Drug‐induced liver injury at a tertiary care centre in Germany: Model for end‐stage liver disease is the best predictor of outcome

Reike-Kunze, Martin; Zenouzi, Roman; Härtel, Johannes; Krech, Till; Weidemann, Sören; Sterneck, Martina; Weiler‐Normann, Christina; Lohse, Ansgar W.; Schramm, Christoph; Sebode, Marcial

doi:10.1111/liv.14985

Cited by 12 publications

(5 citation statements)

References 51 publications

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“…As the studies cover several aspects related to the safety implications of dipyrone therapy, a didactic division has been made to group the issues in the discussion: dipyrone in children [22][23][24][25][26][27], dipyrone during pregnancy [28], dipyrone and blood dyscrasias [29][30][31][32][33][34], dipyrone in specific diseases [35][36][37][38][39][40][41][42][43][44], in addition to anaphylactic reactions and general adverse effects of dipyrone [45][46][47][48][49][50][51]. About the quality of the studies, it is worth mentioning the scarcity of clinical trials, with the majority being of observational retrospective or cohort design (n = 27).…”

Section: Resultsmentioning

confidence: 99%

“…In a retrospective study conducted in a tertiary hospital in Germany, the development of DILI was associated with the use of methimazole in 23 of 154 patients evaluated (14.9%), with two patients requiring liver transplantation [38]. In another cohort of 157 patients, dipyrone was the second drug causing DILI, behind only phenprocoumon, an oral anticoagulant (n = 17 and 21, respectively) [39]. Thus, even if it is relatively low overall frequency, dipyrone-induced DILI is something that should be taken into consideration by healthcare systems.…”

Section: Dipyrone In Specific Diseasesmentioning

confidence: 99%

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One hundred years of dipyrone (metamizole): the recent evidence on its safety

Malheiro

Viana²,

Nascimento³

et al. 2023

PRW

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Dipyrone is a non-opioid analgesic drug used for fever and many types of pain. Due to the risk of induced agranulocytosis, it was banned in the early 1980s in several countries, but is still widely used in Brazil, Mexico, China and others. This study is a systematic review of literature focusing on the recent evidence about dipyrone safety. To this, a literature search was performed for epidemiological studies published between 2015 and 2022, in English, German, Portuguese, and Spanish languages. From the 30 articles that met the inclusion criteria, most of them consisted in observational studies (n = 27). In children, the frequency of adverse events with dipyrone is low, but can affect the renal and circulatory systems. During pregnancy, the drug doesn't seem to be related to teratogenic abnormalities. Agranulocytosis is still a matter of debate. However, the occurrence is rare, with an estimated risk of 1:1,602. In adults, dipyrone is related to several adverse effects on renal, hepatic, respiratory and epidermal systems. Thus, dipyrone seems to have a low incidence of adverse effects, but some can be considered of high severity. Especially in children, elderly and patients who need treatment for long periods, other analgesic options should be evaluated.

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Section: Resultsmentioning

confidence: 99%

Section: Dipyrone In Specific Diseasesmentioning

confidence: 99%

One hundred years of dipyrone (metamizole): the recent evidence on its safety

Malheiro

Viana²,

Nascimento³

et al. 2023

PRW

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“…Anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), and rarely other autoantibodies that might be detected in the serum of patients treated with conventional drugs who experienced liver injury assessed for causality by RUCAM [ 117 , 118 ]. For instance, among a cohort of 139 RUCAM-based iDILI patients, serum ANA results were positive in 95 patients (68.3%) and negative in 44 patients (32.7%), but data remain open for discussion since cases with a possible causality grading were included, herbal and dietary supplements were among the DILI patients, and the original RUCAM was used lacking exclusion of HEV rather than the updated RUCAM [ 117 ]. In 71% of these cases, ANA and/or SMA titers were positive.…”

Section: Progress Of Molecular and Mechanistic Immune Mechanisms In I...mentioning

confidence: 99%

Advances in Idiosyncratic Drug-Induced Liver Injury Issues: New Clinical and Mechanistic Analysis Due to Roussel Uclaf Causality Assessment Method Use

Teschke

Danan²

2023

IJMS

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Clinical and mechanistic considerations in idiosyncratic drug-induced liver injury (iDILI) remain challenging topics when they are derived from mere case narratives or iDILI cases without valid diagnosis. To overcome these issues, attempts should be made on pathogenetic aspects based on published clinical iDILI cases firmly diagnosed by the original RUCAM (Roussel Uclaf Causality Assessment Method) or the RUCAM version updated in 2016. Analysis of RUCAM-based iDILI cases allowed for evaluating immune and genetic data obtained from the serum and the liver of affected patients. For instance, strong evidence for immune reactions in the liver of patients with RUCAM-based iDILI was provided by the detection of serum anti-CYP 2E1 due to drugs like volatile anesthetics sevoflurane and desflurane, partially associated with the formation of trifluoroacetyl (TFA) halide as toxic intermediates that form protein adducts and may generate reactive oxygen species (ROS). This is accompanied by production of anti-TFA antibodies detected in the serum of these patients. Other RUCAM-based studies on serum ANA (anti-nuclear antibodies) and SMA (anti-smooth muscle antibodies) associated with AIDILI (autoimmune DILI) syn DIAIH (drug-induced autoimmune hepatitis) provide additional evidence of immunological reactions with monocytes as one of several promoting immune cells. In addition, in the blood plasma of patients, mediators like the cytokines IL-22, IL-22 binding protein (IL-22BP), IL-6, IL-10, IL 12p70, IL-17A, IL-23, IP-10, or chemokines such as CD206 and sCD163 were found in DILI due to anti-tuberculosis drugs as ascertained by the prospective updated RUCAM, which scored a high causality. RUCAM-based analysis also provided compelling evidence of genetic factors such as HLA (human leucocyte antigen) alleles contributing to initiate iDILI by a few drugs. In conclusion, analysis of published RUCAM-based iDILI cases provided firm evidence of immune and genetic processes involved in iDILI caused by specific drugs.

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“…Anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), and rarely other autoantibodies that might be detected in the serum of patients treated with conventional drugs, who experienced liver injury addressed for causality using RUCAM [60,61]. For instance, among a cohort of 139 RUCAM based iDILI patients, serum ANA results were positive in 95 patients (68.3%) and negative in 44 patients (32.7%), but data remain open for discussion since cases with a possible causality grading were included, herbal and dietary supplements were among the DILI patients, and the original RUCAM was used lacking exclusion of HEV rather than the updated RUCAM [60]. In 71% of these cases ANA and/or SMA titers were positive.…”

Section: Serum Autoantibodiesmentioning

confidence: 99%

Idiosyncratic DILI: Immunology in Cases with Evidence Based on RUCAM

Teschke

2023

J. Mod. Med. Chem.

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Idiosyncratic drug induced liver injury (iDILI) is a multifaceted and fairly well described liver disease, but there is yet some uncertainty on the role of immune systems triggering the liver injury and speculation on the cascade of immune events. Many conclusions were so far based on narratives or cases of iDILI, which did not receive the benefit of a robust causality assessment like by the Roussel Uclaf Causality Assessment Method (RUCAM). This analysis aims to clarify the cascade of immune events that lead to the liver injury by conventional drugs. For this approach, the search focused on iDILI cases with verified diagnosis by RUCAM. Most promising were parameters obtained from the blood as mirror of what happened in the liver during the injurious processes.The focus of this present analysis is on patients with RUCAM based iDILI and concomitant immune-related parameters in the blood. As an example, compelling evidence for a role of immune systems in iDILI was found for circulating mediators in the blood secreted by liver immune cells in patients under a therapy for tuberculosis, detected were also serum anti-cytochrome P450 (CYP) antibodies in patients after anesthesia with sevoflurane or desflurane and thereby reflecting their metabolism by the CYP 2E1 isoform, the occurrence of serum of autoantibodies in patients with drug induced autoimmune hepatitis (DIAIH) due to many drugs, and the role of blood and liver monocytes, which provide direct evidence for the activation of the hepatic innate immune system to the adapted immune system. In essence, patients with RUCAM based iDILI show various immunology features in the blood compatible with the role of the hepatic immune systems in patients with suspected iDILI caused by some but not all drugs.

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Drug‐induced liver injury at a tertiary care centre in Germany: Model for end‐stage liver disease is the best predictor of outcome

Cited by 12 publications

References 51 publications

One hundred years of dipyrone (metamizole): the recent evidence on its safety

One hundred years of dipyrone (metamizole): the recent evidence on its safety

Advances in Idiosyncratic Drug-Induced Liver Injury Issues: New Clinical and Mechanistic Analysis Due to Roussel Uclaf Causality Assessment Method Use

Idiosyncratic DILI: Immunology in Cases with Evidence Based on RUCAM

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