Herb-induced Liver Injury in Asia and Current Role of RUCAM for Causality Assessment in 11,160 Published Cases

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In a few instances, publications erroneously mention in their title specifically only DILI, although HILI cases are also presented in the text.

“In a few instances, publications erroneously mention in their title specifically only DILI, although HILI cases are also presented in the text,24,26,36”

• cites [24] Hao, 2014, RUCAM scale-based diagnosis, clinical features and prognosis of 140 cases of drug-induced liver injury, Zhonghua Gan Zang Bing Za Zhi sourceNot checked — no full text of the source
• cites [26] Ou, 2015, Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital, Springerplus sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [36] Shen, 2019, Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Some improvements were evident in a more recent report focusing on incidence and etiology of DILI in mainland China, published in a 2019 issue of Gastroenterology.

“Instead, some improvements were evident in a more recent report, with the title focusing on incidence and etiology of DILI in mainland China, published in a 2019 issue of Gastroenterology.36”

• cites [36] Shen, 2019, Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceSupported

It may state two separate claims as one.

Cases were also derived from the LiverTox database, with its published problems in assessing a correct causality in liver injury cases.

“Cases were also derived from the LiverTox database,67 with its published problems in assessing a correct causality in liver injury cases.69–71”

• cites [67] Zhu, 2020, The landscape of hepatobiliary adverse reactions across 53 herbal and dietary supplements reveals immune-mediated injury as a common cause of hepatitis, Arch Toxicol sourceNot checked — no full text of the source
• cites [69] Björnsson, 2016, Hepatotoxicity by drugs: The most common implicated agents, Int J Mol Sci sourceSupported
• cites [70] Björnsson, 2016, Categorization of drugs implicated in causing liver injury: Critical assessment based on published case reports, Hepatology sourceSupported
• cites [71] Teschke, 2018, Top-ranking drugs out of 3312 drug-induced liver injury cases evaluated by the Roussel Uclaf Causality Assessment Method, Expert Opin Drug Metab Toxicol sourceNot checked — no full text of the source

Probably not a substantial claim. The authors may not put it forward as true. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.

The problems can well be solved in a new, promised prospective study, whereby the use of RUCAM may again be helpful, now applying its updated version.

“but it seems that the problems can well be solved in a new, promised prospective study, whereby the use of RUCAM may again be helpful, now applying its updated version.36,102–105”

• cites [36] Shen, 2019, Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourcePartly supported

  The causality-assessment methods section (page not available) says investigators used RUCAM to score cases, supporting the reference to its use in this research. The study-design section describes a retrospective study; our copy does not substantiate a promised prospective study or a plan to use updated RUCAM in one. (LLM, conf=0.80)

  Experimental — accuracy not yet measured
• cites [102] Yang, 2019, Can retrospective studies confirm causes of drug-induced liver injury?, Gastroenterology sourceNot checked — no full text of the source
• cites [103] Devarbhavi, 2019, RE: Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceNot checked — no full text of the source
• cites [104] Cong, 2019, RE: Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceNot checked — no full text of the source
• cites [105] Shen, 2019, Reply, Gastroenterology sourceNot checked — no full text of the source

Probably not a substantial claim.

Most publications provided case and RUCAM data of good quality.

“Most publications provided case and RUCAM data of good quality.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Assessed cases were commonly well presented with respect to case data completeness and evaluation.

“Assessed cases were commonly well presented with respect to case data completeness and evaluation (Table 1).”

It may state two separate claims as one.

Starting as early as 2006 with an analysis from Hong Kong, an overall 21 reports of HILI cases were published which had been assessed for causality using RUCAM with results presented by groups with first authors having their working place in mainland China, Hong Kong, or Taiwan.

“Starting as early as 2006 with an analysis from Hong Kong,18 an overall 21 reports of HILI cases were published which had been assessed for causality using RUCAM with results presented by groups with first authors having their working place in mainland China, Hong Kong, or Taiwan.18–38”

• cites [18] Yuen, 2006, Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: a 1-year prospective study, Aliment Pharmacol Ther sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [19] Cheung, 2009, Liver injury associated with the use of Fructus Psoraleae (Bol-gol-zhee or Bu-gu-zhi) and its related proprietary medicine, Clin Toxicol (Phila) sourceNot checked — no full text of the source
• cites [20] Nin Chau, 2011, Causality assessment of herb-induced liver injury using multidisciplinary approach and Roussel Uclaf Causality Assessment Method (RUCAM), Clin Toxicol (Phila) sourceNot checked — no full text of the source
• cites [21] Lin, 2011, Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum, J Hepatol sourceNot checked — no full text of the source
• cites [22] Gao, 2012, Definitive diagnosis of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids, J Dig Dis sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [23] Dong, 2014, Eighteen cases of liver injury following ingestion of Polygonum multiflorum, Complement Ther Med sourceNot checked — no full text of the source
• cites [24] Hao, 2014, RUCAM scale-based diagnosis, clinical features and prognosis of 140 cases of drug-induced liver injury, Zhonghua Gan Zang Bing Za Zhi sourceNot checked — no full text of the source
• cites [25] Gao, 2015, Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome, Drug Des Devel Ther sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [26] Ou, 2015, Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital, Springerplus sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [27] Wang, 2015, Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum, Front Med sourceNot checked — no full text of the source

It may state two separate claims as one.

With 21 evaluable reports, most publications came from mainland China, with Hong Kong and Taiwan, followed by Korea (n=15), Singapore (n=2), and Japan (n=1).

“With 21 evaluable reports, most publications came from mainland China, with Hong Kong and Taiwan, followed by Korea (n=15), Singapore (n=2), and Japan (n=1), while other Asian countries were not contributory.”

Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.

HILI case evaluations in many publications are fragile.

“Contrasting to fragile HILI case evaluations in many publications”

It may state two separate claims as one.

Few reports combined results of both HILI and DILI cases, causing confusion due to mixed data.

“but few combined results of both HILI and DILI cases, causing confusion due to mixed data.24,26,30,36”

• cites [24] Hao, 2014, RUCAM scale-based diagnosis, clinical features and prognosis of 140 cases of drug-induced liver injury, Zhonghua Gan Zang Bing Za Zhi sourceNot checked — no full text of the source
• cites [26] Ou, 2015, Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital, Springerplus sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [30] Zhu, 2016, Hepatobiliary and pancreatic: Comparison between Chinese herbal medicine and Western medicine-induced liver injury of 1985 patients, J Gastroenterol Hepatol sourceNot checked — no full text of the source
• cites [36] Shen, 2019, Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceNot checked yet

It may state two separate claims as one.

Other Asian countries were not contributory; there are virtually no valid reports on RUCAM-based HILI cases from authors residing in other Asian countries like Vietnam, Indonesia, Thailand, or India.

“while other Asian countries were not contributory.”

• Also stated in: § Other Asian countries · plain

  “There are virtually no valid reports on RUCAM-based HILI cases from authors residing in other Asian countries like Vietnam, Indonesia, Thailand, or India.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Shortcomings in Korean articles included forgetting quotation of the used RUCAM publication.

“forgetting quotation of the used RUCAM publication,51,54”

• cites [51] Lee, 2015, Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients, J Ethnopharmacol sourceNot checked — no full text of the source
• cites [54] Cho, 2017, A nationwide study of the incidence rate of herb-induced liver injury in Korea, Arch Toxicol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Lacking unintentional readministration, which provides a score of 0, nevertheless allowed for a high causality grading.

“Similarly, lacking unintentional readministration, which provides a score of 0, nevertheless allowed for a high causality grading.37”

• cites [37] Tan, 2019, RUCAM-based assessment of liver injury by xiang-tian-guo (Swietenia macrophylla) seeds, a plant used for treatment of hypertension and diabetes, Ann Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Zhang et al. used the updated RUCAM of 2016 and adopted a high threshold of liver tests to avoid nonspecific liver injuries.

“The encouraging report of Zhang et al.29 analyzed HILI cases in a perfect way, using the updated RUCAM of 2016, adopting a high threshold of liver tests (LTs) to avoid nonspecific liver injuries”

• cites [29] Zhang, 2016, Systematic review on Chinese herbal medicine induced liver injury, Evid Based Complement Alternat Med sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

In the first report published 2006 by Wai et al., a prospective study design was used that allowed for complete case data, conditions commonly facilitating high causality gradings.

“In the first report published 2006 by Wai et al.,55 a prospective study design was used that allowed for complete case data, conditions commonly facilitating high causality gradings.”

• cites [55] Wai, 2006, Presentation of drug-induced liver injury in Singapore, Singapore Med JNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Li et al. presented a case report on HILI caused by PM using the updated RUCAM of 2016.

“Li et al.31 presented a perfect case report on HILI caused by PM, using the updated RUCAM of 2016.15”

• cites [31] Li, 2017, Idiosyncratic drug-induced liver injury linked to Polygonum multiflorum: A case study by pharmacognosy, Chin J Integr Med sourceNot checked — no full text of the source
• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Korean articles were mostly of good quality, with minor shortcomings.

“Respective articles were mostly of good quality, with minor shortcomings.”

It may state two separate claims as one.

In rare instances, causality gradings were not reported or RUCAM was used for causality grading but the respective publication remained unquoted, even if the updated RUCAM was mentioned in the text.

“In rare instances, causality gradings were not reported35 or RUCAM was used for causality grading but the respective publication remained unquoted,26,34 even if the updated RUCAM was mentioned in the text.34”

• cites [35] Liu, 2019, Polygonum multiflorum-induced liver injury: Clinical characteristics, risk factors, material basis, action mechanism and current challenges, Front Pharmacol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [26] Ou, 2015, Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital, Springerplus sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [34] Li, 2019, Acute liver failure associated with Fructus Psoraleae: a case report and literature review, BMC Complement Altern Med sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Kang et al. described a patient with a positive re-exposure result, as evidenced by a striking increase of serum ALT activity shown in a separate figure and likely following the test criteria published earlier.

“Valuable is, also, the report of Kang et al.,44 who described a patient with a positive re-exposure result, as evidenced by a striking increase of serum alanine aminotransferase (ALT) activity shown in a separate figure and likely following the test criteria published earlier.15”

• cites [44] Kang, 2009, A case of acute cholestatic hepatitis induced by Corydalis speciosa Max, Korean J Hepatol sourceNot checked — no full text of the source
• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

The case series of Dong et al. focuses on PM on a single herb causing HILI in 18 patients, with each having received an individual causality grading of probable or highly probable.

“Similarly, the case series of Dong et al.23 focuses on PM on a single herb causing HILI in 18 patients, with each having received an individual causality grading of probable or highly probable.”

• cites [23] Dong, 2014, Eighteen cases of liver injury following ingestion of Polygonum multiflorum, Complement Ther Med sourceNot checked — no full text of the source

It may state two separate claims as one.

First authors of reports from Korea contributed as experts were numbered overall 15, and thereby represented a substantial number of publications on 526 HILI cases that had been assessed for causality using RUCAM.

“First authors of reports from Korea contributed as experts were numbered overall 15, and thereby represented a substantial number of publications on 526 HILI cases that had been assessed for causality using RUCAM (Table 1).40–54”

• cites [40] Ahn, 2004, Herbal preparation-induced liver injury, Korean J GastroenterolNot checked — no full text of the source
• cites [41] Seo, 2006, Clinical experience of 48 acute toxic hepatitis patients, Korean J HepatolNot checked — no full text of the source
• cites [42] Kang, 2008, Clinical characteristics of 159 cases of acute toxic hepatitis, Korean J Hepatol sourceNot checked — no full text of the source
• cites [43] Sohn, 2008, Liver transplantation for acute toxic hepatitis due to herbal medicines and preparations, J Korean Soc Clin ToxicolNot checked — no full text of the source
• cites [44] Kang, 2009, A case of acute cholestatic hepatitis induced by Corydalis speciosa Max, Korean J Hepatol sourceNot checked — no full text of the source
• cites [45] Kim, 2009, Two cases of toxic hepatitis caused by arrowroot juice, Korean J Hepatol sourceNot checked — no full text of the source
• cites [46] Bae, 2010, Toxic hepatitis associated with Polygoni multiflori, Korean J Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [47] Yang, 2010, Aloe-induced toxic hepatitis, J Korean Med Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [48] Jung, 2011, Drug-induced liver injury: Twenty five cases of acute hepatitis following ingestion of polygonum multiflorum thunb, Gut Liver sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [49] Kim, 2012, A pediatric case of toxic hepatitis induced by Hovenia dulcis, Pediatr Gastroenterol Hepatol Nutr sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Similar omissions of RUCAM quotation have been observed in some publications related to DILI.

“Similar omissions of RUCAM quotation have been observed in some publications related to DILI.11”

• cites [11] Teschke, 2019, Idiosyncratic DILI: Analysis of 46,266 cases assessed for causality by RUCAM and published from 2014 to early 2019, Front Pharmacol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

It seems that most reports were based on a retrospective rather than a prospective study design.

“It seems that most reports were based on a retrospective rather than a prospective study design.”

It may state two separate claims as one.

Korean articles included single case reports, case series and review articles.

“These included single case reports, case series and review articles.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Kim et al., Bae et al., Yang et al., Jung et al., Kim et al., and Woo et al. all provided cases limited to a probable or highly probable causality grading, suggesting complete case data sets or prospective data collection in single case reports.

“and by Kim et al.,45 Bae et al.,46 Yang et al.,47 Jung et al.,48 Kim et al.,49 and Woo et al.,53 who all provided cases limited to a probable or highly probable causality grading, suggesting complete case data sets or prospective data collection in single case reports.”

• cites [45] Kim, 2009, Two cases of toxic hepatitis caused by arrowroot juice, Korean J Hepatol sourceNot checked — no full text of the source
• cites [46] Bae, 2010, Toxic hepatitis associated with Polygoni multiflori, Korean J Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [47] Yang, 2010, Aloe-induced toxic hepatitis, J Korean Med Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [48] Jung, 2011, Drug-induced liver injury: Twenty five cases of acute hepatitis following ingestion of polygonum multiflorum thunb, Gut Liver sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [49] Kim, 2012, A pediatric case of toxic hepatitis induced by Hovenia dulcis, Pediatr Gastroenterol Hepatol Nutr sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [53] Woo, 2015, Drug-induced liver injury: A 2-year retrospective study of 1169 hospitalized patients in a single medical center, Phytomedicine sourceNot checked — no full text of the source

It may state two separate claims as one.

In Japan, the report of Tsuda et al. used RUCAM of 1993 but there are no other RUCAM-based cases of HILI to be used for comparison with worldwide RUCAM-based HILI cases.

“In Japan, the report of Tsuda et al.39 used the RUCAM of 1993 but there are no other RUCAM-based cases of HILI to be used for comparison with worldwide RUCAM-based HILI cases.”

• cites [39] Tsuda, 2010, Discrepancy between clinical course and drug-induced lymphocyte stimulation tests in a case of saireito-induced liver injury accompanied by Sjögren syndrome, J Altern Complement Med sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Hepatitis E virus infection was excluded in all three patients in Tan et al.

“As potential confounding alternative diagnosis, hepatitis E virus (HEV) infection was excluded in all three patients”

• cites [37] Tan, 2019, RUCAM-based assessment of liver injury by xiang-tian-guo (Swietenia macrophylla) seeds, a plant used for treatment of hypertension and diabetes, Ann Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

The second study published 10 years later by Teo et al. presented data from a retrospective analysis of spontaneous reports submitted to the national registry; respective causality gradings were extremely low due to incomplete case data, not unexpected under these study conditions.

“The second study published 10 years later by Teo et al.56 presented data from a retrospective analysis of spontaneous reports submitted to the national registry; respective causality gradings were extremely low due to incomplete case data, not unexpected under these study conditions.”

• cites [56] Teo, 2016, Drug-induced liver injury associated with Complementary and Alternative Medicine: a review of adverse event reports in an Asian community from 2009 to 2014, BMC Complement Altern Med sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Tan et al. carefully assessed the comedicated drug using a separate RUCAM sheet.

“Tan et al.37 also carefully assessed the comedicated drug using a separate RUCAM sheet, as recommended earlier.12,15”

• cites [37] Tan, 2019, RUCAM-based assessment of liver injury by xiang-tian-guo (Swietenia macrophylla) seeds, a plant used for treatment of hypertension and diabetes, Ann Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [12] Danan, 1993, Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries, J Clin Epidemiol sourceNot checked — no full text of the source
• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Gao et al. used RUCAM for the first time in hepatic sinusoidal obstruction syndrome caused by PAs in 23 patients, supporting blood pyrrole-protein adducts as diagnostic biomarkers.

“as shown in their report assessing causality by Gao et al.,25 RUCAM was used for the first time in the hepatic sinusoidal obstruction syndrome caused by PAs in 23 patients, supporting the blood pyrrole-protein adducts as diagnostic biomarkers.25”

• cites [25] Gao, 2015, Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome, Drug Des Devel Ther sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

On top among the Asian countries is currently China, best explained by the large population and heavy use of herbal traditional Chinese medicines, with increasing numbers of publications and cases until 2019.

“On top among the Asian countries is currently China, best explained by the large population and heavy use of herbal traditional Chinese medicines (TCMs), with increasing numbers of publications and cases until 2019.18–38”

• cites [18] Yuen, 2006, Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: a 1-year prospective study, Aliment Pharmacol Ther sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [19] Cheung, 2009, Liver injury associated with the use of Fructus Psoraleae (Bol-gol-zhee or Bu-gu-zhi) and its related proprietary medicine, Clin Toxicol (Phila) sourceNot checked — no full text of the source
• cites [20] Nin Chau, 2011, Causality assessment of herb-induced liver injury using multidisciplinary approach and Roussel Uclaf Causality Assessment Method (RUCAM), Clin Toxicol (Phila) sourceNot checked — no full text of the source
• cites [21] Lin, 2011, Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum, J Hepatol sourceNot checked — no full text of the source
• cites [22] Gao, 2012, Definitive diagnosis of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids, J Dig Dis sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [23] Dong, 2014, Eighteen cases of liver injury following ingestion of Polygonum multiflorum, Complement Ther Med sourceNot checked — no full text of the source
• cites [24] Hao, 2014, RUCAM scale-based diagnosis, clinical features and prognosis of 140 cases of drug-induced liver injury, Zhonghua Gan Zang Bing Za Zhi sourceNot checked — no full text of the source
• cites [25] Gao, 2015, Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome, Drug Des Devel Ther sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [26] Ou, 2015, Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital, Springerplus sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [27] Wang, 2015, Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum, Front Med sourceNot checked — no full text of the source

Probably not a substantial claim.

The quality of HILI case evaluation is insufficient in many countries, including Asian ones.

“Indeed, the quality of HILI case evaluation is insufficient in many countries, including Asian ones, a topic that merits further discussion as outlined below.”

The quote only partly states this claim.

This analysis showed that RUCAM was used as a diagnostic tool in 97/203 studies (47.8%).

“This analysis also showed, for study cohorts with a fairly good case data quality, that RUCAM was used as a diagnostic tool in 97/203 studies (47.8%)”

• cites [66] Wang, 2018, Clinical characteristics and outcomes of traditional Chinese medicine-induced liver injury: a systematic review, Expert Rev Gastroenterol Hepatol sourceNot checked — no full text of the source

It may state two separate claims as one. The quote only partly states this claim.

In the report from Germany, the original RUCAM of 1993 was used and referenced for causality assessment, having provided scores of 6-8 as a probable causality grading for four concomitantly used herbal medicines, preferring one single herb with the highest score of 8.

“In the report from Germany, the original RUCAM of 1993 was used and referenced for causality assessment, having provided scores of 6-8 as a probable causality grading for four concomitantly used herbal medicines, preferring one single herb with the highest score of 8.57”

• cites [57] Teschke, 2009, Severe hepatotoxicity by Indian Ayurvedic herbal products: a structured causality assessment, Ann Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

There is now increasing awareness of the benefits provided by RUCAM among various countries, including China, Korea, and Singapore, as evidenced by reports initially published in 2004 from Korea and in 2006 from China and Singapore, with subsequent articles.

“There is now increasing awareness of the benefits provided by RUCAM among various countries, including China,18–38 Korea,40–54 and Singapore,55,56 as evidenced by reports initially published in 2004 from Korea40 and in 2006 from China18 and Singapore,55 with subsequent articles (Table 1).”

• cites [18] Yuen, 2006, Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: a 1-year prospective study, Aliment Pharmacol Ther sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [19] Cheung, 2009, Liver injury associated with the use of Fructus Psoraleae (Bol-gol-zhee or Bu-gu-zhi) and its related proprietary medicine, Clin Toxicol (Phila) sourceNot checked — no full text of the source
• cites [20] Nin Chau, 2011, Causality assessment of herb-induced liver injury using multidisciplinary approach and Roussel Uclaf Causality Assessment Method (RUCAM), Clin Toxicol (Phila) sourceNot checked — no full text of the source
• cites [21] Lin, 2011, Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum, J Hepatol sourceNot checked — no full text of the source
• cites [22] Gao, 2012, Definitive diagnosis of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids, J Dig Dis sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [23] Dong, 2014, Eighteen cases of liver injury following ingestion of Polygonum multiflorum, Complement Ther Med sourceNot checked — no full text of the source
• cites [24] Hao, 2014, RUCAM scale-based diagnosis, clinical features and prognosis of 140 cases of drug-induced liver injury, Zhonghua Gan Zang Bing Za Zhi sourceNot checked — no full text of the source
• cites [25] Gao, 2015, Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome, Drug Des Devel Ther sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [26] Ou, 2015, Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital, Springerplus sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [27] Wang, 2015, Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum, Front Med sourceNot checked — no full text of the source

It may state two separate claims as one.

Korea ranks at the second position, followed by Singapore in third place.

“Korea ranks at the second position, followed by Singapore in third place (Table 1).”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

The USA report discussed RUCAM without providing a correct reference and attributed a score of 5 corresponding to a possible causality grading.

“The USA report discussed RUCAM without providing a correct reference and attributed a score of 5 corresponding to a possible causality grading,58”

• cites [58] Dalal, 2017, Ayurvedic drug induced liver injury, World J Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Reports of Indian Ayurvedic medicine-related liver injury are sparse in the literature, which we found to include not only herbs but also other complementary and alternative medicines.

“It is well recognized that reports of Indian Ayurvedic medicine-related liver injury are sparse in the literature,60,61 which we found to include not only herbs but also other complementary and alternative medicines.61”

• cites [60] Bunchorntavakul, 2013, Review article: herbal and dietary supplement hepatotoxicity, Aliment Pharmacol Ther sourceNot checked — no full text of the source
• cites [61] Philips, 2019, Complementary and alternative medicine-related drug-induced liver injury in Asia, J Clin Transl Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Respective lists presented by authors of Asian countries in English language are scarce, partly due to the focus on DILI cases with neglect of HILI data.

“Respective lists presented by authors of Asian countries in English language are scarce, partly due to the focus on DILI cases with neglect of HILI data (Table 1).18–56”

• cites 18–56Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

A few publications from authors outside of Asia have presented some case and herb listings of Asian HILI but with limited information.

“A few publications from authors outside of Asia have presented some case and herb listings of Asian HILI but with limited information.”

It may state two separate claims as one.

DILI conditions are more stable than HILI case evaluations because DILI is caused by clearly defined conventional chemical drugs.

“Contrasting to fragile HILI case evaluations in many publications, conditions are more stable for DILI by clearly defined conventional chemical drugs”

• cites [11] Teschke, 2019, Idiosyncratic DILI: Analysis of 46,266 cases assessed for causality by RUCAM and published from 2014 to early 2019, Front Pharmacol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.

Differentiation of HILI from DILI is essential and incorporating HILI among a DILI cohort is misleading, not allowing for a separate characterization of HILI features.

“Differentiation of HILI from DILI is essential and incorporating HILI among a DILI cohort is misleading, not allowing for a separate characterization of HILI features.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

RUCAM instructions clearly recommend the use of RUCAM for prospective studies.

“whereas RUCAM instructions clearly recommend the use of RUCAM for prospective studies.15”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The extraordinary result of 14/18 highly probable causality gradings in Dong et al. is best explained by a careful case evaluation with complete data sets.

“this is best explained by a careful case evaluation with complete data sets allowing for this extraordinary result.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

The term definitive was never proposed or approved in the RUCAM literature, which determines highly probable as the highest grading.

“although this term was never proposed or approved in the RUCAM literature that determines highly probable as the highest grading,12,15”

• cites [12] Danan, 1993, Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries, J Clin Epidemiol sourceNot checked — no full text of the source
• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

RUCAM has a remarkable scientific run among experts of HILI and RUCAM as an appreciated diagnostic algorithm for assessing causality in liver injury cases, shown alone by the large list of RUCAM-based DILI and HILI cases published until 2015.

“RUCAM has a remarkable scientific run among experts of HILI and RUCAM as an appreciated diagnostic algorithm for assessing causality in liver injury cases, shown alone by the large list of RUCAM-based DILI and HILI cases published until 2015.15”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

The DILIN method for causality assessment comes along without any specific element scoring and provides only arbitrary causality gradings as percentage ranges.

“used the method of the Drug-Induced Liver Injury Network (DILIN)67 for causality assessment, which comes along without any specific element scoring and provides only arbitrary causality gradings as percentage ranges;68”

• cites [67] Zhu, 2020, The landscape of hepatobiliary adverse reactions across 53 herbal and dietary supplements reveals immune-mediated injury as a common cause of hepatitis, Arch Toxicol sourceNot checked — no full text of the source
• cites [68] Teschke, 2018, Causality assessment methods in drug-induced liver injury sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

The highest final scores and associated high causality gradings are obtained with complete case data sets and are best achieved by a prospective study design.

“In general, the highest final scores and associated high causality gradings are obtained with complete case data sets and are best achieved by a prospective study design as the primary aim of any causality assessment of liver injury cases.15”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

An update was published later, with two different scales, one for cases of hepatocellular injury and one for the cholestatic or mixed liver injury.

“An update was published later,15 with two different scales, one for cases of hepatocellular injury (Table 2) and one for the cholestatic or mixed liver injury (Table 3).15”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

The LiverTox database is known for inclusion of liver injury cases lacking robust CAMs and is therefore disputed.

“Critical is also the data source of used cases, which were partially retrieved from the USA’s National Institutes of Health LiverTox database,67 known for inclusion of liver injury cases lacking robust CAMs and being therefore disputed.69–71”

• cites [67] Zhu, 2020, The landscape of hepatobiliary adverse reactions across 53 herbal and dietary supplements reveals immune-mediated injury as a common cause of hepatitis, Arch Toxicol sourceNot checked — no full text of the source
• cites [69] Björnsson, 2016, Hepatotoxicity by drugs: The most common implicated agents, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [70] Björnsson, 2016, Categorization of drugs implicated in causing liver injury: Critical assessment based on published case reports, Hepatology sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [71] Teschke, 2018, Top-ranking drugs out of 3312 drug-induced liver injury cases evaluated by the Roussel Uclaf Causality Assessment Method, Expert Opin Drug Metab Toxicol sourceNot checked — no full text of the source

It may state two separate claims as one.

Other CAMs used in the FDA study are known for being not specific for liver injury cases and not based on typical, individually scored liver-related key elements.

“additionally, other CAMs were used,67 known for being not specific for liver injury cases and not based on typical, individually scored liver-related key elements, as amply discussed previously15 and reiterated recently.68”

• cites [67] Zhu, 2020, The landscape of hepatobiliary adverse reactions across 53 herbal and dietary supplements reveals immune-mediated injury as a common cause of hepatitis, Arch Toxicol sourceNot checked — no full text of the source
• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [68] Teschke, 2018, Causality assessment methods in drug-induced liver injury sourceNot checked — no full text of the source

Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.

The RUCAM-based method uniformity will allow for valid comparison of case results between countries and continents.

“the RUCAM-based method uniformity will allow for valid comparison of case results between countries and continents.”

It may state two separate claims as one.

The updated RUCAM is as good as physicians and assessors are handling this method and strictly apply published recommendations.

“The updated RUCAM is as good as physicians and assessors are handling this method and strictly apply published recommendations.15”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim.

Disregarding thresholds impedes clear differentiation between liver injury and LT abnormality.

“Disregarding thresholds impedes clear differentiation between liver injury and LT abnormality.51”

• cites [51] Lee, 2015, Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients, J Ethnopharmacol sourceNot checked — no full text of the source

It may state two separate claims as one.

RUCAM is continuously used without problems, except for some minor questions, addressed and clarified in previous RUCAM publications.

“RUCAM is continuously used without problems,11,15 except for some minor questions, addressed and clarified in previous RUCAM publications.15–17”

• cites [11] Teschke, 2019, Idiosyncratic DILI: Analysis of 46,266 cases assessed for causality by RUCAM and published from 2014 to early 2019, Front Pharmacol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [16] Danan, 2018, Drug-induced liver injury: Why is the roussel uclaf causality assessment method (RUCAM) still used 25 years after its launch?, Drug Saf sourceNot checked — no full text of the source
• cites [17] Danan, 2019, Roussel uclaf causality assessment method for drug-induced liver injury: Present and future, Front Pharmacol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

RUCAM-based causality gradings are defined with highly probable being the top level.

“RUCAM-based causality gradings are defined with highly probable being the top level.15”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Zhang et al. published a systematic review on Chinese HILI and the use of RUCAM in 54 cases with high causality gradings.

“A report of excellence is the careful systematic review on Chinese HILI and the use of RUCAM in 54 cases with high causality gradings, published by Zhang et al.29”

• cites [29] Zhang, 2016, Systematic review on Chinese herbal medicine induced liver injury, Evid Based Complement Alternat Med sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The philosophy behind creating the original RUCAM of 1993 was to facilitate a valid diagnosis for patients with suspected liver injury.

“The philosophy behind creating the original RUCAM of 1993 was to facilitate a valid diagnosis for patients with suspected liver injury.”

Probably not a substantial claim. It may state two separate claims as one.

RUCAM evaluates seven key elements characteristic for liver injury, which are individually scored, and their summed score provides a final score and a final causality grading.

“RUCAM evaluates seven key elements characteristic for liver injury, which are individually scored, and their summed score provides a final score and a final causality grading;15”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Problems were not found at the level of RUCAM itself but rather were related to poor quality case data or the users if they publish incorrect RUCAM-based causality gradings that had been lifted intentionally from possible to probable gradings.

“Problems were not found at the level of RUCAM itself but rather were related to poor quality case data or the users if they publish incorrect RUCAM-based causality gradings that had been lifted intentionally from possible to probable gradings.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The currently favored ALT and ALP threshold values of 2016 have been considered as perfect in China by Yang et al.

“The currently favored ALT and ALP threshold values of 201615 have also been considered as perfect in China by Yang et al.72”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [72] Yang, 2019, Comparison of different liver test thresholds for drug-induced liver injury: Updated RUCAM versus other methods, Front Pharmacol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Scientists from other Asian countries are more cautious using RUCAM.

“Scientists from other Asian countries are more cautious using RUCAM, either to avoid disturbances with the politics of the national TCM-based health system, hospital-related issues, scientific society-based requirements, or that they just prefer their own CAMs”

It may state two separate claims as one.

This led to the development of a liver-specific, quantitative, objective, transparent, and structured diagnostic algorithm which was well validated using cases with positive re-exposure tests as gold standard.

“This led to the development of a liver-specific, quantitative, objective, transparent, and structured diagnostic algorithm12 which was well validated using cases with positive re-exposure tests as gold standard.13”

• cites [12] Danan, 1993, Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries, J Clin Epidemiol sourceNot checked — no full text of the source
• cites [13] Benichou, 1993, Causality assessment of adverse reactions to drugs--II. An original model for validation of drug causality assessment methods: case reports with positive rechallenge, J Clin Epidemiol sourceNot checked — no full text of the source

It may state two separate claims as one.

Some diagnostic biomarkers are well established for HILI and DILI, but others came under scientific fire due to recent actions of the European Medicines Agency (EMA) through the correct and official retraction of its earlier Letter of Support to promote biomarker research and use.

“Some diagnostic biomarkers are well established for HILI and DILI, but others came under scientific fire due to recent actions of the European Medicines Agency (known as the EMA) through the correct and official retraction of its earlier Letter of Support to promote biomarker research and use.65”

• cites [65] Teschke, 2019, Diagnostic biomarkers in liver injury by drugs, herbs, and alcohol: Tricky dilemma after EMA correctly and officially retracted letter of support, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. It may be too vague to check against evidence.

Such modifications must be rejected because they would require a new method validation that has never been provided.

“but this attempt must be rejected because such modifications would require a new method validation that has never been provided.”

It may state two separate claims as one.

RUCAM is applicable for retrospective liver injury cases, but this commonly leads to low final RUCAM scores and low causality gradings because RUCAM partially disqualifies missing data by low or negative scores.

“However, and if worse comes to worst, RUCAM is also applicable and prepared for liver injury cases assessed retrospectively, but this commonly leads to low final RUCAM scores and low causality gradings because RUCAM partially disqualifies missing data by low or negative scores to be subtracted from the final score.”

It may state two separate claims as one.

RUCAM has not been designed for chronic DILI and HILI or when a suspected injury occurs on pre-existing liver disease-both complex conditions where a more accurate approach especially for the timing of the events and the exclusion of alternative causes is needed.

“RUCAM has not been designed for chronic DILI and HILI or when a suspected injury occurs on pre-existing liver disease—both complex conditions where a more accurate approach especially for the timing of the events and the exclusion of alternative causes is needed.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The highest RUCAM-based causality level is highly probable, not definite.

“The highest RUCAM-based causality level is not definite as erroneously described in some publications (Table 1) but clearly termed as highly probable,15”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Results obtained with PM, harvested from various regions of China and assessed for its hepatotoxic potential, showed that liver toxicity was obviously different among the various areas of harvest, and the most toxic PM was from the Sichuan Province.

“These results showed that liver toxicity was obviously different among the various areas of harvest, and the most toxic PM was from the Sichuan Province.”

• cites [88] Lin, 2017, A new perspective on liver injury by traditional Chinese herbs such as Polygonum multiflorum: The geographical area of harvest as an important contributory factor, Front Pharmacol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Changing circadian rhythms may be an approach to gain improved plant quality, to prevent poor quality, or both.

“Changing circadian rhythms may be an approach to gain improved plant quality, to prevent poor quality, or both.82,83”

• cites [82] Dakhiya, 2017, Correlations between circadian rhythms and growth in challenging environments, Plant Physiol sourceNot checked — no full text of the source
• cites [83] Xuan, 2016, Changes in chemical composition, total phenolics and antioxidant activity of Alpinia (Alpinia zerumbet) leaves exposed to UV, Intern Lett Nat Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Using a metabolomic approach, 166 metabolites had been identified in these roots, 63 of which showed significant quantitative changes in different growth years of up to 4 years.

“Using a metabolomic approach based on gas chromatography-mass spectroscopy, 166 metabolites had been identified in these roots, 63 of which showed significant quantitative changes in different growth years of up to 4 years.”

• cites [87] Tong, 2017, Metabolomics approach reveals annual metabolic variation in roots of Cyathula officinalis Kuan based on gas chromatography-mass spectrum, Chin Med sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

From outside of Asia, reports were published by authors of the USA on a few cases of HILI by TCMs.

“From outside of Asia, reports were published by authors of the USA on a few cases of HILI by TCMs.3,67”

• cites [3] Brown, 2017, Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series, Food Chem Toxicol sourceNot checked — no full text of the source
• cites [67] Zhu, 2020, The landscape of hepatobiliary adverse reactions across 53 herbal and dietary supplements reveals immune-mediated injury as a common cause of hepatitis, Arch Toxicol sourceNot checked — no full text of the source

Probably not a substantial claim. It may be too vague to check against evidence.

With a good study design, high-quality HILI cases are to be expected.

“With a good study design, high-quality HILI cases are to be expected.15–17”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [16] Danan, 2018, Drug-induced liver injury: Why is the roussel uclaf causality assessment method (RUCAM) still used 25 years after its launch?, Drug Saf sourceNot checked — no full text of the source
• cites [17] Danan, 2019, Roussel uclaf causality assessment method for drug-induced liver injury: Present and future, Front Pharmacol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.

RUCAM is not destined to check for product quality.

“RUCAM is not destined to check for product quality.”

Probably not a substantial claim.

The updated RUCAM can be used even for HILI cases obtained from retrospective studies.

“No question, the updated RUCAM can be used even for HILI cases obtained from retrospective studies; although, this is not the preferred approach.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In this clinical setting, only herbal TCMs of verified quality are used by the patients under care.

“In this clinical setting, only herbal TCMs of verified quality are used by the patients under care”

• cites [77] Melchart, 2017, Herbal Traditional Chinese Medicine and suspected liver injury: A prospective study, World J Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

They identified a gene which encodes a protein within the cell during the night that then degrades during the day.

“They identified a gene which encodes a protein within the cell during the night that then degrades during the day.”

• cites [82] Dakhiya, 2017, Correlations between circadian rhythms and growth in challenging environments, Plant Physiol sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

A comprehensive list was provided by the exceptional study of Zhang et al.

“Instead, a comprehensive list was provided by the exceptional study of Zhang et al.29”

• cites [29] Zhang, 2016, Systematic review on Chinese herbal medicine induced liver injury, Evid Based Complement Alternat Med sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The circadian clock system in plants controls many important metabolic pathways and functions, including photosynthesis, stomatal opening, and molecular processes leading to gene expression.

“The circadian clock system in plants controls many important metabolic pathways and functions, including photosynthesis, stomatal opening, and molecular processes leading to gene expression.82”

• cites [82] Dakhiya, 2017, Correlations between circadian rhythms and growth in challenging environments, Plant Physiol sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In experimental studies using plant leaves and mimicking the daylight, exposure of ultraviolet-C to the Shell ginger modulates the relative chemical composition, changes the amounts of essential oils and total phenols, and alters the antioxidant activity.

“In experimental studies using plant leaves and mimicking the daylight, exposure of ultraviolet-C (short wavelength) to the Shell ginger (Alpinia zerumbet) of the ginger family (Zingiberaceae) modulates the relative chemical composition, changes the amounts of essential oils and total phenols, and alters the antioxidant activity.83”

• cites [83] Xuan, 2016, Changes in chemical composition, total phenolics and antioxidant activity of Alpinia (Alpinia zerumbet) leaves exposed to UV, Intern Lett Nat Sci sourceNot checked yet

It may state two separate claims as one.

HILI is seemingly not a problem in Korea, similar to Germany, considering the low TCM-related HILI incidence data.

“HILI is seemingly not a problem in Korea,51,54,73 similar to Germany, considering the low TCM-related HILI incidence data.77”

• cites [51] Lee, 2015, Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients, J Ethnopharmacol sourceNot checked — no full text of the source
• cites [54] Cho, 2017, A nationwide study of the incidence rate of herb-induced liver injury in Korea, Arch Toxicol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [73] Lee, 2019, Battle over herb-induced liver injury: Low prevalence confirmed through secondary evaluation and research team’s clarifying rebuttal to unwarranted public claims, J Altern Complement Med sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Transcriptional, translational, and post-translational processes are interlocked by feedback loops among morning- and evening-phased genes.

“Transcriptional, translational, and post-translational processes are interlocked by feedback loops among morning- and evening-phased genes.83”

• cites [83] Xuan, 2016, Changes in chemical composition, total phenolics and antioxidant activity of Alpinia (Alpinia zerumbet) leaves exposed to UV, Intern Lett Nat Sci sourceNot checked yet

It may state two separate claims as one.

Cases presented by the second group of the USA FDA were partially assessed using the updated RUCAM or a unique, not validated evidence-based method.

“In contrast, cases presented by the second group of the USA FDA67 were partially assessed using the updated RUCAM15 or a unique, not validated evidence-based method.”

• cites [67] Zhu, 2020, The landscape of hepatobiliary adverse reactions across 53 herbal and dietary supplements reveals immune-mediated injury as a common cause of hepatitis, Arch Toxicol sourceNot checked — no full text of the source
• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

An earlier vain epidemiology analysis was not RUCAM-based and used mixed cohorts of injury cases by drugs, herbs, or CAMs.

“An earlier vain epidemiology analysis was not RUCAM-based and used mixed cohorts of injury cases by drugs, herbs, or CAMs.78”

• cites [78] Zhou, 2013, Epidemiology of drug-induced liver injury in China: a systematic analysis of the Chinese literature including 21,789 patients, Eur J Gastroenterol Hepatol sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

It was suggested to harvest in the fourth grow year in order to boost herbal quality.

“It was suggested to harvest in the fourth grow year in order to boost herbal quality, and extending these studies to other plants.87”

• cites [87] Tong, 2017, Metabolomics approach reveals annual metabolic variation in roots of Cyathula officinalis Kuan based on gas chromatography-mass spectrum, Chin Med sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Herbal product quality is also modified by biotic or abiotic plant stress, affecting higher plants.

“Herbal product quality is also modified by biotic or abiotic plant stress, affecting higher plants.79”

• cites [79] Teschke, 2018, Liver injury from herbs and “dietary supplements”: Highlights of a literature review from 2015 to 2017, Curr Pharmacol Rep sourceNot checked — no full text of the source

It may state two separate claims as one.

Cases of HILI in association with the use of products derived from Camellia sinensis were not included in this analysis because respective publications by Asian authors are scarce; it is mainly a problem in Western countries.

“Not included in this analysis were cases of HILI in association with the use of products derived from Camellia sinensis, consumed either as green tea beverage or green tea extracts (GTE) because respective publications by Asian authors are scarce; indeed, it is mainly a problem in Western countries, where many RUCAM-based reports were published on liver injury in connection with the use of GTE.97,”

• cites [97] Mazzanti, 2015, Hepatotoxicity of green tea: an update, Arch Toxicol sourceNot checked — no full text of the source
• cites [98] Teschke, 2019, Suspected herb induced liver injury by green tea extracts: Critical review and case analysis applying RUCAM for causality assessment, Jap J Gastroenterol HepatolNot checked yet

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Such studies about variation of phytochemicals in different harvest times is in line with Good Agricultural Practice standards of Chinese traditional herbs in China.

“Such studies about variation of phytochemicals in different harvest times is in line with Good Agricultural Practice standards of Chinese traditional herbs in China.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In the other report, these gradings were provided for a few HILI cases.

“In the other report, these gradings were provided for a few HILI cases.92”

• cites [92] Teschke, 2014, Review article: Herbal hepatotoxicity--an update on traditional Chinese medicine preparations, Aliment Pharmacol Ther sourceNot checked — no full text of the source

It may state two separate claims as one.

In that study, probable causality was attributable to 8/26 cases, possible to 16/26, and excluded to 2/26 using updated RUCAM.

“but a probable causality was attributable to only 8/26 cases, a possible one to 16/26 patients, and an excluded one to 2/26 cases, using the updated RUCAM.77”

• cites [77] Melchart, 2017, Herbal Traditional Chinese Medicine and suspected liver injury: A prospective study, World J Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

A large list with individual RUCAM-based causality grading for various herbal TCMs was also published.

“A large list with individual RUCAM-based causality grading for various herbal TCMs was also published.95”

• cites [95] Teschke, 2015, Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases, Ann Hepatol sourceNot checked — no full text of the source

It may state two separate claims as one.

The respective cohorts in the 2019 Gastroenterology report were grouped under DILI and included liver injury cases caused by herbal TCM and herbal dietary supplements, not allowing for characterization of HILI epidemiology features.

“However, the respective cohorts were grouped under the term of DILI, and represented still not only DILI but also liver injury cases caused by herbal TCM and herbal dietary supplements, representing two different product categories and again providing conditions similar to the shortcomings of the earlier study78 and not allowing for characterization of HILI epidemiology features.36”

• cites [36] Shen, 2019, Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceNot checked yet
• cites [78] Zhou, 2013, Epidemiology of drug-induced liver injury in China: a systematic analysis of the Chinese literature including 21,789 patients, Eur J Gastroenterol Hepatol sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Abiotic stress is caused by environmental attacks, heavy ultraviolet radiation, draft, wounding, or soil contamination by salts or heavy metals.

“Instead, abiotic stress is caused by environmental attacks, heavy ultraviolet radiation, draft, wounding, or soil contamination by salts or heavy metals.83,85,86”

• cites [83] Xuan, 2016, Changes in chemical composition, total phenolics and antioxidant activity of Alpinia (Alpinia zerumbet) leaves exposed to UV, Intern Lett Nat Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [85] Elzaawely, 2007, Changes in essential oils, kava pyrones and total phenolics of Alpinia zerumbet (Pers.) B.L. Burtt. & R.M. Sm. leaves exposed to copper sulphate, Environ Experiment Botany sourceNot checked — no full text of the source
• cites [86] Vongdala, 2018, Heavy metal accumulation in water, soil, and plants of municipal solid waste landfill in Vientiane, Laos, Int J Environ Res Public Health sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The United States Pharmacopeia and DILIN members confirmed that GTE are potentially hepatotoxic by using the updated RUCAM.

“Key issues around liver injury by GTE are obviously settled now, as the United States Pharmacopeia and DILIN members finally made it and confirmed that GTE are potentially hepatotoxic by using the updated RUCAM and thereby breaking boundaries to good medicine based on evidence and a diagnostic algorithm in line with artificial intelligence proposals.99”

• cites [99] Oketch-Rabah, 2020, United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts, Toxicol Rep sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Their discoveries explain how plants, animals, and humans adapt their biological rhythm so that it is synchronized with the Earth's revolutions.

“Their discoveries explain how plants, animals, and humans adapt their biological rhythm so that it is synchronized with the Earth’s revolutions.”

• cites [82] Dakhiya, 2017, Correlations between circadian rhythms and growth in challenging environments, Plant Physiol sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Fixing the harvest year will provide consistency of batches and herbal products with the desired phytochemicals as target ingredients.

“Fixing the harvest year will provide consistency of batches and herbal products with the desired phytochemicals as target ingredients.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

The quality of herbal medicines must be evaluated by toxicology methods, and such approach is a routine measure in a TCM hospital in Germany.

“The quality of herbal medicines must be evaluated by toxicology methods, such approach is a routine measure in a TCM hospital in Germany, as described previously.77”

• cites [77] Melchart, 2017, Herbal Traditional Chinese Medicine and suspected liver injury: A prospective study, World J Hepatol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.

Only a prospective study design that includes the use of the updated RUCAM will provide valid and complete data of HILI cases, with a high causality grading of probable or better highly probable.

“Only a prospective study design that includes the use of the updated RUCAM15 will provide valid and complete data of HILI cases, with a high causality grading of probable or better highly probable.”

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Reports of 2015 presented HILI lists of TCM herbs with established causality or a large list of herbal TCMs causing HILI with exact case numbers but without RUCAM-based causality grading.

“Reports of 2015 presented HILI lists of TCM herbs with established causality93 or a large list of herbal TCMs causing HILI with exact case numbers but without RUCAM-based causality grading.94”

• cites [93] Teschke, 2015, Chinese herbs and their molecules: Clinical and pathophysiological implications for the liver, J Mol Pathophysiol sourceNot checked — no full text of the source
• cites [94] Teschke, 2015, Herbal hepatotoxicity in traditional and modern medicine: actual key issues and new encouraging steps, Front Pharmacol sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Sufficient evidence exists to mandate understanding plant physiology and consideration of plant circadian rhythm in manufacture of good quality herbal products.

“Sufficient evidence exists to mandate understanding plant physiology and consideration of plant circadian rhythm in manufacture of good quality herbal products.82,83”

• cites [82] Dakhiya, 2017, Correlations between circadian rhythms and growth in challenging environments, Plant Physiol sourceNot checked — no full text of the source
• cites [83] Xuan, 2016, Changes in chemical composition, total phenolics and antioxidant activity of Alpinia (Alpinia zerumbet) leaves exposed to UV, Intern Lett Nat Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

It may state two separate claims as one.

Reports of 2016 presented case lists of HILI with TCM herbs and causality assessment by RUCAM or positive re-exposure tests, a country-wise case listing of HILI by herbal TCMs with exact numbers and references, and a large list of RUCAM-based injury cases by herbal TCMs, other herbs and drugs.

“Reports of 2016 presented case lists of HILI with TCM herbs and causality assessment by RUCAM or positive re-exposure tests89 or a country-wise case listing of HILI by herbal TCMs with exact numbers and references,90 and a large list of RUCAM-based injury cases by herbal TCMs, other herbs and drugs, all listed within the publication of the updated RUCAM.15”

• cites [89] Frenzel, 2016, Herbal hepatotoxicity: Clinical characteristics and listing compilation, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [90] Teschke, 2016, Traditional chinese medicine (TCM) and herbal hepatotoxicity: RUCAM and the role of novel diagnostic biomarkers such as microRNAs, Medicines (Basel) sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [15] Danan, 2015, RUCAM in drug and herb induced liver injury: The update, Int J Mol Sci sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The Nobel Prize in Physiology or Medicine 2017 was awarded to Michael W. Young, Michael Rosbash, and Jeffrey C. Hall for their discoveries on the molecular mechanisms controlling circadian rhythms.

“The Nobel Prize in Physiology or Medicine 2017 was awarded to the three US scientists Michael W. Young, Michael Rosbash, and Jeffrey C. Hall for their discoveries on the molecular mechanisms controlling circadian rhythms (the physiological 24-hour body clock).82”

• cites [82] Dakhiya, 2017, Correlations between circadian rhythms and growth in challenging environments, Plant Physiol sourceNot checked — no full text of the source

Probably not a substantial claim.

Establishing the RUCAM-based diagnosis of HILI requires RUCAM scores of ≥6 that provide causality gradings of probable or highly probable.

“Establishing the RUCAM-based diagnosis of HILI requires RUCAM scores of ≥6 that provide causality gradings of probable or highly probable.”

• cites [106] Wang, 2018, Guidelines for the diagnosis and management of herb-induced liver injury, Chin J Integr Med sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Discussions have emerged around the reported RUCAM-based DILI and HILI cases from another report and related Letters to the Editor.

“Focusing on another report36 and the related Letters to the Editor102–104 by various DILI experts from China,102,104 India,103 and Iceland,103 discussions have emerged around the reported RUCAM-based DILI and HILI cases36”

• cites [36] Shen, 2019, Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceNot checked yet
• cites [102] Yang, 2019, Can retrospective studies confirm causes of drug-induced liver injury?, Gastroenterology sourceNot checked — no full text of the source
• cites [103] Devarbhavi, 2019, RE: Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceNot checked — no full text of the source
• cites [104] Cong, 2019, RE: Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceNot checked — no full text of the source

Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it.

Results gathered retrospectively do not allow valid conclusions.

“and it was argued that results gathered retrospectively do not allow valid conclusions.102–104”

• cites [102] Yang, 2019, Can retrospective studies confirm causes of drug-induced liver injury?, Gastroenterology sourceNot checked — no full text of the source
• cites [103] Devarbhavi, 2019, RE: Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceNot checked — no full text of the source
• cites [104] Cong, 2019, RE: Incidence and etiology of drug-induced liver injury in mainland China, Gastroenterology sourceNot checked — no full text of the source

It may state two separate claims as one.

For China, guidelines exist with focus on the diagnosis of HILI, HILI by herbal TCMs, and DILI.

“For China, guidelines exist with focus on the diagnosis of HILI (Fig. 1),106 HILI by herbal TCMs,107 and DILI.108”

• cites [106] Wang, 2018, Guidelines for the diagnosis and management of herb-induced liver injury, Chin J Integr Med sourceNot checked — no full text of the source
• cites [107] Xiao, 2019, Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injuryIssued by China Food and Drug Administration, Acta Pharm Sin B sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites [108] Yu, 2017, CSH guidelines for the diagnosis and treatment of drug-induced liver injury, Hepatol Int sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The reasons for the promising data (low HILI in Singapore) are possibly related to the herbal product quality.

“The reasons of these promising data are possibly related to the herbal product quality.101”