# Efficacy and safety of L-ornithine L-aspartate combined with lactulose in treatment of hepatic encephalopathy: a systematic review and meta-analysis of randomized controlled trial

**Authors:** Hui Zhang, Yujuan Fu, Minghao Lin, Zheng Nan, Dexi Zhao

PMC · DOI: 10.3389/fmed.2025.1581792 · Frontiers in Medicine · 2025-04-30

## TL;DR

Combining L-ornithine L-aspartate with lactulose improves treatment outcomes for hepatic encephalopathy compared to lactulose alone.

## Contribution

A meta-analysis showing LOLA plus lactulose is more effective than lactulose alone for treating hepatic encephalopathy.

## Key findings

- The combination treatment had a 31% higher total effective rate than lactulose alone.
- It significantly reduced AST, ALT, TBIL, and NH3 levels in patients.
- The results were statistically significant with low p-values.

## Abstract

Hepatic encephalopathy (HE) represents a collection of metabolic disturbances and regulatory imbalances within the central nervous system that result from advanced liver conditions.

This article explores the efficacy and safety evaluation of L-ornithine L-aspartate (LOLA) combined with lactulose in the treatment of hepatic encephalopathy based on meta-analysis, providing a rational reference for clinical medication use.

Following the PICOS principle, we searched for literature on the treatment of hepatic encephalopathy with Ornithine aspartate combined with lactulose. The literature search was conducted up to and including September 21, 2024. For studies that met the criteria, the Review Manager 5.4 software was used to perform a meta-analysis.

A total of 12 articles were ultimately included, involving 858 patients, with 433 in the treatment group and 425 in the control group. Meta-analysis results: In terms of the total effective rate (RR: 1.31, 95%CI: 1.22, 1.42), the result is statistically significant (Z = 7.15, P = 0.00001 < 0.05), and for AST, ALT, NH3, TBIL, P = 0.00001 < 0.05. The pooled (RR: 1.31 [95% CI = 1.22, 1.42]), which is statistically significant, LOLA and Lactulose is 31% more effective than Lactulose alone in the control group in treating HE.

This study indicates that the combination of LOLA and lactulose in the treatment of hepatic encephalopathy has a higher total effective rate in clinical practice and can significantly reduce the levels of AST, ALT, TBIL, and NH3.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024592957.

## Linked entities

- **Chemicals:** L-ornithine L-aspartate (PubChem CID 10220941), lactulose (PubChem CID 11333), ALT (PubChem CID 10219674), NH3 (PubChem CID 222)
- **Diseases:** hepatic encephalopathy (MONDO:0001711)

## Full-text entities

- **Genes:** SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}
- **Diseases:** neurotransmitter disturbances (MESH:D014832), hypokalemia (MESH:D007008), toxic hepatitis (MESH:D056486), liver injury (MESH:D017093), abnormal (MESH:D000014), hyponatremia (MESH:D007010), neuropsychiatric symptoms (MESH:D001523), bloating (MESH:C535647), electrolyte disorders (MESH:D014883), hypotension (MESH:D007022), viral hepatitis (MESH:D014777), acid-base imbalances (MESH:D000137), intestinal cramps (MESH:D007410), coma (MESH:D003128), Liver Diseases (MESH:D008107), cardiac insufficiency (MESH:D000309), impaired consciousness (MESH:D003244), Encephalopathies (MESH:D001927), renal impairment (MESH:D007674), inflammatory (MESH:D007249), cirrhosis (MESH:D005355), metabolic, circulatory, and neurological system dysfunction (MESH:D012769), metabolic (MESH:D008659), central nervous system dysfunction (MESH:D002493), Hepatic Encephalopathies (MESH:D006501), alcoholic cirrhosis (MESH:D008104), cerebral edema (MESH:D001929), diarrhea (MESH:D003967), abdominal pain (MESH:D015746), dizziness (MESH:D004244), neurotoxic (MESH:D020258), Chronic Hepatitis (MESH:D006521), icterus (MESH:D007565), gastrointestinal symptoms (MESH:D012817), necrosis (MESH:D009336), arrhythmias (MESH:D001145), ammonia toxicity (MESH:C538320), hyperammonemia (MESH:D022124), injury (MESH:D014947), end-stage cirrhosis (MESH:D007676)
- **Chemicals:** Lactulose (MESH:D007792), tricarboxylic acid (MESH:D014233), NH3 (MESH:D000641), L-ornithine (MESH:D009952), sodium (MESH:D012964), urea (MESH:D014508), acetic acid (MESH:D019342), thiols (MESH:D013438), disaccharide (MESH:D004187), amines (MESH:D000588), Aspartate (MESH:D001224), lactic acid (MESH:D019344), glutamine (MESH:D005973), Aspertate aminotransferase (-), carbon dioxide (MESH:D002245), alcohol (MESH:D000438), hydrogen (MESH:D006859), oxaloacetic acid (MESH:D062907), LOLA (MESH:C002939), potassium (MESH:D011188), Bilirubin (MESH:D001663), NO (MESH:D009569)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** glutamate to glutamine

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12075176/full.md

## References

21 references — full list in the complete paper: https://tomesphere.com/paper/PMC12075176/full.md

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Source: https://tomesphere.com/paper/PMC12075176