Glal KAM, El-Haggar SM, Abd-Elsalam SM, et al. Allopurinol Prevents Cirrhosis-Related Complications: A Quadruple Blind Placebo-Controlled Trial. Am J Med. 2023 Oct 11:S0002-9343(23)00607-1. doi: 10.1016/j.amjmed.2023.09.016. (Original study)

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: 100 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? 0.001]. Allopurinol decreased the RR of overt ascites by 67 % [HR?=?0.33 (0.0098-0.94); p= 0.039] and reduced the RR of SBP by about 75% [HR?=?0.25(0.05-0.76); p= 0.01]. likewise, allopurinol was linked to an 80% reduction in the RR of developing HRS [HR?=?0.2 (0.04-0.87); p= 0.033].

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. [CLINICALTRIALS.


Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Gastroenterology 6 / 7
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

Interesting trial, however, the elevation of liver enzymes seen in the intervention group and the short follow-up period indicates the need for more studies to confirm the results.

Gastroenterology rater

The authors did well conducting this placebo-controlled study.

Gastroenterology rater

A well-conducted clinical trial found the efficacy of a simple pharmacological intervention to prevent cirrhosis-related complications. Some words of caution: the relatively small sample size, unicentric study, and short follow-up. Larger multicentric trials with long-term follow-up are needed to confirm these preliminary results.
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