Sodium benzoate for the treatment of hepatic encephalopathy in humans and animals: a systematic review and meta-analysis

Abstract

Background and aim Hepatic encephalopathy (HE) is a life-threatening condition where brain function is impaired mainly due to high systemic ammonia levels. HE is associated with a high 1-year mortality. No universally accepted guidelines for the treatment of HE exist. Nitrogen scavengers, such as sodium benzoate (SB), have been proven very effective to treat hyperammonemia in patients with urea cycle defects, in acute and chronic settings. We hypothesized that SB can also be an effective treatment of HE caused by end-stage liver disease or portosystemic shunting, as long as liver function is partially intact. The aim of this meta-analysis is to study the effect of SB in humans and animals with HE due to end-stage liver disease or portosystemic shunting. Methods Embase, Medline (Ovid and PubMed), Web-of-Science, Cochrane, and Google Scholar were searched on 19 July 2021, both human and animal studies were eligible. Results Sixteen studies were included, consisting of four clinical trials, five animal studies, and seven case reports, including 314 subjects. Meta-analysis included 284 subjects. The standardized mean difference (SMD) of SB's ammonia-lowering effect was 0.89 SMD [95% confidence interval (CI): 0.27-1.51] in clinical trials and 1.63 SMD (95% CI: -0.12 to 3.39) in animal studies. Considerable heterogeneity was present in the included studies. Conclusion SB seems to be an effective treatment for HE or hyperammonemia caused by end-stage liver disease or portosystemic shunting. However, additional high-quality studies are necessary for more robust conclusions.