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“Did This Drug Cause My Patient's Hepatitis?” and Related Questions
What should the busy internist do when his or her patient, while taking several medications, suddenly develops a new clinical problem, such as hepatitis? Is the acute hepatitis drug related? If so, which drug is to blame?
The case report by May and colleagues in this issue (1) describes a 49-year-old electrician who developed acute scleral icterus and moderate biochemical hepatitis (total bilirubin level, 8.0 times the upper limit of normal; alanine aminotransferase [ALT] level, 6.8 times the upper limit of normal). The patient had been receiving several medications for years; he began taking pioglitazone, first at a low dosage (15 to 30 mg/d) for 6 months and later at a higher dosage (45 mg/d), for 1 week. Because the authors suspected that pioglitazone was the causal agent, they discontinued use of that medication; they continued all the others. The result of a thorough evaluation for other common causes of hepatitis (including other medications) was negative, and a liver biopsy showed a pattern of mixed hepatocellular–cholestatic injury compatible with drug hepatotoxicity. Liver function tests showed considerable improvement 2 weeks after pioglitazone therapy was discontinued. The authors concluded that the hepatitis was probably caused by pioglitazone, even though only one other similar case had been reported previously.
Pertinent Questions for the Practicing Internist
This case report is clear and straightforward, but it does raise some additional interesting questions for the reader.
How Should I Assess Whether a Specific Drug Caused a New Clinical Syndrome in My Patient?
Several algorithms have been developed to help clinicians deal with this question. A simple but useful approach involves addressing five specific questions (2). This approach can be illustrated by applying it to this case.
1. Has this type of adverse reaction been observed previously? The package insert for pioglitazone states that in clinical trials in the United States, 4 of 1525 participants who received active treatment (0.26%) and 2 of 793 participants who received placebo …
