Elevated Liver Enzymes Is Not an Impediment to Allopurinol Dose Escalation: An Observational Cohort Study

Routine liver enzyme monitoring is advocated for while on allopurinol, but supporting guidance is lacking. We assessed the incidence and factors associated with elevated liver enzyme levels in patients with gout commenced on allopurinol.

One hundred and fifty patients with gout and normal baseline serum aminotransferases initiated on allopurinol were followed prospectively over three visits. Raised transaminase levels were defined as mild, moderate, or severe if aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels were raised less than two, two to three, or more than three times above upper normal limits, respectively. Predictors of AST/ALT elevation were assessed using generalized estimating equations.

Mean age was 56.6 years, and 95.3% were men. Median follow-up was 33.5 (interquartile range 22.8-53.1) weeks. A total of 32 (21.5%) drank alcohol, 43 (28.9%) were obese, and 11 (7.3%) had metabolic dysfunction-associated steatotic liver disease. Thirty (20.0%) developed raised AST/ALT levels during follow-up, the majority (86.7%) being mild, while none were severe. Allopurinol was maintained or increased in 18 out of 19 patients with raised serum aminotransferase levels at visit 2. Their elevated AST/ALT levels remained stable (27.8%), improved (11.1%), or resolved (33.3%) at subsequent visit. None had worsening AST/ALT levels. Multivariate analysis revealed that alcohol consumption (adjusted odds ratio [OR] 3.52, 95% confidence interval [CI] 1.41-8.79) and statin nonuse (adjusted OR 3.41, 95% CI 1.04-11.17) were independent predictors of raised transaminase levels. Higher allopurinol dose was not associated with development of liver enzyme elevation (P = 0.193).

Mild asymptomatic AST/ALT elevation is common among patients with gout and is not influenced by allopurinol dose escalation. Alcohol consumption was an independent risk factor for elevated liver enzyme levels, whereas statin use appeared protective. Allopurinol can be safely escalated despite mild-moderate serum aminotransferase elevation.