The mystery of the Hawaii liver disease cluster in summer 2013: A pragmatic and clinical approach to solve the problem.

Background And Aim: In the fall of 2013, the US Centers for Disease Control and Prevention (CDC) published a preliminary report on a cluster of liver disease cases that emerged in Hawaii in the summer 2013. This report claimed a temporal association as sufficient evidence that OxyELITE Pro (OEP), a dietary supplement (DS) mainly for weight loss, was the cause of this mysterious cluster. However, the presented data were inconsistent and required a thorough reanalysis.

Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases.

Traditional Chinese Medicine (TCM) with its focus on herbal use became popular worldwide. Treatment was perceived as safe, with neglect of rare adverse reactions including liver injury. To compile worldwide cases of liver injury by herbal TCM, we undertook a selective literature search in the PubMed database and searched for the items Traditional Chinese Medicine, TCM, Traditional Asian Medicine, and Traditional Oriental Medicine, also combined with the terms herbal hepatotoxicity or herb induced liver injury.

Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment.

Causality assessment of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences (CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment.

Herbalife hepatotoxicity: Evaluation of cases with positive reexposure tests.

Aim: To analyze the validity of applied test criteria and causality assessment methods in assumed Herbalife hepatotoxicity with positive reexposure tests.

Methods: We searched the Medline database for suspected cases of Herbalife hepatotoxicity and retrieved 53 cases including eight cases with a positive unintentional reexposure and a high causality level for Herbalife. First, analysis of these eight cases focused on the data quality of the positive reexposure cases, requiring a baseline value of alanine aminotransferase (ALT) < 5 upper limit of normal (N) before reexposure, with N as the upper limit of normal, and a doubling of the ALT value at reexposure as compared to the ALT value at baseline prior to reexposure.

Herbal hepatotoxicity: suspected cases assessed for alternative causes.

Background And Objectives: Alternative explanations are common in suspected drug-induced liver injury (DILI) and account for up to 47.1% of analyzed cases. This raised the question of whether a similar frequency may prevail in cases of assumed herb-induced liver injury (HILI).

Clinical and causality assessment in herbal hepatotoxicity.

Introduction: Herbal hepatotoxicity represents a poorly understood, neglected and multifaceted disease with numerous confounding variables and missing established causality in the majority of cases. This review discusses overt shortcomings in its clinical and causality assessment and suggests improvements.

Areas Covered: A selective literature search of PubMed using the terms herbal hepatotoxicity, herb-induced liver injury, drug hepatotoxicity and drug-induced liver injury was performed to identify published case reports, spontaneous case reports, case series and review articles regarding hepatotoxicity due to herbs, herbal drugs and herbal dietary supplements.

Herb induced liver injury presumably caused by black cohosh: a survey of initially purported cases and herbal quality specifications.

Herb induced liver injury (HILI) is a particular challenge that also applies to purported cases presumably caused by black cohosh (BC), an herb commonly used to treat menopausal symptoms. We analyzed and reviewed all published case reports and spontaneous reports of initially alleged BC hepatotoxicity regarding quality of case details and causality assessments. Shortcomings of data quality were more evident in spontaneous reports of regulatory agencies compared to published case reports, but assessments with the scale of CIOMS (Council for the International Organizations of Sciences) or its updated version revealed lack of causality for BC in all cases.

Causality assessment in hepatotoxicity by drugs and dietary supplements.

Structured causality assessment of hepatotoxicity by drugs and dietary supplements (DDS) is a major clinical challenge, since temporal associations as the sole criteria for a valid evaluation are not acceptable. Initially, a clear intuition for an ad hoc evaluation is necessary, but only provisional, and must be followed by a diagnostic algorithm using a pretest, main test and post test. The evaluation is based on a variety of items such as latency period, course of alanine aminotransferase and alkaline phosphatase after DDS discontinuation, risk factors, co-medication, previous information on hepatotoxicity of the DDS, response to rechallenge, and exclusion of other diseases.

Suspected hepatotoxicity by Cimicifugae racemosae rhizoma (black cohosh, root): critical analysis and structured causality assessment.

Severe hepatotoxicity has been described as spontaneous or case reports in 42 patients in assumed causal relationship with the treatment by Cimicifugae racemosae rhizoma corresponding to the root of black cohosh (BC) for postmenopausal symptoms. However, an assessment by EMEA (European Medicines Agency) has shown a possible or probable causality in only 4 out of 42 patients. A diagnostic algorithm was now applied in the 4 patients with suspected BC hepatotoxicity, which included the qualitative and quantitative causality assessment of the updated system of the Council for International Organizations of Medical Sciences (CIOMS), allowing the study to objectively assess, score and scale the probability in each case.

Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases.

Background/aims: Hepatotoxicity has been previously suspected by national regulatory agencies in 26 patients in causal relationship with the treatment by kava extracts commonly used as herbal anxiolytic drugs.

Methods: A quantitative causality assessment was undertaken using the system of the Council for International Organizations of Medical Sciences, scale of objective probability scoring.

Results: Causality was unassessable, unrelated, or excluded in 16 patients owing to lack of temporal association and causes independent of kava or comedicated drugs.

Kava hepatotoxicity: a European view.

Kava was well tolerated and considered as devoid of major side effects only until 1998 when the first report of assumed kava hepatotoxicity appeared. Causality of hepatotoxicity for kava +/- comedicated drugs was evident after the use of predominantly ethanolic and acetonic kava extracts in Germany (n=7), Switzerland (n=2), United States (n=1), and Australia (n=1) as well as after aqueous extracts in New Caledonia (n=2). Compliance regarding the recommendation for daily kava dose and duration was ascertained in only a few patients, including 2 from Germany and Switzerland.