Herbal and Dietary Supplements-Induced Liver Injury in Latin America: Experience From the LATINDILI Network.

BACKGROUND: Herbal and dietary supplements (HDS) consumption, a growing cause of hepatotoxicity, is a common practice among Latin-American populations. OBJECTIVES: To evaluate clinical, laboratory features and outcome in HDS-hepatotoxicity included in the Latin America-Drug Induced Liver Injury (LATINDILI) Network. METHODS: A total of 29 adjudicated cases of HDS hepatotoxicity reported to the LATINDILI Network from October 2011 through December 2019 were compared with 322 DILI cases due to conventional drugs and 16 due to anabolic steroids as well as with other series of HDS-hepatotoxicity. RESULTS: From 367 DILI cases, 8% were attributed to HDS. An increasing trend in HDS-hepatotoxicity was noted over time (p = .04). Camellia sinensis, Herbalife® products, and Garcinia cambogia, mostly used for weight loss, were the most frequently adjudicated causative agents. Mean age was 45 years (66% female). Median time to onset was 31 days. Patients presented typically with hepatocellular injury (83%) and jaundice (66%). Five cases (17%) developed acute liver failure. Compared to conventional medications and anabolic steroids, HDS hepatotoxicity cases had the highest levels of aspartate and alanine transaminase (p = .008 and p = .021, respectively), had more re-exposure events to the culprit HDS (14% vs 3% vs 0%; p = .026), and had more severe and fatal/liver transplantation outcomes (21% vs 12% vs 13%; p = .005). Compared to other DILI cohorts, less HDS hepatotoxicity cases in Latin America were hospitalized (41%). CONCLUSIONS: HDS-hepatotoxicity in Latin-America affects mainly young women, manifests mostly with hepatocellular injury and is associated with higher frequency of accidental re-exposure. HDS hepatotoxicity is more serious with a higher chance of death/liver transplantation than DILI related to conventional drugs.

Causality imputation between herbal products and HILI: An algorithm evaluation in a systematic review.

Algorithms can have several purposes in the clinical practice. There are different scales for causality imputation in DILI (Drug-Induced Liver Injury), but the applicability and validity of these for the HILI (Herb-Induced Liver Injury) evaluation is questionable for some scales. The purpose of the study was to determine the clinical and demographic profile of the patients with HILI, and the main algorithmic scales used in its causality assessment. The methodology was a systematic review of articles in English, Spanish, or Portuguese language, from 1979 to 2019, involving humans, with descriptors related to HILI. Qualitative and quantitative statistical analysis were performed. As a result, from a total of 60 articles, 203 HILI reports were selected: 59.9% were women, similar with other studies, and the average age was 45.8 years. Jaundice was the most frequent symptom and regarding the type of lesion, the hepatocellular was the most frequent. In regard to HILI severity, 3.0% were severe and 7.6% were fatal or required liver transplantation. In 72.3% of the cases, the most used algorithm was RUCAM (Roussel Uclaf Causality Assessment Method). The conclusion of the study is that RUCAM was the most used algorithm for causality assessment in HILI. The patients were predominantly female, jaundice was the main symptom, and HILI is reversible in the majority of cases.

Drug-induced liver injury: A management position paper from the Latin American Association for Study of the liver.

Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbs-induced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular.

Evaluation of drug-induced liver injury as etiology for acute liver failure in Brazil.

INTRODUCTION AND OBJECTIVES: Little is known about the etiology of acute liver failure (ALF) in Latin America. The objective of this paper is to investigate the main etiologies of ALF in Brazil, including Drug Induced Liver Injury (DILI) using stringent causality criteria. PATIENTS OR MATERIAL AND METHODS: All the cases of individuals who underwent liver transplantation (LT) in 12 centers in Brazil for ALF were reviewed. When DILI was stated as the cause of ALF, causality criteria were applied on site by the main investigator in order to rule out other etiologies. RESULTS: 325 individuals had ALF mainly for unknown reasons (34%), DILI (27%) and AIH (18%). Reassessment of the 89 cases of DILI, using stringent causality criteria, revealed that in only 42 subjects could DILI be confirmed as the cause of ALF. Acetaminophen (APAP) toxicity (n = 3) or DILI due to herbal and dietary supplements (HDS) (n = 2) were not commonly observed. CONCLUSIONS: Undetermined etiology and DILI are the main causes of ALF in Brazil. However, APAP toxicity and DILI due to HDS are mostly uncommon.

Profile of herbal and dietary supplements induced liver injury in Latin America: A systematic review of published reports.

Hepatotoxicity related to HDS is a growing global health issue. We have undertaken a systematic review of published case reports and case series from LA from 1976 to 2020 to describe the clinical features of HDS related hepatotoxicity in this region. We search in PubMed, Web of Science, Scopus and specific LA databases according to PRISMA guidelines. Only HILI cases published in LA that met criteria for DILI definition were included. Duplicate records or reports that lacked relevant data that precluded establishing causality were excluded. Finally, 17 records (23 cases) were included in this review. Centella asiatica, Carthamus tinctorius, and Herbalife® were the most reported HDS culprit products, the main reason for HDS consumption was weight loss. The clinical characteristics of HDS hepatotoxicity in our study were compared to those of other studies in the USA, Europe and China showing a similar signature with predominance of young females, hepatocellular damage, a high rate of ALF and mortality, more frequent inadvertent re-challenge and chronic damage. This study underscores the challenge in causality assessment when multi-ingredients HDS are taken and the need for consistent publication practice when reporting hepatotoxicity cases due to HDS, to foster HDS liver safety particularly in LA.

Drug induced liver damage in a universitary hospital / Lesão hepática induzida por drogas em um hospital universitário

Introdução: lesão hepática induzida por drogas (DILI) é responsável por um amplo espectro de lesão hepática. Clinicamente, esses eventos são apresentados de várias formas e, para alcançar um diagnóstico diferente, outras causas de lesões devem ser excluídas. Objetivo: identificar e caracterizar casos de hepatotoxicidade induzida por medicamentos, fitoterápicos e suplementos alimentares em Hospital Universitário no Brasil. Metodologia: estudo observacional, retrospectivo. Os dados foram coletados em prontuários do Hospital Universitário, entre agosto de 2009, em agosto de 2014. A causalidade das reações medicamentosas suspeitas foi avaliada pelo Conselho de Organizações Internacionais de Ciências Médicas (CIOMS). Resultados: foram selecionados 30 casos suspeitos, 50% do sexo feminino e média de 39 anos. As classes terapêuticas mais comuns foram: anti-infecciosos; agentes antineoplásicos; drogas do sistema nervoso central, esteroides anabolizantes e suplementos herbáceos e dietéticos (HDS). Lesão colestática ou mista foi observada em 73% desses casos; 60% eram altamente prováveis, de acordo com o CIOMS. Conclusão: DILI é causada por uma grande variedade de drogas, suplementos dietéticos e suplementos dietéticos. Anti-infecciosos e quimioterapia foram responsáveis por grande parte da resposta.

Background: drug Induced Liver Injury (DILI) is responsible for wide spectrum of liver injury. Clinically, these events are presented in various forms and for reaching a different diagnosis other injury causes must be excluded. Aim: identify and characterize cases of hepatotoxicity induced by drugs, herbal and dietary supplements in University Hospital in Brazil. Methodology: observational and retrospective study. Was collected in records of University Hospital, between August 2009 at August 2014. The causality of the drug reactions suspected were evaluated Council for International Organizations of Medical Sciences (CIOMS). Results: we selected 30 suspected cases, 50% was female and average was 39 years. the therapeutic classes most common was: anti-infectives; antineoplastic agents; central nervous system drugs, anabolic steroid and herbal and dietary supplements (HDS). Cholestatic or mixed injury was observed in 73% these cases; 60% were highly probable, according to CIOMS. Conclusion: DILI is caused by a wide variety of drugs, dietary supplements and dietary supplements. Anti-infectives and chemotherapy were responsible for much of the response.

Hepatoportal sclerosis related to the use of herbals and nutritional supplements. Causality or coincidence?

 Introduction and aim. Non-cirrhotic idiopathic portal hypertension (NCIPH), also known as hepatoportal sclerosis (HPS) is a disease of uncertain etiology. However, various pathophysiological mechanisms has been postulated, including chronic or recurrent infections and exposure to drugs or toxins. In this context, it appears to be of multifactorial etiology or resulting from a portal vascular endothelium aggression. It is important to consider whether the use of dietary supplements and herbs can trigger or contribute to the occurance of HPS. We report a possible association of HPS with the consumption of herbals and / or dietary supplements. MATERIAL AND METHODS: We describe two cases of HPS in patients without known etiology causes associated with this disease. RESULTS: Both patients were females who were diagnosed with HPS following the consumption of Herbalife® products and putative anorexigenic agents in the form herbals infusions. Image-based analysis and the assessment of the histopathological alterations found in the livers confirmed the diagnosis. The histopatological analysis of liver samples from both patients showed portal tracts enlarged by fibrosis with disappearance or reduction in the diameter of the portal vein branches. In many portal tracts, portal veins branches were replaced by aberrant thin-walled fendiforme vessels. The bile ducts and branches of the hepatic artery show normal aspects. CONCLUSION: After the exclusion of other etiologic factors and a comprehensive analysis of clinical history, consumption of Herbalife® products and anorexigenic agents was pointed-out as a puttative predisposing factor for the development of the disease.