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      Systematic Review on Chinese Herbal Medicine Induced Liver Injury

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          Abstract

          Background. In recent years, with the popularity of CHM, its hepatotoxicity has also been increasingly noticed. However, there are still veils on causative herbs and clinical characteristics. Aim. To systematically review data on CHM induced liver injury with particular focus on causative herbs and clinical characteristics. Methods. Using terms related to CHM and liver injury, PubMed and three Chinese electronic databases were searched, which was limited to the past 5 years. Publications meeting our eligibility criteria were included and further analyzed. Results. In total, 4 single herbs, 21 patent drugs, and 4 decoctions were reported to be of hepatotoxicity, with He-Shou-Wu being the most common one (65/114). Dang-Gui and other 5 herbs were the most common ingredients of patent drugs and decoctions. All patients were assessed using the RUCAM scale, with 26 being highly probable and 28 being probable. For these 54 cases, the latent period was 30 (47) days, and 81.48% were labeled as hepatocellular injuries. Most patients (96.3%) recovered, apart from the fact that one died and one is receiving liver transplantation. Conclusions. CHM should be used carefully for hepatotoxicity. Liver injury from CHM is similar to that from conventional medicines in clinical characteristics. Details about causative herbs should be illustrated, and more RUCAM should be used in future.

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          Most cited references45

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          Acute liver failure: Summary of a workshop.

          Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use. Currently in the United States, spontaneous survival occurs in approximately 45%, liver transplantation in 25%, and death without transplantation in 30% of adults with ALF. Higher rates of spontaneous recovery (56%) and transplantation (31%) with lower rates of death (13%) occur in children. The outcome of ALF varies by etiology, favorable prognoses being found with acetaminophen overdose, hepatitis A, and ischemia (approximately 60% spontaneous survival), and poor prognoses with drug-induced ALF, hepatitis B, and indeterminate cases (approximately 25% spontaneous survival). Excellent intensive care is critical in management of patients with ALF. Nonspecific therapies are of unproven benefit. Future possible therapeutic approaches include N-acetylcysteine, hypothermia, liver assist devices, and hepatocyte transplantation. Advances in stem cell research may allow provision of cells for bioartificial liver support. ALF presents many challenging opportunities in both clinical and basic research.
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            Reliability of the Roussel Uclaf Causality Assessment Method for assessing causality in drug-induced liver injury.

            The Roussel Uclaf Causality Assessment Method (RUCAM) was developed to quantify the strength of association between a liver injury and the medication implicated as causing the injury. However, its reliability in a research setting has never been fully explored. The aim of this study was to determine test-retest and interrater reliabilities of RUCAM in retrospectively-identified cases of drug induced liver injury. The Drug-Induced Liver Injury Network is enrolling well-defined cases of hepatotoxicity caused by isoniazid, phenytoin, clavulanate/amoxicillin, or valproate occurring since 1994. Each case was adjudicated by three reviewers working independently; after an interval of at least 5 months, cases were readjudicated by the same reviewers. A total of 40 drug-induced liver injury cases were enrolled including individuals treated with isoniazid (nine), phenytoin (five), clavulanate/amoxicillin (15), and valproate (11). Mean +/- standard deviation age at protocol-defined onset was 44.8 +/- 19.5 years; patients were 68% female and 78% Caucasian. Cases were classified as hepatocellular (44%), mixed (28%), or cholestatic (28%). Test-retest differences ranged from -7 to +8 with complete agreement in only 26% of cases. On average, the maximum absolute difference among the three reviewers was 3.1 on the first adjudication and 2.7 on the second, although much of this variability could be attributed to differences between the enrolling investigator and the external reviewers. The test-retest reliability by the same assessors was 0.54 (upper 95% confidence limit = 0.77); the interrater reliability was 0.45 (upper 95% confidence limit = 0.58). Categorizing the RUCAM to a five-category scale improved these reliabilities but only marginally. The mediocre reliability of the RUCAM is problematic for future studies of drug-induced liver injury. Alternative methods, including modifying the RUCAM, developing drug-specific instruments, or causality assessment based on expert opinion, may be more appropriate.
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              Review article: Herbal hepatotoxicity--an update on traditional Chinese medicine preparations.

              Although evidence for their therapeutic efficacy is limited, herbal traditional Chinese medicine (TCM) preparations increasingly gain popularity. In contrast to other herbal products, adverse effects by herbal TCM including liver toxicity were rarely reported. In recent years, more cases were published, providing new clinical challenges.
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi Publishing Corporation
                1741-427X
                1741-4288
                2016
                29 August 2016
                29 August 2016
                : 2016
                : 3560812
                Affiliations
                1The First Clinical Medical School, Beijing University of Chinese Medicine, Beijing, China
                2Department of Gastroenterology and Hepatology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
                3Department of Infectious Disease, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
                Author notes

                Academic Editor: Victor Kuete

                Author information
                http://orcid.org/0000-0002-3675-9233
                http://orcid.org/0000-0002-5826-1671
                Article
                10.1155/2016/3560812
                5019919
                36632130
                372948a0-8fdd-49b8-a9f8-bc3f595aa625
                Copyright © 2016 Peng Zhang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 June 2016
                : 22 July 2016
                : 1 August 2016
                Funding
                Funded by: National Science and Technology Major Project of the 11th Five-Year Plan in China
                Award ID: 2008ZX10005-006
                Categories
                Review Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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