Assessing liver injury associated with antimycotics:Concise literature review and clues from data mining of the FAERS database

AIM: To inform clinicians on the level of hepatotoxicrisk among antimycotics in the post-marketing setting,following the marketing suspension of oral ketocon-azole for drug-induced liver injury(DILI).METHODS: The publicly available international FAERSdatabase(2004-2011) was used to extract DILI cases(including acute liver failure events), where antimycot-ics with systemic use or potential systemic absorptionwere reported as suspect or interacting agents. The re-porting pattern was analyzed by calculating the report-ing odds ratio and corresponding 95%CI, a measure ofdisproportionality, with time-trend analysis where ap-propriate.RESULTS: From 1687284 reports submitted over the8-year period, 68115 regarded liver injury. Of these,2.9% are related to antimycotics(1964 cases, of which 112 of acute liver failure). Eleven systemic antimycotics(including ketoconazole and the newer triazole deriva-tives voriconazole and posaconazole) and terbinafine(used systemically to treat onychomicosis) generated a significant disproportionality, indicating a post-market-ing signal of risk.CONCLUSION: Virtually all antimycotics with systemic action or absorption are commonly reported in clinically significant cases of DILI. Clinicians must be aware of this aspect and monitor patients in case switch is con-sidered, especially in critical poly-treated patients under chronic treatment.

How albumin administration for cirrhosis impacts on hospital albumin consumption and expenditure

AIM:To assess the impact of guidelines for albumin prescription in an academic hospital,which is a referral center for liver diseases.METHODS:Although randomized trials and guidelines support albumin administration for some complications of cirrhosis,the high cost of albumin greatly limits its use in clinical practice.In 2003,a multidisciplinary panel at Sant'Orsola-Malpighi University Hospital(Bologna,Italy)used a literature-based consensus method to list all the acute and chronic conditions for which albumin is indicated as first-or second-line treatment.Indications in hepatology included prevention of post-paracentesis circulatory dysfunction and renal failure induced by spontaneous bacterial peritonitis,and treatment of hepatorenal syndrome and refractory ascites.Although still debated,albumin administration in refractory ascites is accepted by the Italian health care system.We analyzedalbumin prescription and related costs before and after implementation of the new guidelines.RESULTS:While albumin consumption and costs doubled from 1998 to 2002,they dropped 20%after 2003,and remained stable for the following 6 years.Complications of cirrhosis,namely refractory ascites and paracentesis,represented the predominant indications,followed by major surgery,shock,enteric diseases,and plasmapheresis.Albumin consumption increased significantly after guideline implementation in the liver units,whereas it declined elsewhere in the hospital.Lastly,extra-protocol albumin prescription was estimated as<10%.CONCLUSION:Albumin administration in cirrhosis according to international guidelines does not increase total hospital albumin consumption if its use in settings without evidence of efficacy is avoided.