Clinical and Molecular Hepatology

"DILI"

Original Article

Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures for early mortality in acute liver failure: Neha Sharma, Sushmita Pandey, Gaurav Tripathi, Manisha Yadav, Nupur Sharma, Babu Mathew, Abhishak Gupta, Vasundhra Bindal, Sadam H. Bhat, Yash Magar, Rimsha Saif, Sanju Yadav, Amritpal Kaur, Rakhi Maiwall, Shvetank Sharma, Shiv Kumar Sarin, Jaswinder Singh Maras; Clin Mol Hepatol 2025;31(4):1233-1251.
Published online December 13, 2024; DOI: https://doi.org/10.3350/cmh.2024.0554

Background/Aims
Acute liver failure (ALF) has high mortality predominantly due to compromised immune system and increased vulnerability to bacterial and fungal infections.
Methods
Plasma lipidome and fungal peptide-based community (mycobiome) analysis were performed in discovery cohort (ALF=40, healthy=5) and validated in a validation cohort of 230 patients with ALF using high-resolution-mass-spectrometry, artificial neural network (ANN) and machine learning (ML).
Results
Untargeted lipidomics identified 2,013 lipids across 8 lipid group. 5 lipid-species—phosphatidylcholine (PC)[15:0/17:0], PC[20:1/14:1], PC[26:4/10:0], PC[32:0] and TG[4:0/10:0/23:6]—significantly differentiated ALF-NS (FC>10, P<0.05, FDR<0.01). Mycobiome alpha/beta diversity was significantly higher and showed 4 phyla and >20 species significantly dysregulated in ALF-NS linked with lipid metabolism, fatty acid elongation in ER, and others (P<0.05). Lipid and mycobiome diversity values in ALF-NS were strongly correlated (r²>0.7, P<0.05). Multi-modular correlation network showed striking associations between lipid, fungal peptide modules, and clinical parameters specific to ALF-NS (P<0.05). Cryptococcus amylolentus CBS6039 and Penicillium oxalicum 1142 directly correlated with phosphatidylcholine, triglycerides, and severity in ALF-NS (r²>0.85, P<0.05). POD-fungus and POD-lipids showed direct association with infection, necrosis, and hepatic encephalopathy (Beta>1.2, P<0.05). POD-lipid (AUC=0.969 and HR=1.99 [1.02–2.04]) superseded POD-fungus and severity indices for early-mortality prediction. Finally, significant increase in PC (15:0/17:0) level showed highest normalized importance, and ANNs and ML predicted early mortality with >95% accuracy, sensitivity, and specificity. Interestingly, fungal surveillance protein Clec7a was significantly downregulated (>2-fold), leading to a notable increase in fungal infection-mediated choline/phosphatidylcholine and associated enzymes (FC>1.5; Kennedy cycle). This contributed to phosphatidic acid-mediated hyper-inflammation in ALF-NS.
Conclusions
In ALF, the plasma lipidome and mycobiome are dysregulated. Increased circulating phosphatidylcholine could stratify ALF predisposed to early mortality or require emergency liver transplantation.

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Case Report

Drug induced liver injury

Drug-induced liver injury caused by iodine-131: Chei Won Kim, Ji Sun Park, Se Hwan Oh, Jae-Hyung Park, Hyun-Ik Shim, Jae Woong Yoon, Jin Seok Park, Seong Bin Hong, Jun Mi Kim, Trong Binh Le, Jin Woo Lee; Clin Mol Hepatol 2016;22(2):272-275.
Published online May 20, 2016; DOI: https://doi.org/10.3350/cmh.2015.0037

Abstract
PDF

Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some evidence that iodine-131 can induce liver injury . Here we report a rare case of drug-induced liver injury (DILI) caused by iodine-131 in a patient with regional lymph node metastasis after total thyroidectomy. A 47-year-old woman was admitted with elevated liver enzymes and symptoms of general weakness and nausea. Ten weeks earlier she had undergone a total thyroidectomy for papillary thyroid carcinoma and had subsequently been prescribed levothyroxine to reduce the level of thyroid-stimulating hormone. Eight weeks after surgery she underwent iodine-131 ablative therapy at a dose of 100 millicuries, and subsequently presented with acute hepatitis after 10 days. To rule out all possible causative factors, abdominal ultrasonography, endoscopic ultrasonography (on the biliary tree and gall bladder), and a liver biopsy were performed. DILI caused by iodine-131 was suspected. Oral prednisolone was started at 30 mg/day, to which the patient responded well.

Citations

Citations to this article as recorded by

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Bratislava Medical Journal.2025;[Epub] CrossRef
Hepatotoxicity of iodine-131 ablation for post-surgical differentiated thyroid cancer patients with hepatitis B virus infection
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E. Piantanida, S. Ippolito, D. Gallo, E. Masiello, P. Premoli, C. Cusini, S. Rosetti, J. Sabatino, S. Segato, F. Trimarchi, L. Bartalena, M. L. Tanda
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Iodine-131

Reactions Weekly.2016; 1617(1): 140. CrossRef

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Review

Drug induced liver injury

Factors affecting drug-induced liver injury: antithyroid drugs as instances: Reza Heidari, Hossein Niknahad, Akram Jamshidzadeh, Narges Abdoli; Clin Mol Hepatol 2014;20(3):237-248.
Published online September 25, 2014; DOI: https://doi.org/10.3350/cmh.2014.20.3.237

Abstract
PDF

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.

Citations

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