Herbal hepatotoxicity: Analysis of cases with initially reported positive re-exposure tests

BackgroundPositive re-exposure tests are diagnostic hallmarks for hepatotoxicity.ObjectiveTo test validity of positive re-exposures in herb induced liver injury.MethodsWe searched Medline database for cases of herb induced liver injury with positive re-exposures and analysed 34 cases for positive re-exposure test criteria of baseline alanine aminotransferase < 5N before re-exposure, and re-exposure alanine aminotransferase ≥ 2× baseline alanine aminotransferase. Re-exposure test was negative, if baseline alanine aminotransferase < 5N combined with re-exposure alanine aminotransferase < 2× baseline alanine aminotransferase, or if baseline alanine aminotransferase ≥ 5N regardless of the re-exposure alanine aminotransferase including no available re-exposure alanine aminotransferase result.ResultsIn 21/34 cases (61.8%), criteria for a positive re-exposure were fulfilled, with negative tests in 6/34 cases (17.6%) or uninterpretable ones in 7/34 cases (20.6%). Confirmed positive re-exposure tests established potential of herb induced liver injury for Aloe, Chaparral, Chinese herbal mixtures, Chinese Jin Bu Huan, Chinese Syo Saiko To, Germander, Greater Celandine, Green tea, Kava, Mistletoe, Polygonum multiflorum, and Senna, with up to 4 case reports per herb.ConclusionsAmong 34 cases of herb-induced liver injury with initially reported positive re-exposure tests, 61.8% of the cases actually fulfilled established test criteria and provided firm diagnoses of herb induced liver injury by various herbs.