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Item Adenovirus-Related Fulminant Liver Failure After Kidney Transplantation(International Scientific Information, 2022-08-06) Mihaylov, Plamen; Lutz, Andrew J.; Oppliger, Federico; Lin, Jingmei; Surgery, School of MedicineBACKGROUND: Human adenovirus is a well-known pathogen that can potentially lead to severe infection in immunocompromised patients. Adenovirus infections in solid-organ transplant recipients can range from asymptomatic to severe, prolonged, disseminated disease, and have a significant impact on morbidity, mortality, and graft survival. The clinical manifestations vary from asymptomatic and flu-like illness to severe life-threatening viremia with multi-organ failure. Post-transplant adenovirus infection is well described in kidney recipients, but in adult liver transplant recipients the impact of the virus is not well described. In this report, a case of disseminated adenovirus infection with subsequent fatal acute liver failure in a post-kidney transplant patient is presented. CASE REPORT: A 51-year-old man underwent a deceased kidney transplantation for focal segmental glomerulosclerosis. Shortly after the kidney transplantation, he received multiple plasmapheresis with additional steroid treatments for cellular rejection and reoccurrence of his primary kidney disease. Three weeks after the kidney transplant, he developed a disseminated adenovirus infection with subsequent acute liver failure. Despite the early diagnosis and aggressive treatment, the patient died. CONCLUSIONS: Patients with organ transplantation with autoimmune background etiology are usually over-immunosuppressed to avoid early rejection. In this population, opportunistic infections are not rare. Fever, general malaise, and transplant organ dysfunction are the first signs of bacterial or viral infection. Early infectious diseases work-up, including tissue biopsy, is fundamental to establish a diagnosis. Broad antibiotic and possible antiviral aggressive treatment are mandatory.Item Blocking porcine sialoadhesin improves extracorporeal porcine liver xenoperfusion with human blood(Wiley, 2013-07) Waldman, Joshua P.; Vogel, Thomas; Burlak, Christopher; Coussios, Constantin; Dominguez, Javier; Friend, Peter; Rees, Michael A.; Surgery, School of MedicineBACKGROUND: Patients in fulminant hepatic failure currently do not have a temporary means of support while awaiting liver transplantation. A potential therapeutic approach for such patients is the use of extracorporeal perfusion with porcine livers as a form of "liver dialysis". During a 72-h extracorporeal perfusion of porcine livers with human blood, porcine Kupffer cells bind to and phagocytose human red blood cells (hRBC) causing the hematocrit to decrease to 2.5% of the original value. Our laboratory has identified porcine sialoadhesin expressed on Kupffer cells as the lectin responsible for binding N-acetylneuraminic acid on the surface of the hRBC. We evaluated whether blocking porcine sialoadhesin prevents the recognition and subsequent destruction of hRBCs seen during extracorporeal porcine liver xenoperfusion. METHODS: Ex vivo studies were performed using wild type pig livers perfused with isolated hRBCs for 72-h in the presence of an anti-porcine sialoadhesin antibody or isotype control. RESULTS: The addition of an anti-porcine sialoadhesin antibody to an extracorporeal porcine liver xenoperfusion model reduces the loss of hRBC over a 72-h period. Sustained liver function was demonstrated throughout the perfusion. CONCLUSIONS: This study illustrates the role of sialoadhesin in mediating the destruction of hRBCs in an extracorporeal porcine liver xenoperfusion model.Item Genetic and Environmental Risk Factors for Autoimmune Hepatitis(Wiley, 2019-08-02) Lammer, Craig; Medicine, School of MedicineAutoimmune hepatitis (AIH) is a prototypical autoimmune disease, characterized by robust genetic associations with human leukocyte antigen (HLA) alleles, female predominance, and presence of serum autoantibodies; yet all AIH cases are not the same. This heterogeneous disease affects all population demographics and can lead to cirrhosis, liver failure, and liver transplantation depending on the diagnosis, treatment, and response to therapy. Similar to other autoimmune diseases, AIH is a result of immune intolerance and failure of immunological homeostasis. The etiology remains largely unresolved but is likely the result of various environmental exposures in the background of a permissive genetic architecture.Item SARS-CoV-2 vaccination and risk of severe COVID-19 outcomes in patients with autoimmune hepatitis(Elsevier, 2022-10) Efe, Cumali; Taşçılar, Koray; Gerussi, Alessio; Bolis, Francesca; Lammert, Craig; Ebik, Berat; Stättermayer, Albert Friedrich; Cengiz, Mustafa; Gökçe, Dilara Turan; Cristoferi, Laura; Peralta, Mirta; Massoumi, Hatef; Montes, Pedro; Cerda, Eira; Rigamonti, Cristina; Yapalı, Suna; Adali, Gupse; Çalışkan, Ali Rıza; Balaban, Yasemin; Eren, Fatih; Eşkazan, Tuğçe; Barutçu, Sezgin; Lytvyak, Ellina; Zazueta, Godolfino Miranda; Kayhan, Meral Akdogan; Heurgue-Berlot, Alexandra; De Martin, Eleonora; Yavuz, Ahmet; Bıyık, Murat; Narro, Graciela Castro; Duman, Serkan; Hernandez, Nelia; Gatselis, Nikolaos K.; Aguirre, Jonathan; Idilman, Ramazan; Silva, Marcelo; Mendizabal, Manuel; Atay, Kadri; Güzelbulut, Fatih; Dhanasekaran, Renumathy; Montano-Loza, Aldo J.; Dalekos, George N.; Ridruejo, Ezequiel; Invernizzi, Pietro; Wahlin, Staffan; Medicine, School of MedicineBackground Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. Patients and methods We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. Results We included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17–85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10–0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11–0.35). Conclusions SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.