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

Am J Med. 2024 Jan;137(1):55-64. doi: 10.1016/j.amjmed.2023.09.016. Epub 2023 Oct 12.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT05545670.

Keywords: Allopurinol; Ascites; Cirrhosis; Decompensation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Allopurinol / therapeutic use
  • Ascites / etiology
  • Ascites / prevention & control
  • Esophageal and Gastric Varices* / complications
  • Gastrointestinal Hemorrhage / etiology
  • Hepatorenal Syndrome* / drug therapy
  • Hepatorenal Syndrome* / etiology
  • Hepatorenal Syndrome* / prevention & control
  • Humans
  • Liver Cirrhosis / complications
  • Peritonitis* / complications
  • Peritonitis* / prevention & control

Substances

  • Allopurinol

Associated data

  • ClinicalTrials.gov/NCT05545670