Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 16, 2021; 9(20): 5490-5513
Published online Jul 16, 2021. doi: 10.12998/wjcc.v9.i20.5490
Herb-induced liver injury: Systematic review and meta-analysis
Vinícius Remus Ballotin, Lucas Goldmann Bigarella, Ajacio Bandeira de Mello Brandão, Raul Angelo Balbinot, Silvana Sartori Balbinot, Jonathan Soldera
Vinícius Remus Ballotin, Lucas Goldmann Bigarella, School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95070-560, RS, Brazil
Ajacio Bandeira de Mello Brandão, Post-Graduate Program in Medicine, Division of Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90050-110, RS, Brazil
Raul Angelo Balbinot, Silvana Sartori Balbinot, Jonathan Soldera, Department of Clinical Gastroenterology, Universidade de Caxias do Sul, Caxias do Sul 95070-560, RS, Brazil
Author contributions: All authors contributed to study concept and design and drafting of the manuscript; all authors contributed to acquisition of data, analysis, and interpretation of data; Ballotin VR contributed to statistical analysis; Soldera J contributed to study supervision; all authors contributed to critical revision of the manuscript for important intellectual content.
Conflict-of-interest statement: All authors have nothing to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jonathan Soldera, MD, MSc, Associate Professor, Staff Physician, Department of Clinical Gastroenterology, Universidade de Caxias do Sul, Rua Francisco Getúlio Vargas, 1130, Caxias do Sul 95070-560, RS, Brazil. jonathansoldera@gmail.com
Received: February 23, 2021
Peer-review started: February 23, 2021
First decision: March 28, 2021
Revised: April 3, 2021
Accepted: May 25, 2021
Article in press: May 25, 2021
Published online: July 16, 2021
Processing time: 134 Days and 7 Hours
Abstract
BACKGROUND

The use of herbal supplements and alternative medicines has been increasing in the last decades. Despite popular belief that the consumption of natural products is harmless, herbs might cause injury to various organs, particularly to the liver, which is responsible for their metabolism in the form of herb-induced liver injury (HILI).

AIM

To identify herbal products associated with HILI and describe the type of lesion associated with each product.

METHODS

Studies were retrieved using Medical Subject Headings Descriptors combined with Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE, BIREME, LILACS, Cochrane Library for Systematic Reviews, SciELO, Embase, and Opengray.eu. Languages were restricted to English, Spanish, and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually. To access causality, the Maria and Victorino System of Causality Assessment in Drug Induced Liver Injury was used. Simple descriptive analysis were used to summarize the results.

RESULTS

The search strategy retrieved 5918 references. In the final analysis, 446 references were included, with a total of 936 cases reported. We found 79 types of herbs or herbal compounds related to HILI. He-Shou-Wu, Green tea extract, Herbalife, kava kava, Greater celandine, multiple herbs, germander, hydroxycut, skullcap, kratom, Gynura segetum, garcinia cambogia, ma huang, chaparral, senna, and aloe vera were the most common supplements with HILI reported. Most of these patients had complete clinical recovery (82.8%). However, liver transplantation was necessary for 6.6% of these cases. Also, chronic liver disease and death were observed in 1.5% and 10.4% of the cases, respectively.

CONCLUSION

HILI is normally associated with a good prognosis, once the implied product is withdrawn. Nevertheless, it is paramount to raise awareness in the medical and non-medical community of the risks of the indiscriminate use of herbal products.

Keywords: Herb-induced liver injury; Drug induced liver injury; Dietary supplements; Herbal hepatotoxicity; Liver transplantation

Core Tip: The use of herbal supplements has been increasing in the last decades. Despite popular belief that natural products are harmless, they might cause herb-induced liver injury (HILI). This study aimed to identify herbal products associated with HILI. The search strategy retrieved 5918 references. In the final analysis, 446 references were included, with a total of 936 cases reported. We found 79 types of herbs related to HILI. Most of these patients had complete clinical recovery (82.8%). However, liver transplantation was necessary for 6.6% of these cases. Also, chronic liver disease and death were observed in 1.5% and 10.4%, respectively.