A review of drug-induced liver injury databases

Luo, Guangwen; Shen, Yiting; Lei, Yang; Lu, Aiping; Zheng, Xunhua

doi:10.1007/s00204-017-2024-8

Cited by 36 publications

(28 citation statements)

References 63 publications

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“…Drug‐induced liver injuries are a major concern of clinical drug combination use and new drug development. Drug‐induced liver injuries have been systematically recorded in many public databases . For example, the hepatotoxicity produced by currently used antituberculosis chemotherapeutic regimen containing isoniazid, rifampicin and pyrazinamide is a typical example .…”

Section: Low Doses Of Oa Protect Against Hepatotoxicity Induced By a mentioning

confidence: 99%

“…Drug-induced liver injuries have been systematically recorded in many public databases. 48 For example, the hepatotoxicity produced by currently used antituberculosis chemotherapeutic regimen containing isoniazid, rifampicin and pyrazinamide is a typical example. 49 These anti-TB drugs are potentially hepatotoxic, but when administered in combination, their toxic effects are enhanced in a synergistic manner.…”

Section: Oa Protects Against Chronic Liver Injury Fibrosis and Cirmentioning

confidence: 99%

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Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Liu

Lü

et al. 2018

Liver International

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Oleanolic acid (OA) is a triterpenoid that exists widely in fruits, vegetables and medicinal herbs. OA is included in some dietary supplements and is used as a complementary and alternative medicine (CAM) in China, India, Asia, the USA and European countries. OA is effective in protecting against various hepatotoxicants, and one of the protective mechanisms is reprogramming the liver to activate the nuclear factor erythroid 2-related factor 2 (Nrf2). OA derivatives, such as CDDO-Im and CDDO-Me, are even more potent Nrf2 activators. OA has recently been shown to also activate the Takeda G-protein-coupled receptor (TGR5). However, whereas a low dose of OA is hepatoprotective, higher doses and long-term use of OA can produce liver injury, characterized by cholestasis. This paradoxical hepatotoxic effect occurs not only for OA, but also for other OA-type triterpenoids. Dose and length of time of OA exposure differentiate the ability of OA to produce hepatoprotection vs hepatotoxicity. Hepatotoxicity produced by herbs is increasingly recognized and is of global concern. Given the appealing nature of OA in dietary supplements and its use as an alternative medicine around the world, as well as the development of OA derivatives (CDDO-Im and CDDO-Me) as therapeutics, it is important to understand not only that they program the liver to protect against hepatotoxic chemicals, but also how they produce hepatotoxicity.

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Section: Low Doses Of Oa Protect Against Hepatotoxicity Induced By a mentioning

confidence: 99%

Section: Oa Protects Against Chronic Liver Injury Fibrosis and Cirmentioning

confidence: 99%

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Liu

Lü

et al. 2018

Liver International

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“…More than 900 drugs, herbs, and toxins have documented this possibility, being the most frequent cause of acute hepatic failure in developed countries and the biggest responsible factor for drug withdrawal from the market [5][6][7]. In most cases, the incidence of DILI is extremely low, varying between 1/10,000 and 1/100,000 [8]. They are usually idiosyncratic reactions that occur in susceptible patients, without a clear dose-response relation, being associated with certain HLA alleles [3,4].…”

Section: Discussionmentioning

confidence: 99%

Carvedilol-Induced Liver Injury, a Rare Cause of Mixed Hepatitis: A Clinical Case

Rua

Prata

Marques

et al. 2018

GE Port J Gastroenterol

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Introduction: Drug-induced liver injury is an increasingly prevalent consequence of the diversification of available therapeutic weapons, mostly idiosyncratic and with several possible mechanisms and patterns of specific damage for each drug. Carvedilol, a widely used non-selective alpha and beta blocker leads, in very rare cases, to injury of the bile ducts by toxic metabolites, resulting in a mixed-pattern hepatitis with possible progression to chronic cholestatic syndrome and cirrhosis. The authors report the second known case of this important toxicity. Clinical Case: An 83-year-old woman was admitted to the Internal Medicine ward for etiological clarification of a mixed-pattern hepatitis. Clinical history was unremarkable and structural, infectious, and autoimmune causes were excluded by blood tests and imaging exams, ultimately leading to the diagnosis of toxic hepatitis that was further confirmed by liver biopsy with morphologic findings of mixed-pattern liver injury. Carvedilol, started 6 months before, was deemed the causal agent since it was the only drug with a clinically, temporally, analytically, and histologically compatible pattern. The withdrawal of the drug resulted in slow reversal of the referred abnormalities. Conclusion: In very rare cases, carvedilol can cause important liver toxicity as a chronic cholestatic syndrome which can evolve to cirrhosis. It should be taken in consideration as causal agent in similar cases and stopped immediately upon suspicion, as the timely withdrawal results in reversion of the pathological findings.

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“…Drug-induced liver injury (DILI) is a worldwide health problem and is the fifth leading cause of death associated with liver disease (1). It is essentially an adverse reaction to conventional drugs, herbs, dietary supplements, etc.…”

Section: Contextmentioning

confidence: 99%

Silymarin in Preventing Anti-Tuberculosis and Antipsychotic Drug-Induced Liver Injury at Different Doses and Treatment Times: A Systematic Review

Sheng

Zhang

Yin

2019

Iran Red Crescent Med J

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Context: The therapeutic effect, the optimal treatment time, and the dose of silymarin for preventing anti-tuberculosis and antipsychotic drug-induced liver injury (anti-TB/antipsychotic DILI) remains controversial. We conducted the first systematic review and meta-analysis study to evaluate the clinical efficacy of silymarin in the treatment of anti-TB/antipsychotic DILI in several subgroups based on follow-up time and dose. Evidence Acquisition: We searched the keywords and free words of "silymarin (silibinin)" and "Anti-tuberculosis or antipsychotic drug-induced liver injury" in PubMed, Web of Science, Cochrane, Scopus, and clinicaltrials.gov for full text English articles and China Journal Full-text Database (CNKI) and China Medical Bio-Document Database (CBM) for full text Chinese articles. The searched papers were reserved for randomized controlled trials (RCTs). The Jadad quality scale was used to conduct quality assessments. Two observers (SY and HY) independently extracted the data. MD and OR values were calculated to evaluate the clinical efficacy of silymarin in anti-TB/antipsychotic DILI. The Q test and chi-square test were used for heterogeneity analysis. Results: Nine RCTs with 2,712 participants (1,351 in the silymarin group and 1,361 in the control group) satisfying the inclusion criteria were finally examined. Compared to the placebo group, silymarin at less than 300 mg/d dose significantly reduced the occurrence of anti-TB/antipsychotic DILI and serum liver enzymes AST and ALT whether for two weeks, four weeks, or eight weeks [pooled OR: 0.53, 95% CI: 0.35-0.78, P = 0.42, I 2 = 3%; pooled MD:-4.47, 95% CI:-7.00,-1.93, P = 0.70, I 2 = 0%, AST; pooled MD:-3.50, 95% CI:-6.08,-0.91, P = 0.58, I 2 = 0%, ALT]. However, no significant difference was found in serum liver enzyme TBIL compared to the control group [pooled MD:-0.02, 95% CI:-0.07,-0.04, P = 0.69, I 2 = 0%]. Silymarin at 315 mg/d significantly reduced the occurrence of anti-TB/antipsychotic DILI and serum liver enzymes AST, ALT, and TBIL for eight weeks [subtotal OR: 0.17, 95% CI: 0.08-0.39, I 2 = 76%] but no significant difference was found between the over 400 mg/d silymarin group and the control group [subtotal OR: 0.93, 95% CI: 0.20-4.39, I 2 = 76%]. No significant difference was found in the occurrence of adverse events compared to the control group [pooled OR: 0.94, 95% CI: 0.71-1.25, I 2 = 0%]. Compared to the control group, silymarin prolonged the occurrence of anti-TB/antipsychotic DILI [pooled SMD: 1.78, 95% CI: 1.65-1.91, I 2 = 42%]. Conclusions: Silymarin prolonged the occurrence of anti-TB/antipsychotic DILI and reduced the incidence of anti-TB/antipsychotic DILI without significant adverse effects. The optimal treatment time of silymarin to prevent anti-TB/antipsychotic DILI was related to its dose.

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A review of drug-induced liver injury databases

Cited by 36 publications

References 63 publications

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Carvedilol-Induced Liver Injury, a Rare Cause of Mixed Hepatitis: A Clinical Case

Silymarin in Preventing Anti-Tuberculosis and Antipsychotic Drug-Induced Liver Injury at Different Doses and Treatment Times: A Systematic Review

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