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 pat...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.展开更多
BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diag...BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.展开更多
The goal of this review is to provide a comprehensive picture of the role,clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus(HBV)infec...The goal of this review is to provide a comprehensive picture of the role,clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus(HBV)infection.During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations,mainly:invasiveness,costs,low reproducibility,poor acceptance by patients.Elastographic techniques conceived to assess liver stiffness,in particular transient elastography,and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis.Recent evidence highlights that both liver stiffness and some bio-chemical markers correlatewith survival and major clinical end-points such as liver decompensation,development of hepatocellular carcinoma and portal hypertension.Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis.Given their prognostic value,transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes.Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.展开更多
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 inflamma...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).展开更多
AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chr...AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chronic hepatitis B （CHB）.METHODS： One hundred and ten consecutive patients （80 males, 30 females, mean age： 42.6 ± 11.3） with CHB undergoing diagnostic liver biopsy were included. AST-to-Platelet ratio （APRI）, Forns＇ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index （GUCD, Hui＇s model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive （PPV） and negative （NPV） predictive values, accuracy and area under the curve （AUC）. RESULTS： PPV for significant fibrosis was excellent （100%） with Forns and high （〉 92%） with APR1, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker （NPV 〈 65%）. Fibretest had the best PPV and NPV for cirrhosis （87% and 90%, respectively）. Fibrotest showed the best AUC for both significant fibrosis and cirrhosis （0.85 and 0.76, respectively）. Stepwise combination algorithms of APR1, Fibrotest and biopsy showed excellent performance （0.96 AUC, 100% NPV） for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION： In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.展开更多
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 ...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 CriB 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 CriB 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 Crib 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 〉 300 ng/mL can detect moderate to severe fibrosis （stages 2-4） in Crib patients.展开更多
BACKGROUND Noninvasive,practical,and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.AIM To develop a precise noninvasive test to stage liver fibrosis and c...BACKGROUND Noninvasive,practical,and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.AIM To develop a precise noninvasive test to stage liver fibrosis and cirrhosis.METHODS With liver biopsy as the gold standard,we established a new index,[alkaline phosphatase(U/L)+gamma-glutamyl transpeptidase(U/L)/platelet(109/L)(AGPR)],to predict liver fibrosis and cirrhosis.In addition,we compared the area under the receiver operating characteristic curve(AUROC)of AGPR,gammaglutamyl transpeptidase to platelet ratio,aspartate transaminase to platelet ratio index,and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis.RESULTS Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage(P<0.001).In the training cohort,the AUROC of AGPR was 0.83(95%CI:0.78-0.87)for predicting fibrosis(≥F2),0.84(95%CI:0.79-0.88)for predicting extensive fibrosis(≥F3),and 0.87(95%CI:0.83-0.91)for predicting cirrhosis(F4).In the validation cohort,the AUROCs of AGPR to predict≥F2,≥F3 and F4 were 0.83(95%CI:0.77-0.88),0.83(95%CI:0.77-0.89),and 0.84(95%CI:0.78-0.89),respectively.CONCLUSION The AGPR index should become a new,simple,accurate,and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.展开更多
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...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.展开更多
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...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.展开更多
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.Me...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.展开更多
Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combin...Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combined models,and to explore their clinical features.Methods:A total of 104 inpatients with CHB diagnosed and complicated with NAFLD(hepatic steatosis suggested by liver biopsy)were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University.Liver biopsy was performed in all patients.General data,laboratory test results,liver hardness(LSM),FIB-4,APRI,GGT/PLT,AST/PLT and other results of patients were collected and grouped according to different fibrosis stages(S)to explore the clinical and pathological characteristics of patients with<S2 and S2 stages.Receiver operating characteristic curve was used to evaluate the diagnostic value of LSM,FIB-4,APRI,GGT/PLT,AST/PLT and their combined models in patients with significant liver fibrosis in CHB patients with NAFLD.Results:Among the 104 patients,there were 55 patients had S1 fibrosis,32 patients had S2 fibrosis,11 patients had S3 fibrosis and 6 patients had S4 fibrosis.Patients had<S2 fibrosis,ALT 33.75±17.15 U/L,AST 24.00(19.77,29.00)U/L,inflammation above G2 stage accounted for 92.72%,GGT/PLT 0.07(0.10,0.15),AST/PLT 0.09(0.10,0.15),LSM 8.70(6.80,10.10)kPa,FIB-41.07±0.51,APRI 0.26(0.22,0.28).In patients S2 fibrosis,ALT 42.14±21.39 U/L,AST 29.04(24.00,40.32)U/L,inflammation above G2 stage accounted for 97.95%,GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26),GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26).LSM 11.80(8.50,16.65)kPa,FIB-41.39±0.72,APRI 0.35(0.26,0.66),the difference between the two groups was statistically significant(P<0.05).The area under the receiver operator characteristic curves of the subjects of LSM,FIB-4,APRI,GGT/PLT and AST/PLT were 0.716,0.623,0.669,0.644 and 0.669(P<0.05),respectively.In the combined model,the area under the receiver operator characteristic curves of LSM combined with FIB-4,LSM combined with APRI,LSM combined with GGT/PLT and LSM combined with AST/PLT were 0.712,0.719,0.715 and 0.719,respectively(P<0.05).Conclusion:Although the currently commonly used Noninvasive diagnosis of liver fibrosis has certain diagnostic efficacy for significant liver fibrosis in CHB complicated with NAFLD,it cannot replace liver biopsy.Noninvasive Diagnosis can be used as an auxiliary method for regular clinical evaluation of liver biopsy.展开更多
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...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.展开更多
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 l...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.展开更多
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,...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.展开更多
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 h...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.展开更多
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 wer...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.展开更多
Objective:To observe the effect of entecavir on inflammatory reaction, liver function and liver fibrosis in patients with chronic hepatitis B.Method:A total of 100 patients with chronic hepatitis B admitted in our hos...Objective:To observe the effect of entecavir on inflammatory reaction, liver function and liver fibrosis in patients with chronic hepatitis B.Method:A total of 100 patients with chronic hepatitis B admitted in our hospital from February 2015 to October 2016 were randomly divided into observation group (50 cases) and control group (50 cases). The control group were given reduced glutathione and compound glycyrrhizin and other conventional liver protection;the observation group received entecavir dispersible tablets based on the treatment of the control group. The changes of inflammatory factors, liver function and liver fibrosis indexes of patients in both groups were compared.Results:Before treatment, the difference in inflammatory factors, liver function indexes and liver fibrosis indexes between the two groups was not significant. After treatment, the TGF-β1, hs-CRP and TNF-α levels in both groups were significantly lower than those before treatment, in the observation group, TGF-β1 (144.94±36.21) μg/L, hs-CRP level (48.81±10.74) ng/L and TNF-α level (82.43±22.29) pg/mL were significantly lower than those in the control group, there was significant difference between the two groups. After treatment, ALT, and AST levels in both groups were significantly lower than before treatment, compared with before treatment, TBiL level after treatment was not significant. After treatment, the ALT level (35.71±17.81) U/L and AST level (38.82±14.51) U/L in observation group were significantly lower than those in the control group, while the TBiL level in the observation group were not significantly different from that in the control group. After treatment, the levels of HA (91.71 ± 20.81) μg/mL and IV-C (140.82 ± 48.51) μg/L and LN (73.02 ± 21.06) μg/mL in the observation group were significantly lower than those in the control group.Conclusion:Entecavir combined with conventional drug therapy can effectively improve the inflammatory state of patients with chronic hepatitis B, enhance liver function and reduce liver fibrosis.展开更多
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 v...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.展开更多
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 hep...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.展开更多
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...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.展开更多
基金Supported by Grant for Master Degree Students of Hehai University
文摘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.
基金Supported by the National Natural Science Foundation of China,No.82202185and Shanghai Science and Technology Development Foundation,No.22Y11911500.
文摘BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.
文摘The goal of this review is to provide a comprehensive picture of the role,clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus(HBV)infection.During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations,mainly:invasiveness,costs,low reproducibility,poor acceptance by patients.Elastographic techniques conceived to assess liver stiffness,in particular transient elastography,and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis.Recent evidence highlights that both liver stiffness and some bio-chemical markers correlatewith survival and major clinical end-points such as liver decompensation,development of hepatocellular carcinoma and portal hypertension.Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis.Given their prognostic value,transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes.Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.
基金supported by grants from the National Key Basic Research Program of China (No. 2007CB512900)Wang Bao-En Liver Foundation for the Study of Fibrosis (No.20090025)
文摘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).
文摘AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chronic hepatitis B （CHB）.METHODS： One hundred and ten consecutive patients （80 males, 30 females, mean age： 42.6 ± 11.3） with CHB undergoing diagnostic liver biopsy were included. AST-to-Platelet ratio （APRI）, Forns＇ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index （GUCD, Hui＇s model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive （PPV） and negative （NPV） predictive values, accuracy and area under the curve （AUC）. RESULTS： PPV for significant fibrosis was excellent （100%） with Forns and high （〉 92%） with APR1, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker （NPV 〈 65%）. Fibretest had the best PPV and NPV for cirrhosis （87% and 90%, respectively）. Fibrotest showed the best AUC for both significant fibrosis and cirrhosis （0.85 and 0.76, respectively）. Stepwise combination algorithms of APR1, Fibrotest and biopsy showed excellent performance （0.96 AUC, 100% NPV） for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION： In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.
文摘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 CriB 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 CriB 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 Crib 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 〉 300 ng/mL can detect moderate to severe fibrosis （stages 2-4） in Crib patients.
基金Supported by the National Natural Science Foundation of China,No.81372163the Natural Science Foundation of Guangxi,No.2018GXNSFDA138001+2 种基金the Science and Technology Planning Project of Guilin,No.20190218-1the Opening Project of Key laboratory of High-Incidence-Tumor Prevention&Treatment(Guangxi Medical University),Ministry of Education,No.GKE-KF202101the Program of Guangxi Zhuang Autonomous Region Health and Family Planning Commission,No.Z20210706 and No.Z20190665。
文摘BACKGROUND Noninvasive,practical,and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.AIM To develop a precise noninvasive test to stage liver fibrosis and cirrhosis.METHODS With liver biopsy as the gold standard,we established a new index,[alkaline phosphatase(U/L)+gamma-glutamyl transpeptidase(U/L)/platelet(109/L)(AGPR)],to predict liver fibrosis and cirrhosis.In addition,we compared the area under the receiver operating characteristic curve(AUROC)of AGPR,gammaglutamyl transpeptidase to platelet ratio,aspartate transaminase to platelet ratio index,and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis.RESULTS Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage(P<0.001).In the training cohort,the AUROC of AGPR was 0.83(95%CI:0.78-0.87)for predicting fibrosis(≥F2),0.84(95%CI:0.79-0.88)for predicting extensive fibrosis(≥F3),and 0.87(95%CI:0.83-0.91)for predicting cirrhosis(F4).In the validation cohort,the AUROCs of AGPR to predict≥F2,≥F3 and F4 were 0.83(95%CI:0.77-0.88),0.83(95%CI:0.77-0.89),and 0.84(95%CI:0.78-0.89),respectively.CONCLUSION The AGPR index should become a new,simple,accurate,and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.
基金Science and Technology Department of Fujian Province,China,No.2019Y0015 and No.2019J01432Chinese National 13th Five-Year Plan's Science and Technology Projects,No.2017ZX10202201Quanzhou Science and Technology Project of Fujian Province,China,No.2018Z074.
文摘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.
文摘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.
基金the Research Ethics Committee of The First Affiliated Hospital of Zhejiang University School of Medicine(No.2018-918).
文摘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.
基金Natural Science Foundation of Xinjiang Uygur Autonomous Region (No.2022D01C173)National Natural Science Foundation of China (No.81760832)。
文摘Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combined models,and to explore their clinical features.Methods:A total of 104 inpatients with CHB diagnosed and complicated with NAFLD(hepatic steatosis suggested by liver biopsy)were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University.Liver biopsy was performed in all patients.General data,laboratory test results,liver hardness(LSM),FIB-4,APRI,GGT/PLT,AST/PLT and other results of patients were collected and grouped according to different fibrosis stages(S)to explore the clinical and pathological characteristics of patients with<S2 and S2 stages.Receiver operating characteristic curve was used to evaluate the diagnostic value of LSM,FIB-4,APRI,GGT/PLT,AST/PLT and their combined models in patients with significant liver fibrosis in CHB patients with NAFLD.Results:Among the 104 patients,there were 55 patients had S1 fibrosis,32 patients had S2 fibrosis,11 patients had S3 fibrosis and 6 patients had S4 fibrosis.Patients had<S2 fibrosis,ALT 33.75±17.15 U/L,AST 24.00(19.77,29.00)U/L,inflammation above G2 stage accounted for 92.72%,GGT/PLT 0.07(0.10,0.15),AST/PLT 0.09(0.10,0.15),LSM 8.70(6.80,10.10)kPa,FIB-41.07±0.51,APRI 0.26(0.22,0.28).In patients S2 fibrosis,ALT 42.14±21.39 U/L,AST 29.04(24.00,40.32)U/L,inflammation above G2 stage accounted for 97.95%,GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26),GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26).LSM 11.80(8.50,16.65)kPa,FIB-41.39±0.72,APRI 0.35(0.26,0.66),the difference between the two groups was statistically significant(P<0.05).The area under the receiver operator characteristic curves of the subjects of LSM,FIB-4,APRI,GGT/PLT and AST/PLT were 0.716,0.623,0.669,0.644 and 0.669(P<0.05),respectively.In the combined model,the area under the receiver operator characteristic curves of LSM combined with FIB-4,LSM combined with APRI,LSM combined with GGT/PLT and LSM combined with AST/PLT were 0.712,0.719,0.715 and 0.719,respectively(P<0.05).Conclusion:Although the currently commonly used Noninvasive diagnosis of liver fibrosis has certain diagnostic efficacy for significant liver fibrosis in CHB complicated with NAFLD,it cannot replace liver biopsy.Noninvasive Diagnosis can be used as an auxiliary method for regular clinical evaluation of liver biopsy.
文摘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.
文摘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.
文摘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.
基金Supported by Chinese Ministry of Science and Technology Grants the Major Science and Technology Special Project Fund Scheme,No.2013ZX10005002Beijing the Special Clinical Application Research and Translational Grants,No.Z151100004015221
文摘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.
基金Natural Science Foundation of Anhui Province,No.1608085MH164
文摘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.
基金Natural Science Foundation of Jiangsu Province(21412387).
文摘Objective:To observe the effect of entecavir on inflammatory reaction, liver function and liver fibrosis in patients with chronic hepatitis B.Method:A total of 100 patients with chronic hepatitis B admitted in our hospital from February 2015 to October 2016 were randomly divided into observation group (50 cases) and control group (50 cases). The control group were given reduced glutathione and compound glycyrrhizin and other conventional liver protection;the observation group received entecavir dispersible tablets based on the treatment of the control group. The changes of inflammatory factors, liver function and liver fibrosis indexes of patients in both groups were compared.Results:Before treatment, the difference in inflammatory factors, liver function indexes and liver fibrosis indexes between the two groups was not significant. After treatment, the TGF-β1, hs-CRP and TNF-α levels in both groups were significantly lower than those before treatment, in the observation group, TGF-β1 (144.94±36.21) μg/L, hs-CRP level (48.81±10.74) ng/L and TNF-α level (82.43±22.29) pg/mL were significantly lower than those in the control group, there was significant difference between the two groups. After treatment, ALT, and AST levels in both groups were significantly lower than before treatment, compared with before treatment, TBiL level after treatment was not significant. After treatment, the ALT level (35.71±17.81) U/L and AST level (38.82±14.51) U/L in observation group were significantly lower than those in the control group, while the TBiL level in the observation group were not significantly different from that in the control group. After treatment, the levels of HA (91.71 ± 20.81) μg/mL and IV-C (140.82 ± 48.51) μg/L and LN (73.02 ± 21.06) μg/mL in the observation group were significantly lower than those in the control group.Conclusion:Entecavir combined with conventional drug therapy can effectively improve the inflammatory state of patients with chronic hepatitis B, enhance liver function and reduce liver fibrosis.
文摘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.
基金National Natural Science Foundation of China No:81600593.
文摘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.
文摘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.
