A critical analysis of the hepatotoxicity cases described in the literature related to Herbalife (r) products

Abstract

The aim of this study was to assess the hepatotoxicity cases described in the literature, attributed to the consumption of Herbalife ® products, and to determine whether a causal relationship exists between the reported cases of liver injury and the use of these products. A literature search was performed on the PubMed, LILACS and PAHO databases. Seven publications reporting a total of 53 cases of hepatotoxicity linked to the use of Herbalife ® products were retrieved. All of the studies lacked sufficient information to some degree, whether related to patients' history, concomitant use of medication and/or other compounds (including alcohol), observations on interrupted use (dechallenge), results found with markers, viral serology and autoantibodies or observations concerning re-exposure to the products. In addition to these items, the lack of clear information on the type of products evaluated and their respective composition is an important factor to be considered. Furthermore, data quality was also questionable due to the presence of confounding factors, absence of proper exclusion of alternative explanations, and the use of questionable methods for attributing causality. Hence, an association between hepatotoxicity and consumption of these products cannot be proven based on the data collected and rigorous scientific analysis.Uniterms: Hepatotoxicity. Herbalife ® . Herbalife products ®/ consumption/hepatotoxicity. Dietary supplements. Causality assessment.Este estudo teve como objetivo avaliar os casos de hepatotoxicidade descritos em literatura, atribuídos ao consumo de produtos Herbalife ® , e verificar se é possível ou não estabelecer uma relação de causalidade entre eles. Realizou-se levantamento bibliográfico nas bases de dados PubMed, LILACS e PAHO e foram encontrados 7 manuscritos reportando 53 casos de hepatotoxicidade, relacionados ao uso de produtos Herbalife. Observou-se que todos trazem, de alguma forma, quantidade insuficiente de informações em relação ao histórico dos pacientes, ao uso concomitante de medicamentos e/ou outros compostos (incluindo álcool), às observações após a interrupção do uso (dechallenge), aos resultados referentes a marcadores e sorologia virais e autoanticorpos e às observações quanto à reexposição aos produtos. Some-se a estes fatos a falta de identificação clara e comprovada do tipo de produto envolvido, assim como sua composição. Além disso, a qualidade dos dados também é questionável devido à presença de variáveis de confundimento, ausência de exclusão adequada de explicações alternativas e ao uso de métodos discutíveis de atribuição de causalidade. Desta forma, a associação entre hepatotoxicidade e o consumo destes produtos não pode ser comprovada, após observar o conjunto dos dados coletados, utilizando-se rigor técnico-cientifico.

Critical Evaluation for Alternative Causes of Drug Induced and Herbal Induced (DILI/HILI) Hepatotoxicity

“…Unfortunately, in the majority of published cases determined to have been caused by DS consumption, alternative causes for the hepatotoxic events were not considered. As a result, there is now a growing trend to reevaluate these reported cases for alternative causes using the more consistent and objective RUCAM causality assessment method in order to determine the actual causative risk factor(s) for the development of DILI/HILI [1]- [4] though it continues to be largely ignored in the literature.…”

“…This is also discussed in a recent publication which states: "…information collected and described in the literature does not allow speculation about the existence of sensitization in part of the population" [4]. Therefore, the original abnormal serology results and those associated with reexposure that have been reported in the literature may not have been instigated by the consumption of the reported DS, but rather the secondary outcome of a pre-existing medical condition.…”

“…As noted in the aforementioned recent publication, an observed issue with some of the reported cases of hepatotoxicity determined to be caused by DS consumption entails insufficient information related to: "patients' history, concomitant use of medication and/or other compounds (including alcohol), observations on discontinuation of use (dechallenge), results found with markers, viral serology and autoantibodies, observations concerning re-exposure to the suspect products, and specifications of product use" [4]. From a clinical perspective this is concerning.…”

“…Independent medical experts have questioned the methodology by which these cases were evaluated [1]- [4]. In many instances, these same experts are assigning weaker causality outcomes than were previously determined or completely excluded the use of DS as causative.…”

“…A recent publication reveals: "The [RUCAM] scale is specific and validated for hepatotoxicity, which is not the case for the Naranjo scale, the WHO global introspection method or the ad hoc approach. As these approaches are not specific, and not validated for causality assessment of hepatotoxicity, the author consider them obsolete" [4]. Thus, use of the RUCAM causality assessment tool is currently the only way to achieve comparability from one case report to the next and avoid erroneous conclusions of a causal relationship between a DS and liver disease.…”