Chronic HBV Infection:Combination Antiviral Therapy Of Nucleoside Analogues And Related Researches

Background: Chronic hepatitis B virus (HBV) infection is prevalent all of the world, and China is a big country with HBV infection. The key and the most effective treatment is antiviral therapy, which can inhibit viral replication, promote liver diseases recovery, reduce or delay complications, and improve the quality of life. Nucleoside analogues are the most commonly used. Due to many years for antiviral treatment and social burdens of nucleoside analogues, optimization of treatment is an urgent clinical subject. In recent years, combination therapy and individual treatment have gradually become an international consensus. Chronic HBV infection can lead to cirrhosis, hepatocellular carcinoma (HCC) and other serious complications, that seriously threat to human health. Liver fibrosis is a necessary way from chronic HBV infection to cirrhosis, so monitoring, early diagnosis and treatment of liver fibrosis may effectively prevent the occurrence of complications. Recently non-invasive diagnosis of liver fibrosis becomes a hot topic. More than90%of HCC patients caused by HBV, with insidious onset, rapid progress, more patients have lost the chance of operation, and the prognosis is poor, while pathogenesis of HBV-induced HCC and the efficacy of antiviral therapy to prevent HCC are being explored.Objective: To evaluate the clinical efficacy and safety of Telbivudine (TEV) combined with Adefovir dipivoxil (ADV) for chronic hepatitis B (CHB), so as to provide the references for clinical practice and research. To learn about the significance of liver fibrosis monitoring during the course of chronic HBV infection and the latest research progress of transient elastography for diagnosis of liver fibrosis. To probe the main pathogenesis, clinical diagnostics and antiviral treatment of HCC induced by chronic HBV infection, and the efficacy and influence factors of antiviral treatment for preventing HCC, so as to make some contribution for prevention, early detection, diagnosis, and treatment of HCC.Methods: We searched foreign databases as Cochrane Library, PubMed, EMBASE, Web of Science and Chinese ones as CBM, CNKI, VIP and WANFANG with computer for the relevant randomized controlled trial (RCT). Other sources were also retrieved, such as tracing related references. After literature screening, data extraction and quality evaluation independently conducted by two authors according to the protocal, meta-analyses were performed using the RevMan5.1software. To study the significance of monitoring liver fibrosis, diagnosis and treatment progression of liver fibrosis and HCC related with chronic HBV infection by review methods. A retrospective analysis from October2012to June2013in Liver Disease Center of Dong Gang District Affiliated to the First Hospital of Lanzhou University was preformed to analyze clinical data that6patients with chronic HBV arised HCC during standard antiviral treatment.Results: The total of11RCTs involving1010patients were included. The trial group were given TEV combined with ADV, while the control group were given TEV alone or ADV alone. The results of meta-analysis showed that, the combined use was superior to TEV alone or ADV alone in improving HBV DNA negative rates, HBeAg negative rates, and ALT recovery rates at12-,24-,48-weeks, and there were all significant difference (P<0.05). The results of qualitative analysis showed that, the trial group had a lower drug resistance rate, and both were alike in the incidence of adverse reaction.To monitor and assess liver fibrosis related with chronic HBV infection and make timely interventions can effectively prevent cirrhosis and other complications; Transient elastography is a new, quick and easy, non-invasive, economical, and repeated diagnostic technique for liver fibrosis. The pathogenesis of HBV-induced HCC is very complicated and not yet clear, and the main mechanism include direct mechanism and indirect mechanism; The clinical diagnostic methods for HCC mainly include serological methods and imaging methods; Antiviral therapy for HBV-related HCC is the most basic cause treatment.There are6patients with chronic HBV infection in the retrospective analysis.2cases underwent chronic hepatitis,4cases underwent liver cirrhosis. HBeAg negativity in5cases.3patients had diabetes. All viral replication was low or no after antiviral therapy.Conclusion:Compared with TEV alone or ADV alone, TEV combined with ADV could improve the clinical efficacy of treating CHB which is also safe and feasible. Due to the limited quantity and quality of the included studies, the aforementioned conclusion still needs to be further verified by conducting more large-scale and high quality RCTs. Monitoring liver fibrosis is important during the course of chronic HBV infection, and transient elastography as a non-invasive diagnostic methods is currently the principal diagnosis for liver fibrosis. To find out the pathogenesis and master skillfully the clinical diagnostic methods of HBV-related HCC are significant for early discovery, diagnosis, and antiviral therapy for the patients. Suppression of viral replication of patients with chronic HBV infection does not completely eliminate the risk of HCC. Viral load, HBeAg negativity, diabetes, and cirrhosis may be risky factors of HCC.