The hepatic lobule is divided into three zones along the portal-central vein axis. Hepatocytes within each zone exhibit a distinctive gene expression profile that coordinates their metabolic compartmentalization. The zone-dependent heterogeneity of hepatocytes has been hypothesized to result from the differential degree of exposure to oxygen, nutrition and gut-derived toxins. In addition, the gradient of Wnt signaling that increases towards the central vein seen in rodent models is believed to play a critical role in shaping zonation. Furthermore, hepatic zonation is coupled to the site of the homeostatic renewal of hepatocytes. Despite its critical role, the regulatory mechanisms that determine the distinctive features of zonation and its relevance to humans are not well understood. The present study first conducted a comprehensive zone-dependent transcriptome analysis of normal human liver using laser capture microdissection. Upstream pathway analysis revealed the signatures of host responses to gut-derived toxins in the periportal zone, while both the canonical Wnt pathway and the xenobiotic response pathway govern the perivenular zone. Furthermore, we found that the hypoxic environment of the perivenular zone promotes Wnt11 expression in hepatocytes, which then regulates unique gene expression via activation of the non-canonical Wnt pathway. In summary, our study reports the comprehensive zonation-dependent transcriptome of the normal human liver. Our analysis revealed that the LPS response pathway shapes the characteristics of periportal hepatocytes. By contrast, the perivenular zone is regulated by a combination of three distinct pathways: the xenobiotic response pathway, canonical Wnt signaling, and hypoxia-induced noncanonical Wnt signaling.

Occult infection with the hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes (PBMCs), despite constant negative results from tests for HCV RNA in serum. We investigated whether patients who maintained a sustained virologic response 12 weeks after therapy (SVR12) with direct-acting antiviral (DAA) agents for recurrent HCV infection following liver transplantation had occult HCV infections. We performed a prospective study of 134 patients with recurrent HCV infection following liver transplantation who were treated with DAAs, with or without ribavirin, from 2014 through 2016 (129 patients achieved an SVR12). In more than 10% of the patients who achieved an SVR12 (n=14), serum levels of aminotransferases did not normalize during or after DAA therapy, or normalized transiently but then increased sharply after DAA therapy. Of these 14 patients, 9 were assessed for occult HCV infection by reverse transcription quantitative PCR. This analysis revealed that 55% of these patients (n=5) had an occult infection, with the detection of negative strand viral genome, indicating viral replication. These findings indicate the presence of occult HCV infection in some patients with abnormal levels of serum aminotransferases in spite of an SVR 12 to DAAs for HCV infection following liver transplantation.

An orchestration of innate and adaptive immunity determines the infection outcome and whether the host achieves clearance or allows the pathogen to establish persistent infection. The robust activation of the innate immune response plays the most critical role in both limiting viral replication and halting the spread of the pathogen immediately after infection. The magnitude of innate immune activation is coupled with the efficient mounting of the adaptive immunity. Although immunity against HCV infection is known to be inadequate as most cases transitions to chronicity, approximately 25% of acute infection cases result in spontaneous clearance. The exact immune mechanisms that govern the infection outcome remain largely unknown; recent discoveries suggest that the innate immune system facilitates this event. Both infected hepatocytes and local innate immune cells trigger the front line defense program of the liver as well as the recruitment of diverse adaptive immune cells to the site of infection. Although hepatocyte is the target of HCV infection, nearly all cell types that exist in the liver are involved in the innate defense and contribute to the pathophysiology of hepatic inflammation. The main focus of this comprehensive review is to discuss the current knowledge on how each hepatic cell type contribute to the organ system level innate immunity against HCV infection as well as interplay with the viral evasion program. Furthermore, this review article also aims to synchronize the observations from both molecular biological studies and clinical studies with the ultimate goal of improving our understanding of HCV mediated hepatitis.

BACKGROUND: Nationwide nursing shortages have spurred nursing research on burnout and resiliency to better understand the emotional health of nurses and allied staff to retain talent. Our institution implemented resilience rooms in the neuroscience units of our hospital. The goal of this study was to evaluate the effects of resilience room use on emotional distress among staff. METHODS: Resilience rooms opened to staff in the neuroscience tower in January 2021. Entrances were electronically captured via badge readers. Upon exit, staff completed a survey containing items on demographics, burnout, and emotional distress. RESULTS: Resilience rooms were used 1988 times, and 396 surveys were completed. Rooms were most used by intensive care unit nurses (40.1% of entrances), followed by nurse leaders (28.8%). Staff with >10 years of experience accounted for 50.8% of uses. One-third reported moderate burnout, and 15.9% reported heavy or extreme burnout. Overall, emotional distress decreased by 49.4% from entrance to exit. The greatest decreases in distress were recorded by those with the lowest levels of burnout (72.5% decrease). CONCLUSION: Resilience room use was associated with significant decreases in emotional distress. The greatest decreases occurred with the lowest levels of burnout, suggesting that early engagement with resilience rooms is most beneficial.