The role of allopurinol in metabolic dysfunction-associated steatotic liver disease: A randomized clinical trial

Despite being the leading cause of liver-related mortality, the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) remains challenging. This study aimed to assess the effects of allopurinol on hepatic enzymes and ultrasonographic grading of MASLD patients, given the important role of uric acid in MASLD pathogenesis.

This randomized clinical trial enrolled 104 patients with MASLD to receive either 100 mg allopurinol daily in addition to the hypocaloric diet (n = 51) or the hypocaloric diet alone (n = 53) for 6 months. Ultrasonographic grading and serum levels of hepatic enzymes, including aspartate transaminase (AST) and alanine transaminase (ALT), were compared at 6 months compared with baseline. Between-group changes were investigated by the chi-squared test and an analysis of covariance (ANCOVA) adjusted for age, sex, BMI, and baseline values. The correlation between serum uric acid levels and liver enzymes was also assessed using the Pearson correlation coefficient (r).

Ultrasonographic grading of the allopurinol-treated group, but not the control group, significantly improved from baseline (P = 0.001 and P = 0.096). However, there were no significant differences between the two groups. Within the allopurinol-treated group, ALT and AST levels significantly decreased in the sixth month from baseline (P = 0.004 and P = 0.022, respectively), while no significant changes were observed in the control group (P = 0.571 and P = 0.526, respectively) or between the two groups.Unlike the control group, serum uric acid correlated with ALT and AST levels in patients treated with allopurinol at the sixth month.

Allopurinol administration in MASLD patients improved ultrasonographic grading and liver enzymes from baseline. However, the comparison with the control group did not support the beneficial effects.