L-ornithine L-aspartate for people with chronic liver disease and hepatic encephalopathy (poor brain functioning)


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Background

Cirrhosis is a chronic disorder of the liver. People with this condition commonly develop hepatic encephalopathy, a complication that results in poor brain functioning. Some people with cirrhosis develop obvious clinical features of disturbed brain functioning, such as difficulties with speech, balance and daily functioning; they are said to have overt hepatic encephalopathy; the changes may be short-lived, may recur, or may persist for long periods. Other people with cirrhosis may show no obvious clinical changes but some aspects of their brain function, such as attention and the ability to perform complex tasks are found to be impaired when tested; they are said to have minimal hepatic encephalopathy. The reason why people develop hepatic encephalopathy is complex, but the accumulation in the blood of toxins from the gut, particularly of a compound called ammonia, plays a key role. L-ornithine L-aspartate lowers blood ammonia levels and so may have beneficial effects in people with hepatic encephalopathy or help stop them developing it.

Review question

We investigated the use of L-ornithine L-aspartate given either by mouth (oral) or into a vein in an fluid drip (intravenous) for the prevention and treatment of hepatic encephalopathy by reviewing clinical trials in which people with cirrhosis were randomly allocated to treatment with L-ornithine L-aspartate, to an inactive dummy (called placebo), to no treatment, or to another medicine for this condition such as lactulose, probiotics and rifaximin. We included participants with cirrhosis who had overt or minimal hepatic encephalopathy or who were at risk for developing this complication.

Search date

December 2017.

Study funding sources

Six of the 36 randomised clinical trials we included received no funding or any other support from pharmaceutical companies. Seventeen trials received financial support from pharmaceutical companies and a further three received L-ornithine L-aspartate or inactive placebo free of charge; there was no information on funding in the remaining 10 trials.

Study characteristics

We included 33 randomised clinical trials comparing L-ornithine L-aspartate with inactive placebo or no intervention and six randomised clinical trials comparing L-ornithine L-aspartate with other anti-encephalopathy treatments; some trials included more than one comparison. Five of the included trials tested L-ornithine L-aspartate for the prevention of hepatic encephalopathy while 30 trials tested its use as treatment for people with acute, chronic, or minimal hepatic encephalopathy. The length of treatment varied from three to 35 days in the trials testing the intravenous preparation (average eight days) and from seven to 180 days in those testing the oral preparation (average 30 days).

Key results

Our analyses showed L-ornithine L-aspartate might reduce deaths, improve hepatic encephalopathy, and prevent serious side effects compared with placebo or no treatment, but that it had no additional beneficial effects when compared with other medicines used to prevent and treat this condition.

Quality of the evidence

The evidence we found was very weak, and so we are not confident that L-ornithine L-aspartate is of use for preventing or treating hepatic encephalopathy in people with cirrhosis. Many studies were unpublished and so had not been carefully vetted, and many of the published trials received support from the pharmaceutical industry which introduces an element of bias. Accordingly, more information is needed before the value of L-ornithine L-aspartate for preventing and treating hepatic encephalopathy can be determined.