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| 1 | Dysfunction of peripheral blood dendritic cells from patients with chronic hepatitis B virus infection显示文摘AIM To identify the property of dendritic cella (DCs) of peripheral blood monocytes (PBMC) in patlents with chronic HBV infection.METHODS Twenty patients with persistent HBV infectlon were included in this study, 10 healthy subjects being used as a control group. The peripheral blood mononuclear cells (PBMC) of T cell-depleted populations were incubated and induced into mature dendritic cells in the RPMI-1640 medium in the presence of cytokines GMCSF, IL-4, FLt-3, TNF-α and 100 mL@ L-1 of fetal calf serum for a total of 10 - 12 days. The expressions of surface markers on DCs were evaluated using flow cytometric analysis. ELISA method was used to determine the cytokine levels of interleukin-12 (IL-12) and IL-10 in the supernatant produced by DCs. For detection of the stimulatory capacity of DCs to T cell proliferation,mytomycin C-treated DC were incubated with allogenic T cells.RESULTS A typical morphology of mature DCs from healthy subjects and HBV-infected patients was induced in in vitro incubation, but the proliferation ability and cellular number of DCs from HBV-infected patients significantly decreased compared with healthy individuals. In particular, the expression levels of HLADR, CD80 (B7-1) and CD86 (B7-2) on DC surface from patients were also lower than that from healthy individuals (0.46 vs 0.92 for HLA-DR, 0.44 vs 0.88 for CD80 and 0.44 vs 0. 84 for CD86, P< 0.05). The stimulatory capacity and production of IL-12 of DCs from patients in allogenic mixed lymphocyte reaction (AMLR) significantly decreased, but the production level of nitric oxide (NO) by DCa simultaneously increased compared with healthy subjects (86± 15 vs 170±22 μmoI@L 1, P<0.05).CONCLUSION The patients with chronic HBV infection have the defective function and immature phenotype of dendritic cells, which may be associated with the inability of efficient presentation of HBV antigens to host immune system for the clearance of HBV. | Fu-Sheng Wang Li-He Xing Ming-Xu Liu Chuan-Lin Zhu Hui-Gang Liu Hui-Fen Wang Zhou-Yun Lei Division of Biological Engineering,~2 Fourth Department of Liver Diseases,Beijing Institute of Infectious Diseases,Beijing Hospital of Infectious Diseases,Beijing 100039,China | 2001 | World Journal of Gastroenterology2001，7，4： | 131 |
| 2 | 婴儿巨细胞病毒性肝炎(上)显示文摘 | 董永绥 | 2006 | 临床儿科杂志2006，24，1： | 69 |
| 3 | Global epidemiology of hepatitis C virus infection: an up-date of the distribution and circulation of hepatitis C virus genotypes显示文摘AIM To review Hepatitis C virus(HCV) prevalence and genotypes distribution worldwide.METHODS We conducted a systematic study which represents one of the most comprehensive effort to quantify global HCV epidemiology,using the best available published data between 2000 and 2015 from 138 countries(about 90% of the global population),grouped in 20 geographical areas(with the exclusion of Oceania),as defined by the Global Burden of Diseases project(GBD). Countries for which we were unable to obtain HCV genotype prevalence data were excluded from calculations of regional proportions,although their populations were included in the total population size of each region when generating regional genotype prevalence estimates.RESULTS Total global HCV prevalence is estimated at 2.5%(177.5 million of HCV infected adults),ranging from 2.9% in Africa and 1.3% in Americas,with a global viraemic rate of 67%(118.9 million of HCV RNA positive cases),varying from 64.4% in Asia to 74.8% in Australasia. HCV genotype 1 is the most prevalent worldwide(49.1%),followed by genotype 3(17.9%),4(16.8%) and 2(11.0%). Genotypes 5 and 6 are responsible for the remaining < 5%. While genotypes 1 and 3 are common worldwide,the largest proportion of genotypes 4 and 5 is in lower-income countries. Although HCV genotypes 1 and 3 infections are the most prevalent globally(67.0% if considered together),other genotypes are found more commonly in lowerincome countries where still account for a significant proportion of HCV cases.CONCLUSION A more precise knowledge of HCV genotype distribution will be helpful to best inform national healthcare models to improve access to new treatments. | Arnolfo Petruzziello Samantha Marigliano Giovanna Loquercio Anna Cozzolino Carmela Cacciapuoti | 2016 | World Journal of Gastroenterology2016，22，34： | 69 |
| 4 | Immune suppression in chronic hepatitis B infection associated liver disease: A review显示文摘Hepatitis B virus(HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer(HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer(NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC),NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBVinduced immune dysfunction and HBV-related liver diseases are not understood.In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC. | Tian-Yang Li Yang Yang Guo Zhou Zheng-Kun Tu | 2019 | World Journal of Gastroenterology2019，25，27： | 69 |
| 5 | Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis显示文摘AIM To evaluate the antifibrotic effect ofdifferent doses of recombinant human Gamma-Interferon (IFN-γ) intwo rat models of hepaticfibrosis, and to observe its effect on moderatechronic hepatitis B virus fibrosis.METNODS Hepatic fibrosis was successfullyinduced in 150 and 196 rats by subcutaneousinjection of carbon tetrachloride (CCl4) andintraperitoneal injection of dimethylnitrosamine(DMN), respectively. Each of the two modeldose IFN-γ group (15 MU/kg per day, i.m. for 8group (1.67 MU/kg daily, i.m. for 8 weeks).Another group of 10 rats without any treatmentwas used as normal controls. At the end of theexperiment, semi-quantitative histopathologicalscores of inflammation and fibrosis, liver (αsmooth muscle actin (α-SMA) expression level,liver hydroxyl proline content and serumhyaluronic acid levels were compared. And 47medium chronic hepatitis B viral fibrosispatients were studied. They were given IFN-γtreatment, 100MU/day i.m. for the first threemonths and 100MU qod i.m. for the next sixmonths. Semi-quantitative pathological scoresof inflammation and fibrosis and serum hepaticfibrosis indices were compared within the 9months.RESULTS In animal experiment, thepathological fibrosis scores and liver hydroxylproline content were found to be significantlylower in rats treated with different doses of IFN-γ as compared with rats in fibrotic model groupinduced by either CCI4 or DMN, in a dose-dependent manner. For CCI4-induced model,pathological fibrosis scores in high, medium andIow doses IFN-γ groups were 5.10 ± 2.88, 7.70 ±3.53 and 8.00 ± 3.30, respectively, but the scorewas 14.60 ± 7.82 in fibrotic model group.Hydroxyl proline contents were 2.83 ± 1.18, 3.59± 1.22 and 4.80 ± 1.62, in the three IFN-γgroups, and 10.01 ± 3.23 in fibrotic model group.The difference was statistically significant(P<0.01). Similar results were found in DMN-induced model. Pathological fibrosis scoreswere 6.30±0.48, 8.10 ±2.72 and 8.30 ±2.58, inhigh, medium and Iow doses IFN-γ groups, and12.60 ± 3.57 in fibrotic model group. Hydroxylproline contents were 2.72 ± 0.58, 3.14 ± 0.71and 3.62 ± 1.02, in the three IFN-γ groups, and12.79 ± 1.54 in fibrotic model group. Thedifference was statistically significant(P<0.01). Serum hepatic fibrosis indicesdecreased significantly in the 47 patients afterIFN-γ treatment (HA: 433.38 ± 373.00 vs 281.57± 220.48; LN: 161.22± 41.02 vs 146.35 ± 44.67;PCⅢ: 192.59 ± 89.95 vs 156.98 ± 49.22; C-Ⅳ:156.30 ± 44.01 vs 139.14 ± 34.47) and thedifferences between the four indices weresignificant (P<0.05). Thirty-three patientsCONCLUSION All the three doses of IFN-γ areeffective in treating rat liver fibrosis induced byeither CCl4 or DMN, the higher the dose, thebetter the effect. And IFN-γ is effective forpatients with moderate chronic hepatitis B viralfibrosis. | Hong Lei Weng Wei Min Cai Rong Hua Liu Institute of Infectious Diseases, First Affiliated Hospital. Medical School. Zhejiang University, Hangzhou 310003, Zhejiang Province. China | 2001 | World Journal of Gastroenterology2001，7，1： | 53 |
| 6 | Clinical characteristics and outcome of a cohort of 101 patients with hepatocellular carcinoma显示文摘AIM To conduct a cohort study of 101 patients with hepatocellular carcinoma (HCC) presenting to a tertiary care medical referral center in Germany between 1997 and 1999.METHODS AND RESULTS Data were retrospectively analyzed by chart review. In 95cases (72 males and 23 females) sufficient data were available for analysis. Twenty-five (29%)of 8.5 patients were HBsAg or anti-HBc positive,21/85 (25%) were anti-HCV positive, and 6/85(7%) were positive for both HBV and HCV-markers. Age was significantly lower in HBV-positive patients than in the other two groups.Thirty-one (34%) of 90 patients had histories of alcohol abuse, In 79/ 94 (84%) patients,cirrhosis was diagnosed. Of these cirrhotic patients, 29/79 (37%) belonged to Child-Pugh's group (CHILD) A, 32/79 (40%) to CHILD B, and 18/79 (23%) to CHILD C. AFP was elevated in 61/91 (67%) patients. A single tumor nodule was found in 38/94 (40%), more than one nodule in 31/94 (34%), and 25/94 (26%) had a diffusely infiltrating tumor, i.e. the tumor margins could not be seen on imaging procedures. Portal vein thrombosis was present in 19/ 94 (20%).Imaging data consistent with lymph node metastases were found in 10/92 (11%), while distant metastases were found in 8/93 (9%).According to Okuda 28/94 (30%) were grouped to stage Ⅰ, 53/94 (56%) were grouped to stage Ⅱ, and 13/94 (14%) were grouped to stage Ⅲ.Survival data were available for 83 patients. The Kaplan-Meier estimate for median survival was 8.4 months. Factors influencing survival were the Okuda score, the presence of portal vein thrombosis, and the presence of ascites. The presence of non-complicated liver cirrhosis by itself, distant metastases, or infection with hepatitis viruses did not influence survival. AFP positivity by itself did not influence survival,though patients with an AFP value greater than 100μg/L did experience shortened survival.Treatment besides tamoxifen or supportive care was associated with prolonged survival. The influence of therapy on survival was most pronounced in Okuda stage Ⅱ patients. There was longer survival in those Okuda stage Ⅱpatients who were treated with percutaneous ethanol injection.CONCLUSION Even in a Iow incidence area such as Germany, the majority of HCC is caused by viral hepatitis and therefore potentially preventable. Reflecting the high proportion of advanced stage tumors in our patients, the median survival was poor. Patients who received active therapy had a longer survival. | Christian Rabe Tillmann Pilz Christoph Klostermann Marc Berna Hans H.Schild Tilman Sauerbruch Wolfgang H.Caselmann | 2001 | World Journal of Gastroenterology2001，7，2： | 60 |
| 7 | An insight into the diagnosis and pathogenesis of hepatitis C virus infection显示文摘This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved. | Mohammad Irshad Dhananjay Singh Mankotia Khushboo Irshad | 2013 | World Journal of Gastroenterology2013，19，44： | 52 |
| 8 | Detection of serum TNF-α,IFN-γ,IL-6 and IL-8 in patients with hepatitis B显示文摘NTRODUCTIONSinceMuto[1]reportedthatTNFαandIL1wererelatedtofulminanthepatitis,thestudiesontherelationshipbetweencytokinesa... | WANG Jing Yan, WANG Xue Lian and LIU Pei | 1999 | World Journal of Gastroenterology1999，5，1： | 54 |
| 9 | Diagnostic value of PIVKA-Ⅱ and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma显示文摘AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein(AFP) and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ) in chronic hepatitis B(CHB).METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma(HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic(AUROC) curves of PIVKA-Ⅱ, AFP and their combination were calculated and compared.RESULTS: The optimal cutoff values for PIVKA-Ⅱ and AFP were 40 m AU/m L and 10 ng/m L, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-Ⅱ and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-Ⅱ and AFP were not significantly different(0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-Ⅱ was significantly better than that of AFP in patients with cirrhosis(0.870 vs 0.812, P = 0.042). When PIVKA-Ⅱ and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-Ⅱ alone for the differentiation of HCC from nonmalignant CHB(P < 0.05), especially when cirrhosis was present(P < 0.05).CONCLUSION: Serum PIVKA-Ⅱ might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB. | Seung In Seo Hyoung Su Kim Won Jin Kim Woon Geon Shin Doo Jin Kim Kyung Ho Kim Myoung Kuk Jang Jin Heon Lee Joo Seop Kim Hak Yang Kim Dong Joon Kim Myung Seok Lee Choong Kee Park | 2015 | World Journal of Gastroenterology2015，21，13： | 60 |
| 10 | A randomized controlled clinical trial on the treatment of Thymosin-a1 versus interferon-α in patients with hepatitis B显示文摘INTRODUCTIONChronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse sequelae ,such as cirrhosis and hepatocellular carcinoma .The World Health Organization estimates that HBV has infected mord than 350 million people worldwide ,and up to 20% of them will become chromic carricrs and will be at significant risk for cirrhosis and HCC .The ultimate goal of the therapy for chronic hepatitis B is to prevent progression to cirrhosis and to prevent development of HCC. | Jing You Lin Zhuang Bao Zhang Tang Wei Bo Yang Su Ying Ding Wu Li Rong Xue Wu Hong Li Zhang Yan Mei Zhang Shao Ming Yan Lu Zhang ~1Department of Infectious Diseases,The First Affiliated Hospital of Kunming Medical College,Kunming 650032,Yunnan Province,China ~2Departrnent of Hepatology,Kunming Third Municipal People’s Hospital,Kunming 650041,Yunnan Province,China | 2001 | World Journal of Gastroenterology2001，7，3： | 48 |
| 11 | Effect of hepatitis C virus infection on expression of several cancer-associated gene products in hepatocellular carcinoma显示文摘NTRODUCTIONOurpreviousstudiesbyseroepidemiological,molecularepidemiologicalandimmunopathologicalmethodshaverevealedthathepa... | YANG Jian Min, WANG Rong Quan, BU Bao Guo, ZHOU Zi Cheng, FANG Dian Chun and LUO Yuan Hui | 1999 | World Journal of Gastroenterology1999，5，1： | 42 |
| 12 | Th1/Th2 cytokines and their genotypes as predictors of hepatitis B virus related hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC), the predominant type of primary liver cancer, is one of the most serious lifethreatening malignancies, worldwide. In majority of the cases, HCC develops after prolonged and persistent chronic liver disease. hepatitis B virus(HBV) or HCV infection is prominent etiological factors, attributing to this condition. It has been well documented that HBV, being the inducer of chronic inflammation, is the main causative agent in causing HCC, particularly in Asian countries. The HBV infection leads to a wide range of clinical symptoms from carrier state to malignancy. Cytokines being immune-modulatory molecules, are the key mediators in the defense mechanism against viral infection. In this regard, this review will detail the substantial role of key Th1: interleukin 1(IL-1), IL-2, IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4, IL-10 and non Th1/Th2: IL-6, transforming growth factor-β1 cytokines genotypes in analyzing the variability in the clinical manifestations in an HBV-afflicted individual, which might finally, culminates into HCC. Since cytokine production is regulated genetically, the cytokine promoter region single-nucleotide polymorphisms induced changes, greatly affects the cytokine production, thus resulting into differential outcome of immune balance. | Roli Saxena Jyotdeep Kaur | 2015 | World Journal of Hepatology2015，7，11： | 50 |
| 13 | Entecavir vs lamivudine therapy for na?ve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure显示文摘AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a single center,prospective cohort study.Eligible,consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100mg/d.All patients were given standard comprehensive internal medicine.The primary endpoint was survival rate at day 60,and secondary endpoints were reduction in hepatitis B virus(HBV)DNA and alanine aminotransferase(ALT)levels,and improvement in Child-Turcotte-Pugh(CTP)and model for end-stage liver disease(MELD)scores at day 60 and survival rate at week 52.RESULTS:One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B:65 were included in the entecavir group and 54 in the lamivudine group(full analysis set).No significant differences were found in patient baseline clinical parameters.At day 60,entecavir did not improve the probability of survival(P=0.066),despite resulting in faster virological suppression(P<0.001),higher rates of virological response(P<0.05)and greater reductions in the CTP and MELD scores(all P<0.05)than lamivudine.Intriguingly,at week 52,the probability of survival was higher in the entecavir group than in the lamivudine group[42/65(64.6%)vs 26/54(48.1%),respectively;P=0.038].The pretreatment MELD score(B,1.357;95%Cl:2.138-7.062;P=0.000)and virological response at day30(B,1.556;95%Cl:1.811-12.411;P=0.002),were found to be good predictors for 52-wk survival.CONCLUSION:Entecavir significantly reduced HBV DNA levels,decreased the CTP and MELD scores,and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF. | Yang Zhang Xiao-Yu Hu Sen Zhong Fang Yang Tao-You Zhou Guo Chen Yan-Yan Wang Jian-Xing Luo | 2014 | World Journal of Gastroenterology2014，20，16： | 42 |
| 14 | Hepatitis B virus genotypes:Global distribution and clinical importance显示文摘At least 600000 individuals worldwide annually die of hepatitis B virus(HBV)-related diseases,such as chronic hepatitis B(CHB),liver cirrhosis(LC),and hepatocellular carcinoma(HCC).Many viral factors,such as viral load,genotype,and specific viral mutations,are known to affect disease progression.HBV reverse transcriptase does not have a proofreading function,therefore,many HBV genotypes,sub-genotypes,mutants,and recombinants emerge.Differences between genotypes in response to antiviral treatment have been determined.To date,10 HBV genotypes,scattered across different geographical regions,have been identified.For example,genotype A has a tendency for chronicity,whereas viral mutations are frequently encountered in genotype C.Both chronicity and mutation frequency are common in genotype D.LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes.Pathogenic differences between HBV genotypes explain disease intensity,progression to LC,and HCC.In conclusion,genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment. | Mustafa Sunbul | 2014 | World Journal of Gastroenterology2014，20，18： | 42 |
| 15 | Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments显示文摘Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB. | Ceen-Ming Tang Tung On Yau Jun Yu | 2014 | World Journal of Gastroenterology2014，20，20： | 41 |
| 16 | Changes in circulating Foxp3^+ regulatory T cells and interleukin-17-producing T helper cells during HBV-related acute-on-chronic liver failure显示文摘AIM:To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells,to observe T-cell phenotypes during hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACHBLF)and to analyze changes in Th17 and Treg phenotypes during disease progression.METHODS:We measured the expression of seven Th17/Treg differentiation-related genes and serum concentrations of the corresponding cytokines in 18ACHBLF,18 chronic hepatitis B(CHB)disease controls and 10 healthy controls(HCs)by real-time quantitative pCR and enzyme linked immunosorbent assay.peripheral Th17 and Treg cell frequencies were analyzed by flow cytometry.RESULTS:From the onset of ACHBLF,patients presented with a conductive Th17 differentiation cytokine environment accompanied by high Th17 frequency and high serum IL-17 levels,which were sustained throughout the disease course.The Treg-related cytokine IL-2and Foxp3 were also up-regulated from disease onset,and Foxp3 gene expression showed a gradually increasing trend during ACHBLF.The circular phenotype of Treg and Th17 cells showed changes from the onset of ACHGLF.At disease onset,Th17 frequency increased significantly compared with both CHB and HCs,but Treg cell frequency decreased significantly compared with CHB.During the ACHBLF event,Th17 frequency remained higher compared with HCs,but decreased sharply from the peak point to the recovery point;Treg cell frequency increased gradually during the ACHBLF event.Treg and Th17 cell counts correlated with ACHBLF development;in all patients,serum IL-17 levels significantly correlated with patient serum ALT levels.In survivors,Th17 frequency at the onset point and the Treg to Th17 ratio at the peak point correlated with the patient’s model for end stage liver disease(MELD)plus sodium(MELD-Na)score.The Treg to Th17 ratio and the Th17 frequency at onset were significant predictors of patient survival.Low Treg/Th17 cell ratios at the onset predicted poor survival.Survivors exhibited an initial decrease in the circulating Treg/Th17 ratio from the onset to the peak time,and subsequently displayed a continuous increase.CONCLUSION:Treg and Th17 cells showed changes in genes,protein levels and T cell phenotypes during ACHBLF events.An increased Treg/Th17 ratio was associated with the survival of ACHBLF patients. | Xue-Song Liang Cheng-Zhong Li Yin Zhou Wei Yin Ya Yun Liu Wen-Han Fan | 2014 | World Journal of Gastroenterology2014，20，26： | 44 |
| 17 | Hepatitis B:Epidemiology and prevention in developing countries显示文摘Hepatitis B virus(HBV)infection is a serious global public health problem.The infection may be transmitted through sexual intercourse,parenteral contact or from an infected mother to the baby at birth and,if contracted early in life,may lead to chronic liver disease,including cirrhosis and hepatocellular carcinoma.On the basis of the HBV carrier rate,the world can be divided in 3 regions of high,medium and low endemicity.The major concern is about high endemicity countries,where the most common route of infection remains vertical transmission from mother to child.Screening of all pregnant women and passive immunization with human hepatitis B immunoglobulin are not affordable for many developing countries.The infection rate can be reduced by modifying behavior,improving individual education,testing all blood donations,assuring asepsis in clinical practice and screening all pregnant women.However,availability of a safe and efficacious vaccine and adoption of appropriate immunization strategies are the most effective means to prevent HBV infection and its consequences.The unsolved problem for poorest countries,where the number of people currently infected is high,is the cost of the vaccine.A future challenge is to overcome the social and economic hurdles of maintaining and improving a prevention policy worldwide to reduce the global burden of the disease. | Elisabetta Franco Barbara Bagnato Maria Giulia Marino Cristina Meleleo Laura Serino Laura Zaratti | 2012 | World Journal of Hepatology2012，4，3： | 39 |
| 18 | Antiviral therapy for hepatitis B virus associated hepatic failure显示文摘BACKGROUND:Chronic hepatitis B virus(HBV)infection remains a major global health issue,and the prognosis of patients with HBV-associated fulminant hepatic failure is extremely poor.The application of antiviral therapies has led to significant improvements in patient outcomes.This article aimed to review the current strategies in antiviral treatment of HBV-associated fulminant hepatic failure. DATA SOURCES:Literature search was conducted using PubMed on the related subjects.Part of the data was from the most recent work of the authors’laboratory. RESULTS:Hepatitis B immunoglobulin in prevention of recurrent HBV infection after orthotopic liver transplantation(OLT)has been proven effective.However, its cost is high,and significant side effects have been found to induce viral mutations.Lamivudine has a potent suppression for HBV replication and an excellent safety profile in decompensated cirrhotic patients,but its major drawback is the high rate of drug-resistance.Adefovir is effective for lamivudine-resistance strains in the post- OLT situation,and its drug-resistance rate is relatively low. Combination therapies such as hepatitis B immunoglobulin combined with lamivudine and lamivudine combined with adefovir have been widely adopted for prophylaxis against HBV recurrence of infection after OLT.Entecavir, telbivudine,tenofovir and other newer agents have been widely used in antiviral therapy. CONCLUSIONS:The prognosis of HBV-associated ful- minant hepatic failure is being transformed by developments in antiviral therapy.However,it should be noticed that HBV is controlled but never eliminated,and drug-resistance still remains a major issue.Hopefully,newer strategies may help to solve these problems. | Wang, Yu-Ming Tang, Ying-Zi | 2009 | Hepatobiliary & Pancreatic Diseases International2009，8，1： | 36 |
| 19 | Expression of CXC chemokine IP-10 in patients with chronic hepatitis B显示文摘BACKGROUND: Chemokines have strong chemoattractant effects and are involved in a variety of immune and inflammatory reactions, such as attracting activated T lymphocytes, neutrophils, monocytes and natural killer cells via the pathway of G protein-coupled receptors to sites of inflammatory injury and contribute to wound repair. This investigation was designed to assess the levels of chemokine interferon-γ inducible protein-10 (IP-10) and IP-10 mRNA, and the relationship between IP-10 mRNA and HBV-DNA and alanine aminotransferase (ALT) in patients with chronic hepatitis B. METHODS: The levels of IP-10 mRNA in peripheral blood mononuclear cells (PBMCs) were kinetically detected by real-time polymerase chain reaction (PCR). The rate of chemokine/GAPDH was regarded as the extreme level of chemokine. The level of IP-10 in serum was measured by enzyme linked immunosorbent assay (ELISA), and the expression of IP-10 in hepatic biopsy tissue was detected by streptavidin-peroxidase (SP) immunohistochemistry. RESULTS: The level of IP-10 mRNA in the PBMCs of patients was 0.7387±0.0768 (lg cDNA/lg GAPDH); it was significantly higher in patients with chronic hepatitis B than that in normal controls (P<0.001). The level of IP-10 in the serum of patients was 660.9±75.5 pg/ml. There was a significant difference between patients with chronic hepatitis B and normal controls (P<0.05). In patients with chronic hepatitis B, the level of IP-10 mRNA in PBMCs was correlated with the IP-10 plasma level(r=0.7312, P<0.001), and the IP-10 plasma level was fairly correlated with the levels of ALT and HBV-DNA plasma (r=0.7235, P<0.001; r=0.7371, P<0.001). IP-10 was found by immunohistochemical analysis to be selectively upregulated on sinusoidal endothelium. CONCLUSIONS: The expression of IP-10 mRNA in PBMCs, IP-10 plasma concentration and the expression of IP-10 in sinusoidal endothelium are all high in patients with chronic hepatitis B. Chemokine IP-10 may play an important role in trafficking inflammatory cells to the local focus in the liver and induce the development of the chronicity of hepatitis B. | Wang, Jian Zhao, Jin-Hong Wang, Ping-Ping Xiang, Gui-Ju | 2008 | Hepatobiliary & Pancreatic Diseases International2008，7，1： | 36 |
| 20 | Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure显示文摘AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ±0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8 th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis. | Ying-Hua Niu Dong-Lin Yin Hong-Li Liu Rui-Tian Yi Yu-Cong Yang Hong-An Xue Tian-Yan Chen Shu-Lin Zhang Shu-Mei Lin Ying-Ren Zhao | 2013 | World Journal of Gastroenterology2013，19，26： | 36 |
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