA had a beneficial effect on hepatic encephalopathy. When analysing trials with a lactulose or neomycin control, we found no beneficial or detrimental effect of BCAA.
Quality of the evidence
We assessed the quality of the evidence to evaluate aspects that can lead to errors in the judgment of intervention effects. We concluded that we had high quality evidence in our analyses about the effect of BCAA on hepatic encephalopathy. We concluded that we had moderate or low quality evidence in the remaining analyses because the number of participants in the trials was too small and the risk of bias (systematic errors) was unclear or high.
Authors' conclusions:
In this updated review,
we included five additional trials. The analyses showed that BCAA had a
beneficial effect on hepatic encephalopathy. We found no effect on mortality,
quality of life, or nutritional parameters, but we need additional
trials to evaluate these outcomes. Likewise, we need additional
randomised clinical trials to determine the effect of BCAA compared with
interventions such as non-absorbable disaccharides, rifaximin, or other
antibiotics.