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Antiviral therapy is the basic treatment method for improving prognosis recommended in the management guidelines of chronic hepatitis B in China and globally. For patients with chronic HBV infection and normal transaminases, it is difficult in clinical practice to accurately evaluate the progression of hepatitis and identify suitable patients who need antiviral therapy. In order to objectively and accurately evaluate the degree of liver inflammatory activity in such patients, more and more noninvasive evaluation indicators have been used in addition to conventional liver biopsy. This article reviews the new serological indicators that can reflect the degree of liver inflammation and/or fibrosis in patients with chronic HBV infection and normal aminotransferase levels, hoping to provide a reference for antiviral decision-making in these patients.
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Objective To investigate the mechanism of action of integrin α4 (ITGA4) in liver fibrosis based on the anti-liver fibrosis effect of sticky sugar amino acid (SSAA) in rats. Methods A rat model of liver fibrosis was induced by intraperitoneal injection of CCl 4 , and then colchicine and low-, middle-, and high-dose SSAA were used for intervention, with blank control group and SSAA group as control. After 12 weeks of experimental intervention, serum and liver samples were collected to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and HE staining and Sirius Red staining were used to observe the pathological conditions of liver tissue; quantitative real-time PCR was used to measure the transcriptional level of ITGA4, integrin β1 (ITGB1), transforming growth factor-β1 (TGFβ1), alpha-smooth muscle actin (α-SMA), and TIMP2 in liver tissue; Western blot was used to measure the relative protein expression levels of ITGA4, ITGB1, TGFβ1, α-SMA, MMP2, TIMP1, and TIMP2; immunohistochemistry was used to observe the protein expression of TGFβ1 and α-SMA. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for comparison between two groups. Results There were significant increases in AST and ALT in the CCl 4 model group, and intervention with colchicine or low-, middle-, and high-dose SSAA reduced the levels of AST and ALT, with a significant difference between the CCl 4 model group and the other groups (all P < 0.05). HE staining and Sirius Red staining showed disordered structure of hepatic lobules and an increase in collagen fibers in the CCl 4 model group, and the structure of hepatic lobules was improved after intervention with colchicine or low-, middle-, and high-dose SSAA. The CCl 4 model group had significantly higher transcriptional levels of ITGA4, TGFβ1, α-SMA, and TIMP2 than the other groups, and there were significant reductions in the transcriptional levels of each factor after intervention with colchicine or SSAA, with a significant difference between the CCl 4 model group and the other groups (all P < 0.05). The CCl 4 model group had significantly higher protein expression levels of ITGA4, TGFβ1, α-SMA, TIMP2, and TIMP1 and a significantly lower protein expression level of MMP2 than the other groups, and intervention with colchicine or SSAA inhibited the expression of ITGA4, TGFβ1, α-SMA, TIMP2, and TIMP1 and promoted the expression of MMP2. Immunohistochemistry showed that the CCl 4 model group had significantly higher expression levels of TGFβ1 and α-SMA than the other groups, which was inhibited by intervention with colchicine or SSAA. The high-dose SSAA group had the most significant effect in reducing aminotransferases, improving lobular structure, and inhibiting the protein expression of liver fibrosis factors. Conclusion The high expression of ITGA4 in the liver is associated with the development of liver fibrosis, which is consistent with the increases in the expression of TGFβ1 and α-SMA. Inhibiting the expression of ITGA4 can provide more therapeutic targets for liver fibrosis and expand the anti-liver fibrosis mechanism of SSAA.
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Autoimmune hepatitis (AIH) is an inflammatory disease of the liver mediated by autoimmune response, and in the diagnosis and treatment of AIH, it is of great importance to accurately assess the progression of liver inflammation, screen out the patients requiring corticosteroid therapy, and evaluate the therapeutic outcome. This article introduces a variety of new noninvasive techniques which have been discovered by clinical and experimental studies in recent years and have the potential to evaluate the progression of AIH, as well as the advantages and disadvantages of each technique. It is concluded that the new noninvasive techniques have more advantages in guiding the corticosteroid therapy for AIH, but further clinical studies are still needed for verification.
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Hepatitis B virus (HBV) infection is still a public problem that seriously threatens human health. Evaluation of liver fibrosis progression with an efficient noninvasive model is of great significance for condition assessment, disease management, and prognostic evaluation in patients with chronic HBV infection. This article reviews the noninvasive models commonly used in the diagnosis of liver fibrosis in recent years, summarizes the research background, methods, related studies, and advantages and disadvantages of these models, and analyzes the current research status and possible development trends of liver fibrosis assessment models. Recent studies have shown that although current models are not perfect for Chinese patients with chronic HBV infection as the main predisposing factor for liver fibrosis, the excellent performance of noninvasive models in liver fibrosis assessment provides a reference for the assessment of liver fibrosis in patients with chronic HBV infection and can replace liver biopsy to a certain extent.
ABSTRACT
Hepatitis B virus (HBV) infection is still a public problem that seriously threatens human health. Evaluation of liver fibrosis progression with an efficient noninvasive model is of great significance for condition assessment, disease management, and prognostic evaluation in patients with chronic HBV infection. This article reviews the noninvasive models commonly used in the diagnosis of liver fibrosis in recent years, summarizes the research background, methods, related studies, and advantages and disadvantages of these models, and analyzes the current research status and possible development trends of liver fibrosis assessment models. Recent studies have shown that although current models are not perfect for Chinese patients with chronic HBV infection as the main predisposing factor for liver fibrosis, the excellent performance of noninvasive models in liver fibrosis assessment provides a reference for the assessment of liver fibrosis in patients with chronic HBV infection and can replace liver biopsy to a certain extent.
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Objective To observe the efficacy of de novo combination therapy lamivudine plus adefovir , lamivudine monotherapy and entecavir monotherapy in HBeAg-positive CHB patients with genotype B/C. Methods A total of 182 treatment-naive CHB patients in line with treatment standards of Chinese CHB prevention and treatment guidelines were randomly assigned to three groups and treated with lamivudine plus adefovir or lamivudine monotherapy or entecavir monotherapy for 48 weeks. Results Patients in three groups presented no difference in baseline levels. After treatment by three therapies , the group of lamivudine plus adefovir showed a higher biochemical response rates (12 week P < 0.01, 24 week P < 0.01, 48 week P < 0.01), HBeAg-serological rates(12 week P < 0.01, 24 week P < 0.05, 48 week P < 0.05) and completely virological response rates (12 week P < 0.05, 24 week P < 0.05, 48 week P < 0.05) than lamivudine group. In terms of biochemical response rates , the group of lamivudine plus adefovir had certain advantages when compared with entecavir group. Conclusion De novo combination therapy lamivudine plus adefovir is a good antiviral strategy for chronic hepatitis B patients with B/C genotype viral infection in China.
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Objective Through co-culture Kupffer cells with hepatocyte in vitro,to understand the influence of Kupffer cells on the growth、morphology and metabolism of hepatocyte.Methods In-situ IV collagenase two-step perfusion method to digest SD rat liver,apply low speed centrifugalization to isolate parenchymal hepatic cells and densitygradient centrifugation by percoll fluid to isolate Kupffer cells respectively.Inoculate hepatocyte cells into 6 holes culture plate to culture alone and/or co-culture with Kupffer cells in the proportion six to one,the growth,morphous of hepatocyte are observed under the light microscope and the level of albumin and glucose in the culture supernatant are detected by automatic biochemistry meter,and compare synthesis function and metabolism of hepatocytes culture alone and coculture with Kupffer cells.Results The hepatocytes of culture alone their growth and developed to normal hepatocytes morphous quickly,2 weeks later the cells death occurs,after 21 days the hepatocytes culture alone are totaly death,when hepatocytes co-culture with kupffer cells that proliferate slower than that culture alone.The hepatocites beginning to death 48 hours later, and totally death after 10 days co-culture.The culture supernatant was collected and tested the level of albumin and glucose at 24 hours intervals.In culture alone group,the albumin level is significant higher than in co-culture group at 48h、96h、120h、144h、168h(P