Monocyte-derived hepatocyte-like cells for causality assessment of idiosyncratic drug-induced liver injury

Benesic, Andreas; Leitl, Alexandra; Gerbes, Alexander L.

doi:10.1136/gutjnl-2015-309528

Cited by 48 publications

(44 citation statements)

References 47 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The final diagnosis of DILI or AIH was made retrospectively after reassessment of the initially suspected diagnosis based on the course of disease, response to steroid treatment and relapse after withdrawal of immunosuppression and liver histology (Figure ). In addition, the MetaHeps test, using monocyte‐derived hepatocyte‐like (MH) cells to detect drug toxicity with high sensitivity and specificity, was performed for every patient.…”

Section: Methodsmentioning

confidence: 99%

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

Weber¹,

Benesic²,

Rotter³

et al. 2019

Liver International

Self Cite

View full text Add to dashboard Cite

Background Drug‐induced liver injury (DILI) and idiopathic autoimmune hepatitis (AIH) are competing diagnoses in patients with acute liver injury (ALI) and drug intake. In absence of unequivocal markers, scores like RUCAM and AIH are used to distinguish both entities. However, in some cases the diagnosis remains ambiguous. Our aim was to identify a simple parameter to discriminate DILI and AIH shortly after starting corticosteroid treatment. Methods For the current analysis, 44 patients with ALI who took at least one drug and who received corticosteroids were included and comprised 22 DILI and 22 AIH cases. Scores of AIH and RUCAM were calculated at initial presentation, the final diagnosis was made from analysing the course of disease. Changes in the serum alanine aminotransferase (ALT) concentrations after starting corticosteroid treatment were determined and compared between the DILI and AIH groups. Results Fifty‐nine per cent of patients (n = 26) were correctly classified at presentation by AIH score and RUCAM respectively. However, in one‐third (n = 13) of the 44 patients, results were inconclusive and five other patients were misclassified. The decrease in ALT levels 1 week after the initiation of steroid therapy was significantly more pronounced in patients with the final diagnosis of DILI than in AIH patients (accuracy 77%). This difference was also observed in the 18 initially misclassified or inconclusive cases (accuracy 83%). Conclusion Short‐term response of ALT to corticosteroid therapy helps to differentiate DILI and AIH. This finding may be helpful in treatment decision for patients with inconclusive diagnostic scores.

show abstract

Section: Methodsmentioning

confidence: 99%

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

Weber¹,

Benesic²,

Rotter³

et al. 2019

Liver International

Self Cite

View full text Add to dashboard Cite

show abstract

“…We believe that phenotype assessment will guide in identification of DILI, where eventually confirmation may require laboratory confirmation as recently suggested …”

Section: Discussionmentioning

confidence: 81%

Injury pattern recognition to discriminate competing causes of liver injury

Talaat

Tillmann

2019

Liver International

View full text Add to dashboard Cite

Background Competing causes of liver injury may be difficult to discriminate. Characterization of the typical phenotype of each injury defined by latency, time to improvement and biochemical pattern, could be helpful to identify the most likely of competing causes. Methods Liver injury characteristics of both bortezomib‐associated drug‐induced liver injury (DILI) and hepatitis B virus (HBV) reactivation associated with bortezomib are derived from PubMed listed publications. Results Bortezomib‐associated DILI has very short latency of days and AP is found elevated, while liver injury due to HBV reactivation occurs after several months of bortezomib therapy. Therefore, a patient's liver injury pattern occurring 3 months into bortezomib therapy should be attributed to HBV reactivation. Discussion Identification of liver injury characteristics for competing causes of liver injury can be helpful to identify the most likely cause and improve clinical outcome.

show abstract

“…In this system, patient‐specific monocyte‐derived hepatocyte‐like cells (with inducible cytochrome P450 and active urea production) are more susceptible to cytotoxicity induced by the suspected drug compared with cells derived from healthy donors. Moreover, these cells have been demonstrated to outperform RUCAM scores …”

Section: Candidate Biomarkers and In Vitro Screensmentioning

confidence: 99%

Laboratory‐based biomarkers to improve causality assessment in drug‐induced liver injury

Antoine

2017

Clinical Liver Disease

View full text Add to dashboard Cite

show abstract

Monocyte-derived hepatocyte-like cells for causality assessment of idiosyncratic drug-induced liver injury

Abstract: NCT02353455.

Cited by 48 publications

References 47 publications

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

Injury pattern recognition to discriminate competing causes of liver injury

Laboratory‐based biomarkers to improve causality assessment in drug‐induced liver injury

Contact Info

Product

Resources

About