A nationwide study of the incidence rate of herb-induced liver injury in Korea

Cho, Jung‐Hyo; Oh, Dal‐Seok; Hong, Sang-hoon; Ko, Heung; Lee, Nam-Hun; Park, Sang-Eun; Han, Changwoo; Kim, Seung Mo; Kim, Young‐Chul; Kim, Kang‐San; Choi, Chang-Won; Shin, Seon-My; Kim, Ki-Tae; Choi, Hyun Joon; Lee, Jang-Hoon; Kim, Junyoung; Kang, Jiyoung; Lee, Dong‐Soo; Ahn, Yo-Chan; Son, Chang‐Gue

doi:10.1007/s00204-017-2007-9

Cited by 60 publications

(55 citation statements)

References 23 publications

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“…1,2) In recent years, increasing clinical reports have indicated potential hepatotoxicity of FP in patients, [3][4][5] for instance, Cheung et al showed three cases of acute hepatitis after exposed to FP and its related medicine such as Bu-gu-zhi intramuscular injection, 3) and concerns grow over the health effects of FP. However, the hepatotoxic components and the mechanism of FP-induced hepatotoxicity are not fully understood.…”

mentioning

confidence: 99%

Bavachin Induces Apoptosis through Mitochondrial Regulated ER Stress Pathway in HepG2 Cells

Yang

Tang²,

Hao³

et al. 2018

Biological & Pharmaceutical Bulletin

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As a traditional herbal medicine, the fruits of Psoralea corylifolia L. (Fructus Psoraleae (FP)) have been widely used for the treatment of various skin diseases for hundred years. Recently, the emerging FPinduced toxic effects, especially hepatotoxicity, in clinic are getting the public's attention. However, its exact toxic components and mechanisms underlying remain unclear. Bavachin, one of flavonoids in FP, has been documented as a hepatotoxic substance, and the present study aimed to determine the toxicity caused by bavachin and the possible toxic mechanisms involved using human hepatocellular carcinoma (HepG2) cells. Our results showed that bavachin could significantly inhibited cell proliferation and trigger the endoplasmic reticulum (ER) stress in a dose dependent manner. Downregulating ER stress using tauroursodeoxycholic acid (TUDCA) obvious attenuated bavachin-triggerd cell apoptosis. Then, small interfering RNA (siRNA) knock-down of Mitofusion2 (Mfn2) resulted in a remarkable aggravation of ER stress through the inhibition of the phosphorylation of protein kinase B (Akt). Additionally, suppression of reactive oxygen species (ROS) by ROS Scavenger (N-acetyl-l-cystein (NAC)) also reduced bavachin-induced ER stress. Taken together, our study demonstrated that bavachin-induced ER stress caused cell apoptosis by Mfn2-Akt pathway, and that ROS may participate upstream in this mechanism. Here, we not only provide a new understanding of ROS/ Mfn2/Akt pathway in bavachin-induced cytotoxicity via the ER stress, but also identify a new specific intervention to prevent FP-induced hepatotoxicity in the future.

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mentioning

confidence: 99%

Bavachin Induces Apoptosis through Mitochondrial Regulated ER Stress Pathway in HepG2 Cells

Yang

Tang²,

Hao³

et al. 2018

Biological & Pharmaceutical Bulletin

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“…The present result was slightly higher than that of HILI (0.56%, 95% CI [0.07, 1.05]) with 892 patients in a retrospective study(Kim et al, ) and that of HILI (0.43%) with 1169 patients in another retrospective study (Woo et al, ). However, this result was slightly lower than that of HILI (0.60%, 95% CI [0.12, 1.08]) with 1,001 patients in a nationwide prospective study (Cho et al, ) and that of HILI (0.6%) with 4,769 patients in another retrospective study (Lee, Shin, et al, ). These four studies defined the liver injury using the original method (Hayashi, ).…”

Section: Discussionmentioning

confidence: 77%

Liver enzyme abnormalities of inpatients with rheumatic diseases: A 10‐year retrospective study in a Korean medicine hospital

Lee

Kang

et al. 2018

Phytotherapy Research

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Herbal medicines have been used as a treatment option for rheumatic disease (RD), but they often produce liver enzyme abnormality. This study examines the incidence of herb-induced liver injury (HILI) and the relationship between risk factors and liver enzyme abnormality (LEA) in inpatients with RD. HILI was analyzed using the Roussel Uclaf causality assessment method liver injury criteria and causality assessment. Multivariable analysis was performed to assess the relationship between patient characteristics and LEA in RD. The features of LEA were also examined in each RD. Among 352 patients included in this study, 105 patients showed LEA on admission, of which 6 had fulfilled the Roussel Uclaf causality assessment method criteria. The incidence risks of LEA and HILI were 12.55% and 0.58%, respectively. Multivariable analysis showed that LEA on admission and occasional use of alcohol could be risk factors for LEA on follow-up. In an additional analysis with each RD, all rheumatoid arthritis patients with LEA were taking nonsteroidal anti-inflammatory drugs, steroids, and disease-modifying antirheumatic drugs, and 4 out of 5 gout patients with LEA were taking steroids. The use of herbal medicine in RD is relatively safe. However, regular monitoring of liver enzyme tests and examination of alcohol consumption are required.

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“…In particular, there is a lack of prospective studies focusing on cases with causality gradings by Roussel Uclaf Causality Assessment Method (RUCAM) . However, some incidence data for such cases have been published . For instance, a recent report from Germany presented, for the first time, liver‐injury data derived from a prospective, large‐scale hospital‐based study of 21 470 patients, who had no liver disease prior to treatment with herbal traditional Chinese medicines (TCM), in which product falsification and adulteration were excluded.…”

Section: Epidemiology Data In Comparisonmentioning

confidence: 99%

“…It is unclear whether the high quality standard applied to the herbal TCM products used in the German hospital may have contributed to the low case numbers . A low incidence of 0.6% for HILI cases was also reported in a prospective study of 1001 patients with RUCAM‐based causality gradings of possible and higher from Korea . In the US State of Delaware, a small, preliminary, and prospective study involving gastroenterologists only, 6 cases per 100 000 adults were reported, corresponding to 1.2 cases of HDS‐induced liver injury per 100 000 adults .…”

Section: Epidemiology Data In Comparisonmentioning

confidence: 99%

“…Considering the US population of 323.2 million in 2016, around 47.8 million individuals would be affected by a chronic liver disease. This compares with a much lower incidence of DILI, which is commonly estimated to be around 14/100 000 inhabitants and, applied to the USA, this corresponds to around 45 000 DILI cases, that is, a prevalence rate of 1000 times less than in cases of chronic liver disease; it also compares with an extremely low incidence of liver‐injury cases by herbs and DS . This is important in clinical practice, since patients using herbs or DS and experiencing a liver injury or abnormal liver tests are more likely affected by a chronic liver disease than by an acute liver injury by herbs or DS.…”

Section: Introductionmentioning

confidence: 96%

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Is obesity rather than the dietary supplement used for weight reduction the cause of liver injury?

et al. 2018

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Acute liver injury has been attributed to dietary supplements (DS) used for weight loss, but their causal role was much questioned, and obesity as an alternative cause of the liver injury remained unclear. A comprehensive search of the Medline database was conducted with terms that included “DS,” “liver injury,” “obesity,” “obesity‐related liver diseases,” and “nonalcoholic steatohepatitis.” For each term, we focused on the first 50 publications. We undertook a manual search to identify additional reports. Underlying liver diseases and other health issues are common in patients taking DS for weight reduction. These include obesity or morbid obesity, as well as complex metabolic disorders complicated by excess morbidity and mortality due to associated liver diseases. Among these are nonalcoholic fatty liver disease with potential progression to nonalcoholic steatohepatitis and cirrhosis, often classified as cryptogenic with a rare risk of hepatocellular carcinoma. With the exception of hepatocellular carcinoma, these obesity‐related liver diseases were observed to varying degrees in patients, and some even required a liver transplant. This raises the question whether the liver injury that occurred in these patients is due to DS consumed for weight loss or to the underlying obesity‐related liver diseases. This analysis showed that, in many instances, the causal role of obesity has been neglected. Obesity‐associated liver diseases should be considered as differential diagnosis of liver injury in obese patients using DS.

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A nationwide study of the incidence rate of herb-induced liver injury in Korea

Cited by 60 publications

References 23 publications

Bavachin Induces Apoptosis through Mitochondrial Regulated ER Stress Pathway in HepG2 Cells

Bavachin Induces Apoptosis through Mitochondrial Regulated ER Stress Pathway in HepG2 Cells

Liver enzyme abnormalities of inpatients with rheumatic diseases: A 10‐year retrospective study in a Korean medicine hospital

Is obesity rather than the dietary supplement used for weight reduction the cause of liver injury?

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