1. Salvage Therapy In Patients With Lamivudine-resistant CHB Systematic Review 2.MOV10 Expression And The Role Of Research In HBV Infection

Background: Hepatitis B infection (HBV) is a serious global healthproblem. Lamivudine(LAM) resistance has become a serious clinicalchallenge. Previous rescue therapy for LAM resistance CHB patientsinclude switching to entecavir(ETV) and adding adefovir(ADV) ortenofovir(TFV). At present, switching to ETV is not recommended forrescue therapy for LAM resistance CHB patients. The aim of this article wasto study whether Add-on ADV is superior to a switch to ETV as rescuetherapy for LAM-resistant CHB patients. Methods: We searchedMedline/PubMed, EMBASE and the Cochrane library. The search wasdesigned using “adefovir”,“lamivudine”,“entecavir”,“resistance”, or“refractory”, or “resistant”. We obtained full articles and abstracts for allpotentially relevant trials, and the reference lists from retrieved documentswere also searched. Relative risks (RRs) of vriologic response, virologicbreakthrough, normalization of serum alanine aminotransferase (ALT), and HBeAg seroconversion were studies. Factors predicting virologic responseand safety were reviewed. Meta-analysis was performed using fixed effect orrandom-effect methods, depending on the absence or presence of significantheterogeneity. Statistical heterogeneity between trials was evaluated by thechi-square and I-square (I2) tests, with significance set at P <0.10. In theabsence of statistically significant heterogeneity, the fixed-effect methodwas used to combine the results. When heterogeneity was confirmed (P<0.10), the random-effect method was used.The overall effect was testedusing z scores calculated by Fisher’s z’ transformation, with significance setat P <0.05. Data analysis was carried out with the use of Review ManagerSoftware5.0(Cochrane Collaboration, Oxford, United Kingdom). Results:Eight eligible trials (822) patients in total were included. The rate ofvirologic breakthrough in LAM plus ADV groups was lower than that inETV groups(RR=0.23,95%CI:0.12-0.47, P<0.0001) at the end of48weekstreatment.. There were no statistical difference in virologicresponse(RR=1.12,95%CI:0.94-1.33,P=0.2), ALT normalization(RR=1.01,95%CI:0.92-1.11,P=0.9) and HBeAg seroconversion(RR=0.64,95%CI:0.33-1.24,P=0.19) in both groups at the end of48weeks treatment.The baseline of HBV DNA level and HBeAg were factors predictingvirologic response. Additionally, combination therapy or monotherapy wasboth well tolerated. Conclusions: LAM plus ADV combination therapy wasmore potent and durable than a switch to ETV monotherapy for LAM-resistant CHB patients. Studies included this meta-analysis werefewer. Latest evidence of the present research for this topic was consistentwith evidence of previous studies. The previous study, published ininternational journals, has been cited18times (Google academic engine). Itoffered evidence-based medicine evidence for clinical diagnosis andtreatment. Maintain and update data with the published research literature beneeded to increase the strength of the evidence. Chronic hepatitis B virus infection (HBV) is a serious global healthproblem. Approximately350million individuals suffered from chronichepatitis B (CHB) infection worldwide and about1million patients died ofliver failure, cirrhosis and hepatocellular carcinoma (HCC) as a result ofHBV infection each year. Studies have demonstrated that the risk of liverdisease progression in patients with CHB is associated with elevated HBVDNA levels. Therefore, the goal of therapy for CHB patients is to delay orprevent progression of liver disease by suppressing long-term HBV DNAreplication.Antiviral therapy for CHB patients has great progress. It reduced theincidence of hepatic decompensation, liver cirrhosis, HCC and relatedcomplications, and improved the CHB patients’ quality of life. But it stilllacks the treatment which can get rid of the HBV completely. Previousstudies have shown that interaction of HBV and host liver cell leads to CHB,cirrhosis and HCC. Now, it is not fully understand about the mechanism ofHBV replication and regulation which causes the failure of developmentnew drugs for elimination the HBV from host cells. With the development of proteomics technology such asmass-spectrometric and stable isotope label techniques, protein function canbe analysed in a brand new platform. In our previous work, we identifiedsome differentially expressed proteins in CHB patients and health peopleliver biopsy by iTRAQ technique. Over-expression of Moloney leukemiavirus10protein (MOV10) was identified in CHB patients liver biopsy.MOV10belongs to the RNA helicase superfamily-1. Studies found thatit was required for RNA-mediated gene silencing by the RNA-inducedsilencing complex (RISC). The detailed physiological function of MOV10isstill unclear. In this study, we will verify the expression of mov10in the liverbiopsy of patients with CHB and health people, as well as the humanhepatoma cell line in HepG2.2.15and HepG2. We aim to explore the roleof MOV10in HBV replication, which can provide new clues in drug targetresearch.We detected MOV10expression in different tissues and cell lines byreal-time quantitative RT-PCR and Western-blot. MOV10mRNA level andprotein expression increased in CHB patients liver biopsy, as well as inHepG2.2.15compared with HepG2. We found that MOV10mRNA leveland protein expression were dowe-regulated in HepG2.2.15when HBVDNA was undetectable after lamivudine treatment. We observed the effectof MOV10protein changes on HBV replication by siRNA knock-down andplasmid transfection. The results showed that no matter how the supression or overexpression of MOV10protein expression in HepG2.2.15did not leadto a significant difference on the level of HBV DNA, HBsAg and HBeAg inthe supernatant between the control group and the intervention group.Transient changes of MOV10protein expression was no direct impact on theHBV replication.Although our study did not find the effect of host antiviral proteinMOV10on HBV replication, the study found MOV10protein expressionwas up-regulated in HBV infected liver tissues and HepG2.2.15cell, whichsuggested that other biological functions of MOV10protein may also exist.Study found that the MOV10mRNA level and protein expression in cancercells were2-3times higher than that of the normal cells and MOV10was atelomerase-associated protein. We presume MOV10may participate in HCCdevelopment which caused by HBV infection.