Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg（＋） and HBeAg（-） patients

AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time poly...     

Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia

AIM： To identify the distribution of hepatitis B virus （HBV） subgenotype and basal core promoter （BCP） mutations among patients with HBV-associated liver disease in Indonesia.
METHODS： Patients with chronic hepatitis （CH, n =61）, liver cirrhosis （LC, n = 62）, and hepatocellular carcinoma （HCC, n = 48） were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.
RESULTS： HBV genotype B （subgenotypes B2, B3, B4, 85 and B7） the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C （subgenotypes C1, C2 and C3） was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 （84.9%） and C1 （82.2%） were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 （84.9%） and adrq＋ （89.4%） were the most prevalent in HBV genotype B and C, respectively. Double mutation （A1762T/G1764A） in the BCP was significantly higher in LC （59.7%） and HCC （54.2%） than in CH （19.7%）, suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC （46.8%）, but lower in HCC （22.9%） and CH （18.0%）, suggesting that this mutation may be an indicator of cirrhosis.
CONCLUSION： HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.     

Diagnostic value of a group of biochemical markers of liver fibrosis in patients with non‐alcoholic steatohepatitis

OBJECTIVE:  The objectives of this study were to investigate the use of non‐invasive biochemical markers to evaluate the severity of liver fibrosis in patients with non‐alcoholic steatohepatitis (NASH). METHODS:  This was a cross‐sectional study of patients with histopathologically confirmed NASH between January 2005 and December 2006. The patients’ characteristics were recorded and the body mass index was calculated for each patient. All patients underwent ultrasound‐guided liver biopsy and a fibrosis assessment was performed using the Brunt criteria. The non‐invasive laboratory markers measured were insulin resistance, tumor necrosis factor (TNF‐α), type IV collagen and hyaluronic acid (HA). RESULTS:  Thirty patients were recruited, of whom 18 (60%) were men. Their mean age was 45 ± 13.9 (18–71) years. About 83% of patients had fibrosis stage 1–2. In bivariate analysis, age, TNF‐α and type IV collagen concentrations showed a weak but significant correlation with the fibrosis stage. When the patients were grouped into mild fibrosis (stages 1–2) and advanced fibrosis (stages 3–4), the mean concentrations of HA and type IV collagen were significantly higher in those with advanced fibrosis than those with mild fibrosis (180.8 ± 49.63 vs 543.6 ± 360.45 ng/mL; for HA; P = 0.026 and 125.3 ± 32.11 vs 288.0 ± 171.22 ng/mL for type IV collagen; P = 0.010). CONCLUSION:  Our study showed that the degree of liver fibrosis was significantly correlated with age, TNF‐α and type IV collagen concentrations. The level of HA and type IV collagen could differentiate between mild (F1–2) and advanced fibrosis (F3–4).     

The use of autologous blood to improve exercise capacity after total hip arthroplasty: a preliminary report

BACKGROUND: Venesection of red blood cells in healthy well-trained subjects decreased the maximum oxygen uptake parallel with the reduction in hemoglobin (Hb) level. Based on the large Hb decrease that is seen after total joint surgery, one could expect a decrease in performance as well. The purpose of this study was to investigate whether autologous blood enhanced performance on a bicycle ergometer in patients after total hip arthroplasty. STUDY DESIGN AND METHODS: Nine patients scheduled for elective total hip arthroplasty in an accelerated stay program participated in a preoperative autologous blood donation (PABD) program. Weeks before the scheduled surgery, patients donated 4 units of blood and received standard erythropoietin treatment. Physical fitness was assessed during exercise test on a bicycle ergometer. Each patient was matched with three previously tested patients. RESULTS: Patients in both groups were 69.0 years old (range, 66-74 years vs. 61-77 years). None of the patients had relevant cardiovascular abnormalities. On average patients received 3.3 units of blood because 3 units were not transfused. The PABD group showed a Hb decrease of 0.5 g per dL (4%) on the fourth postoperative day versus 4.4 g per dL (31%) in the control group. The decline in power output on Day 4 was significantly less in the PABD group compared with the control group (t test, p = 0.026). CONCLUSION: From this pilot study it can be concluded that correction of the postoperative Hb decrease was associated with a lower decrease in maximum power output, compared to the control group. On Days 23 and 39, however, the difference in performance between the PABD group and control group had disappeared.     

Recruitment of Rab27a to phagosomes controls microbial antigen cross-presentation by dendritic cells

Polyreactive immunoglobulins (Ig) and complement components are present in tissues and blood of healthy individuals. They facilitate pathogen uptake and inactivation in lysosomes of phagocytes and thereby provide rapid protection against infection. Dendritic cells (DCs) are phagocytes that can acquire peptides from phagocytosed antigen to elicit cytotoxic immune responses by CD8⁺ T lymphocytes. The mechanisms that select peptides for cross-presentation are not fully resolved. Here we investigated the role of polyreactive Ig and complement in directing phagosomal antigen processing for cross-presentation. Phagocytosis facilitated by serum opsonization required the presence of Ig for effective antigen cross-presentation of microbe-derived antigen. The presence of complement C3 in serum promoted phagocytosis, yet phagosomes were defective in antigen degradation. The small GTPase Rab27a was recently implicated in antigen cross-presentation and was rapidly recruited to phagosomes only when Ig was present. Our data suggest that prebinding of antigen by polyreactive Ig potentiates the efficiency of antigen cross-presentation to CD8⁺ T cells through recruitment of Rab27a.     

Endocardial/epicardial versus endocardial encircling cryoablation for ventricular tachycardia: A randomized trial

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Afatinib and Cetuximab in Four Patients With EGFR Exon 20 Insertion–Positive Advanced NSCLC

Introduction

EGFR exon 20 insertions comprise 4% to 9% of EGFR mutated NSCLC. Despite being an oncogenic driver, they are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). We hypothesized that dual EGFR blockade with afatinib, an irreversible EGFR TKI, and cetuximab, a monoclonal antibody against EGFR, could induce tumor responses.