Allopurinol Prevents Cirrhosis-Related Complications: A Quadruple Blind Placebo-Controlled Trial.

BACKGROUND: Complications associated with liver cirrhosis are various and potentially fatal. The treatment options to counteract hepatic decompensation are limited. Therefore, the study aimed to explore the use of allopurinol in preventing the recurrence of liver cirrhosis-related complications. METHODS: One hundred patients with hepatic decompensation were randomized into 1:1 ratio to receive either allopurinol 300 mg or placebo tablets once daily for 6 months. The primary endpoint was the incidence of cirrhosis-related complications (overt ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, and hepatic encephalopathy). RESULTS: Six months following treatment, allopurinol reduced the relative risk (RR) of any first complication experienced after enrollment by 56% (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.27-0.62); P ˂ .001). Allopurinol decreased the RR of overt ascites by 67% (HR 0.33; 95% CI, 0.0098-0.94); P = .039] and reduced the RR of spontaneous bacterial peritonitis by about 75% (HR 0.25; 95% CI, 0.05-0.76; P = .01). Likewise, allopurinol was linked to an 80% reduction in the RR of developing hepatorenal syndrome (HR 0.2; 95% CI, 0.04-0.87; P = .033). CONCLUSION: Allopurinol significantly decreased the recurrence of overall liver cirrhosis-related complications. Therefore, allopurinol may constitute a promising agent for patients with hepatic decompensation. These positive outcomes could be a result of its ability to reduce bacterial translocation and inflammation. GOV IDENTIFIER: NCT005545670.

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

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 (P1  = .0001) and significant reduction in Child score (P1  = .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.