**1. Introduction**

Gout is a common and treatable form of inflammatory arthritis resulting from the chronic deposition of monosodium urate crystals, which form in the presence ofincreased urate concentrations [1]. Recent studies have reported that incidence and prevalence rates of gout are rapidly increasing in many countries due to various factors, such as change of dietary habits and comorbid conditions [2,3]. Previous studies have also reported that gout is associated with a number of comorbidities, including cardiovascular disease (CVD), type II diabetes, obesity, dyslipidemia, chronic kidney disease (CKD), nonalcoholic fatty liver disease, and metabolic syndrome [4]. These comorbidities play an important role in determining the medication for treatment options in patients with gout.

Early episodes of acute gouty attack resolve spontaneously within several days or weeks, but repeated acute flares can lead to chronic arthritis with the formation of tophi and joint damage, which contribute to disability and decreased quality of life. Therefore, uric acid-lowering therapy (ULT) as well as prophylaxis of acute attack is one of the treatment goals of gout [5]. A recent guideline for gout management has recommended that when initiating ULT, prophylactic treatment with anti-inflammatory drugs for at least 6 months reduces the frequency of gout flares [6].

Colchicine is a systemic anti-inflammatory agent, and has been regarded as a first line prophylactic drug to prevent gout flare. However, it also has many side effects, such as gastrointestinal symptoms (including diarrhea), muscle pain or weakness, drug-to-drug interactions, renal impairment, and abnormal liver function tests [7]. Therefore, before colchicine treatment, it is necessary to consider the underlying diseases and concomitant medications.

A previous study has shown that colchicine is associated with a risk of hepatotoxicity in gout patients prescribed febuxostat [8], which has also been reported to induce acute liver injury [9]. However, there are few studies regarding hepatic safety of colchicine as a prophylactic therapy in gout patients treated with febuxostat. We investigated whether the concomitant use of colchicine and febuxostat increases hepatotoxicity in gout patients, and evaluated the factors associated with hepatotoxicity in gout patients treated with febuxostat.

#### **2. Materials and Methods**

### *2.1. Study Subjects*

A total of 319 patients initially diagnosed with gout at Kangwon National University Hospital from January 2012 to December 2018 were included. Exclusion criteria were as follows: age at the time of diagnosis <18 years, patients who used uric acid-lowering agents in asymptomatic hyperuricemia, and patients whose follow-up period was less than 3 months. Patients who had a history of allopurinol use were also excluded. A total of 178 gout patients treated with febuxostat were included. The study was approved by the Institutional Review Board of Kangwon National University Hospital and conducted in accordance with the Declaration of Helsinki (IRB protocol number: 2019-12-009).
