The Role of Adverse Event Reporting in the FDA Response to a Multistate Outbreak of Liver Disease Associated with a Dietary Supplement.

OBJECTIVE: Liver disease is a potential complication from using dietary supplements. This study investigated an outbreak of non-viral liver disease associated with the use of OxyELITE Pro(TM), a dietary supplement used for weight loss and/or muscle building. METHODS: Illness details were ascertained from MedWatch reports submitted to the U.S. Food and Drug Administration (FDA) describing consumers who ingested OxyELITE Pro alone or in combination with other dietary supplements. FDA's Forensic Chemistry Center analyzed samples of OxyELITE Pro. RESULTS: From February 2012 to February 2014, FDA received 114 reports of adverse events of all kinds involving consumers who ingested OxyELITE Pro. The onset of illness for the first report was December 2010 and for the last report was January 2014. Thirty-three states, two foreign nations, and Puerto Rico submitted reports. Fifty-five of the reports (48%) described liver disease in the absence of viral infection, gallbladder disease, autoimmune disease, or other known causes of liver damage. A total of 33 (60%) of these patients were hospitalized, and three underwent liver transplantation. In early 2013, OxyELITE Pro products entered the market with a formulation distinct from products sold previously. The new formulation replaced 1,3-dimethylamylamine with aegeline. However, the manufacturer failed to submit to FDA a required "new dietary ingredient" notice for the use of aegeline in OxyELITE Pro products. Laboratory analysis identified no drugs, poisons, pharmaceuticals, toxic metals, usnic acid, N-Nitroso-fenfluramine, pyrrolizidine alkaloids, aristocholic acid, or phenethylamines in the products. CONCLUSIONS: Vigilant surveillance is required for adverse events linked to the use of dietary supplements.

Outbreak of hepatitis A in the USA associated with frozen pomegranate arils imported from Turkey: an epidemiological case study.

BACKGROUND: In May, 2013, an outbreak of symptomatic hepatitis A virus infections occurred in the USA. Federal, state, and local public health officials investigated the cause of the outbreak and instituted actions to control its spread. We investigated the source of the outbreak and assessed the public health measures used. METHODS: We interviewed patients, obtained their shopping information, and did genetic analysis of hepatitis A virus recovered from patients' serum and stool samples. We tested products for the virus and traced supply chains. FINDINGS: Of 165 patients identified from ten states, 69 (42%) were admitted to hospital, two developed fulminant hepatitis, and one needed a liver transplant; none died. Illness onset occurred from March 31 to Aug 12, 2013. The median age of patients was 47 years (IQR 35-58) and 91 (55%) were women. 153 patients (93%) reported consuming product B from retailer A. 40 patients (24%) had product B in their freezers, and 113 (68%) bought it according to data from retailer A. Hepatitis A virus genotype IB, uncommon in the Americas, was recovered from specimens from 117 people with hepatitis A virus illness. Pomegranate arils that were imported from Turkey--where genotype IB is common--were identified in product B. No hepatitis A virus was detected in product B. INTERPRETATION: Imported frozen pomegranate arils were identified as the vehicle early in the investigation by combining epidemiology--with data from several sources--genetic analysis of patient samples, and product tracing. Product B was removed from store shelves, the public were warned not to eat product B, product recalls took place, and postexposure prophylaxis with both hepatitis A virus vaccine and immunoglobulin was provided. Our findings show that modern public health actions can help rapidly detect and control hepatitis A virus illness caused by imported food. Our findings show that postexposure prophylaxis can successfully prevent hepatitis A illness when a specific product is identified. Imported food products combined with waning immunity in some adult populations might make this type of intervention necessary in the future. FUNDING: US Centers for Disease Control and Prevention, US Food and Drug Administration, and US state and local public health departments.