High-dose methotrexate-induced reversible grade 4 hyperbilirubinaemia and transaminitis in an adolescent with Burkitt Leukaemia

2021 ◽  
Vol 14 (1) ◽  
pp. e237512
Author(s):  
Sanjeev Khera ◽  
Randhir Ranjan ◽  
Sateesh Ramachandran ◽  
Ajay Beriwal
Keyword(s):  
Liver Injury ◽  
Clinical Significance ◽  
Short Latency ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Drug Induced ◽  
Common Cause ◽  
Drug Induced Liver Injury ◽  
Dose Methotrexate

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.

Genetic risk factors for drug-induced liver injury in rheumatoid arthritis patients using low-dose methotrexate

2013 ◽  
Vol 14 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Cristina Lucía Dávila-Fajardo ◽  
Jesse J Swen ◽  
José Cabeza Barrera ◽  
Henk-Jan Guchelaar
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Liver Injury ◽  
Genetic Risk ◽  
Low Dose ◽  
Genetic Risk Factors ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Dose Methotrexate

scholarly journals Drug-induced Liver Injury Due to a Horse Chestnut Dietary Supplement

2021 ◽  
Author(s):  
Diogo Costa Santos ◽  
Graça Lérias ◽  
Isabel Madruga
Keyword(s):  
Liver Injury ◽  
Dietary Supplements ◽  
Venous Insufficiency ◽  
Acute Liver Injury ◽  
Western World ◽  
Horse Chestnut ◽  
Drug Induced ◽  
Common Cause ◽  
Drug Induced Liver Injury ◽  
Clinically Significant

Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the Western world. In recent years, natural herbal and dietary supplements have become widely available to the general public and have increased in popularity. Reports of idiosyncratic liver injury caused by such supplements have also increased over the last decade. Horse chestnut is a herb used in dietary supplements primarily for complications of venous insufficiency. Clinically significant acute liver injury has been very rarely associated with its use. We present the case of a 70-year-old man with idiosyncratic horse chestnut-induced liver injury.

Drug-Induced Liver Injury

2015 ◽  
Author(s):  
Thanh Tran ◽  
William M. Lee
Keyword(s):  
Liver Injury ◽  
Prescription Drugs ◽  
Clinical Manifestations ◽  
The United States ◽  
Idiosyncratic Drug Reactions ◽  
Drug Reactions ◽  
Drug Induced ◽  
Common Cause ◽  
Drug Induced Liver Injury ◽  
Study Results

Drug-induced liver injury (DILI) refers to liver damage caused by over-the-counter and prescription drugs as well as herbal and dietary supplements. Hepatocytes, the main factory cells of the liver, are the primary targets of drug-related injury. During hepatocyte injury, loss of cell integrity results in a leak of liver contents, including a variety of enzymes, into the circulation. Currently, more than 1,000 drugs and herbal products have recognized hepatotoxic properties, with acetaminophen (APAP) being the most common cause of acute liver failure in the United States and amoxicillin-clavulanate the most common cause of severe liver injury worldwide. This review of DILI addresses the epidemiology, classification, pathophysiology, clinical manifestations, diagnosis, common idiosyncratic drug reactions, unusual drug reactions, treatment, and prognosis, with special sections on APAP hepatotoxicity and the approval of prescription drugs by the Food and Drug Administration. Figures show histologic features of DILI, mechanisms of liver injury, genome-wide association study results for lumiracoxib, APAP metabolism, and the Rumack-Matthew nomogram. Tables list classification of DILI, features of idiosyncratic drug reactions, histologic patterns of DILI, haplotypes associated with specific drug-related disorders, and the Roussel-Uclaf causality assessment method. This review contains 5 highly rendered figures, 5 tables, and 54 references.

scholarly journals Etiology and Pattern of Drug Induced Liver Injury in a Tertiary Care Hospital of Nepal

2019 ◽  
Vol 21 (3) ◽  
pp. 220-223
Author(s):  
Anuj K.C. ◽  
S. Jha ◽  
S. Thapa
Keyword(s):  
Liver Injury ◽  
Liver Toxicity ◽  
Tertiary Care ◽  
Care Hospital ◽  
Drug Induced ◽  
Common Cause ◽  
Drug Induced Liver Injury ◽  
Common Causes ◽  
The Common ◽  
Mixed Pattern

Drug induced liver injury (DILI) is one of the common cause of liver toxicity. Most of the drugs used today are hepatotoxic. DILI accounts for approximately one-half of the cases of acute liver failure and mimics all forms of acute and chronic liver disease. It is the single most common adverse drug reaction leading to a halt in the development of new medication by pharmaceutical company, failure of new drug to obtain regulatory approval, and withdrawal or restriction of existing drug from the market. The aim of this study is to evaluate common causes and patterns of DILI in our setting. Twenty-seven patients were enrolled in the study. Ant tubercular drugs were most common cause of DILI, accounting for 48.2%. Other common causes of DILI were paracetamol (14.8%) and NSAID’s (11.1%). The most common pattern of liver injury seen was mixed pattern which was present in63%, followed by cholestatic and hepatocellular pattern. Hence, we should be very careful while prescribing these frequently used drugs.

scholarly journals Clinical significance of serum anti-nuclear antibody level in patients with drug-induced liver injury

2016 ◽  
Vol 24 (32) ◽  
pp. 4404
Author(s):  
Jing Hua ◽  
Yun Xu ◽  
Jie Bao ◽  
Xiang-Man Liu ◽  
Su-Ji Gao ◽  
...  
Keyword(s):  
Liver Injury ◽  
Clinical Significance ◽  
Antibody Level ◽  
Drug Induced ◽  
Drug Induced Liver Injury

scholarly journals Efek pemberian metilprednisolon oral terhadap gambaran histopatologik hati tikus wistar (Rattus norvegicus)

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Muhammad Rifaldi ◽  
Poppy M. Lintong ◽  
Meilany F. Durry
Keyword(s):  
Liver Injury ◽  
Low Dose ◽  
Clinical Manifestations ◽  
Control Group ◽  
High Dose ◽  
Drug Induced ◽  
Treatment Groups ◽  
Drug Induced Liver Injury ◽  
Histopathological Features ◽  
Group B

Abstract: Drug-induced liver injury (DILI) is an adverse drug reaction which vary in its clinical manifestations, ranging from an asymptomatic increase in liver enzymes to fulminant hepatic failure. Several drugs can cause DILI, one of which is corticosteroid. Methylprednisolone (MT) is a kind of corticosteroid drug which is considered to be a safe drug and it is not believed to cause DILI and often used for the treatment of severe hepatitis. However, there are some reports of DILI in patients treated with high-dose MT. The objectives of this study was to determine the effect of oral administration of MT on liver’s histological changes of witar rats. This study was using 15 rats which were divided into 3 groups; 1 negative control group (group A) and 2 treatment groups (group B and group C). Group B was given a low-dose oral MT, 2 mg/day, while group C was given oral high-dose MT, 4 mg/day for 14 consecutive days. The results showed steatohepatitis features in both low-dose and high-dose MT administration groups. Histopathological features of both treatment groups are similar. Qualitatively, high-dose MT group showed worse histopathological features than the low-dose MT group. Conclusion: Administration of MT by 2mg/day and 4mg/day may induced steatohepatitis in wistar rat’s liver.Keywords: methylprednisolone, liver histopathological features Abstrak: Drug-induced liver injury (DILI) atau cedera hati akibat obat merupakan reaksi efek samping obat dengan manifestasi klinis yang beragam, mulai dari peningkatan enzim-enzim hati yang bersifat asimptomatik sampai dengan timbulnya gagal hati fulminan. Banyak obat-obatan yang dapat menyebabkan DILI, salah satunya adalah golongan kortikosteroid. Metilprednisolon (MT) adalah obat golongan kortikosteroid yang dianggap sebagai obat yang aman dan tidak diyakini dapat menyebabkan DILI, bahkan sering digunakan untuk terapi pasien hepatitis berat. Akan tetapi, beberapa klinisi melaporkan kasus DILI pada pasien-pasien yang diterapi dengan MT dosis tinggi. Penelitian ini bertujuan untuk mengetahui efek pemberian MT oral terhadap perubahan histologik hati tikus wistar. Jenis penelitian yang dilakukan adalah eksperimental laboratorik menggunakan 15 ekor tikus yang dibagi dalam 3 kelompok; 1 kelompok kontrol negatif (kelompok A) dan 2 kelompok perlakuan (kelompok B dan kelompok C). Kelompok B diberikan MT oral dosis rendah sebanyak 2 mg/hari sedangkan kelompok C diberikan MT oral dosis tinggi sebanyak 4 mg/hari setiap hari selama 14 hari berturut-turut. Hasil penelitian menunjukkan gambaran yang sama secara mikroskopik pada kedua kelompok perlakuan yaitu terjadinya steatohepatitis. Tetapi secara kualitatif, kelompok tikus yang mendapatkan MT dosis tinggi memberikan gambaran histopatologik yang lebih jelek dibandingkan kelompok yang diberi dosis rendah. Simpulan: Pemberian metilprednisolon dosis 2mg/hari dan dosis 4 mg/hari dapat mencetuskan terjadinya steatohepatitis pada hati tikus wistar. Kata kunci: metilprednisolon, gambaran histopatologik hati

Drug-induced liver injury associated with high-dose ceftriaxone: a retrospective cohort study adjusted for the propensity score

2016 ◽  
Vol 72 (8) ◽  
pp. 1003-1011 ◽  
Author(s):  
Kazuhiko Nakaharai ◽  
Yohei Sakamoto ◽  
Kenichiro Yaita ◽  
Yukihiro Yoshimura ◽  
Shun Igarashi ◽  
...  
Keyword(s):  
Cohort Study ◽  
Liver Injury ◽  
Propensity Score ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
High Dose ◽  
Drug Induced ◽  
Drug Induced Liver Injury

scholarly journals A Risk Scoring Model for High-Dose Methotrexate-Induced Liver Injury in Children With Acute Lymphoblastic Leukemia Based on Gene Polymorphism Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Xia He ◽  
Pingli Yao ◽  
Mengting Li ◽  
Hong Liang ◽  
Yilong Liu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Liver Injury ◽  
Ridge Regression ◽  
Predictive Value ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Scoring Model ◽  
Dose Methotrexate ◽  
Risk Scoring

A study on 70 acute lymphoblastic leukemia (ALL) children (age ≤16 years) treated with high-dose methotrexate (HD-MTX) in Sichuan Provincial People’s Hospital was conducted. The aim of the study was to establish a risk-scoring model to predict HD-MTX-induced liver injury, considering gene polymorphisms’ effects. Data screening was performed through t-test, chi-square test, and ridge regression, and six predictors were identified: age, MTRR_AA, MTRR_AG, SLCO1B1_11045879_CC, albumin_1 day before MTX administration, and IBIL_1 day before MTX administration (p < 0.1). Then, the risk-scoring model was established by ridge regression and evaluated the prediction performance. In a training cohort (n = 49), the area under the curve (AUC) was 0.76, and metrics including accuracy, precision, sensitivity, specificity, positive predictive value, and negative predictive value were promising (0.86, 0.81, 0.76, 0.91, 0.81, 0.88, respectively). In a test cohort (n = 21), the AUC was 0.62 and negative predictive value was 0.80; other evaluation metrics were not satisfactory, possibly due to the limited sample size. Ultimately, the risk scores were stratified into three groups based on their distributions: low- (≤48), medium- (49–89), and high-risk (>89) groups. This study could provide knowledge for the prediction of HD-MTX-induced liver injury and reference for the clinical medication.

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