Teschke Rolf, Eickhoff Axel
Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, Leimenstrasse 20, D-63450 Hanau, Germany.
Int J Mol Sci. 2016 Mar 31;17(4):476. doi: 10.3390/ijms17040476.
In 2013, physicians at the Honolulu Queen's Medical Center (QMC) noticed that seven liver disease patients reported the use of OxyELITE Pro (OEP), a widely consumed dietary supplement (DS). Assuming a temporal association between OEP use and disease, they argued that OEP was the cause of this mysterious cluster. Subsequent reexamination, however, has revealed that this QMC cohort is heterogeneous and not a cluster with a single agent causing a single disease. It is heterogeneous because patients used multiple DS's and drugs and because patients appeared to have suffered from multiple liver diseases: liver cirrhosis, liver failure by acetaminophen, hepatotoxicity by non-steroidal antiinflammatory drugs (NSAIDs), resolving acute viral hepatitis by hepatitis B virus (HBV), herpes simplex virus (HSV), and varicella zoster virus (VZV), and suspected hepatitis E virus (HEV). Failing to exclude these confounders and to consider more viable diagnoses, the QMC physicians may have missed specific treatment options in some of their patients. The QMC physicians unjustifiably upgraded their Roussel Uclaf Causality Assessment Method (RUCAM) causality scores so that all patients would appear to be "probable" for OEP. However, subsequent RUCAM reassessments by our group demonstrated a lack of causality for OEP in the evaluated QMC cases. The QMC's questionable approaches explain the extraordinary accumulation of suspected OEP cases at the QMC in Hawaii as single place, whereas similar cohorts were not published by any larger US liver center, substantiating that the problem is with the QMC. In this review article, we present and discuss new case data and critically evaluate upcoming developments of problematic regulatory assessments by the US Centers for Disease Control and Prevention (CDC), the Hawaii Department of Health (HDOH), and the Food and Drug Administration (FDA), as based on invalid QMC conclusions, clarifying now also basic facts and facilitating constructive discussions.
2013年，檀香山女王医疗中心（QMC）的医生注意到，有7名肝病患者报告使用了OxyELITE Pro（OEP），这是一种广泛消费的膳食补充剂（DS）。鉴于OEP使用与疾病之间存在时间关联，他们认为OEP是这一神秘病例群的病因。然而，随后的重新检查发现，这个QMC队列具有异质性，并非由单一因素导致单一疾病的病例群。它具有异质性是因为患者使用了多种膳食补充剂和药物，还因为患者似乎患有多种肝病：肝硬化、对乙酰氨基酚所致肝衰竭、非甾体抗炎药（NSAIDs）所致肝毒性、由乙型肝炎病毒（HBV）、单纯疱疹病毒（HSV）和水痘带状疱疹病毒（VZV）引起的急性病毒性肝炎已痊愈，以及疑似戊型肝炎病毒（HEV）感染。由于未能排除这些混杂因素并考虑更可行的诊断，QMC的医生可能在一些患者中错过了特定的治疗选择。QMC的医生不合理地提高了他们的鲁塞尔·优克福因果关系评估方法（RUCAM）因果关系评分，以便所有患者似乎都“可能”与OEP有关。然而，我们团队随后对RUCAM的重新评估表明，在评估的QMC病例中，OEP与疾病不存在因果关系。QMC的可疑方法解释了夏威夷QMC作为单一地点出现大量疑似OEP病例的异常情况，而美国任何更大的肝脏中心都未公布类似队列，这证实问题出在QMC。在这篇综述文章中，我们展示并讨论新的病例数据，并严格评估美国疾病控制与预防中心（CDC）、夏威夷卫生部（HDOH）和食品药品监督管理局（FDA）基于无效的QMC结论进行的有问题的监管评估的未来发展，同时阐明基本事实并促进建设性的讨论。
