What are the treatment options for gout in patients with elevated liver enzymes (hypertransaminasemia)?

From the Guidelines

Managing gout in patients with elevated liver enzymes requires careful medication selection, with colchicine at a reduced dose of 1.2 mg followed by 0.6 mg 1 hour later being a preferred option due to its efficacy and lower risk of gastrointestinal adverse effects, as supported by moderate-quality evidence 1. When considering treatment for gout with elevated liver enzymes, it's crucial to prioritize medications that minimize liver stress. Non-pharmacological approaches such as weight loss, limiting alcohol consumption, reducing intake of purine-rich foods, and staying well-hydrated are essential first steps. For acute gout flares, the use of NSAIDs may be contraindicated in patients with liver disease, such as cirrhosis, making colchicine a safer alternative, despite its potential for gastrointestinal adverse effects, which can be mitigated by using lower doses, as recommended by the American College of Physicians 1. Prednisolone at a dose of 35 mg for 5 days has been successfully used to treat acute gout, offering another option for patients with liver concerns, although its use should be carefully considered due to potential adverse effects associated with long-term corticosteroid use 1. In terms of long-term urate-lowering therapy, the decision to initiate such treatment should be made cautiously, considering the frequency of gout attacks and the potential benefits and risks of therapy, with a strong recommendation against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks, as per the guidelines 1. Regular monitoring of liver function and adjustment of medication as necessary is critical to balance effective gout management with the protection of liver function. Key considerations include:

• Using colchicine at reduced doses to minimize gastrointestinal adverse effects
• Avoiding NSAIDs in patients with significant liver disease
• Considering prednisolone for acute gout flares when necessary and with caution
• Carefully deciding on long-term urate-lowering therapy based on gout attack frequency and individual patient risk factors
• Regular liver function testing to ensure safe treatment.

From the FDA Drug Label

The clearance of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment compared to healthy subjects For prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended Colchicine Tablets, USP dose is not required, but patients should be monitored closely for adverse effects of colchicine However, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, the treatment course should be repeated no more than once every two weeks.

Treatment for gout with elevated liver enzymes should be approached with caution.

• For patients with mild to moderate hepatic impairment, no dose adjustment is required, but close monitoring for adverse effects is necessary.
• For patients with severe hepatic impairment, dose reduction should be considered for prophylaxis of gout flares, and treatment courses should not be repeated more than once every two weeks for treatment of gout flares. 2

From the Research

Treatment for Gout with Elevated Liver Enzymes

• Gout is a common inflammatory arthritis characterized by swelling, pain, or tenderness in a peripheral joint or bursa, including the development of a tophus 3.
• The treatment of gout involves the use of urate-lowering therapy, such as allopurinol and febuxostat, to prevent flare-ups 3, 4.
• However, febuxostat is associated with an increase in all-cause and cardiovascular mortality and is therefore not routinely recommended 3.
• In patients with gout and elevated liver enzymes, the choice of urate-lowering therapy should be made with caution, as some medications may exacerbate liver damage.
• Allopurinol and febuxostat are both effective in lowering serum urate levels, but febuxostat may be a better option for patients with gout and elevated liver enzymes due to its more favorable safety profile 5, 6.
• A study comparing the persistence rates of allopurinol and febuxostat as first-line urate-lowering therapy in patients with gout found that febuxostat had better persistence rates than allopurinol 5.
• Another study found that allopurinol and febuxostat achieved serum urate goals in patients with gout, and allopurinol was noninferior to febuxostat in controlling flares 6.

Urate-Lowering Therapy Options

• Allopurinol: a xanthine oxidase inhibitor that is commonly used as first-line therapy for gout 3, 4.
• Febuxostat: a xanthine oxidase inhibitor that is an alternative to allopurinol for patients who are intolerant or have contraindications to allopurinol 3, 4.
• Probenecid: a uricosuric agent that increases the excretion of uric acid in the urine 4.
• Benzbromarone: a uricosuric agent that is used in some countries for the treatment of gout 4.
• Pegloticase: a recombinant uricase enzyme that is used for the treatment of severe gout 4.

Considerations for Patients with Elevated Liver Enzymes

• Patients with gout and elevated liver enzymes should be monitored closely for signs of liver damage when taking urate-lowering therapy 7.
• The choice of urate-lowering therapy should be individualized based on the patient's medical history, liver function, and other factors 5, 6.
• Patients with gout and elevated liver enzymes should be educated on the importance of adherence to their medication regimen and regular follow-up with their healthcare provider 5.