Entecavir combined with Fufang Biejia Ruangan tablet in treatment of chronic hepatitis B patients with liver fibrosis: 96-week efficacy analyses / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of long-term therapy with entecavir and Fufang Biejia Ruangan tablet in patients with chronic hepatitis B (CHB)-associated fibrosis and explore the synergistic therapy that accelerates the reversion of liver fibrosis.</p><p><b>METHODS</b>A total of 197 patients with CHB-associated fibrosis were recruited from Nanfang Hospital between June, 2010 and June, 2015. The patients were divided into two groups after matching for age, gender and liver stiffness measurement (LSM), namely group A (n=98) treated with Fufang Biejia Ruangan Tablet plus entecavir, and group B (n=99) to receive entecavir only. HBV DNA quantification, HBV serological indicators, blood biochemical indexes, and results of abdominal ultrasound and FibroScan were recorded every 12 weeks. FibroScan values were converted to Metavir staging.</p><p><b>RESULTS</b>Both groups showed significant decreases in serum levels of HBV DNA, alanine aminotransferase (ALT), and LSM value from baseline (all P<0.05). The median time to achieve Metavir fibrosis staging improvement were 72 weeks in group A and 96 weeks in group B (P<0.05), and the median time to achieve ALT and AST normalization were 12 and 24 weeks in Group A, respectively, significantly shorter than the time in group B (P<0.05). No significant difference was found between the two groups in HBV DNA undetectable rate and HBeAg seroconversion rate.</p><p><b>CONCLUSION</b>The combination therapy with Fufang Biejia Ruangan tablet and entecavir produces a stronger efficacy than entecavir alone in the treatment of chronic hepatitis B patients with liver fibrosis, and Fufang Biejia Ruangan tablet shows an obvious hepatoprotective effect in these patients.</p>

Short-term spontaneous fluctuation of viral load in patients with chronic hepatitis B / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the short-term spontaneous fluctuation of viral load in patients with chronic hepatitis B (CHB) and explore the related factors in treatment naive CHB patients during immune clearance phase.</p><p><b>METHODS</b>A total of 123 treatment naive HBeAg-positive CHB patients with ALT>2 × ULN were enrolled in this study. Paired serum samples were obtained at the first and second visits with an interval of less than 4 weeks. The levels of quantitative HBV DNA (Roche COBAS), quantitative HBsAg, ALT and AST were analyzed. Liver biopsy specimen were collected within 4 weeks and evaluated using Knodell and Ishak histological scoring system.</p><p><b>RESULTS</b>Of the 123 patients, 93 (75.6%) and 30 (24.4%) had HBV DNA fluctuation ≤ 0.5 Log IU/ml and >0.5 Log IU/ml, respectively. Binary logistic multivariate regression analysis identified Knodell necroinflammation score and HBV DNA level as the factors related to HBV DNA fluctuation. Patients with Knodell necorinflammation score ≥ 10 or HBV DNA<7 Log IU/ml had significantly higher rates of HBV DNA fluctuation>0.5 Log IU/ml (50.0% vs 18.3%, P=0.042; 42.9% vs 20.6%, P=0.030).</p><p><b>CONCLUSION</b>Treatment naive CHB patients in immune clearance phase show short-term spontaneous fluctuation of HBV DNA, and nearly 25% of the patients have HBV DNA fluctuation >0.5 Log IU/ml. Such fluctuation is related to liver inflammation and quantity of HBV DNA.</p>

Effect of ozonized saline on signaling passway of Keap1-Nrf2-ARE in rat hepatocytes / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effect of ozonized saline on the activation of the Keap1-Nrf2-ARE signaling pathway in rat liver cells.</p><p><b>METHODS</b>Twenty male Sprague-Dawley rats were randomly divided into ozonized saline (OS) group, model group, ozonized saline control (OSC) group and normal control (NC) group. The rats in OS group and model group were intravenously administered with OS or oxygen saline (5 ml/kg) respectively, once a day for 15 days, and then intraperitoneally injected with CCl4 dissolved in oliver oil. The rats in OSC group were pretreated with OS for 15 days. The rats in NC group were fed normally for 15 days. On the 16th day, the rats in OSC group and NC group were intraperitoneally injected with oliver oil (2 ml/kg) without CCl4. After 24 hours of CCl4 or olive oil intraperitoneal injection, the serum levels of alanine transaminase (ALT) and aspertate aminotransferase (AST) were measured. The liver tissues were also collected for detection of total anti-oxygen capability (TAOC), glutathione (GSH), catalase (CAT), Glutathione peroxidase (GPx). Western Blot was used to detect Nrf2 and immunofluorescence staining assay to display intracelluar distribution of Nrf2.</p><p><b>RESULTS</b>Compared with the rats in model group,the serum ALT and AST levels of rats in OS group were significantly lower (P < 0.01) ,which were (1240.4 ± 188.2) U/L and (1245.4 ± 176.9) U/L vs (539.8 ± 175.3) U/L and (546.0 ± 130.2) U/L, and the TAOC, CAT, GPx and GSH activity of rats in OS group were significantly higher, which were (0.72 ± 0.24) U/mg, (1.05 ± 0.21) mg/g, (676.9 ± 115.1) U/mg and (45.2 ± 14.3) U/mg vs (1.37 ± 0.19) U/mg, (2.23 ± 0.55) mg/g, (1024.6 ± 162.9) U/mg and (68.2 ± 9.9) U/mg, respectively. In contrast with NC group, pretreatment of OS in OSC group elevated TAOC, CAT, GPx and GSH activity (P < 0.01 or P < 0.05). Ozonized saline can strengthen the Nrf2 expression in liver cells.</p><p><b>CONCLUSION</b>Preconditioning injection of ozonized saline can reduce rat's liver injury induced by CCl4. The ozonized saline, as a novel Nrf2 activator, can reduce the oxidative damage of radical oxygen species (ROS) and the deleterious substance by activating the Keap1-Nrf2-ARE signaling pathway and its downstream genes expression.</p>