Evaluation of the diagnostic efficacy of noninvasive diagnosis in patients with chronic viral hepatitis B complicated with nonalcoholic fatty liver disease and significant liver fibrosis

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.

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.

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 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.

Evaluation of hepatic fibrosis parameter model and elastic modulus of liver and spleen for the diagnosis of hepatic fibrosis in chronic hepatitis b

Objective Toinvestigate the diagnostic value of hepatic fibrosis parameter model and elastic modulus of liver and spleen in hepatic fibrosis of chronic hepatitis b.Methods 77 patients with hepatic fibrosis of chronic hepatitis in the infection clinic were recruited from July 2016 to December 2018.According to the classification of hepatic fibrosis,23 patients were classified as S1,20 as S2,18 as S3 and 16 as S4.The serum indexes of liver function in all patients were tested,FIB-4,APRI and GPR model indexes were calculated.SWE values of liver and spleen were evaluated,and the correlation between FIB-4,APRI,GPR and SWE was analyzed.Results The SWE values of liver and spleen in the study group were significantly higher than those in the normal group(P<0.01),and the differences in serum GGT,PLT,AST and portal vein velocity between the two groups were statistically significant(P<0.01).GGT and PLT were correlated with SWE values of liver and spleen,which were statistically significant(P<0.01).The model indexes of fib-4,APRI and GPR in the study group were all higher than those in the normal group,with statistically significant differences(P<0.01).Pearson correlation analysis showed that liver SWE value and spleen SWE value were positively correlated with fib-4,APRI and GPR,and the differences were significant(P<0.01),with a higher correlation with GPR.Conclusion GGT,PLT and GPR are positively correlated with SWE of liver and spleen,and combined detection can improve the early diagnosis accuracy of liver fibrosis.

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.

Noninvasive assessment of liver damage in chronic hepatitis B

AIM:To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index(APRI)and neutrophillymphocyte(N/L)ratio to predict liver damage in chronic hepatitis B(CHB).METHODS:We analyzed 89 patients diagnosed with CHB by percutaneous liver biopsy and 43 healthy subjects.Liver biopsy materials were stained with hematoxylin-eosin and Masson’s trichrome.Patients’fibrosis scores and histological activity index(HAI)were calculated according to the Ishak scoring system.Fibrosis score was recognized as follows:F0-1 No/early-stage fibrosis,F2-6 significant fibrosis,F0-4 non-cirrhotic and F5-6 cirrhotic.Significant liver fibrosis was defined as an Ishak score of≥2.APRI and N/L ratio calculation was made by blood test results.RESULTS:The hepatitis B and control group showed no difference in N/L ratios while there was a significant difference in terms of APRI scores(P<0.001).Multiple logistic regression analysis revealed that the only independent predictive factor for liver fibrosis in CHB was platelet count.APRI score was significantly higher in cirrhotic patients than in non-cirrhotic patients.However,this significance was not confirmed by multiple logistic regression analysis.The optimum APRI score cut-off point to identify patients with cirrhosis was 1.01with sensitivity,specificity,positive predictive value and negative predictive value of 62%(36%-86%),74%(62%-83%),29%(13%-49%)and 92%(82%-97%),respectively.In addition,correlation analyses revealed that N/L ratio has a negative and significant relationship with HAI(r=-0.218,P=0.041).CONCLUSION:N/L ratio was negatively correlated with HAI.APRI score may be useful to exclude cirrhosis in CHB patients.

Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China

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.

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.

Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis:A comparative study

AIM:To assess the values of liver stiffness (LS) in pa-tients with hepatitis B virus (HBV) chronic hepatitis and to compare them with those in patients with hepatitis C virus (HCV) chronic hepatitis. METHODS: The study included 140 patients with HBV chronic hepatitis, and 317 patients with HCV chronic hepatitis, in which LS was measured (FibroScan-Echo-sens) and liver biopsy was performed in the same session (assessed according to the Metavir score). RESULTS:According to the Metavir score of the 140 HBV patients: one had F0,32 had F1, 67 had F2,33 had F3 and 7 had F4. Of the 317 HCV patients:5 had F0, 34 had F1, 146 had F2, 93 had F3 and 39 had F4. For the same severity of fibrosis, the mean values of LS in HBV patients were similar to those in HCV patients:F1,6.5±1.9 kPa vs 5.8±2.1 kPa (P=0.0889); F2,7.1±2 kPa vs 6.9±2.5 kPa (P = 0.3369); F3,9.1±3.6 kPa vs 9.9±5 kPa (P=0.7038); F4,19.8± 8.6 kPa vs 17.3±6.1 kPa (P=0.6574). A signif icant direct correlation between LS measurements and fibrosis was found in HCV patients (Spearman’s r=0.578, P<0.0001), as well as in HBV patients (r=0.408, P<0.0001). The correlation was more signif icant in HCV than in HBV patients (Fisher’s Z-test,Z= 2.210,P=0.0271). CONCLUSION:In our group, the mean values of LS in patients with chronic B hepatitis were similar to those in patients with chronic HCV hepatitis, for the same stage of f ibrosis. Also, LS was correlated with the severity of fibrosis both in HBV and HCV chronic hepatitis patients.

Non-ALT biomarkers for markedly abnormal liver histology among Chinese persistently normal alanine aminotransferase-chronic hepatitis B patients

AIM To determine incidence and clinical biomarkers of marked necroinflammation and fibrosis characteristics among chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (PNALT). METHODS Liver biopsy was performed on 115 CHB patients with PNALT. Necroinflammation and fibrosis were graded by the Knodell histologic activity index and the Ishak fibrosis score, respectively. Correlations between the available clinical parameters and necroinflammation and fibrosis were analysed. RESULTS Marked necroinflammation (Knodell activity index >= 7) and fibrosis (Ishak fibrosis score >= 3) were found in 36.5% and 15.5% of CHB patients with PNALT, respectively. Following a univariate logistic regression analysis, multiple logistic regression analysis indicated that aspartate transaminase (AST) (AUROC = 0.852, cut-off value = 22.5 U/L) serves as an independent predictor of notable liver inflammation, while platelet (PLT) count (AUROC = 0.905, cut-off value = 171.5 x 10(9)/ml) and gamma-glutamyl transpeptidase (GGT) (AUROC = 0.909, cut-off value = 21.5 U/L) level serve as independent predictors of notable liver fibrosis. CONCLUSION A considerable proportion of marked histological abnormalities existed in our cohort, who will benefit from optimal therapeutic strategies administered according to predictive indication by AST, PLT and GGT levels.

Serum ceruloplasmin can predict liver fibrosis in hepatitis B virusinfected patients

BACKGROUND The presence of significant liver fibrosis in hepatitis B virus(HBV)-infected individuals with persistently normal serum alanine aminotransferase(PNALT)levels is a strong indicator for initiating antiviral therapy.Serum ceruloplasmin(CP)is negatively correlated with liver fibrosis in HBV-infected individuals.AIM To examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT.METHODS Two hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated.The association between CP and fibrotic stages was statistically analyzed.A predictive index including CP[Ceruloplasmin hepatitis B virus(CPHBV)]was constructed to predict significant fibrosis and compared to previously reported models.RESULTS Serum CP had an inverse correlation with liver fibrosis(r=-0.600).Using CP,the areas under the curves(AUCs)to predict significant fibrosis,advanced fibrosis,and cirrhosis were 0.774,0.812,and 0.853,respectively.The CPHBV model was developed using CP,platelets(PLT),and HBsAg levels to predict significant fibrosis.The AUCs of this model to predict significant fibrosis,advanced fibrosis,and cirrhosis were 0.842,0.920,and 0.904,respectively.CPHBV was superior to previous models like the aspartate aminotransferase(AST)-to-PLT ratio index,Fibrosis-4 score,gamma-glutamyl transpeptidase-to-PLT ratio,Forn’s score,and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT.CONCLUSION CPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT.Therefore,CPHBV can be a valuable tool for antiviral treatment decisions.

Ceruloplasmin, a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase

AIM To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin(CP) levels and liver fibrosis in chronic hepatitis B(CHB) patients with normal or minimally raised alanine aminotransferase(ALT).METHODS Serum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group(n = 97) and a validation group(n = 96). Liver histology was evaluated by the METAVIR scoring system. Receiver operator characteristic curves were applied to the diagnostic value of CP for measuring liver fibrosis in CHB patients. Spearman rank correlation analyzed the relationship between CP and liver fibrosis. A noninvasive model was set up through multivariate logistic regression analysis.RESULTS Serum CP levels individualized various fibrosis stages via area under the curve(AUC) values. Multivariate analysis revealed that CP levels were significantlyrelated to liver cirrhosis. Combining CP with serum GGT levels, a CG model was set up to predict significant fibrosis and liver cirrhosis in CHB patients with normal or minimally raised ALT. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value were 0.84, 83.1%, 78.6%, 39.6%, and 96.5% to predict liver cirrhosis, and 0.789, 80.26%, 68.38%, 62.25%, and 84.21% to predict significant fibrosis. This model expressed a higher AUC than FIB-4(age, ALT, aspartate aminotransferase, platelets) and GP(globulin, platelets) models to predict significant fibrosis(P = 0.019 and 0.022 respectively) and revealed a dramatically greater AUC than FIB-4(P = 0.033) to predict liver cirrhosis.CONCLUSION The present study showed that CP was independently and negatively associated with liver fibrosis. Furthermore, we developed a novel promising model(CG), based on routine serum markers, for predicting liver fibrosis in CHB patients with normal or minimally raised ALT.

Histopathological evaluation of long-term tenofovir disoproxil fumarate treatment in patients with hepatitis be antigen-negative chronic hepatitis B

BACKGROUND Hepatitis B virus is a universal health problem.There are approximately 250 million people living with hepatitis B worldwide,and approximately 600000 of these people die every year due to the virus.AIM To compare the pretreatment and post-treatment histopathological results of patients with hepatitis be antigen(HBeAg)-negative chronic hepatitis B(CHB)who had been receiving tenofovir disoproxil fumarate(TDF)treatment at our clinic for at least 5 years.METHODS Patients with HBeAg-negative CHB who were being treated with TDF(245 mg/d)were included in the study.Liver biopsies of patients before TDF treatment and liver biopsies after 5 years of TDF treatment were retrospectively compared.RESULTS A total of 50 HBeAg-negative CHB patients were included in the study(mean age:47.9±10.4 years,men:27.54%).Histological improvement was observed in 78%(39)of the patients after 5 years of treatment.After the 5 years of treatment,the mean Ishak score of the patients was 1.3±1.3,and the mean histologic activity index score was 4.1±2.8.A 1.53 point reduction in Ishak fibrosis score was detected after long-term TDF treatment.CONCLUSION Liver biopsies after 5 years of TDF treatment revealed a significant histological response and a regression of the necroinflammatory score compared to pretreatment liver biopsies.To better understand the effects of antiviral treatments on the improvement of liver histology,long-term studies involving larger numbers of patients are needed.

无创方法诊断HBeAg阳性慢性乙型肝炎患者肝内炎症反应程度

目的建立由简单常规实验数据组成的模型,以预测HBeAg阳性且丙氨酸氨基转移酶(ALT)≤2倍正常上限的慢性乙型肝炎(CHB)患者的肝脏炎症反应程度。方法选取2019年4月1日至2021年5月8日151例HBeAg阳性且ALT≤2倍正常上限的CHB患者作为研究对象,根据肝脏病理检查结果分为轻度炎症反应[肝组织炎症分级(G)G0~1]组和中度炎症反应(G≥2)组,采用多因素Logistic回归分析CHB患者发生中度炎症反应的独立危险因素并建立诊断模型。结果53.0%(80/151例)的研究对象出现G≥2。G≥2组ALT、天门冬氨酸氨基转移酶(AST)水平均明显高于G0~1组,胆碱酯酶(ChE)、前蛋白比(PA)、HBsAg均明显低于G0~1组,差异均有统计学意义(P<0.05)。ALT、AST与G分级均呈弱正相关(r=0.212、0.303,P<0.05),ChE、PA、HBsAg与G分级均呈弱负相关(r=-0.371、-0.330、-0.173,P<0.05)。高水平AST、低水平PA、低水平logChE为CHB患者发生中度炎症反应的独立危险因素(P<0.05)。模型CPA对预测发生G≥2的受试者工作特征曲线下面积为0.842(95%CI:0.741~0.935)。当CPA≤0.3,其排除G≥2的阴性预测值为84.21%;当CPA≥0.6时,CPA诊断发生G≥2的阳性预测值为84.00%。结论AST、PA和logChE与HBsAg阳性且ALT≤2倍正常上限的CHB患者的肝内炎症反应程度相关。CPA对发生G≥2具有较好的诊断效能,且该模型涉及的指标简单易得,适合临床推广使用。

血清HBsAg和HBV DNA定量水平预测慢性乙型肝炎患者肝组织炎症活动度和纤维化程度的评价

目的评价血清HBsAg水平和HBVDNA载量预测CHB患者肝组织炎症活动度和纤维化程度的效能。方法740例CHB患者被随机分成训练集和验证集，训练集HBeAg阳性和阴性患者分别为281例和169例，验证集HBeAg阳性和阴性患者分别为170例和120例。肝活检取得肝组织，将肝组织病理学分级和分期≥G2和≥S2、≥G3和≥S3，≥G4和≥S4分别定义为显著炎症和纤维化、严重炎症和纤维化、进展期炎症和纤维化。采用Abbott Architect I2000检测血清HBsAg，采用实时定量PCR法检测血清HBVDNA。结果在HBeAg阳性患者，训练集血清HBsAg水平预测严重纤维化和进展期纤维化的效能达到了中度，其ROC曲线下面积分别为0．707和0．726；基于Youden指数确定的血清HBsAg预测严重纤维化和进展期纤维化的最佳截断点为≤6．683×10^3IU／ml和≤6．427×10^3IU／ml，在训练集其对应的灵敏度和特异度分别为0．682和0．754及0．673和0．634，在验证集则分别为0．667和0．806及0．644和0．619；在HBeAg阴性患者，训练集血清HBVDNA载量有预测显著炎症和显著纤维化的效能，其ROC曲线下面积分别为0．629和0．671。基于Youden指数确定的血清HBVDNA预测显著炎症和显著纤维化的最佳截断点为94．315×10^4IU／ml和≥2．748×10^3IU／ml，在训练集其对应的灵敏度和特异度分别为0．444和0．606及0．795和0．717，在验证集则分别为0．446和0．613及0．797和0．622。结论血清HBsAg水平对HBeAg阳性患者的严重纤维化和进展期纤维化有显著的预测价值，而血清HBVDNA载量对HBeAg阴性患者的显著炎症和显著纤维化有一定的预测意义。

FibroScan检测与慢性肝病临床诊断的相关性研究

目的探讨FibroScan在慢性HBV感染者肝纤维化诊断中的作用。方法选择我院364例进行FibroScan检测的慢性HBV感染者,获取FibroScan检测值(FS值),分析其与肝功能、肾功能和凝血功能指标及超声诊断等级的相关性。结果临床诊断为慢性乙型肝炎170例,肝硬化194例。肝硬化组FS值显著高于慢性乙型肝炎组(P<0.05)。将FS值与临床检验指标进行多重线性回归分析,FS值与ALB、国际标准化比值、CHE、ALP、ALT之间具有相关性,其中ALB对FS值影响最大。不同超声诊断等级分组的FS值差异有统计学意义(P<0.05),FS值与超声诊断等级分组之间相关性较好(rs=0.670)。超声诊断为脾大但无肝硬化患者的FS值高于超声诊断无脾大、无肝硬化的患者(P<0.05)。结论 FibroScan在诊断慢性HBV感染者纤维化严重程度方面有较好的应用价值。

FibroTouch无创诊断慢性HBV感染者肝纤维化程度的临床价值

目的探讨FibroTouch瞬时弹性检测仪无创诊断慢性乙型肝炎病毒(HBV)感染者肝纤维化程度的临床应用价值。方法选择接受肝穿刺检查的慢性HBV感染者187例,所有患者经FibroTouch检测肝脏硬度值(LSM),同时检测肝功能和血常规等血清学指标,以肝穿病理结果作为金标准,绘制肝脏硬度值受试者工作特征曲线(ROC),计算曲线下面积(AUC)。结果 LSM随着肝纤维化程度的加重而增加,与肝纤维化分期呈正相关(rs=0.678,P<0.01)。LSM与白蛋白(ALB)、球蛋白(GLB)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(GGT)、血浆凝血酶原时间(PT)、血小板(PLT)和乙肝表面抗原(HBs Ag)水平均有一定的相关性(P<0.05)。在不排除ALT≥2×正常值上限(ULN)的病例组中,FibroTouch诊断慢性HBV感染者显著肝纤维化期、严重肝纤维化期和肝硬化期的受试者工作曲线下面积(AUROC)分别为0.815、0.884、0.920;对应的最佳截断值分别为7.55、10.15、15.25 k Pa;灵敏度分别是79.2%、83.3%、90.5%;特异度分别为74.7%、87.2%、89.2%;符合率分别为77.0%、86.1%、89.3%。在ALT<2×ULN的病例组中,FibroTouch诊断慢性HBV感染者显著肝纤维化期、严重肝纤维化期和肝硬化期的灵敏度和特异度与全部患者组相比无显著差异。结论 FibroTouch瞬时弹性成像无创诊断肝纤维化程度具有很好的临床应用价值,值得临床进一步推广。

γ-谷氨酰转肽酶/血小板比值对血清转氨酶正常的慢性HBV感染者肝纤维化的预测价值分析

目的探讨γ-谷氨酰转肽酶/血小板比值(GPR)预测转氨酶正常的慢性HBV感染者肝纤维化分期的价值。方法 2010年～2016年我院诊治的血清转氨酶正常的慢性HBV感染者202例,经肝活检诊断肝纤维化,计算GPR、AST与PLT比值指数(APRI)和基于4因素的肝纤维化指数(FIB-4)预测明显肝纤维化(≥F2)、进展期肝纤维化(≥F3)和早期肝硬化(F4)的效能。应用ROC曲线下面积(AUC)判断诊断效能。结果经肝组织病理学检查,本组发现F1、F2、F3和F4分别为82例、60例、39例和21例;F4组GPR、APRI和FIB-4分别为0.4(0.2,1.0)、(0.6±0.2)和1.6 (0.9,1.8),而F3组分别为0.2 (0.2,0.4)、(0.6±0.2)和0.9 (0.9,1.2),F2组则分别为0.2 (0.1,0.3)、0.4±0.2和0.9(0.7,1.3),差异显著(P<0.05);GPR预测明显肝纤维化(≥F2)、进展期肝纤维化(≥F3)和早期肝硬化(F4)的AUC分别是0.739、0.790和0.824,显著高于APRI(分别为0.547、0.731和0.736,P<0.05);GPR预测肝纤维化≥F3的AUC为0.790,显著高于FIB-4(0.748,P<0.05),而FIB-4预测肝纤维化≥F2的AUC为0.777,显著高于GPR(0.739,P<0.05),FIB-4和GPR预测肝硬化(F4)的效能之间无显著性差异(分别为0.824和0.792,P>0.05)。结论 GPR可以预测转氨酶正常的慢性HBV感染者肝纤维化分期,其效能优于APRI,而与FIB-4相比,各有优缺点。GPR可以作为对转氨酶正常的慢性HBV感染者肝纤维化一个无创生化预测指数。

ARFI、Forns指数、FIB-4和APRI无创诊断慢性乙型病毒性肝炎肝纤维化的研究

目的声辐射力脉冲成像技术(ARFI)及血清学诊断模型(Forns指数、FIB-4、APRI)对慢性乙型病毒性肝炎肝纤维化评估的价值。方法 111例确诊为慢性乙型病毒性肝炎患者,根据肝组织活检病理分期结果分组:无明显肝纤维化组(S0、S1)40例,明显肝纤维化组(≥S2)48例、早期肝硬化组(S4)23例。每例患者同期进行ARFI、Forns指数、FIB-4、APRI的评估。比较无创诊断模型与肝脏病理的相关性,并根据受试者工作特征曲线(ROC)分析无创诊断模型对肝纤维化的诊断价值。结果ARFI、Forns指数、FIB-4、APRI 4种无创诊断方法与肝组织活检具有良好的一致性,其皮尔逊相关系数(Pearson correlation coefficient)分别为0.882、0.639、0.589、0.418。明显肝纤维化组(≥S2)及早期肝硬化组,ARFI的诊断价值均优于FIB-4(Z=2.882,P=0.004;Z=3.215,P=0.001)、APRI(Z=4.850,P<0.001;Z=3.198,P=0.001)、Forns指数(Z=2.182,P=0.029;Z=2.798,P=0.005)。结论 ARFI对明显肝纤维化及早期肝硬化的诊断具有较高的价值,值得推广。

CT与FIB-4无创诊断慢性乙型病毒性肝炎肝纤维化的效果分析

目的分析CT与FIB-4无创诊断慢性乙型病毒性肝炎肝纤维化的准确性，并与肝组织活检进行比较，为临床无创诊断肝纤维化提供新的手段。方法连续选取湖北医药学院附属东风医院2012年5月-2014年5月收治的46例慢性乙型病毒性肝炎肝纤维化患者为研究对象，其中男性24例，平均年龄46．5±7．3岁，平均病程3．4±1．8年，平均HBV—DNA（49．4±5．3）×10^2 copies／ml。经该院伦理委员会批准及患者知情同意下均对其实施CT与FIB-4无创检查，并将结果与肝组织活检进行比对。结果CT与FIB-4无创检查与肝组织治检具有良好的一致性（CT：r=0．580，P=0．034；FIB-4：r=0．885，P=0．027）；且FIB-4无创检查结果（包括AUC、截断值、敏感度、特异度、阳性预测值、阴性预测值和准确性）均优于CT检查，差异具有统计学意义（P〈0．05）。结论FIB-4无创诊断慢性乙型病毒性肝炎肝纤维化效果可能成为替代肝组织活检的一种诊断方法，值得在临床中推广使用。