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Retrospective analysis of hepatitis C infected patients treated through an integrated care model

World Journal of Gastroenterology 2016年第38期22卷 8558-8567页

作者： James M Levin Shabnam Dabirshahsahebi Mindy Bauer Eric Huckins Department of Infectious Disease Dean Clinic

AIM To determine if our health system's integrated model reflects sustained virologic response(SVR) outcomes similar to those in clinical trial data, maximizes adherence, and averts drug interactions.METHODS Subjects with chronic hepatitis C had their medical records reviewed from November 1st, 2014 through March 1st, 2016. Patients eligible for treatment were entered into an integrated care model therapy algorithm. The primary outcome was SVR12 based on intention to treat(ITT) analysis. Inclusion criteria consisted of both treatment na?ve and experienced patients over the age of 18 who were at least twelve weeks post-therapy completion with any genotype(GT) or METAVIR score. Secondary outcomes included adherence, adverse events, and number of drug interaction interventions.RESULTS At the time of analysis, 133 patients had reached twelve weeks post therapy with ITT. In the ITT analysis 70 patients were GT 1a, 26 GT 1b, 23 could not be differentiated between GT 1a or 1b, 8 GT 2, 4 GT 3, and 2 patients with multiple genotypes. The ITT treatment regimens consisted of 97 sofosbuvir(SOF)/ledipasvir(LDV), 8 SOF/LDV and ribavirin(RBV), 7 SOFand Simeprevir(SMV), 6 3D and RBV, 1 3D, 11 SOF and RBV, and 1 SOF, peg interferon alpha, and RBV. The overall SVR12 rate was 93% in the ITT analysis with a total of 6 patients relapsing. In patients with cirrhosis, 89% obtained SVR12. All 33 patients who were previous treatment failures achieved SVR12. Drug-drug interactions were identified in 56.4% of our patient population, 69 of which required interventions made by the pharmacist. The most common side effects were fatigue(41.4%), headache(28.6%), nausea(18.1%), and diarrhea(8.3%). No serious adverse effects were reported.CONCLUSION Dean Health System's integrated care model successfully managed patients being treated for hepatitis C virus(HCV). The integrated care model demonstrates high SVR rates amongst patients with different levels of fibrosis, genotypes, and HCV treatment history.

关键词： Hepatitis C Medication adherance Direct acting antiviral Sustained viral response Integrated care model

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Precore/basal core promoter mutants quantification throughout phases of hepatitis B virus infection by Simpleprobe

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World Journal of Gastroenterology 2015年第21期21卷 6639-6648页

作者： Wen-Hui Tu Ying Lv Yong-Mei Zhang Wei Hou Jin-Yu Wang Yi-Jun Zhang Hong-Yan Liu Hao-Xiang Zhu Yan-Li Qin Ri-Cheng Mao Ji-Ming Zhang Department of Infectious Disease Huashan HospitalFudan University Department of Infectious Disease Taizhou Municipal Hospital Department of Infectious Disease Public Health Clinical Center of ShanghaiFudan University

AIM:To investigate precore/basal core promoter(PC/BCP) mutants throughout hepatitis B virus(HBV) infection and to determine their relationship to hepatitis B early antigen(HBeA g) titers.METHODS:We enrolled 191 patients in various stages of HBV infection at the Huashan Hospital and the Taizhou Municipal Hospital from 2010 to 2012.None of the patients received antiviral therapy.HBV DNA from serum,was quantified by real-time PCR.The HBV genotype was determined by direct sequencing of the S gene.We used the Simpleprobe ultrasensitivequantitative method to detect PC/BCP mutants in each patient.We compared the strain number,percentage,and the changes in PC/BCP mutants in different phases,and analyzed the relationship between PC/BCP mutants and HBe Ag by multiple linear regression and logistic regression.RESULTS:Patients with HBV infection(n = 191) were assigned to groups by phase:Immune tolerance(IT) = 55,Immune clearance(IC) = 67,Low-replicative(LR) = 49,and HBeA g-negative hepatitis(ENH) = 20.Of the patients(male,112; female,79) enrolled,122 were HBe Ag-positive and 69 were HBe Ag-negative.The median age was 33 years(range:18-78 years).PC and BCP mutation detection rates were 84.82%(162/191) and 96.86%(185/191),respectively.In five HBe Ag-negative cases,we detected double mutation G1896A/G1899 A.The logarithm value of PC mutant quantities(log10 PC) significantly differed in IT,IC,and LR phases,as well as in the ENH phase(F = 49.350,P < 0.001).The logarithm value of BCP mutant quantities(log10 BCP) also differed during the four phases(F = 25.530,P < 0.001).Log10 PC and log10 BCP values were high in the IT and IC phases,decreased in the LR phase,and increased in the ENH phase,although the absolute value at this point remained lower than that in the IT and IC phases.PC mutant quantity per total viral load(PC%) and BCP mutant quantity per total viral load(BCP%) differed between phases(F = 20.040,P < 0.001; F = 10.830,P < 0.001),with PC% and BCP% gradually increasing in successive phases.HBeA g titers negatively correlat

关键词： precore mutant basal core promotermutant Hepatitis B virus Quantification Hepatitis Bearly antigen titers

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Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis

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World Journal of Gastroenterology 2024年第11期30卷 1556-1571页

作者： Yan-Chao Hu Xiang-Chun Ding Hui-Juan Liu Wan-Long Ma Xue-Yan Feng Li-Na Ma Department of Infectious Disease General Hospital of Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina infectious disease Clinical Research Center of Ningxia Yinchuan 750004Ningxia Hui Autonomous RegionChina

BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been determined.AIM To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC patients.METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020.Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only.Fecal samples were collected at the onset and conclusion of the 12-wk intervention period.The structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were assessed.RESULTS Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria.Additionally,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.

关键词： Hepatitis B cirrhosis N1115 ready-to-eat lactobacillus Inflammation Liver function Lachnospiraceae incertae sedis Probiotic

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Association between TLR7 copy number variations and hepatitis B virus infection outcome in Chinese

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World Journal of Gastroenterology 2017年第9期23卷 1602-1607页

作者： Fang Li Xu Li Gui-Zhou Zou Yu-Feng Gao Jun Ye Department of Infectious Disease The Second Affiliated Hospital of Anhui Medical University Department of Infectious Disease The First Affiliated Hospital of Anhui Medical University

AIM To explore whether copy number variations (CNVs) of toll-like receptor 7 (TLR7) are associated with susceptibility to chronic hepatitis B virus (HBV) infection.METHODS This study included 623 patients(495 males and 128 females) with chronic hepatitis B virus infection(CHB) and 300 patients (135 females and 165 males) with acute hepatitis B virus infection (AHB) as controls. All CHB patients were further categorized according to disease progression after HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). Copy numbers of the TLR7 gene were measured using the Accu Copy method. χ2 tests were used to evaluate the association between TLR7 CNVs and infection type. P values, odds ratios, and 95% confidence intervals(CIs) were used to estimate the effects of risk. RESULTS A m o n g m a l e p a t i e n t s, t h e r e w e r e s i g n i f i c a n t differences between the AHB group and CHB group in the distribution of TLR7 CNVs. Low copy numberof TLR7 was significantly associated with chronic HBV infection (OR = 0.329, 95%CI: 0.229-0.473, P disease progression.

关键词：像使用费的受体 7 肝炎 B 病毒拷贝数字变化基因危险性

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Hepatitis B virus-persistent infection and innate immunity defect: Cell-related or virus-related?

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World Journal of Clinical Cases 2018年第9期6卷 233-241页

作者： Jian Tang Zhen-Yu Wu Rong-Juan Dai Jing Ma Guo-Zhong Gong Department of Infectious Disease the Second Xiangya Hospital Central South University Department of Infectious Disease the First Affiliated Hospital of University of South China

The outcomes of hepatitis B virus(HBV) infection are closely related to the age at which infection was acquired. Infection acquired in adult life tends to be selflimited, in contrast to perinatal acquirement, for which chronic persistence of the HBV is a general outcome. Innate immunity plays an indispensable role in early virus infection, facilitating virus clearance. However, it has been reported that HBV is under-recognized and poorly eliminated by the innate immune system in the early stages of infection, possibly explaining the long-lasting persistence of viremia afterwards. Furthermore, due to the existence of covalently closed circular DNA, chronic HBV clearance is very difficult, even when patients are given interferon-α and nucleotide/nucleoside analogs for antiviral therapy. The mechanism by which HBV evades innate immune recognition and establishes persistent infection remains a subject of debate. Besides, some researchers are becoming more interested in how to eradicate chronic HBV infection by restoring or boosting innate immunity. This review aimed to summarize the current knowledge on how intrahepatocyte signaling pathways and innate immune cells act after the onset of HBV infection and how these actions are related to the persistence of HBV. We anticipate the insights presented herein to be helpful for future development of novel immune therapeutic strategies to fight HBV infection.

关键词： Hepatitis B virus Innate immunity Immune evasion Pattern recognition receptor Toll-like receptor Natural killer cells Kupffer cells Dendritic cells

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Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients

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Chinese Medical Journal 2021年第10期134卷 1160-1167页

作者： Jun Li Zhao Wu Gui-Qiang Wang Hong Zhao China HepB-Related Fibrosis Assessment Research Group Department of Infectious Disease Center for Liver DiseasePeking University First HospitalBeijing 100034China The Collaborative Innovation Center for Diagnosis and Treatment of infectious diseases Zhejiang UniversityHangzhouZhejiang 310000China Department of Infectious Disease Peking University International HospitalBeijing 100034China 不详

Background:Hepatitis B core-related antigen(HBcrAg)is a promising disease-monitoring marker for chronic hepatitis B(CHB).We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.Methods:One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks.We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen(HBeAg)-positive and HBeAg-negative patients.We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy.Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.Results:HBeAg-positive patients(n=93)had higher baseline HBcrAg(median 7.4 vs.5.3 log10 U/mL P<0.001)and greater HBcrAg declines(median 1.6 vs.0.9 log10 U/mL P=0.007)than HBeAg-negative patients after 78 weeks of therapy.At baseline,HBcrAg correlated with hepatitis B virus(HBV)DNA in both HBeAg-positive(r=0.641,P<0.001)and-negative patients(r=0.616,P<0.001),with hepatitis B surface antigen(HBsAg)in HBeAg-positive patients(r=0.495,P<0.001),but not with anti-hepatitis B virus core antibody(anti-HBc).Weak correlations existed between HBcrAg,histology activity index(HAI;r=0.232,P=0.025),and Ishak fibrosis score(r=-0.292,P=0.005)in HBeAg-positive patients.At 78 weeks,significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive(r=-0.263,P=0.014)and HBeAg-negative patients(r=-0.291,P=0.045).Decreased HBcrAg significantly correlated with reduced HBV DNA(r=0.366,P=0.001;r=0.626,P<0.001)and HBsAg(r=0.526,P=0.001;r=0.289,P=0.044)in HBeAg-positive and-negative patients,respectively,and with reduced HAI in HBeAg-positive patients(r=0.329,P=0.001).Patients with HBeAg loss(n=29)showed a larger reduction in HBcrAg than those without(median 2.3 vs.1.3 log10 U/mL,P=0.001).In multivariate analysis,decreased HBcrAg was an independent predictor of HB

关键词： Chronic hepatitis B Hepatitis B core-related antigen Hepatitis B e antigen Antiviral therapy

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Sphingosine kinase 1 dependent protein kinase C-δ activation plays an important role in acute liver failure in mice

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World Journal of Gastroenterology 2015年第48期21卷 13438-13446页

作者： Yan-Chang Lei Ling-Ling Yang Wen Li Pan Luo Department of Infectious Diseases Zhejiang Hospital infectious disease Hospital of Nanchang University

AIM: To investigate the role of protein kinase C(PKC)-δ activation in the pathogenesis of acute liver failure(ALF) in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced ALF.METHODS: BALB/c mice were randomly assigned to five groups, and ALF was induced in mice by intraperitoneal injection of D-Ga IN(600 mg/kg) and LPS(10 μg/kg). Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels at different time points within one week were determined using a multiparameteric analyzer. Serum levels of high-mobility group box 1(HMGB1), tumor necrosis factor(TNF)-α, interleukin(IL)-1β, IL-6, and IL-10 as well as nuclear factor(NF)-κB activity were determined by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of PKC-δ in liver tissue and peripheral blood mononuclear cells(PBMCs) was analyzed by Western blot.RESULTS: The expression and activation of PKC-δ were up-regulated in liver tissue and PBMCs of mice with D-Gal N/LPS-induced ALF. Inhibition of PKC-δ activation with rottlerin significantly increased the survival rates and decreased serum ALT/AST levels at 6, 12 and 24 h compared with the control group(P disease.

关键词： Acute liver failure Protein kinase C-δ Sphingosine kinase 1 Nuclear factor-κB

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Serum interleukin-34 level can be an indicator of liver fibrosis in patients with chronic hepatitis B virus infection

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World Journal of Gastroenterology 2018年第12期24卷 1312-1320页

作者： Yin-Qiu Wang Wen-Jun Cao Yu-Feng Gao Jun Ye Gui-Zhou Zou Department of Infectious Disease The Second Affiliated Hospital of Anhui Medical University

AIM To investigate whether serum interleukin(IL)-34 levels are correlated with hepatic inflammation and fibrosis in patients with chronic hepatitis B virus(HBV) infection. METHODS In this study, serum IL-34 levels were assessed by enzyme-linked immunosorbent assay in 19 healthy controls and 175 patients with chronic HBV infection undergoing biopsy. The frequently used serological markers of liver fibrosis were based on laboratory indexes measured at the Clinical Laboratory of the Second Affiliated Hospital of Anhui Medical University. Liver stiffness was detected by transient elastography with Fibro Touch. The relationships of non-invasive makers of liver fibrosis and IL-34 levels with inflammation and fibrosis were analyzed. The diagnostic value of IL-34 and other liver fibrosis makers wereevaluated using areas under the receiver operating characteristic curves, sensitivity and specificity.RESULTS Serum IL-34 levels were associated with inflammatory activity in the liver, and IL-34 levels differed among phases of chronic HBV infection(P = 0.001). By comparing serum IL-34 levels among patients with various stages of liver fibrosis determined by liver biopsy, we found that IL-34 levels ≥ 15.83 pg/m L had a high sensitivity of 86.6% and a specificity of 78.7% for identifying severe fibrosis(S3-S4). Furthermore, we showed that IL-34 is superior to the fibrosis-4 score, one of the serum makers of liver fibrosis, in identifying severe liver fibrosis and early cirrhosis in patients with HBV-related liver fibrosis in China.CONCLUSION Our results indicate that IL-34, a cytokine involved in the induction of activation of profibrogenic macrophages, can be an indicator of liver inflammation and fibrosis in patients with chronic HBV infection.

关键词： Interleukin 34 Hepatitis B virus Liver fibrosis Diagnosis

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Serial Interval and Reproductive Number of COVID-19 Among 116 Infector-infectee Pairs—Jingzhou City,Hubei Province,China,2020

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China CDC weekly 2020年第27期2卷 491-495页

作者： Tian Liu Li Qi Menglei Yao Keqing Tian Maowen Lin Hong Jiang Minmin Zeng Jigui Huang Department of Infectious Diseases Prevention and Control Jingzhou Center for Disease Control and PreventionJingzhou cityHubei ProvinceChina Chinese Field Epidemiology Training Program Chinese Center for Disease Control and PreventionBeijingChina Department of Infectious Diseases Prevention and Control Chongqing Municipal Center for Disease Control and PreventionChongqingChina State Key Laboratory of infectious disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina

What is already known about this topic?The key epidemiological parameters including serial interval,basic reproductive number(R0),and effective reproductive number(Rt)are crucial for coronavirus disease 2019(COVID-19)control and prevention.Previous studies provided different estimations but were often flawed by some limitations such as insufficient sample size and selection bias.What is added by this report?In this study,a total of 116 infector-infectee pairs meeting strict inclusion criteria were selected for analysis.The mean serial interval of COVID-19 was 5.81 days(standard deviation:3.24).The estimated mean with 95%confidence interval of R0 was 3.39(3.07–3.75)and 2.98(2.62–3.38)using exponential growth(EG)and maximum likelihood(ML)methods,respectively.The Rt in the early phase of the epidemic was above 1 with the peak of 4.43 occurring on January 8,and then showing subsequent declines and approaching 1 on January 24.What are the implications for public health practices?This study supports previous findings that COVID-19 has high transmissibility and that implementing comprehensive measures is effective in controlling the COVID-19 outbreak.

关键词： approaching limitations measures

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GRK6 expression in patients with hepatocellular carcinoma

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Asian Pacific Journal of Tropical Medicine 2013年第3期6卷 220-223页

作者： Ya-Ping Li Department of Infectious Disease Huanggang Center Hospital

Objective:To investigate the expression and potential roles of G protein—coupled receptor kinase 6[GRK6]in hepatocellular carcinoma(HCC) patients.Methods:Immunohistochemistry and Western blot was performed to determine GRK6 expression in 73 HCC samples.And the correlation with clinieopathological features was also analyzed.Results:GKK6 expression was significantly higher in HCC than that in normal hepatic tissue.GRK6 was positively correlated with proliferation marker Ki-67,clinical stage,metastasis and survival time.Conclusions: Our results suggested that GUK.6 overexpression plays an important role in HCC.Monitoring the expression of GRK6 maybe helpful in early diagnosis and prognosis of HCC.

关键词： Hepatocellular carcinoma GRK6 Ki-67

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