Late-Onset Acute Liver Injury From Azathioprine

Schwartz, Benjamin; Al-Sabti, Ram; Reau, Nancy

doi:10.14309/crj.0000000000000847

Cited by 8 publications

(7 citation statements)

References 12 publications

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“…With this report, we suggest clinicians to retain a high level of suspicion towards azathioprine as the causative agent of liver injury, regardless of when the therapy was started, because potential life-threatening hepatotoxicity should be expected even more than 1 year since treatment onset 13 14 24…”

Section: Discussionmentioning

confidence: 97%

“…This preferential metabolic way, which is termed ‘metabolic shunting’, occurs in about 15% of the azathioprine users, in a time that ranges from 5 months to 10 years from treatment start, with a median of 21 months 24…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, Schwartz et al 24 presented a case of azathioprine-induced liver injury that occurred after 32 months of drug administration at a stable dose. In their paper, they suggest the ‘metabolic shunting’ as the more likely mechanism of liver injury in patients that develop hepatotoxicity after long-term treatment with stable dose of azathioprine.…”

Section: Discussionmentioning

confidence: 99%

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Severe azathioprine-induced liver injury 22 months after initiation of treatment

et al. 2022

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Drug-induced liver injury (DILI) is the leading cause of acute liver failure in high-income countries. Acute cholestasis is one of the most common forms of hepatotoxicity induced by azathioprine. It usually begins during the first year of treatment, with most cases reported during the first month. We describe an uncommon case of DILI that occurred after 22 months of drug administration. A woman in her 50s was hospitalised because of jaundice and asthenia. She had been treated with azathioprine for myasthenia gravis during the last 2 years. Acute cholestatic injury was diagnosed. After ruling out most common causes of cholestasis, azathioprine was withdrawn and subsequent histological findings in liver biopsy were consistent with drug-induced cholestatic liver damage. After discontinuation of azathioprine, biochemical parameters progressively normalised and remarkable clinical improvement was achieved. With this report, we suggest that azathioprine should be considered among the causes of liver injury, despite long treatment duration.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Severe azathioprine-induced liver injury 22 months after initiation of treatment

et al. 2022

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“…In other cases, azathioprine can also cause the onset of acute liver damage of a cholestatic type, which manifests itself with jaundice, fatigue, increased transaminases and alkaline phosphatase. This pathological condition usually resolves with discontinuation of azathioprine [32].…”

Section: Compounds Of 5-aminosalicylic Acidmentioning

confidence: 99%

Inflammatory Bowel Disease Therapies and Acute Liver Injury

Catanzaro,

Marotta,

Yazdani

et al. 2024

Preprint

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Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

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“…This inevitably could result in adverse reactions in particular with long-time use [4]. Due to their widespread distribution within the body, these drugs may even cause some side effects on bone marrow [5,6], blood [7], skin [8], and other tissues [9]. Consequently, to meet the clinical requirements, some therapies such as repair of the intestinal mucosal barrier, balancing the gut microbiota, or specific and targeted distribution are usually considered as the strategy for new courses of treatment.…”

Section: Introductionmentioning

confidence: 99%

Study on the Anti-Ulcerative Colitis Effect of Pseudo-Ginsenoside RT4 Based on Gut Microbiota, Pharmacokinetics, and Tissue Distribution

Yu,

Wang,

et al. 2024

IJMS

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The purpose of this study was to explore the therapeutic effect of the oral administration of pseudo-ginsenoside RT4 (RT4) on ulcerative colitis (UC), and to determine the rate of absorption and distribution of RT4 in mice with UC. Balb/c mice were induced using dextran sulfate sodium salts (DSS) to establish the UC model, and 10, 20, or 40 mg/kg of RT4 was subsequently administered via gavage. The clinical symptoms, inflammatory response, intestinal barrier, content of total short-chain fatty acids (SCFAs), and gut microbiota were investigated. Caco-2 cells were induced to establish the epithelial barrier damage model using LPS, and an intervention was performed using 4, 8, and 16 µg/mL of RT4. The inflammatory factors, transient electrical resistance (TEER), and tight-junction protein expression were determined. Finally, pharmacokinetic and tissue distribution studies following the intragastric administration of RT4 in UC mice were performed. According to the results in mice, RT4 decreased the disease activity index (DAI) score, restored the colon length, reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and boosted the levels of immunosuppressive cytokine IL-10, increased the content of SCFAs, improved the colonic histopathology, maintained the ultrastructure of colonic mucosal epithelial cells, and corrected disturbances in the intestinal microbiota. Based on the results in caco-2 cells, RT4 reduced the levels of TNF-α, IL-6, and IL-1β; protected integrity of monolayers; and increased tight-junction protein expression. Additionally, the main pharmacokinetic parameters (Cmax, Tmax, t1/2, Vd, CL, AUC) were obtained, the absolute bioavailability was calculated as 18.90% ± 2.70%, and the main distribution tissues were the small intestine and colon. In conclusion, RT4, with the features of slow elimination and directional distribution, could alleviate UC by inhibiting inflammatory factors, repairing the intestinal mucosal barrier, boosting the dominant intestinal microflora, and modulating the expression of SCFAs.

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Late-Onset Acute Liver Injury From Azathioprine

Cited by 8 publications

References 12 publications

Severe azathioprine-induced liver injury 22 months after initiation of treatment

Severe azathioprine-induced liver injury 22 months after initiation of treatment

Inflammatory Bowel Disease Therapies and Acute Liver Injury

Study on the Anti-Ulcerative Colitis Effect of Pseudo-Ginsenoside RT4 Based on Gut Microbiota, Pharmacokinetics, and Tissue Distribution

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