Eight RCTs (646 patients, range 20 to 160) were included in the review. Four trials were at low risk of bias. Three trials were at high risk of bias due to blinding issues or use of per-protocol analysis due to incomplete outcome data. One trial had unclear risk of bias.
Hepatic encephalopathy: Hepatic encephalopathy was statistically significantly reduced in patients with both minimal and overt hepatic encephalopathy who received CL-ornithine-CL-aspartate compared to placebo/no intervention (RR 1.49, 95% CI 1.10 to 2.01; five RCTs). There was evidence of significant heterogeneity (I²=76%).
Similar findings in favour of CL-ornithine-CL-aspartate were reported in subgroup analyses including only overt or minimal hepatic encephalopathy patients. Subgroup analyses in trials at low risk of bias resulted in no statistically significant differences for any patient group compared to control. Results on other subgroup and sensitivity analyses were reported in the review.
Serum ammonia: CL-ornithine-CL-aspartate compared to placebo/no intervention statistically significantly lowered post-treatment fasting ammonia levels (MD -18.26, 95% CI -26.96 to -9.56; four RCTs), increased the change in fasting serum ammonia (MD 9.84, 95% CI 6.44 to 13.24; four RCTs) and increased the post-treatment value of postprandial serum ammonia (MD -20.54, 95% CI -28.71 to -12.36). None of the pooled analyses for serum ammonia found evidence of heterogeneity.
Other outcomes: There were no statistically significant differences in mortality, adverse events or tolerance rates between patients who received CL-ornithine-CL-aspartate and patients who received placebo/no intervention.
Comparisons between CL-ornithine-CL-aspartate and lactulose revealed significantly increased abdominal pain and flatulence with lactulose. No other statistically significant differences between CL-ornithine-CL-aspartate and other treatments were found for any of the outcomes measured.