Acute liver failure induced by idiosyncratic reaction to drugs: Challenges in diagnosis and therapy

Tujios, Shannan R.; Lee, William M.

doi:10.1111/liv.13535

Cited by 80 publications

(54 citation statements)

References 57 publications

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“…Drug-induced liver injury (DILI), caused both by pharmaceutical compounds and herbal and dietary supplements, represents a significant challenge for pharmaceutical companies, regulatory agencies and clinicians, and accounts for over 50% of acute liver failure cases in westernized countries. 1 The bulk of these incidents are caused by intentional or accidental overdose with acetaminophen, which leads to an intrinsic form of DILI. Following exposure to a toxic parent compound or metabolite, intrinsic DILI is characterized by a predictable, dose-dependent hepatotoxicity that occurs subsequent to a short latency period.…”

mentioning

confidence: 99%

Serum biomarkers of drug‐induced liver injury: Current status and future directions

Church

Watkins

2018

J of Digest Diseases

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Drug‐induced liver injury (DILI), which is caused by drugs and herbal or dietary supplements, remains a serious concern for drug developers, regulators, and clinicians; however, serum biomarkers utilized to detect and monitor DILI have not changed in decades and have limitations. Data‐driven mathematical modeling that incorporates the release and clearance kinetics of traditional biomarkers has improved their use in the prediction of liver safety liabilities for new drug candidates. Several newer biomarkers have shown promise in terms of liver specificity, predicting the outcome of DILI events, and providing insight into its underlying mechanisms. For these new biomarkers to be qualified for regulatory acceptance, it will require their assessment in large numbers of patients who are receiving a wide range of compounds and who develop a broad spectrum of liver injuries. The ongoing and evolving international biomarker consortia should play a major role in this effort, which is likely to transform the assessment of liver safety in clinical trials and in the clinic.

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confidence: 99%

Serum biomarkers of drug‐induced liver injury: Current status and future directions

Church

Watkins

2018

J of Digest Diseases

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“…25 As an impact of the aforementioned discrepancy in the definition of ALF, the actual incidence of the pathology is regarded to be underdiagnosed. 18,26,27 ALF is considered to be more common in women than in men as well as in white individuals than in the rest of the races. 8,14 The median age of patients upon presentation is 38 years.…”

Section: Definitionsmentioning

confidence: 99%

“…37 In the United States, acetaminopheninduced ALF represents about 46% of the overall ALF cases, being followed by idiosyncratic DILI with a percentage of 11%. 26 Of note, acetaminophen-associated ALF has been linked to a better outcome in terms of highest rate of spontaneous recovery as well as the lowest rate of death compared with other causes. 24 On the contrary, other etiologies being implicated in ALF such as DILI or AIH have a slower course and are associated with a 27% and 15% possibility of spontaneous recovery, respectively.…”

Section: Etiologymentioning

confidence: 99%

“…Medications Being Linked With Acute Liver Failure26,30,60 CategoriesSubstance "Ecstasy"), phenprocoumon, tolcapone, troglitazone substantial for the clinician to keep in mind that every alteration of mental status combined with prolongation of INR/ coagulation abnormalities and jaundice should be suspected of ALF. Further complaints and signs include fever, anorexia, fatigue, abdominal pain, bleeding, and hemodynamic instability.…”

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confidence: 99%

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Acute Liver Failure

Doulberis¹,

Kotronis

Gialamprinou

et al. 2019

Journal of Clinical Gastroenterology

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Acute liver failure is a rare hepatic emergent situation that affects primarily young people and has often a catastrophic or even fatal outcome. Definition of acute liver failure has not reached a universal consensus and the interval between the appearance of jaundice and hepatic encephalopathy for the establishment of the acute failure is a matter of debate. Among the wide variety of causes, acetaminophen intoxication in western societies and viral hepatitis in the developing countries rank at the top of the etiology list. Identification of the clinical appearance and initial management for the stabilization of the patient are of vital significance. Further advanced therapies, that require intensive care unit, should be offered. The hallmark of treatment for selected patients can be orthotopic liver transplantation. Apart from well-established treatments, novel therapies like hepatocyte or stem cell transplantation, additional new therapeutic strategies targeting acetaminophen intoxication and/or hepatic encephalopathy are mainly experimental, and some of them do not belong, yet, to clinical practice. For clinicians, it is substantial to have the alertness to timely identify the patient and transfer them to a specialized center, where more treatment opportunities are available. FIGURE 1. The 3 main well-established classifications for ALF. (i) Williams-Schalm and O'Grady system (ii) Bernuau system, and (iii) Mochida (Japanese) system. ALF indicates acute liver failure.

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“…While APAP remains the most common cause of drug-induced liver injury, idiosyncratic drug-induced liver injury (IDILI) ranks second in overall causes of acute liver failure [88]. A number of drugs from diverse classes of therapeutics have been associated with IDILI (Table 1).…”

Section: Idiosyncratic Drug-induced Liver Injurymentioning

confidence: 99%

Mechanisms of Inflammatory Liver Injury and Drug-Induced Hepatotoxicity

Woolbright

Jaeschke

2018

Curr Pharmacol Rep

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Purpose of Review This article provides a brief overview of mechanisms of inflammatory liver injury and how this applies to drug hepatotoxicity with a particular emphasis on the role of inflammation in acetaminophen-induced liver injury. Recent Findings Significant progress has been made in the last decade in our understanding of the initiation of sterile inflammation after necrotic cell death by the release of damage-associated molecular patterns and their recognition by toll-like receptors and others on macrophages. These events trigger the formation of cytokines and chemokines directly or with assistance of inflammasome activation thereby activating and recruiting leukocytes including neutrophils and monocyte-derived macrophages into the necrotic areas. Although this sterile inflammatory response is mainly geared towards the removal of necrotic cell debris and preparation of regeneration, there are conditions where these innate immune cells can aggravate the initial injury. The mechanisms and controversial findings of the innate immunity are being discussed in detail. In contrast, drug metabolism and formation of a reactive metabolite that binds to proteins in the absence of extensive cell death, can induce an adaptive immune response, which eventually also results in severe liver injury. However, the initiating event appears to be the formation of protein adducts, which act as haptens to activate an adaptive immune response. Overall, these mechanisms are less well understood. Summary The past decade has revolutionized our understanding of the mechanisms that control the interplay between cell death and innate or adaptive immune responses. This report provides an update on these mechanisms.

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Acute liver failure induced by idiosyncratic reaction to drugs: Challenges in diagnosis and therapy

Cited by 80 publications

References 57 publications

Serum biomarkers of drug‐induced liver injury: Current status and future directions

Serum biomarkers of drug‐induced liver injury: Current status and future directions

Acute Liver Failure

Mechanisms of Inflammatory Liver Injury and Drug-Induced Hepatotoxicity

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