Tumor necrosis factor-alpha-induced reduction of glomerular filtration rate in rats with fulminant hepatic failure.

The mechanism of renal failure during fulminant hepatic failure (FHF) or end-stage of liver disease is not fully understood. The present study aims to delineate the mechanisms of decreased glomerular filtration rate (GFR) in acute hepatic failure. A rat model of renal insufficiency in severe liver injury was established by lipopolysaccharide (LPS) plus D-galactosamine (GalN) exposure. GFR was evaluated by continuous infusion of fluorescein isothiocyanate-inulin with implanted micro-osmotic pumps. GalN/LPS intoxication resulted in severe hepatocyte toxicity as evidenced by liver histology and biochemical tests, whereas renal morphology remained normal. GFR was reduced by 33% of the controls 12 h after GalN/LPS exposure, accompanied with a decreased serum sodium levels, a marked increase in serum TNF-α and ET-1 levels as well as significantly upregulated renal type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) expression. The upregulated IP3R1 expression was abrogated by the treatment of anti-TNF-α antibodies, but not by 2-aminoethoxydiphenylborate (2-APB), which blocks the inositol 1,4,5-trisphosphate signaling pathway. Treatments with either TNF-α antibodies or 2-APB also significantly improved the compromised GFR, elevated serum urea nitrogen and creatinine levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. The extent of acute liver injury as reflected by serum ALT levels was much more attenuated by anti-TNF-α antibodies than by 2-APB. Liver histology further confirmed that anti-TNF-α antibodies conferred better protection than 2-APB in GalN/LPS-exposed rats. LPS-elicited TNF-α over-production is responsible for decreased GFR through IP3R1 overexpression, and the compromised GFR resulted in the development of acute renal failure in rats with FHF.

In-hospital Mortality and Causes of Death in People Diagnosed With HIV in a General Hospital in Shenyang, China: A Cross-Sectional Study.

Background: Acquired immune deficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV) infection, is a serious public health issue. This study investigated the correlated factors and possible changing trend of in-hospital death in patients diagnosed with HIV in the past decade in our hospital. Methods: We retrospectively collected data of firstly hospitalized patients with HIV in the Department of Infectious Disease in the First Affiliated Hospital of China Medical University from January 1, 2010 to December 31, 2019, and compared various factors that correlated with in-hospital death, including age, sex, opportunistic infections, and antiretroviral therapy (ART) status. Cox regression analysis was used to identify the risk factors for death. Results: In total, 711 patients were recruited for this study, and 62 patients died in the hospital. The in-hospital mortality rate was 8.72%. Tuberculosis (TB), malignancies, and thrombocytopenia were associated with mortality. Antiviral treatment before admission was found to be a protective factor. There was a declining trend in in-hospital mortality from 19.2% in 2010 to 6.3% in 2019 (linear-by-linear association test, p < 0.001), partly due to intensified medical care strategy. Conclusions: Till date, AIDS-defining illnesses remain the major cause of hospital admission and in-hospital mortality. TB and malignancies were correlated risk factors for in-hospital mortality. ART before admission was found to be beneficial, and considering the decreasing rate of in-hospital mortality, the implementation of intensified medical care strategy requires further effort.

Baseline factors associated with mortality within six months after admission among hospitalized HIV-1 patients in Shenyang, China.

OBJECTIVE: Short-term mortality rates remain high among critically ill human immunodeficiency virus-1 (HIV-1) patients though long-term mortality rates have dropped. Baseline risk factors for short-term mortality have not yet been determined in China. In this paper, we herein describe clinical characteristics, laboratory findings, causes of clinical deterioration, and risk factors associated with mortality among HIV-1 patients within six months after hospital admission. METHODS: We carried out a prospective study of hospitalized patients in advanced stages of HIV infection. These patients started antiretroviral therapy three or four weeks after admission. Follow-up was conducted for a period of six months. We used a multivariate logistic-regression analysis to identify risk factors associated with mortality. RESULTS: A total of 141 patients met our inclusion criteria. The mean age was 41 years. Fever and weight loss were the most common clinical manifestations of advanced HIV disease. Oral candidiasis, tuberculosis, cytomegaloviremia, and pneumocystis pneumonia were the most common opportunistic infections. Significantly decreased CD4+ T-cell counts, hypoalbuminemia, anemia, hyponatremia, as well as elevated C-reactive protein (CRP) and glutamic alanine transaminase levels were common laboratory test abnormalities. The mortality rate was 21.3%. The patients who died were more likely than the survivors to have low CD4+ T-cell counts as well as low creatinine, hemoglobin, albumin, and serum sodium levels while also having longer intervals of fever and higher CRP levels. A multivariate analysis demonstrated that the independent risk factors for mortality were active tuberculosis [odds ratio (OR): 2.681; 95% confidence interval (CI), 1.006-7.142; p=0.049], hyponatremia (OR: 3.027; 95% CI, 1.238-7.401; p=0.015), and being at clinical stage 4 (as defined by the World Health Organization) (OR: 9.492; 95% CI, 1.200-75.065; p=0.033) within the first six months of admission. CONCLUSION: Special consideration should be given to patients who have active tuberculosis, are at clinical stage 4, and present with hyponatremia upon admission as these were found to be important factors associated with mortality within six months of hospital admission in HIV-1 patients.

Alterations of blood-brain barrier and associated factors in acute liver failure.

Brain edema in acute liver failure (ALF) remains lethal. Cytotoxic mechanisms associated with brain edema have been well recognized, but the role of vasogenic mechanisms of brain edema has not been explored. Intact tight junctions (TJs) between brain capillary endothelial cells are critical for normal BBB function. Recent reports found significant alterations in the tight junction elements including occludin and claudin-5, suggesting a vasogenic injury in the blood-brain barrier (BBB) integrity. However, the role of TJ in ALF has not been completely understood. This paper reviews the role of the paracellular tight junction in the increased selective BBB permeability that leads to brain edema in ALF and furthermore explores the effect of systemic inflammatory cytokines on the tight junction dysfunction.

Association of polymorphisms in the interleukin-4 gene with response to hepatitis B vaccine and susceptibility to hepatitis B virus infection: a meta-analysis.

OBJECTIVE: The aim of this meta-analysis is to evaluate the associations between functional polymorphisms in the interleukin-4 (IL4) gene and individuals' responses to hepatitis B vaccine and their susceptibility to hepatitis B virus (HBV) infection. METHODS: A literature search on articles published before December 1st, 2012 was conducted in PubMed, Embase, Web of Science and China BioMedicine (CBM) databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using the STATA 12.0 software. RESULTS: Eight studies were eligible for inclusion in this meta-analysis, including five cross-sectional studies on individual's response to hepatitis B vaccine and three case-control studies on HBV infection risk. The meta-analysis results showed that the T allele of rs2243250, the T allele of rs2070874, and the C allele of rs2227284 in IL4 gene were associated with high responses to hepatitis B vaccine. Further subgroup analysis by ethnicity showed that there was a significant association between IL4 genetic polymorphisms and an individual's responses to hepatitis B vaccine among Asian populations, but similar association was not found among Caucasian populations. However, there was no evidence indicating a correlation between IL4 genetic polymorphism and susceptibility to HBV infection. CONCLUSION: Our current meta-analysis suggests that rs2243250, rs2070874 and rs2227284 polymorphisms in IL4 gene may play an important role in determining the response to hepatitis B vaccine, especially among Asian populations. However, further studies are still needed to evaluate the associations between IL4 genetic polymorphisms and HBV infection risk.