Hepatocytes infected with hepatitis C virus change immunological features in the liver microenvironment

Hepatitis C virus (HCV) infection is remarkably efficient in establishing viral persistence, leading to the development of liver cirrhosis and hepatocellular carcinoma (HCC). Direct-acting antiviral agents (DAAs) are promising HCV therapies to clear the virus. However, recent reports indicate potential increased risk of HCC development among HCV patients with cirrhosis following DAA therapy. CD8+ T-cells participate in controlling HCV infection. However, in chronic hepatitis C patients, severe CD4+ and CD8+ T-cell dysfunctions have been observed. This suggests that HCV may employ mechanisms to counteract or suppress the host T-cell responses. The primary site of viral replication is within hepatocytes where infection can trigger the expression of costimulatory molecules and the secretion of immunoregulatory cytokines. Numerous studies indicate that HCV infection in hepatocytes impairs antiviral host immunity by modulating the expression of immunoregulatory molecules. Hepatocytes expressing whole HCV proteins upregulate the ligands of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and transforming growth factor β (TGF-β) synthesis compared to those in hepatocytes in the absence of the HCV genome. Importantly, HCV-infected hepatocytes are capable of inducing regulatory CD4+ T-cells, releasing exosomes displaying TGF-β on exosome surfaces, and generating follicular regulatory T-cells. Recent studies report that the expression profile of exosome microRNAs provides biomarkers of HCV infection and HCV-related chronic liver diseases. A better understanding of the immunoregulatory mechanisms and identification of biomarkers associated with HCV infection will provide insight into designing vaccine against HCV to bypass HCV-induced immune dysregulation and prevent development of HCV-associated chronic liver diseases.

The Immune Landscape in Nonalcoholic Steatohepatitis

The liver lies at the intersection of multiple metabolic pathways and consequently plays a central role in lipid metabolism. Pathological disturbances in hepatic lipid metabolism are characteristic of chronic metabolic diseases, such as obesity-mediated insulin resistance, which can result in nonalcoholic fatty liver disease (NAFLD). Tissue damage induced in NAFLD activates and recruits liver-resident and non-resident immune cells, resulting in nonalcoholic steatohepatitis (NASH). Importantly, NASH is associated with an increased risk of significant clinical sequelae such as cirrhosis, cardiovascular diseases, and malignancies. In this review, we describe the immunopathogenesis of NASH by defining the known functions of immune cells in the progression and resolution of disease.

FDG-PET/MRI fused data sets for the detection of liver metastases in patients undergoing systemic anticancer treatment

To retrospectively describe imaging characteristics of liver metastases on fused FDG-PET/MRI data sets and to compare the diagnostic accuracy of MRI and fused FDG-PET/MRI data sets for the detection of liver metastases in patients undergoing systemic anticancer treatment. 43 oncological patients [mean age: 56 +/- 11 years] were investigated by FDG-PET/CT and liver MRI. FDG-PET data from PET/CT scans were fused with MRI. 556 lesions were evaluated. 5 different evaluation algorithms were used for FDG-PET/MRI evaluation. The sensitivity, specifity, PPV, NPV and accuracy of MRI and FDG-PET/MRI data for the detection of liver metastases were calculated. A mean follow-up of 647 days served as reference standard. McNemar's test was used to test for statistically significant differences between MRI and FDG-PET/MRI [p<0.5]. The sensitivity, specificity, PPV, NPV and accuracy of MRI for the detection of liver metastases were 86%, 81%, 97%, 47%, and 85% and 50%, 100%, 100%, 22%, and 56%, for FDGPET/MRI. FDG-PET/MRI was significantly less accurate than MRI alone [p<.001]. In opposite to patients before systemic anticancer therapy the fusion of FDG-PET data with liver MRI cannot be recommended for the detection of liver metastases in patients undergoing systemic oncological therapy

Retinal prostheses for the blind

<p><b>INTRODUCTION</b>Using artificial means to treat extreme vision impairment has come closer to reality during the past few decades. The goal of this research has been to create an implantable medical device that provides useful vision for those patients who are left with no alternatives. Analogous to the cochlear implants for some forms of hearing loss, these devices could restore useful vision by converting visual information into patterns of electrical stimulation that excite the remaining viable inner retinal neurons in patients with retinitis pigmentosa or age-related macular degeneration.</p><p><b>METHODS</b>Data for this review were selected through a comprehensive literature search.</p><p><b>RESULTS</b>Advances in microtechnology have facilitated the development of a variety of prostheses that can be implanted in the visual cortex, around the optic nerve, or in the eye. Some of these approaches have shown the promise of providing useful visual input to patients with visual impairments.</p><p><b>CONCLUSION</b>While the development of various retinal prostheses have shown promise in limited clinical trials, there are distinct advantages and disadvantages for each type of prosthesis. This review will focus primarily on the Epiretinal Intraocular Retinal Prosthesis, studied by our group, but will also briefly review other modalities: the subretinal prosthesis, cortical prosthesis, and optic nerve prosthesis.</p>