Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with hepatotoxicity. Drug-induced liver injury (DILI) in patients under NSAIDs is more frequently presented by hepatocellular damage with elevated serum alanine aminotransferase (ALT) levels (1).
Objectives To evaluate the hepatocellular toxicity due to NSAIDs on the basis of changes in serum ALT levels in patients with gouty arthritis (GA).
Methods 376 patients with GA registered in our database were included in our retrospective study. Males made 92,8% (n=349). Mean age was 57 (50–62) years; mean duration of gout – 7 (3–10) years. NSAIDs were prescribed to the patients with gouty attack by generalists, and then all patients were addressed to the Rheumatology Clinics. Serum ALT levels were determined at the onset of gout attack and 3–10 days after starting NSAIDs therapy. All NSAIDs used were generics. The hepatotoxicity was considered when ALT level was 2 times (or more) upper limits of normal values (42 U/l for men and 35 U/l for women) according to DILI criteria. ALT level at baseline was within the normal limits in 80,8% (n=304) of cases, its elevation was identified in 19,2% (n=72).
Results We divided the patients into 3 groups according to the type of changes in serum ALT levels after receiving NSAIDs:
Group 1: 69,4% (n=261) of patients with normal ALT 24 (17–30) U/l before and 24 (18–32) U/l after treatment (p>0,05).
Group 2: 11,4% (n=43) of patients with normal basal ALT 26 (21–35) U/l and its elevation to 77 (72–88) U/l (p<0,001) after NSAIDs therapy.
Group 3: 19,2% (n=72) of patients with elevated basal ALT 57 (46–91) U/l, who had different type of ALT response to NSAIDs therapy. We identified 3 subgroups within the third group:
Subgroup A: 7% (n=5) of patients with elevated ALT level at the beginning of gout attack – 92 (62–123,5) U/l and higher value after treatment – 151 (129–215) U/l (p<0,001). Subgroup B: 23,6% (n=17) of patients with elevated ALT before treatment – 53 (47,5–62) U/l and non-significant changes after therapy – 51 (44,5–63,5) U/l (p >0,05). Subgroup C: 69,4% (n=50) of patients with elevated ALT before treatment – 59 (49–89) U/l and reduced and/or normal ALT level after therapy – 42 (29–57) U/l (p<0,001). While the patients from subgroup A have demonstrated supplementary hepatotoxicity due to NSAIDs on the basis of pre-existing liver injury, the absence of changes in ALT levels in subgroup B has been suggested in favor of a chronic liver injury. Subgroup C has reflected the effect of NSAIDs to decrease and even normalize the elevated basal ALT value. This may be linked to a hepatic inflammation, which is likely associated with alcohol intake, but hyperuricemia could also be involved.
Conclusions 69,4% (261 from 376) of patients with GA having normal basal ALT values did not demonstrate any changes in ALT level after NSAIDs treatment; in 11,4% of patients, hepatocellular NSAIDs–induced hepatotoxicity was revealed. In the group of patients with elevated basal ALT level, the response of ALT to NSAIDs treatment was as follows: no significant changes – 23,6%, elevated value – 7%, reduced or normalized value – 69,4%. The last subgroup (C) requires more detailed study.
Schmeltzer P. A., Kosinski A. S., Kleiner D. E. et al. Liver injury from nonsteroidal anti-inflammatory drugs in the United States. Liver International 2016;36(4): 603–609.
Disclosure of Interest None declared