Nitazoxanide versus rifaximin in preventing the recurrence of hepatic encephalopathy: A randomized double‐blind controlled trial

Abstract

Background/Purpose: Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver cirrhosis. HE is associated with poor survival and detrimental effects on quality of life (QOL). The drawbacks of the long-term use of rifaximin in HE necessitates searching for alternative therapies. In this context, our study aimed at evaluating the safety and efficacy of nitazoxanide (NTZ) as compared to rifaximin (RFX) in preventing the recurrence of HE and assessing its impact on QOL. Patients and Methods: This prospective, randomized, double-blind controlled study included 60 patients who were randomly assigned to receive either rifaximin 550 mg twice daily (group 1; n = 30) or nitazoxanide 500 mg twice daily (group 2; n = 30) for 24 weeks. During the study period, the patients' neurological symptoms, mental status, and performance were monitored. The serum levels of HE triggers (ammonia, TNF-α, and octopamine) were assessed. The patients' health-related quality of life was also evaluated. Results: Six months after treatment, patients on NTZ therapy showed a statistically significant improvement in CHESS score and mental status. NTZ provided 136 days of remission vs 67 days of remission for patients on RFX (P 1 = .0001) and significant reduction in Child score (P 1 = .018). Additionally, NTZ showed a statistically significant decrease in serum ammonia, TNF-α, and octopamine levels as compared to rifaximin. Regarding QOL, NTZ group showed an improvement in total Chronic Liver Disease Questionnaire (CLDQ) score. Both groups experienced minor controllable side effects. Conclusion: Nitazoxanide may represent a suitable and safe alternative therapy to rifaximin in preventing the recurrence of hepatic encephalopathy.

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates

“…In experimental studies in mice, nitazoxanide (100 mg/kg/d) attenuated dyslipidaemia, liver steatosis [ 204 ], fibrosis, inflammation, and HCB, demonstrating synergistic effects with the pan-PPAR agonist elafibranor [ 205 ]. Moreover, the anti-anaerobic activity of nitazoxanide may determine its use in preventing the recurrence of hepatic encephalopathy as a viable alternative to rifaximin (NCT04161053) [ 206 ].…”

Hepatic Encephalopathy: Current and Emerging Treatment Modalities

“…Nitazoxanide (NTZ) is an antimicrobial agent with wide safety profile that has broad-spectrum activity against urease-producing bacteria leading to decreased ammonia production. 52,53 This antibiotic has been evaluated in HE treatment as an alternative to rifaximin. 52 In a pilot study including 34 patients with grade 2-3 HE, administration of NTZ for 1 week showed similar efficacy to rifaximin, and it was superior in quality of life improvement.…”

“…52,53 This antibiotic has been evaluated in HE treatment as an alternative to rifaximin. 52 In a pilot study including 34 patients with grade 2-3 HE, administration of NTZ for 1 week showed similar efficacy to rifaximin, and it was superior in quality of life improvement. 54 A randomized trial of 120 patients with cirrhosis and overt HE showed that NTZ plus lactulose administration vs lactulose and placebo resulted in a significantly better improvement in Clinical HE Staging Scale score (P < .001).…”

“…55 Finally, in the most recent RCT with 60 patients, NTZ vs rifaximin administration led to a statistically significant reduction in plasma ammonia and prolongation of the remission period (136 vs 67 days, respectively; P ¼ .0001). 52 Although promising, further studies are required to prove the efficacy and explore the safety profile of NTZ in patients with cirrhosis and HE.…”

Gut Microbes and Hepatic Encephalopathy: From the Old Concepts to New Perspectives

“…A newer agent currently used in clinical trials for the treatment of HE is nitazoxanide, a broad-spectrum antibiotic and antiparasitic agent with activity against gut anaerobes. However, studies on the effect of microbiota composition are still lacking (Glal et al, 2021).…”