SAT0432 GOUTY ARTHRITIS AND DRUG-INDUCED LIVER INJURY AFTER THE TREATMENT WITH NSAIDS
Authors: Eleanora Mikhnevich, Tatsiana Rayeuneva, Ekaterina Leonchik
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> In order to relieve the pain during acute gout attacks, most patients take high doses of nonsteroidal anti-inflammatory drugs (NSAIDs), which can provoke the hepatotoxicity, or DILI (drug-induced liver injury). <h3>Objectives:</h3> To define the timing of DILI formation after the treatment with NSAIDs and its severity in patients with gouty arthritis (GA). <h3>Methods:</h3> 738 patients with GA from our database who meet the criteria of the ACR (1977) were included into the study. NSAIDs-induced liver damage is known to be mainly hepatocellular. The dynamic ALT concentration in blood before the start of NSAIDs and during the treatment has been assessed. Hepatocellular toxicity was determined according to the DILI classification criteria based on the blood ALT level increased &gt; 2 times to the upper limit of norm (42 U/l for men and 35 U/l for women). Inclusion criteria for the study group (n = 88) were: normal ALT before the treatment with NSAIDs, its increase during the treatment and return to the norm after the treatment. Exclusion criterion was chronic hepatitis of any etiology. The comparison group (n = 650) consisted of patients with normal blood ALT level throughout the treatment. <h3>Results:</h3> Among 738 patients with GA, 11.9% (n = 88) developed the hepatotoxicity following the NSAIDs therapy. No significant differences in age (54 (44-59.5) and 57 (52-63) years; p&gt; 0.05) and gender (men 93.3% and 87.6%; p &gt; 0.5) between the study and comparison groups were found. In the study group, the duration of NSAIDs administration was 10 (6–14) days, which did not differ from that in the comparison group — 9.5 (7–12) days (p&gt; 0.05). In patients with DILI, the elevated ALT was o, bserved as follows: 2-3 times in 74 patients (84.1%); 3 to 5 times in 10 (11.4%); more than 5 times in 4 patients (4.5%). So, minimal cytolysis was presented more frequently than more severe forms (p &lt; 0.05). In the subgroup with the ALT concentration &gt; 3-5 times (n = 10), 6 patients received Diclofenac in high doses, 2 patients were treated with Nimesulide, 1 patient with Etodolac and 1 with Dexalgin during the observation period. The elevation of ALT concentration &gt; 5 times was observed in 3 patients taking Diclofenac i/m and Nimesulide per os, simultaneously, and in 1 patient taking Diclofenac in high doses. Patients with DILI were taking the following medications: Diclofenac 48.9% (n = 43); Nimesulide 18.2% (n = 16); Meloxicam 5.7% (n = 5), the combination of NSAIDs 20.5% (n = 18) without statistical differences (p &gt; 0.05). The number of patients who abused alcohol in DILI and control groups did not differ significantly — 53.4% and 48.2%, respectively (p&gt;0.05). <h3>Conclusion:</h3> In patients with GA, the hepatocellular DILI was observed in 11.9% cases after the treatment with NSAIDs during 10 days (from 6 to 14 days). Among patients with DILI, 84.1% (n = 74) had NSAIDs-induced hepatitis with minimal cytolysis. Mild cytolysis was seen in 10 (11.4%), moderate in 4 patients (4.5%). In our study, no severe or fatal DILI has been noted. No significant differences for particular drugs in the hepatotoxicity incidence have been found (p &gt; 0.05). <h3>Disclosure of Interests:</h3> None declared