Publications

@article{Bjornsson2023-vk,

title = {A new framework for advancing in drug-induced liver injury 

 research. The Prospective European DILI Registry},

author = {Einar S Bj\"{o}rnsson and Camilla Stephens and Edmond Atallah and Mercedes Robles-Diaz and Ismael Alvarez-Alvarez and Alexander Gerbes and Sabine Weber and Guido Stirnimann and Gerd Kullak-Ublick and Helena Cortez-Pinto and Jane I Grove and M Isabel Lucena and Raul J Andrade and Guruprasad P Aithal},

year  = {2023},

date = {2023-01-01},

journal = {Liver Int.},

volume = {43},

number = {1},

pages = {115\textendash126},

publisher = {Wiley},

abstract = {BACKGROUND \& AIMS: No multi-national prospective study of 

 drug-induced liver injury (DILI) has originated in Europe. The 

 design of a prospective European DILI registry, clinical 

 features and short-term outcomes of the cases and controls is 

 reported. METHODS: Patients with suspected DILI were 

 prospectively enrolled in the United Kingdom, Spain, Germany, 

 Switzerland, Portugal and Iceland, 2016-2021. DILI cases or 

 non-DILI acute liver injury controls following causality 

 assessment were enrolled. RESULTS: Of 446 adjudicated patients, 

 246 DILI patients and 100 had acute liver injury due to other aetiologies, mostly autoimmune hepatitis (n = 42) and viral hepatitis (n = 34). DILI patients (mean age 56 years), 57% 

 women, 60% with jaundice and 3.6% had pre-existing liver 

 disease. DILI cases and non-DILI acute liver injury controls had 

 similar demographics, clinical features and outcomes. A single 

 agent was implicated in 199 (81%) DILI cases. 

 Amoxicillin-clavulanate, flucloxacillin, atorvastatin, 

 nivolumab/ipilimumab, infliximab and nitrofurantoin were the 

 most commonly implicated drugs. Multiple conventional 

 medications were implicated in 37 (15%) and 18 cases were 

 caused by herbal and dietary supplements. The most common single 

 causative drug classes were antibacterials (40%) and 

 antineoplastic/immunomodulating agents (27%). Overall, 13 

 (5.3%) had drug-induced autoimmune-like hepatitis due to 

 nitrofurantoin, methyldopa, infliximab, methylprednisolone and 

 minocycline. Only six (2.4%) DILI patients died (50% had 

 liver-related death), and another six received liver 

 transplantation. CONCLUSIONS: In this first multi-national 

 European prospective DILI Registry study, antibacterials were 

 the most commonly implicated medications, whereas antineoplastic 

 and immunomodulating agents accounted for higher proportion of 

 DILI than previously described. This European initiative 

 provides an important opportunity to advance the study on DILI.},

keywords = {drug aetiologies, drug-induced autoimmune-like hepatitis, Drug-induced liver injury, outcomes, prospective study},

pubstate = {published},

tppubtype = {article}

}

@article{Atallah2021-yd,

title = {Biomarkers of idiosyncratic drug-induced liver injury (DILI) - 

 a systematic review},

author = {Edmond Atallah and Cristiana Freixo and Ismael Alvarez-Alvarez and F J Cubero and Alexander L Gerbes and Gerd A Kullak-Ublick and Guruprasad P Aithal},

year  = {2021},

date = {2021-11-01},

journal = {Expert Opin. Drug Metab. Toxicol.},

volume = {17},

number = {11},

pages = {1327\textendash1343},

publisher = {Informa UK Limited},

abstract = {INTRODUCTION: Idiosyncratic drug-induced liver injury (DILI) is 

 an unpredictable event, and there are no specific biomarkers 

 that can distinguish DILI from alternative explanations or 

 predict its clinical outcomes. AREAS COVERED: This systematic 

 review summarizes the available evidence for all biomarkers 

 proposed to have a role in the diagnosis or prognosis of DILI. 

 Following a comprehensive search, we included all types of 

 studies in humans. We included DILI cases based on any threshold 

 criteria but excluded intrinsic DILI, commonly caused by 

 paracetamol overdose. We classified studies into diagnostic and 

 prognostic categories and assessed their methodological quality. 

 After reviewing the literature, 14 studies were eligible. EXPERT 

 OPINION: Diagnostic studies were heterogeneous with regard to 

 the study population and outcomes measured. Prognostic models 

 were developed by integrating novel biomarkers, risk scores, and 

 traditional biomarkers, which increased their prognostic ability 

 to predict death or transplantation by 6 months. This systematic 

 review highlights the case of need for non-genetic biomarkers 

 that distinguish DILI from acute liver injury related to 

 alternative etiology. Biomarkers with the potential to identify 

 serious adverse outcomes from acute DILI should be validated in 

 independent prospective cohorts with a substantial number of 

 cases.},

keywords = {biomarkers, DILI, Drug-induced liver injury, hepatotoxicity, systematic review},

pubstate = {published},

tppubtype = {article}

}

@article{Atallah2021-ru,

title = {Zanubrutinib-induced liver injury: a case report and literature 

 review},

author = {Edmond Atallah and Pramudi Wijayasiri and Nicole Cianci and Khorrum Abdullah and Abhik Mukherjee and Guruprasad P Aithal},

year  = {2021},

date = {2021-05-01},

journal = {BMC Gastroenterol.},

volume = {21},

number = {1},

pages = {244},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Zanubrutinib is a Bruton's tyrosine kinase inhibitor 

 that has been recently licensed in refractory mantle cell 

 lymphoma and under assessment in phase 3 clinical trials for 

 other B cell malignancies. To date, there are no reported cases 

 of hepatotoxicity secondary to zanubrutinib. We report the first 

 case of severe liver injury due to zanubrutinib. CASE 

 PRESENTATION: A 56-year-old Caucasian male with a history of 

 relapsed lymphoplasmacytic lymphoma was admitted to the hospital 

 with new-onset jaundice, choluria, and pruritus for 10 days. He 

 had been on zanubrutinib as part of a clinical trial for 30 

 months. His blood profile showed a severe hepatocellular injury 

 with jaundice (alanine transaminase 2474 IU/L and total 

 bilirubin 141 umol/L with mild coagulopathy). He had an 

 extensive work-up including virology, autoimmune, and metabolic 

 profiles in addition to abdominal ultrasound with no alternative 

 explanation found for his liver injury. Zanubrutinib-induced 

 liver injury was suspected, and causality assessment by the 

 updated Roussel Uclaf Causality Assessment Method score showed a 

 probable causal relationship with zanubrutinib. His liver 

 histology was also consistent with drug-induced liver injury. 

 His liver biochemistry improved following cessation of 

 zanubrutinib and normalised after 8 weeks. CONCLUSION: We report 

 the first case of severe liver injury secondary to zanubrutinib 

 after 30 months of treatment. This case raises clinical 

 awareness regarding zanubrutinib-induced liver toxicity and the 

 importance of drug withdrawal in the event of liver injury.},

keywords = {Case report, Drug-induced liver injury, hepatotoxicity, RUCAM, Zanubrutinib},

pubstate = {published},

tppubtype = {article}

}

@article{Nicoletti2021-sw,

title = {Genetic risk factors in drug-induced liver injury due to 

 isoniazid-containing antituberculosis drug regimens},

author = {Paola Nicoletti and Harshad Devarbhavi and Ashish Goel and Radha Venkatesan and Chundamannil E Eapen and Jane I Grove and Samreen Zafer and Einar Bjornsson and M Isabel Lucena and Raul J Andrade and Munir Pirmohamed and Mia Wadelius and Dominique Larrey and Anke-Hilse Maitland-van der Zee and Luisa Ibanez and Paul B Watkins and Ann K Daly and Guruprasad P Aithal},

year  = {2021},

date = {2021-04-01},

journal = {Clin. Pharmacol. Ther.},

volume = {109},

number = {4},

pages = {1125\textendash1135},

publisher = {Wiley},

abstract = {Drug-induced liver injury (DILI) is a complication of treatment 

 with antituberculosis (TB) drugs, especially in isoniazid 

 (INH)-containing regimens. To investigate genetic risk factors, 

 we performed a genomewide association study (GWAS) involving 

 anti-TB DILI cases (55 Indian and 70 European) and controls 

 (1,199 Indian and 10,397 European). Most cases were treated with 

 a standard anti-TB drug regimen; all received INH. We imputed 

 single nucleotide polymorphism and HLA genotypes and performed 

 trans-ethnic meta-analysis on GWAS and candidate gene genotypes. 

 GWAS found one significant association (rs117491755) in 

 Europeans only. For HLA, HLA-B*52:01 was significant 

 (meta-analysis odds ratio (OR) 2.67, 95% confidence interval (CI) 1.63-4.3},

keywords = {adverse drug reactions, Drug-induced liver injury, genetic polymorphisms, HLA genes, isoniazid, N-acetyltransferase 2},

pubstate = {published},

tppubtype = {article}

}