“Autoimmune(-Like)” Drug and Herb Induced Liver Injury: New Insights into Molecular Pathogenesis

Sebode, Marcial; Schulz, Lisa; Lohse, Ansgar W.

doi:10.3390/ijms18091954

Cited by 40 publications

(30 citation statements)

References 159 publications

(182 reference statements)

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“…Based on our patient characteristics, the patient was found to be in the "highly probable" category. A subset of DILI named "autoimmune-like DILI" has been identified and is difficult to differentiate from "autoimmune hepatitis (AIH)" due to the considerable overlap of clinical and laboratory features [7]. In the event of autoimmune-like DILI, ALT and AST return to normal soon after the discontinuation of the offending agent in most cases without the requirement for immunosuppressants.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune-like Drug-induced Liver Injury Caused by Atorvastatin and Demonstration of the Safety Profile of Pravastatin: A Case Report and Literature Review

Khan

Ahmed

Mohammed

et al. 2020

Cureus

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Statin-induced liver injury is a well-recognized but rare phenomenon with hepatocellular, cholestatic, and mixed phenotypes. Most studies do not recommend regular monitoring of liver function tests (LFTs) after starting statins unless clinically indicated. We report a case of autoimmune-like atorvastatin-induced liver injury (aminotransferases > 5 times the upper limit of normal) that was detected on routine follow-up after three months in an asymptomatic patient. In addition to elevation in transaminases, the patient had weakly positive ANAs. Antismooth muscle antibody (ASMA) was positive in titers of 1:680. Screening for viral hepatitis A-E was negative. Other diagnostic investigations showed complete blood examination, including eosinophils, renal function tests, electrolytes, total protein, albumin, prothrombin time, activated partial thromboplastin time (aPTT), international normalized ratio (INR), serum ferritin, and iron saturation to be in the normal range. Ultrasound and computed tomography (CT) abdomen showed normal liver, gall bladder, biliary tree, and pancreas. The patient was managed as a case of autoimmune-like drug-induced liver injury (DILI) caused by atorvastatin and the medication was discontinued. LFTs returned to completely normal 30 days after the discontinuation of atorvastatin. Furthermore, switching to pravastatin for dyslipidemia management four months after stopping atorvastatin did not lead to hepatotoxicity, illustrating the safety profile of pravastatin in patients who are unable to tolerate atorvastatin.

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Section: Discussionmentioning

confidence: 99%

Autoimmune-like Drug-induced Liver Injury Caused by Atorvastatin and Demonstration of the Safety Profile of Pravastatin: A Case Report and Literature Review

Khan

Ahmed

Mohammed

et al. 2020

Cureus

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“…In human patients, CH is a risk factor for some drug reactions. [283][284][285] D-penicillamine (D-Pen) is the Cu chelator of choice (Table 10).…”

Section: Drugs and Toxinsmentioning

confidence: 99%

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

Webster

Cullen

Penninck

et al. 2019

Veterinary Internal Medicne

183

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This consensus statement on chronic hepatitis (CH) in dogs is based on the expert opinion of 7 specialists with extensive experience in diagnosing, treating, and conducting clinical research in hepatology in dogs. It was generated from expert opinion and information gathered from searching of PubMed for manuscripts on CH, the Veterinary Information Network for abstracts and conference proceeding from annual meetings of the American College of Veterinary Medicine and the European College of Veterinary Medicine, and selected manuscripts from the human literature on CH. The panel recognizes that the diagnosis and treatment of CH in the dog is a complex process that requires integration of clinical presentation with clinical pathology, diagnostic imaging, and hepatic biopsy. Essential to this process is an index of suspicion for CH, knowledge of how to best collect tissue samples, access to a pathologist with experience in assessing hepatic histopathology, knowledge of reasonable medical interventions, and a strategy for monitoring treatment response and complications.

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“…The presence of autoantibodies associated with herbal medicines has been previously well described, which agrees with our findings. 6,25,40 We did not apply the Roussel Uclaf Causality Assessment Method (commonly known as RUCAM) to assess DILI causality, since this tool has not been validated in patients with concurrent acute liver injury. However, our biopsy findings inarguably confirmed a second insult, most probably CAM-related DILI due to the heterogeneity in biopsy findings, that skewed from the expected findings.…”

mentioning

confidence: 99%

Outcomes and Toxicology of Herbal Drugs in Alcoholic Hepatitis – A Single Center Experience from India

Philips¹,

Rajesh²,

George³

et al. 2019

Journal of Clinical and Translational Hepatology

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Background and Aims: We aimed to study clinical outcomes and liver biopsy features of alcoholic hepatitis (AH) patients on complementary and alternative medicines (CAMs) and to analyze the retrieved drugs for chemical and toxic components linked to drug-induced liver injury. Methods: We retrospectively assessed clinical, biochemical and liver biopsy features of AH patients on CAM with drug-induced liver injury (AH-CAM, n = 27) and compared them to a control group (classical AH, n = 29) on standard of care. Patients without liver biopsy evaluation and other causes for liver disease were excluded. Samples of the CAMs (n = 42) from patients were retrieved and assessed for chemical and toxins. Results: All were males, and significantly worse clinical presentation, biochemical severity, and liver disease scores were notable in patients with AH-CAM. Traditional Ayurvedic-polyherbal formulations were the most commonly used CAM. On liver histology, varying grades of severe-necrosis, severe hepatocellular, canalicular, cholangiolar cholestasis with predominant lymphocytic-portal-inflammation and varying grades of interface-hepatitis were noted in AH-CAM. Analysis of CAMs revealed presence of heavy metals up to 100,000 times above detectable range and adulterants, such as antibiotics, chemotherapy agents, nonsteroidal anti-inflammatory drugs, alcohols, antidepressants, anxiolytics, and recreational drugs. On follow up, a significantly higher number of patients with AH on CAM died at end of 1, 3-and-6-months compared to controls (37% vs. 83%, 29% vs. 62%, 18% vs. 52% respectively; p < 0.001). Conclusions: Patients with AH and CAM-related druginduced liver injury have extremely poor short-term survival in the absence of liver transplantation compared to those patients with AH on evidence-based management. Early transplant referral and educating on and curbing of CAM use in severe liver disease through strict monitoring of unregulated traditional health practices can help ease the burden of liver-related death.

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“Autoimmune(-Like)” Drug and Herb Induced Liver Injury: New Insights into Molecular Pathogenesis

Cited by 40 publications

References 159 publications

Autoimmune-like Drug-induced Liver Injury Caused by Atorvastatin and Demonstration of the Safety Profile of Pravastatin: A Case Report and Literature Review

Autoimmune-like Drug-induced Liver Injury Caused by Atorvastatin and Demonstration of the Safety Profile of Pravastatin: A Case Report and Literature Review

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

Outcomes and Toxicology of Herbal Drugs in Alcoholic Hepatitis – A Single Center Experience from India

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