Hepatotoxicity reassurance for febuxostat-treated patients with gout and fatty liver disease
medwireNews: Results of an observational study provide preliminary evidence suggesting that patients with gout and fatty liver disease (FLD) who are treated with febuxostat do not have an elevated risk for hepatotoxicity.
As reported in The Journal of Rheumatology, the investigation included 134 South Korean gout patients with comorbid FLD, of whom 23.9% were treated with febuxostat and 76.1% were taking allopurinol. A total of 20 febuxostat-treated patients had previously received allopurinol, with the majority of these individuals switching to febuxostat due to lack of effectiveness.
Over a median follow-up of 84 weeks, 9.4% of the 32 patients in the febuxostat group developed hepatotoxicity, defined as elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) to at least three times the upper limit of normal from baseline levels within the normal range, or doubling of AST/ALT from elevated baseline levels.
This compared with a hepatotoxicity rate of 35.3% over a median duration of 56 weeks for the 102 patients treated with allopurinol, a significant difference. Hepatotoxicity developed after a median of 21.0 weeks in the febuxostat group and 17.5 weeks in the allopurinol group.
“These findings indicate that febuxostat was well tolerated in patients with FLD, being associated with fewer cases of hepatotoxicity when compared with allopurinol,” say Seokchan Hong and fellow researchers from Asan Medical Center in Seoul, South Korea.
In a multivariate analysis, febuxostat use was associated with a significant 71.8% lower risk for hepatotoxicity relative to allopurinol use. On the other hand, patients with diabetes had a significant 3.5-fold higher risk for liver enzyme elevations than those without, and the use of colchicine was associated with a significant 11.5-fold elevated risk.
Hong and team note that the mechanism linking colchicine treatment and hepatotoxicity “was unclear,” but “could be because colchicine [is] primarily metabolized and excreted by the liver.”
The researchers caution that their study had a number of limitations, including a small number of febuxostat-treated patients. Moreover, “it was not clear whether hepatotoxicity was directly related to drug use,” they add.
Nevertheless, they stress that this was the first study to compare the hepatic safety of febuxostat and allopurinol in gout patients with FLD.
“Given the increasing worldwide occurrence of FLD, our results provide preliminary evidence of the safety of febuxostat” in this patient population, the team concludes.
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