Browsing by Author "Yoshida, Eric M."

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    Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis
    (Springer Nature, 2018-08) Kowalec, Kaarina; Wright, Galen E.B.; Drögemöller, Britt I.; Aminkeng, Folefac; Bhavsar, Amit P.; Kingwell, Elaine; Yoshida, Eric M.; Traboulsee, Anthony; Marrie, Ruth Ann; Kremenchutzky, Marcelo; Campbell, Trudy L.; Duquette, Pierre; Chalasani, Naga; Wadelius, Mia; Hallberg, Pär; Xia, Zongqi; Jager, Philip L. De; Denny, Joshua C.; Davis, Mary F.; Ross, Colin J.D.; Tremlett, Helen; Carleton, Bruce C.; Medicine, School of Medicine
    Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-β (IFN-β). Up to 60% of IFN-β-exposed MS patients develop abnormal biochemical liver test results1,2, and 1 in 50 experiences drug-induced liver injury3. Since genomic variation contributes to other forms of drug-induced liver injury4,5, we aimed to identify biomarkers of IFN-β-induced liver injury using a two-stage genome-wide association study. The rs2205986 variant, previously linked to differential expression of IRF6, surpassed genome-wide significance in the combined two-stage analysis (P = 2.3 × 10-8, odds ratio = 8.3, 95% confidence interval = 3.6-19.2). Analysis of an independent cohort of IFN-β-treated MS patients identified via electronic medical records showed that rs2205986 was also associated with increased peak levels of aspartate aminotransferase (P = 7.6 × 10-5) and alkaline phosphatase (P = 4.9 × 10-4). We show that these findings may be applicable to predicting IFN-β-induced liver injury, offering insight into its safer use.
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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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    Persistence of Virologic Response after Liver Transplant in Hepatitis C Patients Treated with Ledipasvir/Sofosbuvir Plus Ribavirin Pretransplant
    (2017) Yoshida, Eric M.; Kwo, Paul; Agarwal, Kosh; Duvoux, Christophe; Durand, François; Peck-Radosavljevic, Markus; Lilly, Leslie; Willems, Bernard; Vargas, Hugo; Kumar, Princy; Brown, Robert S.; Horsmans, Yves; De-Oertel, Shampa; Arterburn, Sarah; Dvory-Sobol, Hadas; Brainard, Diana M.; McHutchison, John G.; Terrault, Norah; Rizzetto, Mario; Müllhaupt, Beat; Medicine, School of Medicine
    Introduction. Recurrence of HCV infection in patients with chronic hepatitis C virus (HCV) at the time of liver transplantation is nearly universal and reduces the likelihood of graft and patient survival. Materials and methods. We evaluated outcomes of 17 patients (16 with HCV genotype 1 and 1 with genotype 4) who received up to 12 or 24 weeks of ledipasvir/sofosbuvir plus ribavirin prior to or up to the time of liver transplant in the SOLAR-1 and SOLAR-2 trials. In all patients, HCV RNA was < 15 IU/mL prior to transplant. At screening, 6 patients were Child-Pugh-Turcotte (CPT) class B and 11 were CPT class C. Seven patients underwent transplant prior to completing assigned treatment, with 4 treated for < 12 weeks. The primary endpoint was posttransplant virologic response 12 weeks after transplant (pTVR12) in patients with HCV RNA < 15 IU/mL at their last measurement prior to transplant. Results. Overall, 94% (16/17) achieved pTVR12. All who achieved pTVR12 received at least 11 weeks of treatment. The single patient who did not achieve pTVR12 discontinued study drug on day 21 and underwent liver transplant the following day. The patient had HCV RNA < 15 IU/mL at post-transplant week 2 but died 15 days post-transplant because of multi-organ failure and septic shock. Conclusion. Among a small population of HCV patients with decompensated cirrhosis, virologic response to ledipasvir / sofosbuvir plus ribavirin prior to liver transplantation was maintained after transplantation, even if treatment was stopped early. Administration of ledipasvir / sofosbuvir plus ribavirin before liver transplant can prevent post-transplant HCV recurrence.