Prospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 18, 2017; 9(29): 1141-1157
Published online Oct 18, 2017. doi: 10.4254/wjh.v9.i29.1141
Herbal Traditional Chinese Medicine and suspected liver injury: A prospective study
Dieter Melchart, Stefan Hager, Sabine Albrecht, Jingzhang Dai, Wolfgang Weidenhammer, Rolf Teschke
Dieter Melchart, Institute for Complementary and Integrative Medicine, University Hospital Zurich and University of Zurich, CH-8091 Zurich, Switzerland
Dieter Melchart, Wolfgang Weidenhammer, Competence Centre for Complementary Medicine and Naturopathy (CoCoNat), University Hospital Munich rechts der Isar, Technical University of Munich, D-80801 Munich, Germany
Stefan Hager, Sabine Albrecht, Jingzhang Dai, Hospital for Traditional Chinese Medicine, D-93444 Bad Kötzting, Germany
Jingzhang Dai, Beijing University of Chinese Medicine, Beijing 100029, China
Rolf Teschke, Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Medical Faculty of the Goethe University, D-63450 Hanau, Frankfurt/Main, Germany
Author contributions: Melchart D had full access to all of the study data and takes full responsibility for the integrity of the data; Melchart D, Hager S, Albrecht S, Dai J and Weidenhammer W contributed to study conception and design; Melchart D, Hager S, Albrecht S, Dai J and Weidenhammer W contributed to acquisition of data; Melchart D, Hager S, Albrecht S, Dai J, Weidenhammer W and Teschke R contributed to analysis and interpretation of data; Melchart D, Weidenhammer W and Teschke R contributed to drafting of the manuscript; Melchart D, Hager S, Albrecht S, Dai J, Weidenhammer W and Teschke R contributed to critical revision of the manuscript; Melchart D, Weidenhammer W and Teschke R contributed to statistical analysis.
Institutional review board statement: All scientific activities are authorized and reviewed by an Academic Exchange Agreement between the Beijing University of Chinese Medicine and Technische Universität München.
Informed consent statement: All patients gave their written consent prior to the study inclusion on admission to the hospital.
Conflict-of-interest statement: Albrecht, Hager and Dai belong to the medical personnel of the TCM hospital in Bad Kötzting. Melchart is head of the scientific board of the TCM hospital in Bad Kötzting taking part in voluntary service. None financial disclosure of all authors is declared.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Dieter Melchart, MD, Professor, Competence Centre for Complementary Medicine and Naturopathy (CoCoNat), University Hospital Munich rechts der Isar, Technical University of Munich, Kaiserstrasse 9, D-80801 Munich, Germany. dieter.melchart@tum.de
Telephone: +49-89-7266970 Fax: +49-89-72669721
Received: May 15, 2017
Peer-review started: May 27, 2017
First decision: July 11, 2017
Revised: July 26, 2017
Accepted: August 16, 2017
Article in press: August 17, 2017
Published online: October 18, 2017
Processing time: 144 Days and 7.7 Hours
Abstract
AIM

To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine (TCM) in order to evaluate the frequency of newly detected liver injury.

METHODS

Patients with normal values of alanine aminotransferase (ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method (RUCAM) was used.

RESULTS

This report presents for the first time liver injury data derived from a prospective, hospital-based and large-scale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal (ULN) in 844 patients (3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients (0.12%) experienced higher ALT values of ≥ 5 × ULN (300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated.

CONCLUSION

In 26 (0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality.

Keywords: Traditional Chinese Medicine; Herbal medicine; Liver injury; Roussel Uclaf Causality Assessment Method; Herb induced liver injury

Core tip: Worldwide research on herbal medicine safety is still limited. Adverse effects are range from clinically not relevant to more severe ones including suspected liver injury. We conducted a prospective hospital-based study to report the number of new liver injury in patients with no liver disease prior to treatment with herbal Traditional Chinese Medicine. Liver injury was detected in 26/21470 patients (0.12%) with alanine aminotransferase values of ≥ 5 × upper limit normal. The Roussel Uclaf Causality Assessment Method assessed the causality of suspected cases and showed a causality level of “possible” for the majority of the liver injury cases.