Epidemiology and management of chronic hepatitis E infection in solid organ transplantation: a comprehensive literature review

Hepatitis E virus (HEV) infection has emerged as a global public health issue. Although it often causes an acute and self‐limiting infection with low mortality rates in the western world, it bears a high risk of developing chronic hepatitis in immunocompromised patients with substantial mortality rates. Organ transplant recipients who receive immunosuppressive medication to prevent rejection are thought to be the main population at risk for chronic hepatitis E. Therefore, there is an urgent need to properly evaluate the clinical impact of HEV in these patients. This article aims to review the prevalence, infection course, and management of HEV infection after solid organ transplantation by performing a comprehensive literature review. In addition, an in‐depth emphasis of this clinical issue and a discussion of future development are also presented. Copyright © 2013 John Wiley & Sons, Ltd.     

Prognosis of a large cohort of patients with hepatocellular carcinoma in a single European centre

BACKGROUND/AIM: Only a few follow up data are available for patients with hepatocellular carcinoma (HCC) in Europe and the USA. Therefore, we analysed all HCC patients admitted to our hospital between 1988 and 1999. METHODS: We documented aetiology, stage (HCC: Okuda and UICC classifications, liver cirrhosis: Child-Pugh score), and diagnostic and therapeutic measures of 281 consecutive HCC patients. Survival time was calculated as a function of staging and therapy. RESULTS: Cirrhosis was diagnosed in all patients. Seventy-two patients underwent liver resection, 28 liver transplantation, 31 transarterial chemoembolization and 14 percutaneous ethanol injection. One hundred and thirty-six patients received no treatment. The Okuda and the Child-Pugh classification predicted a significant decrease of median survival time, whereas the UICC classification was less powerful. CONCLUSIONS: HCC occurred only in patients with liver cirrhosis. Survival time correlated with therapy (or no therapy) and with the Child-Pugh Score. In European patients the Okuda classification is superior to the UICC classification and should be compared to novel classification systems.     

β Cell death and dysfunction during type 1 diabetes development in at-risk individuals

Role of the funding source: Funding from the NIH was used for support of the participating clinical centers and the coordinating center. The funding source did not participate in the collection or the analysis of the data.BACKGROUND. The β cell killing that characterizes type 1 diabetes (T1D) is thought to begin years before patients present clinically with metabolic decompensation; however, this primary pathologic process of the disease has not been measured.METHODS. Here, we measured β cell death with an assay that detects β cell–derived unmethylated insulin (INS) DNA. Using this assay, we performed an observational study of 50 participants from 2 cohorts at risk for developing T1D from the TrialNet Pathway to Prevention study and of 4 subjects who received islet autotransplants.RESULTS. In at-risk subjects, those who progressed to T1D had average levels of unmethylated INS DNA that were elevated modestly compared with those of healthy control subjects. In at-risk individuals that progressed to T1D, the observed increases in unmethylated INS DNA were associated with decreases in insulin secretion, indicating that the changes in unmethylated INS DNA are indicative of β cell killing. Subjects at high risk for T1D had levels of unmethylated INS DNA that were higher than those of healthy controls and higher than the levels of unmethylated INS DNA in the at-risk progressor and at-risk nonprogressor groups followed for 4 years. Evaluation of insulin secretory kinetics also distinguished high-risk subjects who progressed to overt disease from those who did not.CONCLUSION. We conclude that a blood test that measures unmethylated INS DNA serves as a marker of active β cell killing as the result of T1D-associated autoimmunity. Together, the data support the concept that β cell killing occurs sporadically during the years prior to diagnosis of T1D and is more intense in the peridiagnosis period.TRIAL REGISTRATION. Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00097292","term_id":"NCT00097292"}}NCT00097292.FUNDING. Funding was from the NIH, the Juvenile Diabetes Research Foundation, and the American Diabetes Association.     

Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells

FOXP3⁺ Tregs are central for the maintenance of self-tolerance and can be defective in autoimmunity. In multiple sclerosis and type-1 diabetes, dysfunctional self-tolerance is partially mediated by a population of IFNγ-secreting Tregs. It was previously reported that increased NaCl concentrations promote the induction of proinflammatory Th17 cells and that high-salt diets exacerbate experimental models of autoimmunity. Here, we have shown that increasing NaCl, either in vitro or in murine models via diet, markedly impairs Treg function. NaCl increased IFNγ secretion in Tregs, and reducing IFNγ — either by neutralization with anti-IFNγ antibodies or shRNA-mediated knockdown — restored suppressive activity in Tregs. The heightened IFNγ secretion and loss of Treg function were mediated by the serum/glucocorticoid-regulated kinase (SGK1). A high-salt diet also impaired human Treg function and was associated with the induction of IFNγ-secreting Tregs in a xenogeneic graft-versus-host disease model and in adoptive transfer models of experimental colitis. Our results demonstrate a putative role for an environmental factor that promotes autoimmunity by inducing proinflammatory responses in CD4 effector cells and Treg pathways.     

Coexistence of folie communiquée and folie simultanée

Objective. The authors report a case during which they observed serious subtypes of induced delusional psychosis (folie communiquée and folie simultanée) without any common genetic background or premorbid psychosis in the case of the secondary patient. Method. The clinical phenomenology of the case is described. Results. Mild intellectual disability and environmental–psychological factors (social isolation and the symbiotic-like interpersonal relatedness) play an essential aetiological role in the case of the secondary recipient patient. Conclusion. The authors emphasize the importance of subclassification of induced delusional psychosis for further aetiological and clinical research.