慢性乙型肝炎患者肝纤维化无创诊断模型的评价

目的：通过对慢性乙型肝炎病毒（HBV）感染患者各个肝纤维化非创伤性诊断模型的验证和分析比较,评价其诊断价值,为慢性乙型肝炎肝纤维化临床诊断和疗效评价提供依据。方法：选取112例慢性HBV感染患者,进行肝组织活检的病理学分期,并检测血清指标,用灵敏度等诊断试验评价指标和受试者操作特征（ROC）曲线等方法评估APRI指数、Forns指数、S指数、APAG指数和Fibroindex等模型的诊断价值。结果：各指标组合模型对肝纤维化程度都具有一定诊断价值,其中APAG模型和S指数模型表现较佳。APAG指数模型判断有无显著性肝纤维化、重度肝纤维化和早期肝硬化时的ROC曲线下面积（AUC）分别为0.858、0.891和0.930,以0.27为界定值排除显著性肝纤维化的敏感性、特异性和阴性预测值分别为98%、24%和92%：以0.8为界定值诊断显著肝纤维化的敏感性、特异性和阳性预测值分别为64%、91%和90%,47.3%患者可被正确预测有无显著性肝纤维化。S指数模型判断有无显著性肝纤维化、重度肝纤维化和早期肝硬化时的ROC曲线下面积（AUC）分别为0.837、0.847和0.866,以0.1为界定值排除显著性肝纤维化的敏感性、特异性和阴性预测值分别为94%、47%和85%：以0.5为界定值诊断显著肝纤维化的敏感性、特异性和阳性预测值分别为59%、91%和90%,53.6%患者可被正确预测有无显著性肝纤维化。结论：肝纤维化非创伤性诊断模型能较好地区分存在显著性肝纤维化的慢性乙型肝炎患者,其中以APAG模型和S指数模型较为简便有效,可以避免部分患者行肝穿刺检查。     

Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients

BACKGROUND: Determining the stage of fibrosis by liver biopsy is important in managing patients with hepatitis C virus infection. We investigated the predictive value of the proprietary FibroTest score to accurately identify significant fibrosis in Australian hepatitis C patients. METHODS: Serum obtained from 125 confirmed hepatitis C patients before antiviral therapy was analyzed for haptoglobin, alpha(2)-macroglobulin, apolipoprotein A1, bilirubin, and gamma-glutamyltransferase activity, and the FibroTest score was computed. Liver fibrosis pathology was staged according to a defined system on a scale of F0 to F4. We used predictive values and a ROC curve to assess the accuracy of FibroTest scores. RESULTS: The prevalence of significant fibrosis defined by liver biopsy was 0.38. The most useful single test for predicting significant fibrosis was serum alpha(2)-macroglobulin (cutoff value, 2.52 g/L; sensitivity, 75%; specificity, 67%). The negative predictive value of a FibroTest score <0.1 was 85%, and the positive predictive value of a score >0.6 was 78%. Although 33 of the 125 patients had FibroTest scores <0.1 and were therefore deemed unlikely to have fibrosis, 6 (18%) had significant fibrosis. Conversely, of the 24 patients with scores >0.6 who were likely to have significant fibrosis, 5 (21%) had mild fibrosis. Of the 125 patients in the cohort, 57 (46%) could have avoided liver biopsy, but discrepant results were recorded in 11 of those 57 (19%). CONCLUSION: The FibroTest score could not accurately predict the presence or absence of significant liver fibrosis.     

肝硬化判别评分诊断慢性乙型病毒性肝炎肝纤维化的临床价值

目的:探讨肝硬化判别评分诊断慢性乙型病毒性肝炎肝纤维化的临床价值。方法:172例慢性乙型病毒性肝炎患者均接受肝组织病理检查,并同时检测肝功能、血常规和凝血功能,用ROC曲线评价肝硬化判别评分诊断无或轻度肝纤维化(S0/S1)、显著肝纤维化(S2/S3/S4)、严重肝纤维化(S3/S4)和肝硬化(S4)的能力。结果:S4的肝硬化判别评分明显高于S0、S1、S2和S3(P<0.01);肝纤维化分期和肝硬化判别评分的相关系数rs=0.375(P<0.01);肝硬化判别评分诊断显著肝纤维化的ROC曲线下的面积0.726,阳性预测值95.3%,肝硬化的AUC 0.814,阴性预测值96.5%,严重肝纤维化的AUC仅有0.626,敏感度38.8%。结论:肝硬化判别评分和肝纤维化分期有一定的相关性,肝硬化判别评分可以用于评估慢性乙型病毒性肝炎患者有无显著肝纤维化或肝硬化,但对S2和S3的区分能力有限。     

Accuracy of liver surface nodularity quantification on MDCT for staging hepatic fibrosis in patients with hepatitis C virus

Purpose

To evaluate semi-automated measurement of liver surface nodularity (LSN) on MDCT in a cause-specific cohort of patients with chronic hepatitis C virus infection (HCV) for identification of hepatic fibrosis (stages F0–4).

Methods

MDCT scans in patients with known HCV were evaluated with an independently validated, semi-automated LSN measurement tool. Consecutive LSN measurements along the anterior liver surface were performed to derive mean LSN scores. Scores were compared with METAVIR fibrosis stage (F0–4). Fibrosis stages F0–3 were based on biopsy results within 1 year of CT. Most patients with cirrhosis (F4) also had biopsy within 1 year; the remaining cases had unequivocal clinical/imaging evidence of cirrhosis and biopsy was not indicated.

Results

288 patients (79F/209M; mean age, 49.7 years) with known HCV were stratified based on METAVIR fibrosis stage: F0 (n = 43), F1 (n = 29), F2 (n = 53), F3 (n = 37), and F4 (n = 126). LSN scores increased with increasing fibrosis (mean: F0 = 2.3 ± 0.2, F1 = 2.4 ± 0.3, F2 = 2.6 ± 0.5, F3 = 2.9 ± 0.6, F4 = 3.8 ± 1.0; p < 0.001). For identification of significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (≥ F4), the ROC AUCs were 0.88, 0.89, and 0.90, respectively. The sensitivity and specificity for significant fibrosis (≥ F2) using LSN threshold of 2.80 were 0.68 and 0.97; for advanced fibrosis (≥ F3; threshold = 2.77) were 0.83 and 0.85; and for cirrhosis (≥ F4, LSN threshold = 2.9) were 0.90 and 0.80.

Conclusion

Liver surface nodularity assessment at MDCT allows for accurate discrimination of intermediate stages of hepatic fibrosis in a cause-specific cohort of patients with HCV, particularly at more advanced levels.

     

Prediction of liver fibrosis and cirrhosis in chronic hepatitis B infection by serum proteomic fingerprinting: a pilot study

BACKGROUND: Most noninvasive predictive models of liver fibrosis are complicated and have suboptimal sensitivity. This study was designed to identify serum proteomic signatures associated with liver fibrosis and to develop a proteome-based fingerprinting model for prediction of liver fibrosis. METHODS: Serum proteins from 46 patients with chronic hepatitis B (CHB) were profiled quantitatively on surface-enhanced laser desorption/ionization (SELDI) ProteinChip arrays. The identified liver fibrosis-associated proteomic fingerprint was used to construct an artificial neural network (ANN) model that produced a fibrosis index with a range of 0-6. The clinical value of this index was evaluated by leave-one-out cross-validation. RESULTS: Thirty SELDI proteomic features were significantly associated with the degree of fibrosis. Cross-validation showed that the ANN fibrosis indices derived from the proteomic fingerprint strongly correlated with Ishak scores (r = 0.831) and were significantly different among stages of fibrosis. ROC curve areas in predicting significant fibrosis (Ishak score >or=3) and cirrhosis (Ishak score >or=5) were 0.906 and 0.921, respectively. At 89% specificity, the sensitivity of the ANN fibrosis index in predicting fibrosis was 89%. The sensitivity for prediction increased with degree of fibrosis, achieving 100% for patients with Ishak scores >4. The accuracy for prediction of cirrhosis was also 89%. Inclusion of International Normalized Ratio, total protein, bilirubin, alanine transaminase, and hemoglobin in the ANN model improved the predictive power, giving accuracies >90% for the prediction of fibrosis and cirrhosis. CONCLUSIONS: A unique serum proteomic fingerprint is present in the sera of patients with fibrosis. An ANN fibrosis index derived from this fingerprint could differentiate between different stages of fibrosis and predict fibrosis and cirrhosis in CHB infection.     

Transient elastography: a new noninvasive method for assessment of hepatic fibrosis

Chronic hepatitis is accompanied by progressive deposit of hepatic fibrosis, which may lead to cirrhosis. Evaluation of liver fibrosis is, thus, of great clinical interest and, up to now, has been assessed with liver biopsy. This work aims to evaluate a new noninvasive device to quantify liver fibrosis: the shear elasticity probe or fibroscan®. This device is based on one-dimensional (1-D) transient elastography, a technique that uses both ultrasound (US) (5 MHz) and low-frequency (50 Hz) elastic waves, whose propagation velocity is directly related to elasticity. The intra- and interoperator reproducibility of the technique, as well as its ability to quantify liver fibrosis, were evaluated in 106 patients with chronic hepatitis C. Liver elasticity measurements were reproducible (standardized coefficient of variation: 3%), operator-independent and well correlated (partial correlation COEFFICIENT = 0.71, p < < 0.0001) to fibrosis grade (METAVIR). The areas under the receiver operating characteristic (ROC) curves were 0.88 and 0.99 for the diagnosis of patients with significant fibrosis (≥ F2) and with cirrhosis ( = F4), respectively. The Fibroscan® is a noninvasive, painless, rapid and objective method to quantify liver fibrosis. (E-mail: laurent.sandrin@echosens.com)     

Usefulness of six non-proprietary indirect markers of liver fibrosis in patients with chronic hepatitis C.

BACKGROUND: The aim of the study was to perform a comprehensive diagnostic evaluation of six popular, non-proprietary, indirect markers of liver fibrosis in a cohort of patients with chronic hepatitis C representing the full spectrum of disease severity. METHODS: A total of 167 consecutive, hepatitis C virus RNA positive, untreated patients with chronic hepatitis C were studied. Liver biopsy with histological evaluation and age/platelet index, aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, Bonacini's discriminant score, Forn's fibrosis index and FibroIndex were assessed in all patients. RESULTS: The area under the receiver operating characteristic curves of the six tests was always greater when performed to discriminate patients with METAVIR score F4 than when assessed to discriminate patients with METAVIR score > or =F2. At step-wise discriminant analysis the only indirect marker of fibrosis entered was FibroIndex, with the following correct classification of the patients: total=52.1, patients with scores F0-F1=62.2, patients with scores F2-F3=26.0 and patients with score F4=68.4. CONCLUSIONS: The ability to correctly classify patients using a panel of non-proprietary indirect markers of liver fibrosis is far from being ideal. Among them, FibroIndex appears to possess the best discriminating capacity. The simultaneous use of several indirect markers of liver fibrosis does not improve their diagnostic accuracy.     

超声检查对肝脏硬化程度的诊断价值

目的探讨超声检查对肝硬化的诊断价值。方法对42例慢性肝炎、24例肝硬化患者在肝脏病理活检前或后2 d内行超声检查,依超声对肝脏表面、边缘、实质和肝内静脉四方面检查的综合积分评价肝脏硬化程度,并与病理分期作对比。结果不同病理分期超声检查肝脏硬化综合积分值显著不同(F=130.25,P<0.01),病理分期越高,积分值也越大;肝脏硬化的超声检查综合积分值与病理分期呈显著正相关(r=0.989,P<0.01),根据经验公式Y=X/2-2,由已知的肝硬化综合积分值(X)便可得出病理分期(Y)的程度;曲线分析方法显示肝硬化综合积分值等于10为诊断肝硬化(早期肝硬化)的最佳临界值,其诊断的敏感性为87.5%,特异性为97.5%。结论超声检查可较好地评价肝硬化的纤维化程度,为肝硬化的诊断提供了可靠的半定量指标。     

自身免疫性肝病患者肝纤维化血清标志物检测的意义

目的 探讨血清透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)和层粘连蛋白(LN)对自身免疫性肝病(ALD)患者肝纤维化诊断及鉴别的意义.方法 采用增强化学发光免疫分析法对37例原发性胆汁性肝硬化(PBC)患者、25例自身免疫性肝炎(AIH)患者、33例肝硬化患者、37例病毒性肝炎患者及20例健康体检者血清HA、PCⅢ、CⅣ、LN进行检测,并对部分患者在治疗6个月后再次检测上述指标,同时和部分肝功能指标进行相关性分析.结果 ALD患者4项肝纤维化指标均高于健康对照组(均P<0.05);AIH组4项指标均高于病毒性肝炎组(均P<0.01),ROC曲线下面积分别为0.823、0.849、0.824和0.830; PBC组CⅣ和LN低于肝硬化组(P<0.05);两组ALD患者在经治疗6个月后,上述指标均明显下降(均P<0.05).结论 肝纤维化血清标志物HA、PCⅢ、CⅣ和LN对于ALD患者肝纤维化的诊断及和病毒性肝炎的鉴别具有一定价值,并能间接反映肝脏炎症的情况.     

The APRI may be enhanced by the use of the FIBROSpect II in the estimation of fibrosis in chronic hepatitis C

BACKGROUND: Multiple serum markers to estimate hepatic fibrosis in chronic liver disease have been proposed. The AST/Platelet Ratio Index (APRI) is a simple biochemical index that has been shown to be useful and accurate in about 50% of patients with chronic hepatitis C. We determined if the combination of the APRI and the FIBROSpect II, a commercially available hepatic fibrosis marker that measures 3 components of the extracellular hepatic matrix, would further help distinguish mild from significant fibrosis in a group of patients with chronic hepatitis C. METHODS: In an outpatient setting, 93 consecutive patients were studied who were undergoing staging liver biopsy for chronic hepatitis C who had a liver biopsy length>or=1.5 cm. All had blood drawn at the time of the biopsy. Liver biopsies were staged for fibrosis by the Batts Ludwig criteria (F0-F4). Patients with previous anti-viral therapy, hepatocellular carcinoma, an organ transplant, or co-infection with HIV or hepatitis B were excluded. The APRI was calculated and FIBROSpect II determined. RESULTS: The AUC of the ROC curve for the APRI and FIBROSpect II were 0.887 and 0.879 respectively. Using cutoffs of or=1.2 for significant fibrosis, the APRI correctly estimated 19 of 20 patients with mild fibrosis for an NPV of 95.0%, and 31 of 33 patients with significant fibrosis for a PPV of 93.6%. The FIBROSpect II also works best utilizing 2 cutoffs, and using cutoffs of or=85 it correctly identified 18 of 18 patients with mild fibrosis and all 26 patients with significant fibrosis for an NPV and PPV of 100% for both. Among the 40 patients who could not be classified by the APRI, an additional 16 could be correctly classified using the FIBROSpect II with cutoffs of or=85. This lowered the indeterminate zone from 43.0 to 25.8%. By combining the APRI and the FIBROSpect II, the AUC for the ROC curve improved significantly to 0.931 (p=0.013). CONCLUSIONS: The APRI and the FIBROSpect II are both accurate tests for separating mild from significant fibrosis. By using the APRI as the initial screen, >50% of patients with mild or significant fibrosis can be correctly identified. If the patient falls in the indeterminate zone, then the more expensive FIBROSpect II could be obtained. This strategy could decrease the number of liver biopsies.     

Diagnostic significance of type IV collagen and hyaluronic acid in the serum of patients with chronic hepatitis C for staging hepatic fibrosis

AIM: To evaluate diagnostic value of serologic fibrosis markers (hyaluronic acid--HA and type IV collagen C-IV) in patients with chronic hepatitis C (CHC) and hepatic cirrhosis (HC). MATERIAL AND METHODS: HA and C-IV were measured in 88 CHC patients with fibrosis stage 1 (n = 63) and 3 (n = 25), 13 patients with acute hepatitis C (AHC), 28 patients with hepatic cirrhosis (HC), 19 patients with pulmonary fibrosis (PF). The control group consisted of 32 healthy subjects. RESULTS: HA concentrations in the serum of CHC patients with mild to severe inflammation and fibrosis (F1 and F3) were normal (100 ng/ml). For HC diagnosis, HA test proved highly sensitive and specific (in HA 100 ng/ml sensitivity was 100%, specificity 84.6%), but this method cannot stage hepatic fibrosis. HA test was inferior to C-IV test. A mean C-IV concentration in the serum of CHC patients at the stage of marked fibrosis (F3) is significantly higher than in F1, in HC (A) patients higher than in patients with CHC F3. CONCLUSION: It is shown than concentration of C-IV above 196 ng/ml can differentiate fibrosis stage 1 from stage 3 with specificity 58.7 and sensitivity 88%.     

Standardization of ROC curve areas for diagnostic evaluation of liver fibrosis markers based on prevalences of fibrosis stages

BACKGROUND: The area under the ROC curve (AUC) is widely used as an estimate of the diagnostic value for fibrosis markers. Whether there is variability in the AUC related to the prevalence of fibrosis stages defining advanced and nonadvanced fibrosis is unknown. The aim of this study was to assess the relationships between the AUC and the prevalence of each fibrosis stage and to elaborate simple methods of standardization. METHODS: The AUCs of FibroTest (FT) for the diagnosis of advanced fibrosis were estimated in patients with chronic hepatitis C using an integrated database including 1312 patients with FT and biopsy, and in an overview of 18 diagnostic studies. RESULTS: In the integrated database considering stage prevalence, the FT AUC for advanced fibrosis varied (P <0.001) from 0.67 (only stage F2 as advanced fibrosis and only F1 as nonadvanced fibrosis) to 0.98 (only F4 as advanced fibrosis and only F0 as nonadvanced fibrosis). The same results were observed in the overview, in which the FT AUC varied (P <0.001) from 0.65 to 0.89 according to fibrosis stage prevalence. Two approaches for expressing standardized AUCs were developed: one approach assumed a uniform prevalence distribution of each fibrosis stage; the other approach used the prevalence distribution of fibrosis stages observed in the population. CONCLUSIONS: The expressions of the AUCs of fibrosis markers should be standardized according to the prevalence of fibrosis stages defining advanced and nonadvanced fibrosis.     

血清高尔基体蛋白73在肝硬化诊断及分级中的价值

目的:探讨血清高尔基体蛋白73(GP73)在慢性乙型肝炎(乙肝)、肝硬化中的表达及其与肝硬化分期间的关系。方法:采用酶联免疫吸附试验,定量检测198名正常对照组、171例慢性乙肝组患者、144例肝硬化患者和164例原发性肝细胞肝癌(HCC)患者血清中GP73水平,计算GP73检测受试者工作特征(ROC)曲线下面积及GP73检测对肝硬化诊断的灵敏度与特异度。检测慢性乙肝组和肝硬化组的乙肝病毒(HBV)-DNA载量和HBeAg水平,并对肝硬化组进行血清肝纤维化指标检测及Child-Pugh分级,分析以上指标与GP73水平间的相关性。结果:正常对照组、慢性乙肝组、肝硬化组和肝癌组的中位GP73水平分别为40.80 ng/mL、42.49 ng/mL、83.46 ng/mL和45.19 ng/mL,肝硬化组GP73水平明显高于正常对照组及慢性乙肝组(P<0.05)。结论:血清GP73水平在肝硬化患者代偿期即升高,而随着肝硬化的进展,其呈显著上升趋势,且与HBV活动相关。因此,GP73可作为肝硬化诊断及慢性肝病进展期病情监测的新指标。     

Efficacy and Safety of Faldaprevir,Deleobuvir, and Ribavirin in Treatment-Naive Patients with Chronic Hepatitis C Virus Infection and Advanced Liver Fibrosis or Cirrhosis

Patients with advanced hepatic fibrosis or cirrhosis with chronic hepatitis C virus (HCV) infection represent an unmet need. The HCV NS3/4A inhibitor, faldaprevir, was evaluated in combination with the nonnucleoside NS5B inhibitor, deleobuvir, with or without ribavirin in treatment-naive patients with HCV genotype 1 infection in the SOUND-C2 study. Here, the efficacy and safety of this interferon-free regimen in a subset of patients with advanced liver fibrosis, including those with compensated cirrhosis, were assessed. Patients (n = 362) were randomized to once-daily faldaprevir with either twice-daily (BID) or three-times-daily (TID) deleobuvir for 16 (TID16W), 28 (TID28W and BID28W), or 40 (TID40W) weeks with or without ribavirin (TID28W-NR). Patients were classified according to fibrosis stage (F0 to F2 versus F3 to F4) and the presence of cirrhosis (yes/no). In total, 85 (24%) patients had advanced fibrosis/cirrhosis (F3 to F4) and 33 (9%) had cirrhosis. Within each treatment arm, differences in rates of sustained virologic response 12 weeks after completion of treatment (SVR12) between patients with mild to moderate fibrosis (F0 to F2) versus F3 to F4 did not show a consistent pattern and were not statistically significant (63% versus 47% for TID16W, 53% versus 76% for TID28W, 48% versus 67% for TID40W, 70% versus 67% for BID28W, and 40% versus 36% for TID28W-NR, respectively; P > 0.05 for each arm). The most frequent adverse events in patients with/without cirrhosis were gastrointestinal and skin events, which were mostly mild or moderate in intensity. The degree of liver fibrosis did not appear to affect the probability of achieving SVR12 following treatment with the interferon-free regimen of faldaprevir, deleobuvir, and ribavirin. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01132313","term_id":"NCT01132313"}}NCT01132313.)     

Replacement of hystological findings: serum hyaluronic acid for fibrosis, high-sensitive C-reactive protein for necroinflamation in chronic viral hepatitis

Because of limitations in biopsy procedure, several non-invasive tests have been developed for predicting the histological findings in chronic hepatitis. A fibrosis (F) score 1 or above and necroinflammation [histological activity index (HAI)] score 4 or above are required to initiate the treatment in chronic viral hepatitis. Literature includes many studies on hyaluronic acid (HA) as a non-invasive procedure in predicting histological findings but lacks on high-sensitive-C-reactive protein (hsCRP). We evaluated the diagnostic value of HA and hsCRP in patients with chronic viral hepatitis. Ninety-eight subjects (42 chronic viral hepatitis, 28 cirrhosis and 28 healthy controls) were included in the study. Liver biopsies were performed on 42 chronic hepatitis patients and assessed by Ishak scoring system. All sera were stored at -70 degrees C until assay. Many laboratory parameters related to viral hepatitis, HA and hsCRP were studied following the instructions. We tried to determine a cut-off value for HA to represent > or =F1 score and that for hsCRP to represent > or =4 HAI score. Hepatitis B virus was the predominant aetiology of chronic hepatitis in our study. Mean HA levels were 113, 754 and 24 ng/ml in patients with chronic hepatitis, cirrhosis and controls, respectively (anova, p < 0.001). A HA level >64.7 ng/ml had a 100% specificity for diagnosing chronic hepatitis. A value > or =154 ng/ml had a 100% specificity, 100% positive predictive value and 90% negative predictive value for diagnosing liver cirrhosis (Area 1.00; p < 0.0001). A cut-off value of 63 ng/ml for HA had a 100% specificity for diagnosing fibrosis score > or =1 in chronic hepatitis (Area 0.86; p < 0.001). An hsCRP level >0.56 mg/dl had a 100% specificity and 12% sensitivity for diagnosing chronic hepatitis (Area 0.71; p = 0.002), while cut-off of 0.53 mg/dl had 75% specificity for diagnosing HAI > or = 4 in chronic hepatitis (Area 0.32; p = 0.132). This study supported the HA level in predicting fibrosis score > or =1 with a cut-off value of 63 ng/ml. Cut-off of 154 ng/ml had a strong worth for cirrhosis. A cut-off of hsCRP for predicting HAI score > or =4 warrants further evaluation in wider study populations. We concluded that we are a bit closer to the strategy for guiding therapy in patients with chronic hepatitis, without a liver biopsy.     

乙型肝炎肝硬化患者血清miR-25-3p 和IBSP 表达及临床意义

目的 研究乙型肝炎肝硬化患者血清微小核糖核酸（miRNA,miR）-25-3p 和整合素结合唾液蛋白(integrinbinding sialoprotein,IBSP) 表达及临床意义。方法 选取2018 年5 月～ 2019 年5 月南通市第六人民医院诊治的乙型肝炎肝硬化患者120 例为肝硬化组,并将其分为肝硬化失代偿并发腹腔积液组（47 例）和非肝硬化失代偿并发腹腔积液组（73例）,以同期诊治的慢性乙型肝炎患者80 例为肝炎组,健康体检者60 例为对照组。应用酶联免疫吸附法检测各组血清IBSP 表达,荧光定量PCR 检测各组血清miR-25-3p 的表达。比较肝硬化组不同临床特征患者血清miR-25-3p 和IBSP 水平差异。Pearson 线性相关分析血清miR-25-3p 和IBSP 与肝功能评分的相关性。多因素Logistic 回归分析影响肝硬化失代偿并发腹腔积液的危险因素。受试者工作曲线（ROC）分析miR-25-3p 和IBSP 及联合检测对肝硬化失代偿并发腹腔积液的诊断价值。结果 肝硬化组、肝炎组及对照组血清miR-25-3p 水平分别为5.22±0.41,1.16±0.34 和0.92±0.32,IBSP 蛋白水平分别为9.34±1.28ng/ml, 3.15±0.37ng/ml 和1.02±0.30ng/ml。肝硬化组血清miR-25-3p 和IBSP 蛋白明显高于肝炎组（t=73.327, 42.067）及对照组（t=4.238, 34.486）,差异均有统计学意义（均P ＜ 0.05）。肝硬化组患者血清miR-25-3p 和IBSP 蛋白表达水平与肝纤维化、消化道出血及腹腔积液有关（t=10.194 ～ 34.744, 均P ＜ 0.05）。肝硬化组患者血清miR-25-3p 和IBSP 蛋白表达与清蛋白-胆红素评分（albumin-bilirubin, ALBI）、终末期肝病模型评分（modelfor end-stage liver disease, MELD）、肝硬化Child -Pugh 评分均呈明显正相关（r=0.457 ～ 0.584,均P ＜ 0.05）。多因素Logistic 回归分析结果血清miR-25-3p 升高（OR:1.202,95%CI:1.059 ～ 1.642）,IBSP 升高（OR:1.229, 95%CI:1.081 ～ 1.719）是肝硬化失代偿并发腹腔积液的独立危险因素。ROC 曲线显示,miR-25-3p 和IBSP 联合诊断肝硬化失代偿及并发腹腔积液的曲线下面积（AUC）大于miR-25-3p 和IBSP 单独诊断(Z=3.727,4.163,均P=0.000)。结论 乙型肝炎肝硬化患者血清中miR-25-3p 和IBSP 蛋白水平升高,二者联合检测对乙型肝炎肝硬化失代偿并发腹腔积液具有较高诊断价值。     

Diagnostic Accuracy of 2-D Shear Wave Elastography for the Non-Invasive Staging of Liver Fibrosis in Patients with Elevated Alanine Aminotransferase Levels

This study assessed the diagnostic accuracy of 2-D shear wave elastography (2-D-SWE) for the non-invasive staging of liver fibrosis and compared the findings with those for biochemical markers (the aspartate aminotransferase-to-platelet index and fibrosis-4 index) of liver fibrosis in patients with elevated alanine aminotransferase (ALT) levels (>5?×?the upper limit of normal). Patients with chronic liver diseases and elevated ALT levels who underwent liver biopsy were consecutively included. Receiver operating characteristic (ROC) curves were constructed to assess overall accuracy and to identify optimal cutoff values. After exclusions, data from 105 patients were analyzed. The areas under the ROC curves (AUROCs) for significant fibrosis, severe fibrosis and cirrhosis were 0.83, 0.86 and 0.91, respectively. The optimal cutoff values for predicting significant fibrosis, severe fibrosis and cirrhosis were 10.6, 13.2 and 17.6?kPa, respectively. The AUROCs of 2-D-SWE were significantly higher than those of biochemical markers for predicting significant fibrosis, severe fibrosis and cirrhosis (all p values?<?0.05). Therefore, the diagnostic performance of 2-D-SWE in assessing liver fibrosis stages in patients with elevated ALT levels was promising. The optimal cutoff values were increased but appropriate for this cohort because the baseline levels of liver stiffness measurements were increased in these patients, even in the absence of fibrosis.     

Mayo评分与Child分级评估肝硬化患者预后

目的:通过研究Mayo评分和Child分级与肝硬化患者预后的关系,比较两种方法预测肝硬化患者预后的价值。方法:回顾分析106例肝炎后肝硬化患者的临床资料,计算入院当天Mayo评分与Child分值,通过ROC曲线及截断值进行比较分析。结果:各组患者生存者与死亡者的Mayo评分与Child分值均有显著差异(P<0.05),3个月与2年生存期的患者两体系ROC曲线下面积有显著差异(P<0.05),而生存期1年的患者两体系ROC曲线下面积无显著差异(P>0.05)。结论:Mayo评分与Child分级均准确评估各生存期预后;Mayo评分适宜评估急、危重患者,而Child分级较适宜评估中长期患者。Mayo评分不仅适用于预测原发性胆汁性肝硬化患者预后,同样适用于肝炎后肝硬化患者。     

超声弹性成像在肝纤维化分期中的应用研究

目的 探讨超声弹性成像(RTE)在肝纤维化分期中的应用价值.方法 选择不同病理分期的肝纤维化患者224例,应用RTE评分标准将患者分级,对比其与病理检查分期的相关性,并界定肝纤维化与肝硬化的RTE评级的分界点.结果 肝脏RTE分级为F0、F1、F2级的患者,病理分期多为纤维化(S0、S1、S2、S3)(P<0.05);RTE分级为F4级的患者,病理分期多为肝硬化(S4)(P<0.05);RTE分级为F3时,病理分期分布差异无统计学意义(P>0.05).RTE评分方法与病理分期方法在评价肝纤维化程度时有较高的一致性(Kappa值=0.816).结论 RTE可作为较客观地评价肝纤维化分期的辅助检查方法;此外,乃级可认为是肝纤维化与肝硬化分界点.     

Mean platelet volume as a fibrosis marker in patients with chronic hepatitis B

Introduction: Many noninvasive tests have been studied for the diagnosis and determining the liver fibrosis score (LFS). In this study, we aimed to research the correlation of mean platelet volume (MPV) and stage of liver fibrosis in patients with chronic hepatitis B (CHB). Patients and Methods: Fifty‐nine patients with CHB were enrolled retrospectively into the study. Age–sex matched 25 healthy subjects were used as control group. The following data were obtained from computerized patient registry database: HBV‐DNA level, hepatitis B e‐antigen seropositivity, liver enzymes and function tests, white blood cell count, platelet count, hemoglobin, histological activity index, LFS, and MPV. Patients were divided into two groups: patients without significant fibrosis (F0, F1, or F2) (Group 1) and patients with advanced fibrosis (F3, F4) (Group 2). Results: A statistically significant increase in MPV was seen in patients with CHB compared with healthy controls (8.49±0.84 fl vs.7.65±0.42 fl, P<0.001). Receiver operating characteristic curve analysis suggested that the optimum MPV level cut‐off points for CHB was 8.0 fl, with sensitivity, specificity, PPV, and NPV of 68, 76, 86, and 50%, respectively. MPV levels were significantly higher in Group 2 (8.91±0.94 fl, P: 0.009) compared with Group 1 (8.32±0.74 fl). ROC curve analysis suggested that the optimum MPV level cut‐off points for Group 2 was 8.45 fl, with sensitivity, specificity, positive and negative predictive value of 77, 59, 45, and 85%, respectively. Multivariable logistic regression model, which consisted of HAI, ALT, HBV‐DNA, platelet count, and MPV, was performed. We showed that MPV was independently associated with advanced fibrosis (P: 0.031). Conclusion: We suggest that MPV might help in the assessment of fibrosis in CHB. It should not be considered a stand‐alone test for this use owing to nonspecificity with other diseases. J. Clin. Lab. Anal. 25:162–165, 2011. © 2011 Wiley‐Liss, Inc.