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Kao, W.Y., Su, C.W., Huang, Y.S., Chou, Chapter

Kao, W.Y., Su, C.W., Huang, Y.S., Chou, Y.C., Chen, Y.C., Chung, W.H., ... & Wu, J.C. Risk of oral antifungal agent-induced liver injury in Taiwanese. British Journal of Clinical Pharmacology, 77(1), 180-189.

The researchers claim that drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United States and a major issue in other countries. DILI is a serious health problem that has major ramifications on physicians, patients, pharmaceutical industry and government regulators. The use of oral antifungal agents has resulted in some well publicized cases of serious liver injuries leading to death even though the incident rates of DILI are low. Almost half of patients in Taiwan infected with oychomycosis refuse to be treated with oral antifungal agents because of concerns regarding potential liver injury. There has not been a study of antifungal-agent produced DILI for people in Taiwan and the current study attempted to examine the incidence of liver injures associated with oral antifungal use in Taiwan and to identify the risk factors for untoward liver issues in Taiwanese participants who use oral antifungal agents.

The Longitudinal Health Insurance Database (years 2002-2008) was utilized from the National Health Insurance program in Taiwan covering greater than 98% of the population in that country. A total of 90,847 patients who used antifungal agents were identified in the study of which 69, 665 were compared to a randomly extracted control group...

Five oral antifungal agents were investigated in this study: griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine.
There was a bit of variance in the incident rates of patients per 10000 each year who were diagnosed with DILI while using oral antifungal agents (the range 1.58 -- 8.39 per 10000 patients over the eight years of the study). Incidence rates also varied over the type of oral antifungal agent with fluconazole having the highest (31.6/10000) and terbinafine the lowest (1.6). The incident rate of adverse liver outcomes increased for most antifungal agents when the treatment duration increased with ketoconazole having the highest incident rate under these conditions.

Overall 52 DILI patients who had used antifungal agents were identified in the data. Fifty of these were hospitalized and six died. All of the fatal cases were exposed to fluconazole. The only other variable that was significantly different between survivors and non-survivors was the mean age of the participant (M = 53.7 for survivors; M = 75.8 for non-survivors). Thirty four of the patients had also used antibiotics and 32 had used NSAIDs. Overall patients who took antifungal agents were more likely than control patients to develop DILI (relatively risk = 1.73) and this finding remained robust after adjusting for age and gender as well as medical conditions such as hypertension, diabetes, hyperlipidaemia, cardiovascular issues/disease, chronic renal disease, and hepatitis B or C…

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