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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide and hepatitis B virus (HBV) infection is one of most important risk factors for HCC. The development of HBV-related HCC involves a complex interaction between host and virus, and related risk factors include HBV viral load, HBeAg, and host susceptibility. Screening methods for HCC include radiological examination such as ultrasound and serological markers such as α-fetoprotein, and protein induced by vitamin K antagonist-II and alpha-fetoprotein (AFP) variants may help with the diagnosis of AFP-negative HCC. Appropriate measures such as HBV vaccination and antiviral therapy can help to prevent HCC. The long-term goal of antiviral therapy for chronic hepatitis B is to reduce complications such as liver cirrhosis and HCC. nucleos(t)ide analogues can effectively inhibit replication of virus, but they cannot eradicate covalently closed circular DNA in the nucleus of hepatocytes. There is still an urgent need for a cure for hepatitis B. This article reviews the epidemiology, risk factors, screening methods, and preventive strategies for HBV-related HCC.
ABSTRACT
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide and hepatitis B virus (HBV) infection is one of most important risk factors for HCC. The development of HBV-related HCC involves a complex interaction between host and virus, and related risk factors include HBV viral load, HBeAg, and host susceptibility. Screening methods for HCC include radiological examination such as ultrasound and serological markers such as α-fetoprotein, and protein induced by vitamin K antagonist-II and alpha-fetoprotein (AFP) variants may help with the diagnosis of AFP-negative HCC. Appropriate measures such as HBV vaccination and antiviral therapy can help to prevent HCC. The long-term goal of antiviral therapy for chronic hepatitis B is to reduce complications such as liver cirrhosis and HCC. nucleos(t)ide analogues can effectively inhibit replication of virus, but they cannot eradicate covalently closed circular DNA in the nucleus of hepatocytes. There is still an urgent need for a cure for hepatitis B. This article reviews the epidemiology, risk factors, screening methods, and preventive strategies for HBV-related HCC.
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In recent years,direct-acting antiviral agents (DAAs) have achieved great success in the treatment of hepatitis C and have replaced interferon/ribavirin.However,since DAAs were launched not long ago,there lacks sufficient knowledge of their toxic and side effects,interactions with other drugs,and safety in patients complicated by other serious chronic diseases.The results of many large-scale clinical trials show that DAAs have good safety in different populations and serious toxic and side effects are rare,but drug interactions need to be taken seriously.The addition of ribavirin in DAA regimen or prolongation of DAA treatment does not increase patients' benefits and may cause more adverse events.Moreover,at the same time of DAA treatment,liver injury caused by HCV cannot be neglected,and continuous treatment should be given.
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Hepatitis C virus (HCV) is a global health problem and people are generally susceptible to HCV.Main routes of transmission include blood transmission,sexual transmission,and mother-to-child transmission.Anti-HCV screening of blood products has substantially red uced the blood transmission of HCV.Remarkable breakthrough has been made in the treatment of hepatitis C with direct-acting antiviral agents and the trend of HCV transmission has been significantly curbed.Since HCV infection is occult,hepatitis C vaccine has not been successfully developed,and there lack effective blocking measures for mother-to-child transmission,which will become one of the major route of HCV transmission.Reducing the rate of mother-to-child transmission of HCV is very important in preventing neonatal HCV infection and reducing the incidence rate of HCV infection.In recent years,many researchers have concentrated on the detailed mechanisms and risk factors of mother-to-child transmission of HCV and made great achievements;however,there are still controversies over some issues.This article reviews the research advances in the specific mechanisms of mother-to-child transmission of HCV in China and other countries.
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ObjectiveTo investigate the accuracy of liver stiffness (LS) measured by FibroScan in the diagnosis of primary liver cancer through a meta-analysis. MethodsThe databases of PubMed, Embase, CBM, CMCI, VIP, and CNKI were searched, and a manual search was performed for related journals, to collect the articles on LS measured by FibroScan in the diagnosis of primary liver cancer published from January 2003 to June 2015. QUADAS was applied for quality evaluation and data extraction, and Meta Disc 1.4 software was applied for the Meta-analysis. ResultsA total of 6 English articles which met the inclusion criteria were included. The tests for heterogeneity showed no threshold effect, but the presence of heterogeneity caused by other reasons. In the articles included, the cut-off value for LS in the diagnosis of primary liver cancer was 11-53.7 kPa, and the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, with their respective 95% confidence intervals, were 0.66(0.61-0.71), 0.78(0.76-0.79), 3.19(239-4.25), 0.45(0.30-0.66), and 8.63(4.34-17.18), respectively. The area under the summary receiver operating characteristic curve was 0.8268, and the Q index was 0.7597. ConclusionLS measured by FibroScan has good accuracy in the diagnosis of primary liver cancer, and holds promise for clinical application.
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Liver failure is a clinical critical illness, and its complications have various clinical manifestations, often resulting in local or systemic invasive fungal disease (IFD). The damage of other organs may occur secondary to IFD in liver failure patients, thus worsening liver injury. This will ultimately lead to multiple organ failure with extremely high fatality, so it is very difficult to manage. To investigate the causes, symptoms, diagnosis, treatment, prognosis, and prevention of IFD in liver failure, this article reviews the consensus and controversy over IFD in liver failure in recent years and describes the significance and prospect of its research, with the purpose of improving the clinical diagnosis and treatment of IFD in liver failure.
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An animal model of hepatitis C virus (HCV)infection involves the use of an animal to build the model for simulating the whole process of HCV infection in humans.Establishing an ideal animal model for HCV infection is conducive to study on the pathogenesis of chro-nic hepatitis C,including virus-host interactions,viral variability,and host immune response patterns.Additionally,it provides a more ef-fective technical strategy for screening antiviral drugs and developing preventive vaccines.This article summarizes well-known animal mod-els of HCV infection,such as those established in chimpanzees,tree shrews,and mice.The advantages and drawbacks of each kind of ani-mal models are analyzed.In recent years,the establishment of small animal models,particularly those in transgenic mice,has opened up a new field in the development of animal models of HCV infection,which will be the hotspot and emphasis of relevant animal model studies.
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Objective To construct the lentiviral vector encoding CLEC4M and prepare K -562 cells with stable overexpression of CLEC4M.Methods The gene sequence of normal CLEC4Mwas cloned by reverse transcription PCR and then inserted into GV166 vector to construct GV166-CLEC4Mlentiviral expression vector,and then lentiviral packaging was performed by transfection of293T cells.The ob-tained lentiviral liquid was used to infect human leukemia cell line K-562.Real-time PCR and Western blot were used to detect the over-expression of CLEC4M in K-562 cells.Results Sequencing showed that the recombinant lentiviral expression plasmid GV166-CLEC4M was successfully constructed.Lentiviruses could efficiently infect K-562 cells,according to real-time PCR.CLEC4Mwas successfully o-ver-expressed in K-562 cells at mRNA and protein levels.Conclusion The construction of lentiviral vector encoding CLEC4M lays a foundation for further study of CLEC4M gene involved in HCV entry into host cells.
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Objective To observe the protective effects of Toll-like receptor(TLR)-4 siRNA against acute liver injury in mice induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Methods One hundred and fifty C57BL/6 male mice were divided into 5 groups: phosphate buffered solution(PBS)pretreatment group,negative control plasmid pretreatment group,TS4 pretreatment group,TS6 pretreatment group and TS7 pretreatment group.Acute liver injury was induced in mice by intraperitoneal coinjection of LPS(10 ng/g)and D-GalN(1 mg/g).In vivo delivery of siRNA was performed via the tail vein by hydrodynamic injections(50 μg siRNA dissolved in 1 mL PBS)24 h and 48 h before coinjection of LPS and D-GalN. Expression of TLR-4 in liver tissues was measured by immunohistochemistry.The changes of TLR-4,tumor necrosis factor(TNF)-α and macrophage nflammatory protein(MIP)-2 mRNA levels in liver tissues were determined by reverse transcriptasepolymerase chain reaction(RT-PCR)analysis.MIP-2 and TNF-α concentrations in the sera of mice were determined by enzyme-linked immunosorbent assay(ELISA). Levels of alanine transaminase (ALT) and aspartate transaminase(AST) in serum were measured by standard autoanalyzer techniques. Liver pathological changes were observed by haematoxylin-eosin staining, while cell apoptosis levels in liver were determined by terminal deoxynucleotidyl-mediated-dUTP nick end labeling (TUNEL)assay. The difference of survival rates in 5 groups was analyzed by Fisher's exact probability test.ResultsPretreatment with TLR-4 siRNA down-regulated the TLR-4 mRNA and protein expressions,and significantly decreased the mortality and liver injury caused by coinjection of LPS and D-GalN in C57BL/6 mice.TLR-4 siRNA significantly down-regulated the TNF-α and MIP-2 mRNA expression and cytokine levels as determined by RT-PCR and ELISA,respectively. TLR-4 siRNA abrogated hepatocyte necrosis and inflammatory infiltration and also remarkably reduced serum concentrations of transaminases. The percentage of TUNEL-positive hepatocytes was significantly reduced in TLR-4 siRNA pretreatment group(TS4 pretreatment group: 0.065±0.015 vs PBS pretreatment group; 0.346±0.062,P＜0.05).ConclusionIt suggest that inhibition of TLR-4 expression by TLR-4 siRNA may provide potential application value for preventing liver injury.
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Objective To study the cause of protective immunodeficiency of patients with hepatitis C. Methods An antigen capture ELISA in which HCV synthetic peptides SP42, CP10 and CP9 derived from HCV NS4 and core gene region, respectively, were used as solid-phase antigens was used to detect the differences in light chain isotype expression of anti-HCV antibodies. Results Antibodies in 84 sera of HCV-infected patients against HCV SP42, CP10 and CP9 were characterized by a skewed light chain isotype expression. Eighty-two out of 84 sera of HCV infection (97 62%) showed at least one of the three anti-HCV antibodies skewed from the normal ratio of light chain isotype kappa/lambda. The kappa/lambda ratios of anti-HCV antibodies in all patients with hepatitis C were found to be unique and constant during one year follow-up, and 11 of them received two years follow-up. Conclusions Anti-HCV response was stable and clonally restricted in HCV infection. B-cell clonal dominance may be the cause of human protective immunodeficiency after HCV infection.
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Objective To detect hepatitis C virus (HCV) RNA in amniotic fluid of gravida and investigate mother-to-infant transmission of HCV. Methods Thirty-four HCV seropositive gravida (experimental group) were engaged. Fluorescence quantitative polymerase chain reaction (PCR) based on amplisensor assay and reverse transcription -PCR (RT-nPCR) was used. Serum HCV RNA positive sera were genotyped by RFLP analysis of PCR products from 5′NC region. Sera and amniotic fluid samples of 40 normal gravida were set as the control group. Results In the experimental group, HCV RNA was detected in amniotic fluid (5.9%, 2/34) of 2 cases. HCV RNA titers were 10 5 and 10 6 copy/ml respectively. No HCV RNA was detected in the amniotic fluid and sera of the control (n=40). Conclusions HCV RNA was rarely detected in amniotic fluid. The amniotic fluid is not the main route of HCV mother-to-infant transmission.
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Objective To study the expression and distribution of TIMP 1 and TIMP 2 in liver tissue of cirrhosis patient and to investigate the roles and pathogenesis of TIMP 1 and TIMP 2 in liver cirrhosis. Methods TIMP 1 and TIMP 2 proteins and mRNA were detected with immunohistochemistry and in situ hybridization methods using monoclonal antibodies and cDNA probes. Results mRNA and proteins of TIMP 1 and TIMP 2 were detected in all the liver tissues from 40 liver cirrhosis patients, all in cytoplasm but not nucleus. TIMP 1 and TIMP 2 were found co exist in all samples, while TIMP 1 concentration was higher. Conclusions mRNA and protein of TIMP 1 and TIMP 2 are found in all the cirrhosis patient samples. Liver TIMP 1 and TIMP 2 concentrations increase with the progression of liver cirrhosis, decrease the degradation of extracellular matrix proteins, resulting in the initiation and the development of liver fibrosis and liver cirrhosis.
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Bacterial translocation is a major contributor to sepsis and multisystem organ failure.This paper reviews the studies in recent years.We will briefly introduce the advance in bacterial translocation,and expound its pathogenesis,prognosis,diagnosis,therapy,as well as significance and prospects.
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Objective To investigate the efficacy of thymosin alpha-1(T?_1,Zadaxin)monotherapy for chronic HBV infection by a meta-analysis of the published data. Methods Randomized controlled trials on thymosin alpha-1 monotherapy in chronic HBV infection were searched from electronic databases such as MEDLINE、PUBMED and Blackwell. Results Meta-analysis of 7 randomized controlled studies investigating the safety and efficacy of thymosin alpha-1 monotherapy for the treatment of chronic hepatitis B showed that 6 months treatment with thymosin alpha-1(1.6 mg twice weekly)almost tripled the sustained response rate(38%)compared with controls(13%).Conclusion These results suggest that a 6-month course of thymosin alpha-1 therapy is effective and safe in patients with chronic hepatitis B;thymosin alpha-1 can effectively reduce HBV replication in CHB with patients. Compared with IFN-?,thymosin alpha-1 which has less side effects is better tolerated and seems to induce a gradual and more sustained normalization of ALT and loss of HBV DNA.
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Objective To observe the inhibition of asON phosphorothioate to the TIMP-1 gene and protein expression in the liver tissue of immune- induced hepatic fibrosis rats. Methods According to the analysis of modulator, structure protein, encoding sequence of TIMP-1 genome, we designed four different groups of asONs. These asONs were injected into the hepatic fibrosis rat models through coccygeal vein. The results were observed by RT-PCR, immunohistochemistry and in situ hybridization with collagen Ⅰ、Ⅲ, special staining of collagen fiber, electron microscope. Results The asON phosphorothioate of TIMP-1 could be expressed in vivo, and could block the TIMP-1 gene and protein expression in the liver of immune- induced hepatic fibrosis rats on the level of mRNA, which could promote the degradation of collagen Ⅰ、Ⅲ(P
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An experimental immunity hepatic fibrosis rat model was prepared by means of immunologic assault with human serum albumin, and normal rats served as a control group. The immunohistochemistry methods and in situ hybridization were respectively used to detect TIMP 2 mRNA and related antigens in the liver,and to investigate the localization and expression of TIMP 2 in the liver of both normal and experimental hepatic fibrosis rats. The results showed that TIMP 2 mRNA and related antigens in the livers of experimental group were expressed in myofibroblasts and fibroblasts, especially in the portal area and fibrous septum. The positive signal was located in the cytoplasm, but not in the nucleus. On the other hand, there was a high level of expression of TIMP 2 in the liver of the experimental group.It is suggested that in the process of hepatic fibrosis, fibroblasts and myofibroblasts are the major cells expressing TIMP 2. The severer the hepatic fibrosis in the injured liver is, the higher the levels of TIMP 2 related antigens and gene expression are.