scholarly journals Drug-induced hepatocellular injury due to herbal supplement ashwagandha

2021 ◽  
Vol 51 (4) ◽  
pp. 363-365
Author(s):  
Peter J Ireland ◽  
Timothy Hardy ◽  
Alastair D Burt ◽  
Mhairi C Donnelly
Keyword(s):  
Herbal Supplement ◽  
Hepatocellular Injury ◽  
Drug Induced

scholarly journals Identification of Serum Biomarkers to Distinguish Hazardous and Benign Aminotransferase Elevations

2019 ◽  
Author(s):  
Joel H Vazquez ◽  
Melissa M Clemens ◽  
Felicia D Allard ◽  
Eric U Yee ◽  
Stefanie Kennon-McGill ◽  
...  
Keyword(s):  
Liver Injury ◽  
Drug Safety ◽  
Serum Biomarkers ◽  
High Dose ◽  
Hepatocellular Injury ◽  
Drug Induced ◽  
Safety Testing ◽  
Apap Overdose ◽  
High Dose Dexamethasone ◽  
Duct Ligation

Abstract The standard circulating biomarker of liver injury in both clinical settings and drug safety testing is alanine aminotransferase (ALT). However, ALT elevations sometimes lack specificity for tissue damage. To identify novel serum biomarkers with greater specificity for injury, we combined unique animal models with untargeted proteomics, followed by confirmation with immunoblotting. Using proteomics, we identified 109 proteins in serum from mice with acetaminophen (APAP)-induced liver injury that were not detectable in serum from mice with benign ALT elevations due to high-dose dexamethasone (Dex). We selected four (alcohol dehydrogenase 1A1 [Aldh1a1], aldehyde dehydrogenase 1 [Adh1], argininosuccinate synthetase 1 [Ass1], and adenosyhomocysteinase [Ahcy]) with high levels for further evaluation. Importantly, all four were specific for injury when using immunoblots to compare serum from Dex-treated mice and mice with similar lower ALT elevations due to milder models of APAP or bromobenzene-induced liver injury. Immunoblotting for ALDH1A1, ADH1, and ASS1 in serum from APAP overdose patients without liver injury and APAP overdose patients with mild liver injury revealed that these candidate biomarkers can be detected in humans with moderate liver injury as well. Interestingly, further experiments with serum from rats with bile duct ligation (BDL)-induced liver disease indicated that Aldh1a1 and Adh1 are not detectable in serum in cholestasis and may therefore be specific for hepatocellular injury and possibly even drug-induced liver injury (DILI), in particular. Overall, our results strongly indicate that ALDH1A1, ADH1, and ASS1 are promising specific biomarkers for liver injury. Adoption of these biomarkers could improve pre-approval drug safety assessment.

scholarly journals Kratom-Induced Cholestatic Liver Injury and Its Conservative Management

2019 ◽  
Vol 7 ◽  
pp. 232470961983613 ◽  
Author(s):  
Christopher T. Fernandes ◽  
Umair Iqbal ◽  
Sean P. Tighe ◽  
Aijaz Ahmed
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Chronic Liver Disease ◽  
The United States ◽  
Chronic Liver ◽  
Herbal Supplement ◽  
Herbal Supplements ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Analgesic Effects

Drug-induced liver injury (DILI) is a common cause of hepatotoxicity associated with prescription-based and over-the-counter exposure to medications and herbal supplements. Use of unapproved and inadequately tested herbal supplements can cause DILI. Therefore, thorough history-taking on exposure to herbal supplements must be an integral part of clinical evaluation of DILI. Kratom is an herbal supplement or remedy that has been known for its analgesic effects and has also been used for self-treatment of opiate withdrawals. A 52-year-old man was seen for evaluation of yellow discoloration of the eyes and skin. He reported taking kratom for right shoulder strain for at least a couple of months. On workup, his total bilirubin was noted to be 23.2 mg/dL, which peaked at 28.9 mg/dL. He was noted to have mild elevation of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Extensive laboratory tests were ordered and known causes of chronic liver disease ruled out. Magnetic resonance imaging of the abdomen was unremarkable without stigmata of portal hypertension or signs of chronic liver disease. He demonstrated no evidence of coagulopathy or hepatic encephalopathy during his illness. He underwent liver biopsy, which demonstrated histologic evidence of acute cholestatic hepatitis highly suspicious of DILI. He was advised to avoid kratom or other herbal supplements in future and prescribed ursodeoxycholic acid with significant improvement in his liver chemistries. Kratom is associated with significant liver enzymes derangements leading to DILI. Kratom is not approved for use in the United States and should be avoided.

scholarly journals TAMH: A Useful In Vitro Model for Assessing Hepatotoxic Mechanisms

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Madison Davis ◽  
Brendan D. Stamper
Keyword(s):  
Liver Injury ◽  
Transforming Growth Factor ◽  
Chemical Exposure ◽  
Health Concern ◽  
Hepatocellular Injury ◽  
Drug Induced ◽  
Endogenous Factors ◽  
Drug Induced Liver Injury

In vitro models for hepatotoxicity can be useful tools to predict in vivo responses. In this review, we discuss the use of the transforming growth factor-αtransgenic mouse hepatocyte (TAMH) cell line, which is an attractive model to study drug-induced liver injury due to its ability to retain a stable phenotype and express drug-metabolizing enzymes. Hepatotoxicity involves damage to the liver and is often associated with chemical exposure. Since the liver is a major site for drug metabolism, drug-induced liver injury is a serious health concern for certain agents. At the molecular level, various mechanisms may protect or harm the liver during drug-induced hepatocellular injury including signaling pathways and endogenous factors (e.g., Bcl-2, GSH, Nrf2, or MAPK). The interplay between these and other pathways in the hepatocyte can change upon drug or drug metabolite exposure leading to intracellular stress and eventually cell death and liver injury. This review focuses on mechanistic studies investigating drug-induced toxicity in the TAMH line and how alterations to hepatotoxic mechanisms in this model relate to the in vivo situation. The agents discussed herein include acetaminophen (APAP), tetrafluoroethylcysteine (TFEC), flutamide, PD0325901, lapatinib, and flupirtine.

scholarly journals Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Grace Guzman ◽  
Eric R. Kallwitz ◽  
Christina Wojewoda ◽  
Rohini Chennuri ◽  
Jamie Berkes ◽  
...  
Keyword(s):  
Liver Injury ◽  
Autoimmune Hepatitis ◽  
Plasma Cells ◽  
Hepatic Necrosis ◽  
Serum Markers ◽  
Black Cohosh ◽  
Herbal Supplement ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Immune Mediated

There are a growing number of cases detailing acute hepatic necrosis in patients taking black cohosh (Cimicifuga racemosa), an over-the-counter herbal supplement for management of menopausal symptoms. Our aim is to illustrate two cases of liver injury following the use of black cohosh characterized by histopathological features mimicking autoimmune hepatitis. Both patients reported black cohosh use for at least six months and had no evidence of another cause of liver disease. Their liver biopsies showed a component of centrilobular necrosis consistent with severe drug-induced liver injury. In addition, the biopsies showed characteristics of autoimmune-like liver injury with an interface hepatitis dominated by plasma cells. Although serum markers for autoimmune hepatitis were not particularly elevated, both patients responded to corticosteroids, supporting an immune-mediated component to the liver injury. Liver injury following the use of black cohosh should be included in the list of differential diagnoses for chronic hepatitis with features mimicking autoimmune hepatitis.

scholarly journals The Characteristics, Prevalence, and Risk Factors of Drug-Induced Liver Injury Among Brucellosis Inpatients in Xinjiang, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Maermaer Tuohutaerbieke ◽  
Xinjie Li ◽  
Yue Yin ◽  
Wei Chen ◽  
Dongmei Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Injury ◽  
Serum Albumin ◽  
Rating Scale ◽  
Normal Liver ◽  
Hepatocellular Injury ◽  
Drug Induced ◽  
International Consensus ◽  
Drug Induced Liver Injury ◽  
Drug Of Choice

Background: We investigated the prevalence, demographic and clinical features, and risk factors associated with drug-induced liver injury (DILI) during the treatment of brucellosis inpatients in a retrospective study.Methods: We collected the clinical data of 782 brucellosis inpatients admitted at the Shawan County People’s Hospital, Xinjiang, from 2015–2019. All cases were re-evaluated using the international consensus of DILI criteria and RUCAM rating scale. 71 patients were confirmed as DILI cases and compared with 523 other patients with normal liver function.Results: It was indicated that DILI occurred with a prevalence of about 9.08% among brucellosis inpatients receiving drug therapy. Hepatocellular injury was the most common type of DILI (61.97%, 95% confidence interval [CI] 50.34–72.37), followed by mixed (23.94%, 95% CI 15.52–35.04) and cholestatic types (14.08%, 95% CI 7.83–24.02). In addition, 13.64% of the hepatocellular DILI cases fulfilled Hy’s law criteria and only two cases (2.82%) progressed to severe DILI. Most patients adopted the combination of rifampicin, antipyretic analgesics, anti-infective agents, and traditional Chinese medicine for the treatment of brucellosis, with all the 71 patients taking rifampicin as the drug of choice. Multivariable logistic regression analyses indicated that obesity, regular alcohol intake, and decreased serum albumin were the independent risk factors of DILI in patients with brucellosis after adjusting for gender, age, and ethnicity.Conclusion: DILI occurred in a minority of inpatients diagnosed with brucellosis receiving rifampicin-based therapeutic regimen. In addition, obesity, alcohol abuse, and decreased serum albumin were valuable predictors of the risk of DILI in patients with brucellosis.

Prednisolone: role in amoxicillin–clavulanate-induced cholestatic liver injury

2021 ◽  
Vol 14 (4) ◽  
pp. e239488
Author(s):  
Melvin Qiyu Lee ◽  
Royale Chigozie ◽  
Irfan Khan ◽  
Gerard O'Mara
Keyword(s):  
Liver Injury ◽  
Liver Function Tests ◽  
Hepatocellular Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
The Us ◽  
Common Causes ◽  
Amoxicillin Clavulanate ◽  
The Common ◽  
Cholestatic Liver Injury

A 68-year-old patient presented with symptoms of a urinary tract infection. A deterioration in the patient’s liver function tests (LFTs) was noted 1 week following completion of a course of amoxicillin–clavunalate. This progressively worsened, reaching its peak by day 30. Our investigations excluded other possible causes for deranged LFTs and there was no improvement of same despite reduced dosing of potentially hepatotoxic medications.A trial of 30 mg/day prednisolone was commenced, resulting in an immediate and progressive improvement in LFTs to baseline over a period of 22 days and an improvement in constitutional symptoms such as tiredness and poor appetite. Drug-induced liver injury (DILI) is one of the common causes of acute hepatitis and a leading cause of acute liver failure in the US and Europe. Patterns of DILI can be generally divided into: (1) hepatocellular injury, (2) cholestatic injury and (3) mixed injury.

scholarly journals Acute Hepatitis due to Garcinia Cambogia Extract, an Herbal Weight Loss Supplement

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Akshay Sharma ◽  
Elisa Akagi ◽  
Aji Njie ◽  
Sachin Goyal ◽  
Camelia Arsene ◽  
...  
Keyword(s):  
Weight Loss ◽  
Acute Hepatitis ◽  
Previous History ◽  
Herbal Supplement ◽  
Drug Induced ◽  
Garcinia Cambogia ◽  
Drug Induced Liver Injury ◽  
Supplement Use ◽  
Life Threatening ◽  
History Of

The Drug Induced Liver Injury Network reports dietary supplements as one of the most important causes of drug induced hepatotoxicity, yet millions of people use these supplements without being aware of their potential life-threatening side effects. Garcinia cambogia (GC) extract is an herbal weight loss supplement, reported to cause fulminant hepatic failure. We present a case of a 57-year-old female with no previous history of liver disease, who presented with acute hepatitis due to GC extract taken for weight loss, which resolved after stopping it and got reaggravated on retaking it. Obtaining a history of herbal supplement use is critical in the evaluation of acute hepatitis.

Case of cholestatic drug-induced liver injury (DILI) associated with black cohosh

2021 ◽  
Vol 14 (5) ◽  
pp. e240408
Author(s):  
Himmat Singh Brar ◽  
Rachana Marathi
Keyword(s):  
Liver Injury ◽  
Liver Enzymes ◽  
American Woman ◽  
Black Cohosh ◽  
Herbal Supplement ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Postmenopausal Symptoms ◽  
Autoimmune Pathology ◽  
History Of

Drug-induced liver injury is an uncommon yet fatal cause of liver injury. Black cohosh is a herbal supplement that is derived from Actaea racemosa. It has been used for vasomotor symptoms in postmenopausal women, but it can cause liver injury. A 50-year-old Afro-American woman presented with a 2-month history of malaise, itching and severe jaundice. The labs showed elevation of bilirubin and alkaline phosphatase. The patient had a history of black cohosh use for postmenopausal symptoms before she developed her current symptoms. The extensive workup for infective and autoimmune pathology was negative. Black cohosh was discontinued. The patient improved clinically, and her liver enzymes normalised 6 months after the discontinuation of black cohosh. This report emphasises the need to recognise black cohosh as a potential hepatotoxic agent and to monitor the liver enzymes for a patient on black cohosh.

scholarly journals Zanubrutinib-induced liver injury: a case report and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Edmond Atallah ◽  
Pramudi Wijayasiri ◽  
Nicole Cianci ◽  
Khorrum Abdullah ◽  
Abhik Mukherjee ◽  
...  
Keyword(s):  
Liver Injury ◽  
Kinase Inhibitor ◽  
Liver Toxicity ◽  
Causality Assessment ◽  
Hepatocellular Injury ◽  
Severe Liver ◽  
Drug Induced ◽  
Blood Profile ◽  
First Case ◽  
Clinical Awareness

Abstract Background Zanubrutinib is a Bruton’s tyrosine kinase inhibitor that has been recently licensed in refractory mantle cell lymphoma and under assessment in phase 3 clinical trials for other B cell malignancies. To date, there are no reported cases of hepatotoxicity secondary to zanubrutinib. We report the first case of severe liver injury due to zanubrutinib. Case presentation A 56-year-old Caucasian male with a history of relapsed lymphoplasmacytic lymphoma was admitted to the hospital with new-onset jaundice, choluria, and pruritus for 10 days. He had been on zanubrutinib as part of a clinical trial for 30 months. His blood profile showed a severe hepatocellular injury with jaundice (alanine transaminase 2474 IU/L and total bilirubin 141 umol/L with mild coagulopathy). He had an extensive work-up including virology, autoimmune, and metabolic profiles in addition to abdominal ultrasound with no alternative explanation found for his liver injury. Zanubrutinib-induced liver injury was suspected, and causality assessment by the updated Roussel Uclaf Causality Assessment Method score showed a probable causal relationship with zanubrutinib. His liver histology was also consistent with drug-induced liver injury. His liver biochemistry improved following cessation of zanubrutinib and normalised after 8 weeks. Conclusion We report the first case of severe liver injury secondary to zanubrutinib after 30 months of treatment. This case raises clinical awareness regarding zanubrutinib-induced liver toxicity and the importance of drug withdrawal in the event of liver injury.

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