Introduction 

Hepatic encephalopathy (HE), a neuropsychiatric disorder and complication of end-stage cirrhosis, is linked to high mortality. Prophylaxis of HE is preferred, especially for cirrhotic patients with infection, gastrointestinal bleeding, post-transjugular intrahepatic portosystemic shunt (TIPS) or electrolyte imbalance. Lactulose and lactitol are used as first-line drugs for secondary prevention. However, lactulose therapy, possibly leading to dehydration, resulted in frequent noncompliance. Studies had shown a potential role of rifaximin as compared to other antibiotics, in the treatment and prevention of HE. However, data from clinical studies was not clear regarding the use of rifaximin for primary prevention post-TIPS and without predisposing factors in cirrhosis. 

Aim

To assess the efficacy and safety of rifaximin in the prophylaxis of hepatic encephalopathy 

Patient Profile 

Method

Study Design

• Meta-analysis of fourteen randomized controlled trials
• Identified studies that evaluated the efficacy and safety of rifaximin for cirrhotic patients (as of March 2022)

Endpoints

• Incidence of HE
• Mortality rate
• Adverse event rate

Results 

Efficacy 

• Rifaximin reduced the risk of HE (relative risk, RR −0.47, p=0.01) in patients with cirrhosis, but did not affect mortality rate (RR 0.03)
• Subgroup analysis showed that rifaximin was effective in both the primary (RR −0.35, P =0.68) and secondary (RR −0.56, P<0.001) prevention of HE
• Rifaximin was beneficial for preventing HE in alcohol-related (RR −0.59) or virus-associated (RR −0.41) cirrhosis
• Rifaximin was beneficial for preventing HE in cirrhotic patients who underwent TIPS (RR −0.35, P=0.35) or did not undergo TIPS (RR −0.51, P<0.001)

Figure 1: Effect of rifaximin in reducing the risk of HE 

Safety   

Conclusion 

• This meta-analysis showed that rifaximin was beneficial for primary and secondary prevention of HE in patients with end-stage cirrhosis 
• Benefits were regardless of the etiology of cirrhosis (caused by virus or alcohol), whether the patient received TIPS, rifaximin was as effective as lactulose in primary and secondary prevention of HE in cirrhosis, and the combination was superior to lactulose alone
• Moreover, rifaximin prophylaxis of HE did not increase mortality or adverse events

Medicine 2025; 104: 5(e39905)