Nonsteroidal Anti-Inflammatory Drug–Induced Hepatotoxicity
Section snippets
Epidemiology
Because the relatively high-risk agents causing hepatotoxicity have been replaced by apparently safer drugs, relatively rare adverse reactions to commonly prescribed low-risk agents have become the most important cause of liver injury. This is exemplified by NSAIDs that are among the most common drugs causing idiosyncratic hepatotoxicity in several recently published series (Table 1) [7], [8], [9], [10], [11], [12], [13]. Despite these reports highlighting the importance of NSAIDs as a cause of
Sulindac
Among NSAIDs, sulindac has been the drug most consistently associated with hepatotoxicity. By 1993 there had been 91 cases of liver injury reported to the FDA with 43% showing a cholestatic pattern of liver blood test abnormalities, 25% a hepatocellular pattern, and the rest a mixed pattern [23]. In these reports the female/male ratio was 3.5:1 and 69% were over the age of 50 years. Most patients (67%) were jaundiced and four patients died. Features of hypersensitivity, such as fever, rash, and
Diclofenac-induced liver injury: a paradigm of idiosyncratic hepatotoxicity
Diclofenac is a widely prescribed NSAID, which can cause rare, but potentially serious, hepatotoxicity. Because of its widespread use, diclofenac hepatotoxicity has been one of the most common causes of hepatic adverse drug reactions, with 180 confirmed cases reported to the FDA during the first 3 years of marketing [19]. Consistent with its worldwide exposure and its association with liver injury, diclofenac on its own is among the most common drugs associated with idiosyncratic hepatotoxicity
The importance of nonsteroidal anti-inflammatory drug–induced liver injury
Because of their common use, NSAIDs contribute significantly to the overall burden of drug-induced liver injury. The importance of any drug as a cause of liver injury lies not in the overall number of cases, however, but in the severity of some reactions. Despite the availability of liver transplantation, 26% (95% CI, 13%–43%) of those who develop jaundice caused by severe NSAID-induced hepatotoxicity die [60]. Adverse hepatic reactions can mimic a wide spectrum of hepatobiliary diseases. Early
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