Elevated liver enzymes is not an impediment to allopurinol dose escalation: an observational cohort study

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

150 patients with gout and normal baseline serum aminotransferases initiated on allopurinol were followed prospectively over three visits. Raised transaminases were defined as mild, moderate or severe if AST or ALT was raised <2, 2-3 or >3 times above upper normal limits, respectively. Predictors of AST/ALT elevation were assessed using Generalized Estimating Equations.

Mean age was 56.6 years, 95.3% were men. Median follow-up was 33.5(IQR 22.8-53.1) weeks. 32(21.5%) drank alcohol, 43(28.9%) were obese and 11(7.3%) had metabolic dysfunction-associated steatotic liver disease. 30(20.0%) developed raised AST/ALT during follow-up, majority (86.7%) was mild while none were severe. Allopurinol was maintained or increased in 18 out of 19 patients with raised serum aminotransferases at Visit-2. Their elevated AST/ALT remained stable (27.8%), improved (11.1%) or resolved (33.3%) at subsequent visit. None had worsening AST/ALT. Multivariate analysis revealed that alcohol consumption (adjusted OR 3.52, 95%CI 1.41-8.79) and statin non-user (adjusted OR 3.41, 95%CI 1.04-11.17) were independent predictors of raised transaminases. Higher allopurinol dose was not associated with development of liver enzyme elevation (p=0.193).

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