Publications

@article{Aithal2023-js,

title = {Holding opposing ideas and the half-life of truth},

author = {Guruprasad P Aithal},

year  = {2023},

date = {2023-07-01},

journal = {J. Hepatol.},

volume = {79},

number = {1},

pages = {e20\textendashe21},

publisher = {Elsevier BV},

keywords = {hepatotoxicity, liver fibrosis, Methotrexate, psoriasis, rheumatoid arthritis},

pubstate = {published},

tppubtype = {article}

}

@article{Atallah2023-ec,

title = {Risk of liver fibrosis associated with long-term methotrexate 

 therapy may be overestimated},

author = {Edmond Atallah and Jane I Grove and Colin Crooks and Esther Burden-Teh and Abhishek Abhishek and Sulleman Moreea and Kelsey M Jordan and Aftab Ala and David Hutchinson and Richard J Aspinall and Ruth Murphy and Guruprasad P Aithal},

year  = {2023},

date = {2023-05-01},

journal = {J. Hepatol.},

volume = {78},

number = {5},

pages = {989\textendash997},

publisher = {Elsevier BV},

abstract = {BACKGROUND \& AIMS: The risk of significant liver fibrosis from 

 prolonged methotrexate (MTX) exposure has been estimated at 

 around 5%, prompting intensive monitoring strategies. However, 

 the evidence is derived from retrospective studies that 

 under-reported risk factors for liver disease. We evaluated the 

 risk of long-term MTX therapy on liver fibrosis in a 

 longitudinal cohort study using two non-invasive markers. 

 METHOD: Between 2014-2021, adult patients diagnosed with 

 rheumatoid arthritis (RA) or psoriasis for $geq$2 years were 

 recruited prospectively from six UK sites. The MTX group 

 included patients who received MTX for $geq$6 months, whereas 

 the unexposed group included those who never received MTX. All 

 patients underwent full liver profiling, with transient 

 elastography (TE) and enhanced liver fibrosis (ELF) marker 

 measurements. RESULTS: A total of 999 patients (mean age 60.8 

 $±$ 12 years, 62.3% females) were included. Of 976 with valid 

 TE values, 149 (15.3%) had liver stiffness $geq$7.9 kPa. Of 

 892 with a valid ELF, 262 (29.4%) had ELF $geq$9.8. Age and 

 BMI were independently associated with elevated liver stiffness 

 and ELF. Neither MTX cumulative dose nor duration was associated 

 with elevated liver stiffness. Diabetes was the most significant 

 risk factor associated with liver stiffness $geq$7.9 kPa (adjusted odds ratio = 3.19; 95% CI 1.95-5.20; p \<0.001). 

 Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF $geq$9.8 (odds ratio = 1.76; 95% CI 1.20-2.56; p = 0.003), suggesting the degree of joint 

 inflammation in RA may confound ELF as a non-invasive marker of 

 liver fibrosis. CONCLUSION: The risk of liver fibrosis 

 attributed to MTX itself might have been previously 

 overestimated; there is a need to consider modifying current 

 monitoring guidelines for MTX. IMPACT AND IMPLICATIONS: Current 

 guidelines recommend intensive (2-3 monthly) monitoring 

 strategies for patients on long-term methotrexate therapy due to 

 the potential risk of liver fibrosis. Evaluation of the 

 association using two validated non-invasive markers of liver 

 fibrosis, liver stiffness and enhanced liver fibrosis score, in 

 a large cohort of patients with rheumatoid arthritis or 

 psoriasis shows that the reported risk has previously been 

 overestimated. The clinical focus should be to improve patients' 

 metabolic risk factors, diabetes and BMI, that are independently 

 associated with liver stiffness. There is a need to consider 

 modifying current treatment monitoring guidelines for 

 methotrexate.},

keywords = {Enhanced Liver Fibrosis, hepatotoxicity, liver   fibrosis, liver stiffness, Methotrexate, psoriasis, rheumatoid arthritis, transient elastography},

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}

}