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Does L-ornithine L-aspartate provide any Benefit in Hepatic Encephalopathy?


Clinical trial shows that LOLA is an effective treatment for hepatic encephalopathy

The liver is an essential body organ and liver disease is a major cause of mortality and morbidity worldwide. Cirrhosis is a condition in which your liver is scarred and permanently damaged. In 2019, cirrhosis was associated with 2.4% of global deaths. Hepatic encephalopathy is a severe complication of liver cirrhosis. A clinical trial  investigated the efficacy of a drug called L-ornithine L-aspartate (LOLA) in the management of hepatic encephalopathy.

What is Hepatic Encephalopathy?

Hepatic encephalopathy (HE) is a condition that occurs when the liver is unable to properly filter toxins from the blood. These toxins can then build up and affect the brain, leading to symptoms like confusion, disorientation, and even coma. Severe hepatic encephalopathy is a medical emergency that requires immediate treatment.

Hepatic encephalopathy occurs in 30%–40% of patients with liver cirrhosis and is associated with a mortality of more than 50% in the first year alone. The chief neurotoxin implicated in the development of HE is ammonia (NH3), which is released from the kidney, muscle, and intestine. Ammonia enters the portal vein and the systemic circulation directly or by bypassing the liver through the portosystemic shunts in patients with cirrhosis. NH3 crosses the blood–brain barrier, resulting in swelling of the brain cells, which disturbs brain transmission, leading to HE.

LOLA is the combination of natural amino acids ornithine and aspartate. It works by detoxifying NH3 in cirrhosis patients. However, data on the use of intravenous L-ornithine L-aspartate (LOLA) in the treatment of overt HE (OHE) is limited.

Clinical Trial

The trial tested LOLA as a potential treatment option in patients suffering from hepatic encephalopathy due to liver cirrhosis. It involved 140 patients who were randomly assigned to receive either LOLA or a placebo. 70 patients received a combination of LOLA, lactulose, and rifaximin while the remaining 70 patients received a combination of a placebo, lactulose, and rifaximin. LOLA was given as a continuous intravenous infusion at a dose of 30 g over 24 h for 5 days. Ammonia levels, TNF-α, ILs, and endotoxins were measured on days 0 and 5. The primary outcome was the improvement in the symptoms of HE on day 5.

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The results of the clinical study were clear: LOLA was significantly more effective than the placebo at improving symptoms of hepatic encephalopathy.

Patients who received LOLA experienced a more significant improvement in their symptoms compared to those who received the placebo (92.5% vs 66%). Additionally, the recovery times and the 28-day mortality rates were lower in the LOLA group.

The researchers also found that LOLA was well-tolerated by patients and did not cause any serious adverse effects.


The results of this clinical trial suggest that LOLA can be an effective adjunct treatment for severe hepatic encephalopathy. The combination of LOLA with lactulose and rifaximin was more effective than only lactulose and rifaximin in improving grades of HE, and recovery time from encephalopathy, with lower 28-day mortality. If you or a loved one have this condition, talk to your doctor to see if LOLA might be an appropriate treatment option for you.
Hepatology, May 2022

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This content is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of such advice or treatment from a personal physician. All readers/viewers of this content are advised to consult their doctors or qualified health professionals regarding specific health questions. CenTrial Data Ltd. does not take responsibility for possible health consequences of any person or persons reading or following the information in this educational content. Treatments and clinical trials mentioned may not be appropriate or available for all trial participants. Outcomes from treatments and clinical trials may vary from person to person. Consult with your doctor as to whether a clinical trial is a suitable option for your condition. Assistance from generative AI tools may have been used in writing this article.