Browsing by Author "Kumar, Rahul"

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    Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome
    (Wolters Kluwer, 2022) Efe, Cumali; Kulkarni, Anand V.; Beretta-Piccoli, Benedetta Terziroli; Magro, Bianca; Stättermayer, Albert; Cengiz, Mustafa; Clayton-Chubb, Daniel; Lammert, Craig; Bernsmeier, Christine; Gül, Özlem; Higuera-de la Tijera, Fatima; Anders, Margarita; Lytvyak, Ellina; Akın, Mete; Purnak, Tugrul; Liberal, Rodrigo; Peralta, Mirta; Ebik, Berat; Duman, Serkan; Demir, Nurhan; Balaban, Yasemin; Urzua, Álvaro; Contreras, Fernando; Venturelli, Maria Grazia; Bilgiç, Yılmaz; Medina, Adriana; Girala, Marcos; Günşar, Fulya; Londoño, Maria-Carlota; Androutsakos, Theodoros; Kisch, Ayelen; Yurci, Alper; Güzelbulut, Fatih; Çağın, Yasir Furkan; Avcı, Enver; Akyıldız, Murat; Dindar-Demiray, Emine Kübra; Harputluoğlu, Murat; Kumar, Rahul; Satapathy, Sanjaya K.; Mendizabal, Manuel; Silva, Marcelo; Fagiuoli, Stefano; Roberts, Stuart K.; Soylu, Neşe Karadağ; Idilman, Ramazan; Yoshida, Eric M.; Montano-Loza, Aldo J.; Dalekos, George N.; Ridruejo, Ezequiel; Schiano, Thomas D.; Wahlin, Staffan; Medicine, School of Medicine
    Background and aims: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. Approach and results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.
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    MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB–NFIB fusion gene
    (Wiley, 2017) Kim, Jisun; Geyer, Felipe C.; Martelotto, Luciano G.; Ng, Charlotte K. Y.; Lim, Raymond S.; Selenica, Pier; Li, Anqi; Pareja, Fresia; Fusco, Nicola; Edelweiss, Marcia; Kumar, Rahul; Gularte-Merida, Rodrigo; Forbes, Andre N.; Khurana, Ekta; Mariani, Odette; Badve, Sunil; Vincent-Salomon, Anne; Norton, Larry; Reis-Filho, Jorge S.; Weigelt, Britta; Pathology and Laboratory Medicine, School of Medicine
    Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer, has been shown to be driven by MYB pathway activation, most often underpinned by the MYB–NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB–NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB–NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1–ACTN1 and MYBL1–NFIB), which were associated with MYBL1 overexpression. A third AdCC harboured a high-level MYB amplification, which resulted in MYB overexpression at the mRNA and protein levels. RNA-sequencing and whole-genome sequencing revealed no definite alternative driver in the fourth AdCC studied, despite high levels of MYB expression and the activation of pathways similar to those activated in MYB–NFIB-positive AdCCs. In this case, a deletion encompassing the last intron and part of exon 15 of MYB, including the binding site of ERG-1, a transcription factor that may downregulate MYB, and the exon 15 splice site, was detected. In conclusion, we demonstrate that MYBL1 rearrangements and MYB amplification probably constitute alternative genetic drivers of breast AdCCs, functioning through MYBL1 or MYB overexpression. These observations emphasize that breast AdCCs probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB–NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms. Copyright © 2017 Pathological Society of Great Britain and Ireland.