Drug‐Induced Liver Injury

DiPaola, Frank; Fontana, Robert J.

doi:10.1002/9781119237662.ch24

Cited by 4 publications

(5 citation statements)

References 188 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the prevalence of DILI is lower as compared to other causes of liver injury, such as alcohol, hepatisis or steatosis, it can lead to life-threatening complications. DILI can be of two types: (i) intrinsic (due to injury caused by a known on-target drug) or (ii) idosyncratic (due to injury caused by an unknown factor and cannot be explained by known pharmacological elements e.g., herbal preparations of unknown compositions) ( DiPaola and Fontana, 2018 ). Among intrinsic causes, acetaminophen induced DILI is the most common.…”

Section: Drivers Of Liver Fibrosismentioning

confidence: 99%

Cellular Mechanisms of Liver Fibrosis

et al. 2021

View full text Add to dashboard Cite

The liver is a central organ in the human body, coordinating several key metabolic roles. The structure of the liver which consists of the distinctive arrangement of hepatocytes, hepatic sinusoids, the hepatic artery, portal vein and the central vein, is critical for its function. Due to its unique position in the human body, the liver interacts with components of circulation targeted for the rest of the body and in the process, it is exposed to a vast array of external agents such as dietary metabolites and compounds absorbed through the intestine, including alcohol and drugs, as well as pathogens. Some of these agents may result in injury to the cellular components of liver leading to the activation of the natural wound healing response of the body or fibrogenesis. Long-term injury to liver cells and consistent activation of the fibrogenic response can lead to liver fibrosis such as that seen in chronic alcoholics or clinically obese individuals. Unidentified fibrosis can evolve into more severe consequences over a period of time such as cirrhosis and hepatocellular carcinoma. It is well recognized now that in addition to external agents, genetic predisposition also plays a role in the development of liver fibrosis. An improved understanding of the cellular pathways of fibrosis can illuminate our understanding of this process, and uncover potential therapeutic targets. Here we summarized recent aspects in the understanding of relevant pathways, cellular and molecular drivers of hepatic fibrosis and discuss how this knowledge impact the therapy of respective disease.

show abstract

Section: Drivers Of Liver Fibrosismentioning

confidence: 99%

Cellular Mechanisms of Liver Fibrosis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Older age is also a risk factor for DILI since aging decreases cytochrome mediated hepatic metabolism and older patients more often present with a cholestatic pattern of liver injury compared with younger individuals. 12,13,30 Patient gender may also influence the risk of DILI; for example, the immune-mediated model of DILI found more severe hepatitis in females. 12,29,30 Our patient was an 81-year-old woman with advanced chronic kidney disease (CKD G4), which could have contributed to the hepatotoxic side effects by reducing renal clearance of the various medication she was taking, resulting in higher plasma levels.…”

Section: Discussionmentioning

confidence: 99%

“…12,13,30 Patient gender may also influence the risk of DILI; for example, the immune-mediated model of DILI found more severe hepatitis in females. 12,29,30 Our patient was an 81-year-old woman with advanced chronic kidney disease (CKD G4), which could have contributed to the hepatotoxic side effects by reducing renal clearance of the various medication she was taking, resulting in higher plasma levels. As such, our patient had several risk factors that enhanced susceptibility to DILI before taking her first dose of anastrozole.…”

Section: Discussionmentioning

confidence: 99%

“…7–11 Three major types of DILI have been described: hepatocellular, cholestatic, and mixed liver injury due to a major underlying mechanism. 12,13 The fourth type of hepatotoxicity, that is, indirect liver injury, is not a completely accepted category of DILI. 14 In the United States, pharmaceuticals were linked to about 20% of the jaundice cases seen in the elderly in the year 2000.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes

Potměšil

Szotkowská

2020

Therapeutic Advances in Chronic Disease

View full text Add to dashboard Cite

Anastrozole is a selective non-steroidal aromatase inhibitor that blocks the conversion of androgens to estrogens in peripheral tissues. It is used as adjuvant therapy for early-stage hormone-sensitive breast cancer in postmenopausal women. Significant side effects of anastrozole include osteoporosis and increased levels of cholesterol. To date, seven case reports on anastrozole hepatotoxicity have been published. We report the case of an 81-year-old woman with a history of breast cancer, arterial hypertension, type 2 diabetes mellitus, hyperlipidemia, and chronic renal insufficiency. Four days after switching hormone therapy from tamoxifen to anastrozole, icterus developed along with a significant increase in liver enzymes (measured in the blood). The patient was admitted to hospital, where a differential diagnosis of jaundice was made and anastrozole was withdrawn. Subsequently, hepatic functions quickly normalized. The observed liver injury was attributed to anastrozole since other possible causes of jaundice were excluded. However, concomitant pharmacotherapy could have contributed to the development of jaundice and hepatotoxicity, after switching from tamoxifen to anastrozole since several the patient’s medications were capable of inhibiting hepatobiliary transport of bilirubin, bile acids, and metabolized drugs through inhibition of ATP-binding cassette proteins. Telmisartan, tamoxifen, and metformin all block bile salt efflux pumps. The efflux function of multidrug resistance protein 2 is known to be reduced by telmisartan and tamoxifen and breast cancer resistance protein is known to be inhibited by telmisartan and amlodipine. Moreover, the activity of P-glycoprotein transporters are known to be decreased by telmisartan, amlodipine, gliquidone, as well as the previously administered tamoxifen. Finally, the role of genetic polymorphisms of cytochrome P450 enzymes and/or drug transporters cannot be ruled out since the patient was not tested for polymorphisms.

show abstract

Section: Main Causes Of Dili and Hilimentioning

confidence: 99%