Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Changing liver stiffness predict regression in advanced fibrosis patients with chronic hepatitis B,but not in moderate fibrosis patients

Background and objective:Liver stiffness measurement(LSM)may effectively correlate to the presence of liver fibrosis,but it is controversial to use for the prediction of clinical outcomes.Therefore,we aimed to evaluate the predictive value of liver stiffness for the regression of liver fibrosis.Methods:In this study,we collected data from a clinical cohort of patients who are received anti-virus therapies for 48 weeks.180 naive chronic hepatitis B(CHB)patients,who received paired LSM and liver biopsy with pre-and post-treatments were analyzed.Two methods(FibroScan and iLivTouch)test LSM.Result:The area under the receiver operating characteristics curve(AUROC)of changing LSM for fibrosis regression is higher in advanced fibrosis patients(F5/6)than in moderate fibrosis patients(F3/4)in both FibroScan(0.719,95%CI,0.590–0.848;P=0.003;vs 0.617,95%CI,0.379–0.856,P=0.282)and iLivTouch(0.707,95%CI,0.567–0.847;P=0.011;vs 0.583,95%CI,0.422–0.744;P=0.377).A higher kappa value was received in advanced stage than in moderate stage both in FibroScan(0.392,P=0.001 vs 0.265,P=0.053)and iLivTouch(0.326,P=0.019 vs 0.030,P=0.833).Cut-off set as 4.10 kPa(sen,69.4%;spe,73.9%)in FibroScan,as 4.25 kPa(sen,56.8%;spe,72.2%)in iLivTouch.Conclusion:The changing LSM can be used for predicting the liver fibrosis regression in advanced stage of CHB patients.

Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF β1/Smad3 and NF-κB signaling pathways

BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.

Evaluation of Non-Invasive Markers of Liver Fibrosis in Chronic Hepatitis B Patients in a Sub-Saharan African Setting: Transient Elastography versus APRI, FIB4, GTT/Platelet Scores

Background: Non-invasive markers which use routine laboratory tests are less expensive and highly needed to assess and stage liver fibrosis in chronic hepatitis B patients in Sub-Saharan Africa. We aimed at evaluating liver fibrosis, using the Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis Index Based on 4 factors (FIB4), and Gamma-glutamyl transpeptidase to Platelet Ratio (GPR) in chronic hepatitis B patients with transient elastography as the reference so as to choose an alternative to transient elastography. Method: We carried out a cross-sectional study using the records of patients who attended the Douala General Hospital and Marie O Polyclinic Douala from 2012 to 2017. Non-invasive tests were compared with Transient Elastography. The Spearman coefficient was used to determine correlation. The sensitivity, specificity, positive predictive values and negative predictive values were used to get the optimal cut-off values. The diagnostic accuracy was estimated by calculating the area under the Receiver Operating Characteristic Curve (ROC). P Results: Of the 243 patient records studied, the median age or interquartile range (IQR) was 35 (29 - 42) years with a male predominance of 73.7%. More than 60% of the study population had normal transaminases. Significant fibrosis was found in 88 (36.2%) patients and 32 (13.7%) patients had cirrhosis. APRI had the best cut-off values and highest area under the ROC Curve, for significant fibrosis and cirrhosis with 0.55 (0.823 95% CI [0.769 - 0.869], P Conclusion: APRI, had the best diagnostic properties to detect liver fibrosis and cirrhosis in patients with Chronic Hepatitis B in Douala. The cut-off values are 0.55 and 0.65 for significant fibrosis and cirrhosis respectively.

Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection

There are approximately 240 million patients with chronic hepatitis B virus(HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the "gold standard" for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBVinfected patients, owing to its high applicability, interlaboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBVinfected patients for clinicians.

Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model:A comparative study

AIM:To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B(CHB) patients.METHODS:Seventy-eight CHB patients were consecutively enrolled in this study.Liver biopsy was performed and blood serum was obtained at admission.Histological diagnosis was made according to the METAVIR system.Significant fibrosis was defined as stage score ≥ 2,severe fibrosis as stage score ≥ 3.The diagnostic accuracy of 6 noninvasive liver fibrosis models,including serum aspartate aminotransferase(AST) to platelet ratio index(APRI),FIB-4,Forn's index,Fibrometer,Hepascore,and Shanghai Liver Fibrosis Group's index(SLFG),was investigated.RESULTS:The APRI,FIB-4 and Forn's index under receiver operating characteristic curve(AUROC) for sig-nificant fibrosis were 0.71,0.75 and 0.79,respectively,with a diagnosis accuracy of 67%,77% and 80%,respectively,and 0.80,0.87 and 0.86,respectively,under the AUROC for severe fibrosis.The Hepascore,SLFG,and Fibrometer were 0.80,0.83 and 0.85,respectively under the AUROC for significant fibrosis(P < 0.01).The diagnosis accuracy of Hepascore and SLFG was 86% and 88%,respectively.The Hepascore,SLFG,and Fibrometer were 0.95,0.93,and 0.94,respectively,under the AUROC for severe fibrosis(P < 0.01).CONCLUSION:The models containing direct serum markers have a better diagnostic value than those not containing direct serum markers.

Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B?

AIM: To determine the association between the neutrophil to lymphocyte(N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B(CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant.RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean(N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis.CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.

On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B

BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.

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

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.

Noninvasive Measurement of Liver Fibrosis by Transient Elastography and Influencing Factors in Patients with Chronic Hepatitis B―A Single Center Retrospective Study of 466 Patients

The noninvasive measurement of liver stiffness (LS) was evaluated by transient elastogra-phy (FibroScan) and the possible influencing factors from the patients’ clinical situations including age,gender,liver inflammation represented by alanine transaminase (ALT) and total billirubin (TBIL) level,HBV replication (HBV DNA loads),portal vein pressure (portal vessel diameter,PVD),splenic thick-ness (SPT) and body mass index (BMI) were analyzed in patients with chronic hepatitis B (CHB).A to-tal of 466 patients including 31 patients with acute-on-chronic liver failure (ACLF),and 435 patients with chronic hepatitis B (CHB) among which 82 patients were diagnosed with liver cirrhosis (LC) by clinical manifestations and liver B-type ultrasonic inspection were enrolled at Tongji Hospital from April to December 2009.LS was measured by a FibroScan device (EchoSens,France).Simultaneously,ALT and TBIL levels,HBV DNA loads,PVD,SPT and BMI in all patients were also tested.Forty-one healthy volunteers served as controls.The values of LS were correlated positively with ages of CHB patients and significantly higher in males than in females.In patients with BMI>28 kg/m2 (obesity) and abnormal levels of ALT and TBIL,LS values were significantly increased as compared with those hav-ing normal levels of ALT and TBIL.The patients with ACLF had the highest LS value.Furthermore,LS values in the patients with LC were significantly higher than those in patients without LC.It is concluded that noninvasive measurement of liver fibrosis by FibroScan provides an alternative method to evaluate liver fibrosis of patients with CHB.In order to properly illustrate the stiffness value taken by transient elastography,patients’ gender should be taken into consideration and it is also suggested to avoid possible influencing factors including liver inflammation (high levels of ALT and TBIL) and obesity (high BMI).

Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection

BACKGROUND Transient elastography(FibroScan)is a new and non-invasive test,which has been widely recommended by the guidelines of chronic hepatitis B virus(HBV)management for assessing hepatic fibrosis staging.However,some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging.AIM To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection.METHODS The data of 416 patients with chronic HBV infection who accepted FibroScan,liver biopsy,clinical,and biological examination were collected from two hospitals retrospectively.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis.Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed.Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation.A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan.RESULTS In the overall cohort,the optimal diagnostic values of liver stiffness measurement(LSM)using FibroScan for significant fibrosis(≥F2),severe fibrosis(≥F3),and cirrhosis(F4)were 7.3 kPa[area under the curve(AUC)=0.863],9.7 kPa(AUC=0.911),and 11.3 kPa(AUC=0.918),respectively.The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1%(142/416 patients).The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels,and a higher proportion of moderate to severe hepatic inflammation,compared with the group of patients who showed concordance in fibrosis staging between the two methods.Liver inflammation activity over 2(OR=3.53)was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan.Patients with liver inflammation activity≥2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage,whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity<2(all P<0.05).A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan,and the AUC was 0.701.CONCLUSION Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage.A combination of other related noninvasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.

Serum chitinase-3-like protein 1 is a biomarker of liver fibrosis in patients with chronic hepatitis B in China

Background:Serum chitinase-3-like protein 1(CHI3L1)is a potential biomarker for fibrosis assessment.We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virusrelated fibrosis.Methods:Serum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B(CHB)patients.Significant fibrosis was defined as a liver stiffness>9.7 kPa.The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic(ROC)analysis.Results:Serum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis(≥F2)than in those without significant hepatic fibrosis(<F2)(56.5 ng/mL vs.81.9 ng/mL,P<0.001).In CHB patients,the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6%and 59.1%,respectively,with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728(95%CI:0.637–0.820).Conclusions:Serum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver fibrosis.Moreover,CHI3L1 is feasible in monitoring disease progression.

Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B

AIM:To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B (CHB). METHODS: A total of 137 consecutive patients with CHB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase (ALT) level. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), the likelihood ratio (LR) of aminotransferase/platelet ratio index (APRI)≥1.5 or <1.5 in combination with different hyaluronic acid (HA) cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis (fibrosis stages 2 and 4) and no to mild fibrosis/cirrhosis (fibrosis stages 0 and 1). RESULTS: The APRI correlated with fibrosis stage in CHB patients. The APRI≥1.5 in combination with a cut-off HA cut-off point >300 ng/mL could detect moderate to severe fibrosis (stages 2-4) in CHB patients. The PPV was 93.7%, the specificity was 98.9%. The APRI <1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION: The APRI≥ 1.5 in combination with a HA cut-off point >300ng/mL can detect moderate to severe fibrosis (stages 2-4) in CHB patients.

Ultrastructure of oval cells in children with chronic hepatitis B,with special emphasis on the stage of liver fibrosis:The first pediatric study

AIM:To investigate the ultrastructure of oval cells in children with chronic hepatitis B,with special emphasis on their location in areas of collagen fibroplasia. METHODS:Morphological investigations were conducted on biopsy material obtained from 40 children,aged 3-16 years with chronic hepatitis B. The stage of fibrosis was assessed histologically using the arbitrary semiquantitative numerical scoring system proposed by Ishak et al. The material for ultrastructural investigation was fixed in glutaraldehyde and paraformaldehyde and processed for transmission-electron microscopic analysis. RESULTS:Ultrastructural examination of biopsy specimens obtained from children with chronic hepatitis B showed the presence of two types of oval cells,the hepatic progenitor cells and intermediate hepatic-like cells. These cells were present in the parenchyma and were seen most commonly in areas of intense periportal fibrosis (at least stage 2 according to Ishak et al) and in the vicinity of the limiting plate of the lobule. The activated nonparenchymal hepatic cells,i.e. transformed hepatic stellate cells and Kupffer cells were seen in close proximity to the intermediate hepatic-like cells. CONCLUSION:We found a distinct relationship between the prevalence of oval cells (hepatic progenitor cells and intermediate hepatocyte-like cells) and fibrosis stage in pediatric patients with chronic hepatitis B.

Analysis of influencing factors of chronic hepatitis B complicated with nonalcoholic fatty liver disease

Objective:To investigate the influencing factors of chronic hepatitis B with nonalcoholic fatty liver disease,and to provide a reference for screening and clinical treatment of high-risk groups.Methods:A case-control study was conducted.According to the inclusion and exclusion criteria,133 cases of newly diagnosed patients with CHB combined with NAFLD were enrolled in the Affiliated Hospital of North China University of Technology and Tangshan Infectious Disease Hospital from January 2015 to January 2018.139 cases of newly diagnosed patients with CHB diagnosed in the same period were selected as the control group.The clinical data,initial laboratory examination and imaging findings of the two groups of patients were compared to analyze the influencing factors of chronic hepatitis B combined with nonalcoholic fatty liver disease.Results:1 The BMI,ALT,AST,GGT,FBG,TG and CAP in the case group were significantly higher than those in the control group,the difference was statistically significant(P<0.05).The control group HDL-C,HBcAb,type III procollagen amino terminal peptide,The type IV collagen,laminin and LSM were higher than the case group,the difference was statistically significant(P<0.05).The case group was more likely to be associated with complications,and the difference was statistically significant(P=0.01).2 Univariate analysis showed that About the author:Zhang Guoshun,male,chief physician,professor,master's tutor,doctoral,mainly engaged in research and prevention of liver diseases,13930565676,zguoshun@sina.com.Fund Project:China Hepatitis Prevention Foundation Funded Project(No.:TQGB20170015);Hebei Province Medical Science Research Key Project(No.20170933);North China University of Technology Graduate Innovation Project(No.2019S49)patients in the case group had BMI≥25Kg/m2,GGT>45U/L,type IV collagen≤140ng/ml,laminin≤140ng/ml,CAP≥283dB/m,hyperglycemia,high glycerol The proportion of patients with lipemia was significantly higher than that of the control group,the difference was statistically significant(P<0.05);3 binary logistic regression analysis showed that GGT,FBG,BMI,laminin,CAP were predictive of chronic hepatitis B combined with non-An effective indicator of alcoholic fatty liver disease.Conclusion 1GGT,BMI,FBG,laminin and CAP are the influencing factors of CHB combined with NAFLD.The occurrence of 2NAFLD is closely related to obesity,hyperglycemia and hypertriglyceridemia.The HBcAb and liver fibrosis indexes are decreased when CHB combined with NAFLD,and the mechanism is still unclear.

Effect of Compound Biejiaruangan Tablets combined with entecavir therapy on liver fibrosis process and immune response state in patients with chronic hepatitis b

Objective:To study the effect of Compound Biejiaruangan Tablets combined with entecavir therapy on liver fibrosis process and immune response state in patients with chronic hepatitis b.Methods: Patients with chronic viral hepatitis b who were treated in the Affiliated Hospital of Inner Mongolia Medical University between May 2015 and March 2017 were selected as the research subjects and divided into the combined group who accepted Compound Biejiaruangan Tablets combined with entecavir therapy and the control group who accepted entecavir monotherapy. The contents of collagen metabolism indexes and inflammatory response molecules in serum as well as the contents of immune cells in peripheral blood were determined before treatment and 24 weeks after treatment.Results: 24 weeks after treatment, PC-III, C-IV, MMP1, MMP2, TIMP1, IL-1β, IL-18, MIF, RANTES, MIP-1 and MIP-1β contents in serum as well as Th2, Treg and Th17 contents in peripheral blood of both groups of patients were significantly lower than those before treatment whereas Th1 contents in peripheral blood were significantly higher than those before treatment, and PC-III, C-IV, MMP1, MMP2, TIMP1, IL-1β, IL-18, MIF, RANTES, MIP-1 and MIP-1β contents in serum as well as Th2, Treg and Th17 contents in peripheral blood of combined group of patients were significantly lower than those of control group whereas Th1 content in peripheral blood was significantly higher than that of control group.Conclusion: Compound Biejiaruangan Tablets combined with entecavir therapy can delay the liver fibrosis process and improve the immune response state in patients with chronic hepatitis b.

Correlation of serum TGF-β1 content with liver fibrosis and Th1/Th2 immune levels in patients with chronic hepatitis b

Objective:To investigate the correlation of serum TGF-β1 content with liver fibrosis and Th1/Th2 immune levels in patients with chronic hepatitis b.Methods: A total of 178 patients who were diagnosed with chronic hepatitis b in our hospital between February 2015 and August 2017 were selected as chronic hepatitis b group, and 100 healthy volunteers who received physical examination in our hospital during the same period were selected as normal control group. The differences in serum levels of TGF-β1, liver fibrosis indexes and Th1/Th2 cytokines were compared between the two groups, and the Pearson test was adopted to evaluate the correlation between serum TGF-β1 content and disease severity in patients with chronic hepatitis b.Results: Serum TGF-β1 level of chronic hepatitis b group was higher than that of normal control group;serum liver fibrosis indexes CⅣ, PC-Ⅲ, HA and LN levels were higher than those of normal control group;serum Th1 cytokines IFN-γ and IL-12 levels were lower than those of normal control group whereas Th2 cytokines IL-4 and IL-13 levels were higher than those of normal control group. Pearson test showed that the serum TGF-β1 level in patients with chronic hepatitis b was positively correlated with the degree of liver fibrosis and Th1/Th2 immune imbalance.Conclusions: Serum TGF-β1 expression is abnormally high in patients with chronic hepatitis b and directly correlated with the degree of liver fibrosis and immune imbalance.

Influence of compound glycyrrhizin on liver functions, liver fibrosis indexes and inflammatory factors of patients with chronic hepatitis B

Objective:To investigate influence of Compound Glycyrrhizin on liver functions, liver fibrosis indexes and inflammatory factors of patients with chronic hepatitis B.Methods:A total of 96 cases of patients with chronic hepatitis B treated in our hospital from Jan2015 to Jun2016 were selected as subjects, and randomly divided to be 48 cases of observation group and 48 cases of control group. Patients in both of the two groups were received routine liver protecting drug treatment. For observation group, Compound Glycyrrhizin injection was given on the basis of routine treatment. Variations of liver function indexes, liver fibrosis indexes and inflammatory factors between the two groups before and after treatment were compared and observed.Results:No obvious difference showed on AST, ALT, ALB TBIL levels between two groups of patients before treatment;After treatment, AST, ALT, TBIL in two groups of patients were significantly decreased, ALB were significantly increased. Significant difference showed comparing with prior treatment;After treatment, AST, ALT and TBIL levels in observation group were (29.53±9.44) U/L, (32.36±10.93) U/L and (10.12±3.22) μmol/L, which were significantly lower than in control group. ALB levels in observation group were (43.57±12.42) g/L, which were significantly higher than ALB levels in control group. Before treatment, no statistical difference showed on HA, LN, IV-C and PCIII levels between two groups of patients. After treatment, HA, LN, IV-C and PCIII in two groups of patients were significantly decreased, which showed significant difference comparing with prior treatment;After treatment, HA, LN, IV-C and PCIII levels in observation group were (97.33±31.75) μg/L, (77.52±23.72) μg/L, (82.92±24.55) μg/L, (15.33±5.11) μg/L, which were significantly lower than in control group. Before treatment, no significant difference showed on IL-2, IL-6 and TNF- levels between two groups of patients;After treatment, IL-2 levels in two groups of patients were significantly increased, IL-6 and TNF-α were significantly decreased, the differences showed significance;After treatment, IL-2 levels in observation group were (131.48±30.63) U/mL, which were higher than IL-2 levels in control group. IL-6 and TNF-αlevels in observation group were (45.23±16.45) μg/L, (41.75±17.53) ng/L, which were lower than IL-6 and TNF-α levels in control group, differences showed significance.Conclusion:Compound Glycyrrhizin could effectively release liver fibrosis and inflammatory reactions for patients with chronic hepatitis B, and could further improve liver functions.

Effect of different nucleoside analogues on liver fibrosis and peripheral blood dendritic cell function of patients with chronic hepatitis B

Objective: To study the effect of different nucleoside analogues on liver fibrosis and peripheral blood dendritic cell function of patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who received antiviral therapy in Infectious Diseases Hospital of Shanghai Huangpu District between April 2014 and October 2016 were selected as the research subjects and divided into 3 groups, group A received entecavir therapy, group B received adefovir dipivoxil therapy and group C received lamivudine therapy. 24 weeks and 48 weeks after treatment, the levels of liver fibrosis indexes in serum as well the levels of DC and the expression of surface markers in peripheral blood of the three groups were measured respectively. Results: After treatment, serum hyaluronic acid (HA), procollagen III (PC-III), laminin (LN) and collagen type IV (C-IV) levels of all groups were significantly lower than those before treatment, and the number of myeloid DC (mDC) and plasmacytoid DC (pDC) in peripheral blood as well as the expression levels of DC surface molecules CD80, CD86, CD1αand HLA-DR in peripheral blood were significantly higher than those before treatment. After treatment, the serum levels of HA, PC-III, LN and C-IV in group A were significantly lower than those in group B and C, and the number of mDC and pDC in peripheral blood as well as the expression of DC surface molecules CD80, CD86, CD1α and HLA-DR in peripheral blood were significantly higher than those in group B and C. Conclusion: Antiviral therapy by nucleoside analogues can effectively inhibit liver fibrosis and improve peripheral blood DC function in patients with chronic hepatitis B, and Entecavir function is better than that of adefovir dipivoxil and lamivudine.

Influence of antiviral drugs combined with antioxidant therapy on liver injury and fibrosis process in patients with chronic hepatitis B cirrhosis

Objective:To study the influence of antiviral drugs combined with antioxidant therapy on liver injury and fibrosis process in patients with chronic hepatitis B cirrhosis.Methods: A total of118 patients with chronic hepatitis B cirrhosis who were treated in Dongying Hospital for Infectious Diseases between May 2013 and February 2016 were retrospectively analyzed and divided into the control group (n=60) who underwent routine antiviral therapy and the observation group (n=58) who underwent antiviral drugs combined with antioxidant therapy. Serum levels of oxidative stress indexes, liver function indexes and liver fibrosis indexes were compared between two groups of patients before and after treatment.Results:Before treatment, there were no significant differences in serum oxidative stress indexes, liver function indexes and liver fibrosis indexes between two groups of patients. 3 months after treatment, serum oxidative stress index SOD level in observation group was higher than that in control group while AOPPs level was lower than that in control group;serum liver function indexes AST, ALT and TBIL levels in observation group were lower than those in control group while ALB level was higher than that in control group;serum liver fibrosis indexes HA,Ⅳ-C, PCIII and LN levels in observation group were lower than those in control group.Conclusion:Antiviral drugs combined with antioxidant therapy can significantly reduce oxidative stress injury in patients with chronic hepatitis B cirrhosis so as to protect the liver function and inhibit the liver fibrosis process.