LIVER OUTCOMES IN GOUT PATIENTS TREATED WITH FEBUXOSTAT AND ALTERED LIVER FUNCTION TESTS

Background/Purpose: patients with significantly altered liver function test (LFTs) at screening do not qualify for clinical trials. Therefore, scarce data are available on the impact on altered LFTs with febuxostat. To assess whether febuxostat has an impact in LFTs in patients with altered LFTs at baseline, compared with patients with normal LFTs.

Methods: prospective follow-up of a cohort of patients initiating febuxostat for hyperuricemia of gout. ASAT, ALAT, and GGT were measured at baseline and at 3-6-12 months during follow-up. Child-Plough stage > 1 were not included. General characteristics of patients were obtained at entrance in the cohort, including parameters of gout severity, previous urate-lowering therapy, ethanol intake, hyperlipidemia, renal function impairment, and diabetes. Altered LFTs were defined as ASAT/ALAT > 1.5 or GGT > 2.5 upper normal limit (UNL). Liver ultrasonography was obtained prior to febuxostat in patients with altered LFTs at baseline and in those who developed altered LFTs during follow-up.

Results: 86 patients included, 83, 69, and 59 patients with data at 3, 6, and 12 months of follow-up, respectively, 96% with previous failure or intolerance/adverse events to at least one urate-lowering drug. General comorbidities:  47% renal function impairment (11% CKD 4-5), 29% ethanol intake > 20 g/day, 70% hypertension, 50% hyperlipidemia, 22% diabetes, 40% on diuretics, and 26% heart failure; 35% on the upper stratum of the Kaiser Permanent Pyramid of complexity. Of 23 (27%) patients with altered LFTs at baseline (ASAT, ALAT, and GGT were altered in 4, 9, and 18 % respectively), diseases were: 1 von Gierke Disease, 1 liver transplantation, 1 hemochromatosis, 2 alcoholic cirrhosis, 3 stasis liver due to heart failure, and 9 fatty liver. Six patients had altered LFTs but normal ultrasonography. Altered LFTs at baseline were more prevalent in patients with previous high ethanol intake (14/25 vs. 12/61, 56% vs. 19%, respectively; p<0.05).

No patient withdrew due to altered liver function test. Three patients developed sustained altered LFTs, ultrasonography showing lithiasis, fatty liver, and iron overload and four patients showed normalization of LFTs during follow-up. There was no significant change in paired means in any LFTs but a descent of ASAT/ALAT at 6 months and of GGT at 6 and 12 months (Table).

Conclusion: in this prospective cohort of patients with severe gout but not liver insufficiency, patients with altered LFTs, including patients including chronic liver disease, showed no signal of worsening of LFTs compared to patients with normal LFTs at baseline. There was even an improvement in LFTs in the long-term in patients with previously altered LFTs.