Buchananself8824

OBJECTIVES Nucleos(t)ide analogues (NUCs) are not routinely recommended for patients with hepatitis B e antigen-positive chronic hepatitis B virus (HBV) infection who have persistently elevated serum HBV DNA level (>20,000 IU/mL) but normal alanine aminotransferase (1,000,000 IU/mL (immune-tolerant phase), which was significantly (P = 0.002) different compared with those with an intermediate serum HBV DNA level (20,000-1,000,000 IU/mL). DISCUSSION The cumulative HCC risk in the untreated pEDNA group was minimal and comparable with that of the IC group. Further studies are required to determine whether early NUC treatment, indeed, reduces the HCC risk in patients with an intermediate serum HBV DNA level.OBJECTIVES Immune activation and intestinal microbial dysbiosis could induce diarrhea-predominant irritable bowel syndrome (IBS-D). We examined the roles of ileal immunoglobulin A (IgA) and IgA-coated bacteria in IBS-D pathogenesis. METHODS Peripheral blood, fecal samples, and ileal and cecal biopsies were collected from 32 healthy volunteers and 44 patients with IBS-D. Quantitative reverse transcriptase polymerase chain reaction was used to assess differential gene expression. IgA levels in the blood and fecal samples were quantified by an enzyme-linked immunosorbent assay. IgA cells were assessed by immunofluorescence imaging. Flow-cytometry-based IgA bacterial cell sorting and 16S rRNA gene sequencing (IgA-SEQ) was used to isolate and identify fecal IgA bacteria. RESULTS Fecal IgA, particularly IgA1, was upregulated in patients with IBS-D. IgA class switch and B cell-activating factor-receptor were increased in the terminal ileum of patients. The intestinal microbiota composition was altered in patients compared with that in controls. IgA-SEQ showed that the proportion of fecal IgA-coated bacteria was increased significantly in patients with IBS-D. IgA bacteria in patients with IBS-D showed higher abundances of Escherichia-Shigella, Granulicatella, and Haemophilus compared with healthy controls and IgA bacteria in patients with IBS-D. The Escherichia-Shigella IgA coating index was positively correlated with anxiety and depression. The Escherichia-Shigella relative abundance, luminal IgA activity, and some altered IgA-coated bacteria were positively associated with the clinical manifestations of IBS-D. DISCUSSION Microbial dysbiosis may promote the terminal ileal mucosa to produce higher levels of IgA, increasing the proportion of IgA-coated bacteria by activating IgA class switching, which might regulate local inflammation and clinical manifestations in IBS-D. IgA may mediate the effects of microbial dysbiosis on the pathogenesis of IBS-D.Current conventional endoscopes have restricted the accuracy of treatment delivery and monitoring. Over the past decade, there have been major developments in nanotechnology and light triggered therapy, potentially allowing a better detection of challenging lesions and targeted treatment of malignancies in the gastrointestinal tract. Theranostics is a developing form of personalized medicine because it combines diagnosis and targeted treatment delivered in one step using advances in nanotechnology. This review describes the light-triggered therapies (including photodynamic, photothermal, and photoimmunotherapies), nanotechnological advances with nanopowder, nanostent, nanogels, and nanoparticles, enhancements brought to endoscopic ultrasound, in addition to experimental endoscopic techniques, combining both enhanced diagnoses and therapies, including a developed prototype of a "smart" multifunctional endoscope for localized colorectal cancer, near-infrared laser endoscope targeting the gastrointestinal stromal tumors, the concept of endocapsule for obscure gastrointestinal bleed, and a proof-of-concept therapeutic capsule using ultrasound-mediated targeted drug delivery. Hence, the following term has been proposed encompassing these technologies "Theranostic gastrointestinal endoscopy." Future efforts for integration of these technologies into clinical practice would be directed toward translational and clinical trials translating into a more personalized and interdisciplinary diagnosis and treatment, shorter procedural time, higher precision, higher cost-effectiveness, and less need for repetitive procedures.The progressive miniaturization of photonic components presents the opportunity to obtain unprecedented microscopic images of colonic polyps in real time during endoscopy. This information has the potential to act as "optical biopsy" to aid clinical decision-making, including the possibility of adopting new paradigms such as a "resect and discard" approach for low-risk lesions. The technologies discussed in this review include confocal laser endomicroscopy, optical coherence tomography, multiphoton microscopy, Raman spectroscopy, and hyperspectral imaging. These are in different stages of development and clinical readiness, but all show the potential to produce reliable in vivo discrimination of different tissue types. A structured literature search of the imaging techniques for colorectal polyps has been conducted. The significant developments in endoscopic imaging were identified for each modality, and the status of current development was discussed. Of the advanced imaging techniques discussed, confocal laser endomicroscopy is in clinical use and, under optimal conditions with an experienced operator, can provide accurate histological assessment of tissue. The remaining techniques show potential for incorporation into endoscopic equipment and practice, although further component development is needed, followed by robust prospective validation of accuracy. Optical coherence tomography illustrates tissue "texture" well and gives good assessment of mucosal thickness and layers. Multiphoton microscopy produces high-resolution images at a subcellular resolution. Raman spectroscopy and hyperspectral imaging are less developed endoscopically but provide a tissue "fingerprint" which can distinguish between tissue types. Molecular imaging may become a powerful adjunct to other techniques, with its ability to precisely label specific molecules within tissue and thereby enhance imaging.OBJECTIVES The precipitous increase in nonalcoholic steatohepatitis (NASH) is accompanied by a dramatic increase in the incidence of NASH-related hepatocellular carcinoma (HCC). HCC in NASH has a higher propensity to arise without pre-existing cirrhosis compared with other chronic liver diseases. Dynasore in vitro METHODS To identify the potential links between liver and gut in NASH-related hepatocarcinogenesis, we compared the gut microbiota and mediators of bile acid (BA) signaling in the absence or presence of cirrhosis through the analysis of stool and serum samples from patients with NASH non-HCC and NASH-HCC and healthy volunteers. RESULTS Serum levels of total and individual BA were higher in NASH compared with healthy controls. Furthermore, serum levels of the primary conjugated BAs glycine-conjugated cholic acid, taurine-conjugated cholic acid, glycine-conjugated chenodeoxycholic acid, and taurine-conjugated chenodeoxycholic acid were significantly increased in cirrhotic vs noncirrhotic patients, independent of the occurrence of HCC. By contrast, serum FGF19 levels were higher in patients with NASH-HCC and associated with tumor markers as well as an attenuation of BA synthesis. Specific alterations in the gut microbiome were found for several bacteria involved in the BA metabolism including Bacteroides and Lactobacilli. Specifically, the abundance of Lactobacilli was associated with progressive disease, serum BA levels, and liver injury in NASH and NASH-HCC. DISCUSSION Here, we demonstrate a clear association of the altered gut microbiota and primary conjugated BA composition in cirrhotic and noncirrhotic patients with NASH-HCC. Microbiota-associated alterations in BA homeostasis and farnesoid X receptor signaling, via FGF19, might thus contribute to fibrogenesis, liver injury, and tumorigenesis in NASH-HCC.OBJECTIVES Nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4) score, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) score, and AST-alanine aminotransferase (ALT) ratio are noninvasive fibrosis scoring systems for the staging of liver fibrosis in patients with chronic liver disease. METHODS In a large cohort of patients with nonalcoholic fatty liver disease, we compared AST-ALT ratio, NFS, FIB-4 score, and APRI score in predicting advanced fibrosis (defined as fibrosis stage ≥ 3) in histologically confirmed African American (AA) and white patients. We identified 907 patients 677 (74.6%) white and 230 (25.3%) AA patients with nonalcoholic fatty liver disease. RESULTS Of the 907 patients, 115 (12.8%) patients had advanced fibrosis (stages 3 and 4) in the total cohort 6 (2.6%) AAs, and 109 (16.2%) whites. In AAs, the area under the receiver operating characteristic (area under the curve) for predicting advanced fibrosis was 0.58 by NFS, 0.86 by APRI score, 0.77 by FIB-4 score, and 0.65 by AST-ALT ratio. In whites, the area under the receiver operating characteristic for predicting advanced fibrosis was 0.82 by NFS, 0.82 by APRI score, 0.88 by FIB-4 score, and 0.76 by AST-ALT ratio. In the AA population, NFS > 0.675, FIB-4 score > 2.67, and APRI score > 1.5 each has a negative predictive value of 98%, whereas the negative predictive values in whites are 91%, 88%, and 85%, respectively. DISCUSSION Noninvasive fibrosis scoring systems can reliably exclude advanced fibrosis in both AAs and whites and have acceptable discriminatory ability to predict advanced fibrosis in whites. The utility of noninvasive fibrosis scoring systems in predicting advanced fibrosis in AAs needs further validation in a larger multicenter cohort.OBJECTIVES Hepatic encephalopathy (HE) is common in advanced cirrhosis and is characterized by marked neuropsychiatric abnormalities. However, despite its severity and effects on brain function, the impact of HE on psychological status of patients has not been adequately assessed. The aim of this study was to evaluate the effect of HE on psychological status of patients and their informal caregivers. METHODS Fifteen patients with cirrhosis and episodic or persistent HE and their corresponding informal caregivers were included. Semistructured interviews were performed in patients and caregivers. Quality of life (QoL) was assessed by the short-form 36 in both patients and caregivers, and the Zarit burden score was measured in caregivers. The analysis of interviews was performed using qualitative methodology. RESULTS HE causes a major psychological impact on patients with HE. The first episode of HE caused a very significant impact that was reported with deep feelings, mainly of fear, anger, misery, anxiety, and sorrow, which persisted with time. Symptoms causing more psychological impact on patients were impaired ability to walk and speak. All effects were associated with a marked impairment in QoL. The psychological impact was also marked in caregivers who had a major burden, as assessed by the Zarit score. Moreover, QoL, particularly the mental component score, was markedly impaired in caregivers in intensity similar to that of patients. DISCUSSION HE has a profound psychological impact on patients and their informal caregivers, associated with a marked negative influence on QoL. The psychological effects of HE on patients and caregivers should be evaluated and treated.