Alanine aminotransferase influencing performances of routine available tests detecting hepatitis B-related cirrhosis.

The performances of routine tests such as FIB-4 and APRI in detecting cirrhosis and significant fibrosis in chronic hepatitis B (CHB) have been shown to be discrepant between studies. Novel tests such as red cell distribution width-platelet ratio (RPR), γ-glutamyl transpeptidase to platelet ratio (GPR) and easy liver fibrosis test (eLIFT) are introduced recently. To evaluate the aminotransferase influence on the performance of these routine tests, a total of 1005 CHB patients who underwent liver biopsies and routine tests were retrospectively analysed. The diagnostic cut-offs referring to likelihood ratio were determined for excluding or including cirrhosis diagnosis and also for ruling in significant fibrosis diagnosis. The performances of RPR, FIB-4, eLIFT and APRI in detecting cirrhosis seemed improved at higher ALT levels, while GPR was conversely impaired. The likelihood ratio was âˆ for APRI cut-off 2 diagnosing cirrhosis in ALT < 2 upper limit of normal (ULN), 14.6 for APRI cut-off 1.5 determining significant fibrosis in ALT ≤ 5ULN and 20.6 for FIB-4 cut-off 3.2 diagnosing ≥ F3 in the total cohort, respectively. The optimal cut-offs for cirrhosis diagnosis were increased with higher ALTs by tests which included aminotransferase, but not for RPR. The proportions of patients classified as having cirrhosis or no cirrhosis stratified by ALT level cut-offs were superior. Stepwise applying RPR, GPR and eLIFT would determine 60% of patients as having cirrhosis or no cirrhosis with an accuracy of 93.0%. In conclusion, the performance of aminotransferase comprising tests in detecting cirrhosis in CHB were influenced by ALT levels. Thus, ALT stratified cut-offs may be a preferred alternative. In resource-limited settings, stepwise applying routine tests could be recommended as a preferred measurement for cirrhosis detection.

Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals.

BACKGROUND & AIMS: Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis. METHODS: We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index <30 kg/m2 were examined with the medium probe and those with a body mass index ≥30 kg/m2 were examined with the extra-large probe. Linear regression models were conducted after adjusting for potential confounding factors of LSMs. We performed several sensitivity analyses. RESULTS: We established LSM ranges for healthy individuals measured with both probes-these did not change significantly in sensitivity analyses of individuals with platelets ≥150,000/mm3 and levels of alanine aminotransferase ≤33 IU/L in men or ≤25 IU/L in women. In multivariate analysis, factors that modified LSMs with statistical significance included diabetes, dyslipidemia, waist circumference, level of aspartate aminotransferase, and systolic blood pressure at examination time. Significant increases in LSMs were associated with the metabolic syndrome in individuals examined by either probe. Diabetes in obese individuals increased the risk of LSMs in the range associated with advanced fibrosis. CONCLUSIONS: In a systematic review and meta-analysis of data from individual participants, we established a comprehensive set of LSM ranges, measured by TE in large cohorts of healthy individuals and persons susceptible to hepatic fibrosis. Regression analyses identified factors associated with increased LSMs obtained by TE with the medium and extra-large probes.

Stepwise application of fibrosis index based on four factors, red cell distribution width-platelet ratio, and aspartate aminotransferase-platelet ratio for compensated hepatitis B fibrosis detection.

BACKGROUND AND AIM: Fibrosis index based on four factors (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width-platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB-4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis. METHODS: A total of 246 compensated CHB patients who underwent liver biopsies, transient elastography, and routine blood tests including complete blood count were included. Dual cut-offs were determined to exclude or include cirrhosis diagnosis. Performance of stepwise combining routine biomarkers including RPR, FIB-4, and APRI were statistically analyzed. RESULTS: The Metavir F0, F1, F2, F3, and F4 were identified in 2.4%, 22.0%, 32.1%, 24.0%, and 19.5% of the eligible patients, respectively. The area under receiver operating characteristics curves for detecting significant fibrosis and cirrhosis were 0.853 and 0.883 for transient elastography; 0.719 and 0.807 for FIB-4; 0.638 and 0.791 for RPR; 0.720 and 697 for APRI; and 0.618 and 0.760 for mean platelet volume-platelet ratio, respectively. The proportion of patient determined as cirrhosis or non-cirrhosis was 65.9% by transient elastography, 36.9% by FIB-4, 30.5% by RPR, and 19.5% by APRI, respectively. These numbers for determining significant fibrosis were 49.6%, 24.2%, 21.5%, and 23.6% in the same order. Detected by stepwise application of FIB-4, RPR, and APRI, 41.5% and 52.8% of patients could be determined the state of significant fibrosis and cirrhosis, respectively. CONCLUSIONS: In source-limited settings without transient elastography, stepwise applying FIB-4, RPR, and APRI could free nearly half of CHB patients from liver biopsies in detecting significant fibrosis and cirrhosis.

An Innovative model of magnetically intercalated expanded graphite for calculating radar attenuation performance at 2-18 GHz.

With the emergence of various filtering technologies, the radar jamming efficiency of the technology based on radar cross section is ever lower, therefore cannot meet military requirements. In this context, the jamming technology based on attenuation mechanism has been developed and plays an increasingly important role in disturbing radar detecting. Magnetically expanded graphite (MEG) has excellent attenuation efficiency because it can cause dielectric loss as well as magnetic loss. Moreover, MEG features good impedance matching, which makes more incidence of electromagnetic waves into the material; and its multi-layer structure is conducive for electromagnetic wave reflection and absorption. In this work, the structure model of MEG was established by analyzing the layered structure of expanded graphite (EG) and the dispersion of intercalated magnetic particles. The electromagnetic parameters of thus-modeled MEG were calculated based on the equivalent medium theory; and effects of EG size, magnetic particle type and volume fraction on the attenuation performance were studied by the variational method. It is indicated that MEG with 500-µm diameter has the best attenuation effect and the highest increment of absorption cross section appears at 50% volume fraction of the magnetic particles at 2 GHz. The imaginary part of complex permeability of the magnetic material has the most significant influence on the attenuation effect of MEG. This study provides guidance for the design and application of MEG materials in disturbing radar detecting field.

Is transient elastography valuable for high-risk esophageal varices prediction in patients with hepatitis-B-related cirrhosis?

BACKGROUND AND AIM: The aim of this study was to evaluate the clinical value of transient elastography (TE) for high-risk esophageal varices (HREV) prediction in hepatitis-B-related cirrhosis patients. METHODS: A total of 238 patients with hepatitis B cirrhosis were prospectively enrolled. All patients had undergone TE and upper gastrointestinal endoscopy. Diagnostic value was assessed by the area under ROC curve (AUROC), predictive value and likelihood ratio. RESULTS: The size of esophageal varices correlated with liver stiffness with Kendall's tau_b 0.236 overall and 0.425 in patients with ALT ≥ 5 × upper limit of normal (ULN). The AUROC of TE predicting HREV was 0.73 (95% confidence interval 0.66-0.80) overall and 0.92 (0.82-1.01) for patients with ALT ≥ 5 × ULN. In patients with ALT ≥ 5 × ULN, cut-off 36.1 kPa predicted HREV with a 100% negative predictive value (NPV), an indefinite negative likelihood ratio (NLR), a 72.7% positive predictive value (PPV) and a positive likelihood ratio (PLR) of 9.3. The AUROC of HREV-predicting model, constructed by ultrasonography and TE (USLS), was 0.84 (0.77-0.90) in the training set and 0.85 (0.76-0.94) in the validating set. Cut-off 3.30 excluded HREV with NPV 0.946 and NLR 0.10, and cut-off 5.98 determined HREV with PPV 0.870 and PLR 10.24. Using USLS, nearly 50% of patients could avoid endoscopic screening. The model's predictive values were maintained at similar accuracy in the validation set. Differences of AUROC in USLS, liver stiffness/spleen diameter to platelet ratio score and ultrasonic score were not significant. CONCLUSIONS: TE may predict HREV in patients with ALT ≥ 5 × ULN. Overall, the clinical values of TE and USLS for HREV prediction should be evaluated by further studies.

Larger biopsies evaluation of transient elastography for detecting advanced fibrosis in patients with compensated chronic hepatitis B.

BACKGROUND AND AIM: Although larger biopsies sample had been recommended for the study of non-invasive liver fibrosis assessment, few studies with larger biopsies for transient elastography (TE) detecting liver fibrosis had been reported. The present study tries to re-evaluate the performance of TE for detecting advanced fibrosis (≥F3) with larger biopsies in patients with compensated chronic hepatitis B. METHODS: A total of 375 compensated patients were analyzed, who had undergone liver biopsy, reliable TE and routine blood tests. RESULTS: The area under the receiver operating characteristic curve (AUC) was influenced by liver biopsy sample: 0.873 (95% confidence interval 0.838-0.909) in total patients, 0.880 (0.844-0.917) in length ≥ 15 mm, 0.897 (0.863-0.932) in length ≥ 20 mm and 0.911 (0.874-0.949) in length ≥ 25 mm. In patients with sample length ≥ 20 mm, the cutoffs to exclude and confirm advanced fibrosis were 7.1 kPa and 12.7 kPa, respectively. Stratified by alanine aminotransferase of two times the upper limit of normal (ALT 2 × ULN), transient elastography detecting advanced fibrosis with the most efficiency by 72.5% of patients obviated from liver biopsy. In patients with normal bilirubin and ALT < 2 × ULN, the area was 0.921 (0.860-0.982), and cutoffs for excluding and confirming diagnosis were 7.4 kPa and 10.6 kPa, respectively; 80% of patients could be classified with or without advanced fibrosis (AF). In patients with normal bilirubin and ALT ≥ 2 × ULN, the corresponding numbers were 0.885 (0.824-0.947), 7.5 kPa, 12.7 kPa and 79.2%, respectively. CONCLUSIONS: Inadequate sample study would underestimate the efficiency of TE on detecting advanced fibrosis. With ALT 2 × ULN stratified cutoffs, TE determined nearly 80% of patients with normal bilirubin as AF or non-AF and obviated them from liver biopsies.

Ultrasonic spleen thickness-based indexes surpass Baveno VI criteria in high-risk gastroesophageal varices detection.

AIMS: To evaluate the efficiency of ultrasonic spleen thickness (UST), routine variables and (expanded) Baveno VI criteria for high-risk gastroesophageal varices (HRGOV) detection in cirrhotic patients. METHODS: In total, 305 cirrhotic patients were retrospectively enrolled in the deriving cohort and 328 cirrhotic patients with hepatitis B sustained viral response were prospectively enrolled in the validation cohort. HRGOV was defined as medium and severe gastroesophageal varices (GOV), mild GOV with red signs or Child-Pugh C. The cut-offs for HRGOV were determined by likelihood ratio indicating strong evidences. Algorithms of Spleen thickness-Age-Liver stiffness measurement (LSM, by Fibroscan®)-Albumin (SALA) and Spleen thickness-Platelet-Albumin (SPA) were derived by multivariate analyses. RESULTS: The area under receiver operating characteristics curve of SALA, SPA, UST, platelet, and LSM were 0.849, 0.835, 0.808, 0.746, and 0.655 in the deriving cohort, and improved to 0.901, 0.904, 0.858, 0.876, and 0.811 in the validation cohort, respectively. While SALA, SPA, UST, platelet, Baveno VI criteria (BVI), and expanded BVI spared 46.6%, 38.0%, 29.2%, 21.0%, 12.1%, and 23.6% esophagogastroduodenoscopy in the deriving cohort, these numbers were improved to 68.1%, 66.8%, 27.1%, 37.8%, 36.0%, and 61.0% in the validating cohort, respectively; however, the negative likelihood ratio of expanded BVI was up to 0.16. SPA spared less esophagogastroduodenoscopy than SALA, which can be supplemented by stepwise applying UST and SPA. Sequentially combining UST and SALA, BVI and SALA exempted additional 10-5% endoscopies. CONCLUSIONS: SPA, without LSM, improves HRGOV detection comparing with BVI. UST based algorithms combination can achieve the best efficiency especially in sustained virus response hepatitis B.

[Transient elastography accurately predicts the severity of disease in patients with chronic hepatitis B].

OBJECTIVE: To evaluate the value of transient elastography (TE) for predicting severity of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: A total of 969 patients with CHB was enrolled and recruited for analysis, which had been received TE scan, including 258 patients of liver biopsy, and 117 patients of gastric endoscopy. RESULTS: A total of 35 patients was excluded from analysis due to TE failure or unreliable TE. Liver stiffness measurement (LSM) was independently influenced by bilirubin, AST, liver fibrosis and inflammation, ultrasonic score and albumin. TE predicted Child-Pugh C, B/C, liver fibrosis S4, ≥ S3 and ≥ S2 with respective area under receiver operating characteristics curves (AUROC) 0.907 (95%CI 0.886 - 0.928), 0.920(95%CI 0.899 - 0.940), 0.871(95%CI 0.819 - 0.923), 0.852(95%CI 0.805 - 0.899) and 0.807(95%CI 0.749 - 0.865), respectively. While LSM < 32.2 kPa excluded Child-Pugh C with 99.4% probability, LSM ≥ 35.3 kPa determined Child-Pugh B/C with positive predictive value (PPV) 0.820. For compensated CHB, cut-offs of LSM 23.3, 15.2 and 10.8 kPa diagnosed cirrhosis, liver fibrosis ≥ S3 and ≥ S2 with positive likelihood ratio nearly 10.0 and PPV 0.692, 0.882 and 0.980, respectively; and cut-offs 8.8 kPa, 6.6 kPa excluded cirrhosis, liver fibrosis ≥ S3 with negative likelihood ration nearly 0.1 and negative predictive value 0.977 and 0.903, respectively. Correlation coefficient between LSM and grades of esophageal varices was only 0.180, and AUROC for TE predicting EV was of no clinical value. CONCLUSION: TE relatively make accurate prediction in the severity of liver fibrosis and classification of Child-Pugh. Patients with LSM ≥ 10.8 kPa should be considered for receiving antivirus treatment.

Routine indexes for cirrhosis and significant fibrosis detection in patients with compensated chronic hepatitis B.

BACKGROUND AND AIM: Fibrosis index based on the four factors (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) were not well validated in patients with chronic hepatitis B (CHB). The aim of this study was to validate the performances of these indexes and construct novel indexes for liver fibrosis assessment. METHODS: A total of 1438 consecutive antivirus treatment-naïve patients with CHB were analysed, and two novel indexes (named HeBCI and HeBFI) were derived for cirrhosis and significant fibrosis detection. RESULTS: For cirrhosis, the area under receiver operating characteristic curves (AUROCs) were 0.841 for HeBCI, 0.708 for FIB-4 and 0.623 for APRI in the model set, and 0.779, 0.690, 0.595 in the validation set. For significant fibrosis, the AUROCs were 0.781 for HeBFI, 0.693 for APRI and 0.641 for FIB-4 in the model set, and 0.776, 0.729, 0.641 in the validation set. HeBCI determined 750 (52.2%) patients as having cirrhosis or non-cirrhosis with an accuracy of 86%. HeBFI detected 673 (46.8%) patients with or without significant fibrosis with an accuracy of 76.6%. CONCLUSIONS: As economical and convenient indexes, HeBCI and HeBFI are suitable to serve as outpatient tools for detecting significant fibrosis and cirrhosis to reduce the need of liver biopsy significantly in resource-limited settings.

Model consisting of ultrasonographic and simple blood indexes accurately identify compensated hepatitis B cirrhosis.

BACKGROUND AND AIM: Several models for significant fibrosis or cirrhosis have been introduced for hepatitis C, but are seldom for hepatitis B. The present study retrospectively evaluates the relationship between ultrasonography, blood tests, and fibrosis stage, and constructs a model for predicting compensated cirrhosis. METHODS: A total of 653 patients with chronic hepatitis B who underwent liver biopsies, ultrasonographic scanning, and routine blood tests were retrospectively analyzed. The patients were divided into the model set and validation set. Blood tests and ultrasonographic indexes were analyzed statistically. An ultrasonographic scoring system consisting of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly was introduced. RESULTS: There were significant differences between cirrhosis and other fibrosis stages in ultrasonographic indexes of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly. Ultrasonographic scores were significantly different between F4 and other fibrosis, and significantly correlated with fibrosis stage. Apart from alanine aminotransferase and alkaline phosphatase, blood tests and patients' age were correlated with fibrosis, and were significantly different between patients with and without cirrhosis. The model for cirrhosis indexes consisting of ultrasonographic score, patient's age, and variables, including platelet, albumin, and bilirubin predicted cirrhosis with area under receiver-operator curve of 0.907 in the model set and 0.849 in the validation set. Using proper cut-off values, nearly 81% patients could be accurately assessed for the absence or presence of cirrhosis. CONCLUSION: The model consisting of ultrasonographic score, patients' age, blood variables of platelet, albumin, and bilirubin can identify hepatitis B cirrhosis with a high degree of accuracy. The application of this model would greatly reduce the number of biopsies.

[Changes of serum HBsAg in HBeAg positive chronic hepatitis patients with sustained viral response to long-term lamivudine treatment].

OBJECTIVE: HBsAg loss is rare in chronic hepatitis B patients, even in the patients with long-term nucleos(t)ide analogue therapy; therefore information about serum HBsAg kinetics will be of value in understanding this unusual occurrence. METHODS: Forty-five consecutive patients were studied, which were all HBeAg positive and never had antiviral therapy prior to lamivudine treatment; they then achieved rapid and good viral responses (defined as undetectable HBV DNA [Roche Lightcycler, less than 1000 copies/ml] at treatment week 24 and they remained so until week 156). Abbott Architect HBsAg assay was used to quantify serum HBsAg and HBV genotypes were determined by direct sequencing. RESULTS: Twenty-six (57.8%) patients had HBeAg loss during the observation and one patient had HBsAg loss following his HBeAg seroconversion. Serum HBsAg levels decreased to 39.5% (median) of their baseline values at week 12, but no further significant reductions of serum HBsAg were found afterwards. Changes of serum HBsAg were comparable between patients with or without HBeAg loss. Serum HBsAg levels at their baselines were higher in HBV genotype B (HBV/B, n = 21) patients than in genotype C (HBV/C, n = 24) patients. HBV/B patients achieved many more HBsAg reductions than HBV/C ones (75.5 vs. 26.0%, median, P less than 0.05) in the first 12 treatment weeks, however HBsAg levels at week 156 were comparable between these two subgroups. HBsAg changes mainly showed two distinct patterns: a biphasic pattern (HBsAg levels were less than 60% of baseline ones at week 12 and 24, n = 25) and a maintaining pattern (HBsAg levels were greater than 80% of the baseline ones at week 12 and 24, n = 14). Logistic regression analysis showed that low serum HBsAg at baseline (odds ratio 0.020, 95% confidence interval 0.002-0.743, P less than 0.05) and HBV/C infection (odds ratio 8.206, 95% confidence interval 1.070-62.948, P less than 0.05) were the determinants of the occurrences of the maintaining pattern. CONCLUSION: In patients we examined, their HBsAg changes were mainly presented as either a biphasic pattern or a maintaining pattern, which were associated with HBV genotypes (B/C) but not with HBeAg loss. This might explain that why HBsAg loss is a rare occurrence even with long-term lamivudine therapy.

[Long-term prognosis and quality of life of survivors with hepatitis B virus-related acute-on-chronic liver failure].

OBJECTIVE: To explore the long-term prognosis and health-related quality of life of patients surviving hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: The clinical data were collected from patients with HBV-ACLF, who were hospitalized in our department between November, 2011 and October, 2016 and survived for more than 90 days. The patients were followed for occurrence of newly diagnosed cirrhosis, decompensation events, hepatocellular carcinoma and death. The quality of life of the patients was evaluated using SF-36 score, and the patients with chronic hepatitis B (CHB) and cirrhosis treated during the same period served as controls. RESULTS: A total of 223 ACLF survivors were included in this study. According to the presence of cirrhosis on admission, the enrolled patients were divided into chronic hepatitis B-related ACLF (CHB-ACLF) group (n=130) and liver cirrhosis ACLF (CIR-ACLF) group (n=93). The 12-, 24- and 50-month survival rates in CHB-ACLF group were 97%, 95.7% and 93.9%, respectively, significantly higher than the rates in CIR-ACLF group (91%, 86% and 74%, respectively; P=0.007). In patients with CHB-ACLF, the 12-, 24- and 36-month progression rates of cirrhosis were 37.9%, 58.4% and 68.7% respectively. Multivariate Cox regression identified the peak value of serum creatinine (HR=1.015, P=0.026) and INR (HR=2.032, P=0.006) within 28 days as independent risk factors and serum sodium at baseline (HR=0.84, P=0.035) as an independent protective factor of occurrence of cirrhosis. The score of mental health on SF-36 in ACLF group was significantly lower than the national norms, and the scores for general health and body pain of ACLF patients were significantly higher than those in patients with CHB or cirrhosis. CONCLUSION: The long-term prognosis of ACLF survivors with and without cirrhosis can be different. Acute attacks are associated with an increased rate of cirrhosis progression in CHB patients who recovered from ACLF, possibly in relation with the severity of extra-hepatic organ injuries. The physical and social functions of long-term survivors of ACLF do not significantly decline, but their psychological status can be affected.

Clinical Application of Vibration Controlled Transient Elastography in Patients with Chronic Hepatitis B.

Evaluation of the extent and progression of liver fibrosis and cirrhosis is of critical importance in the management and prognosis of patients with chronic hepatitis B. Due to the limitation of liver biopsy, non-invasive methods, especially liver stiffness measurement (LSM) by vibration controlled transient elastography, have been developed and widely applied for liver fibrosis assessment. LSM aims to reduce, but not to substitute, the need for liver biopsy for fibrosis/cirrhosis diagnosis. While LSM may have potential utility in monitoring treatment response, its applications in prediction of liver complications in terms of portal hypertension and esophageal varices, as well as disease prognosis, have been gradually validated. Here, we review the latest clinical applications of LSM in patients with chronic hepatitis B.

Combining routine markers improves the accuracy of transient elastography for hepatitis B cirrhosis detection.

BACKGROUND AND AIM: Vibration Controlled Transient Elastography (VCTE) is a non-invasive test for liver fibrosis and cirrhosis but may be inaccurate in some patients, especially in those with chronic hepatitis B. This study aims at improving the accuracy of VCTE in cirrhosis detection by combining ultrasound and routine blood parameters. METHODS: Hepatitis B patients with liver biopsies samples ≥20mm underwent VCTE, ultrasound and blood tests, and were divided into training set (n=170) and validation set (n=75). RESULTS: An algorithm consisting of VCTE, international normalization ratio (INR), ultrasonic hepatic vessel and platelet count (CIR-4) and a VCTE-based cirrhosis six-index score (CIR-6) comprised VCTE, INR, platelet, albumin, ultrasonic hepatic vessel and liver parenchyma were derived. In training set, area under receiver operating characteristics curve of CIR-6 and CIR-4 to detect cirrhosis was 0.946 and 0.945, respectively, which was superior to that of VCTE 0.907. CIR-4 could save more liver biopsies. In validation set, CIR-6 detected cirrhosis with accuracy similar to that in training set. However, the sensitivity of CIR-4 and VCTE in validation set lowered to 0.538 and 0.846, respectively. CONCLUSIONS: Combining routine markers improve the accuracy of VCTE for cirrhosis detection in hepatitis B patients. CIR-6 may be more valuable.

[Evaluation of non-invasive indices for liver histology in patients with chronic hepatitis B].

OBJECTIVE: To assess the correlation of routine blood and serum biochemical indices with liver histology, and identify the sensitive non-invasive ones indicative of liver inflammation and fibrosis in patients with chronic hepatitis B. METHODS: A total of 252 patients were enrolled in this retrospective analysis. The indices including the patients' age, gender, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, globulin, total bilirubin, prothrombin time (PT) and its activity (PTA), WBC, and platelet count were analyzed statistically. RESULTS: The status of liver inflammation was correlated to patients' routine blood indices (P<0.05). Serum AST, total bilirubin, WBC, and platelet count was related significantly to the degree of liver inflammation, but serum ALT and AST alone did not describe exactly the degree of liver inflammation. The status of liver fibrosis was independent of patients' serum ALT, but correlated to other routine blood indices (P<0.05). The patients' age, serum AST, total bilirubin and platelet count had significant relation to the stage of liver fibrosis, and the age, blood PT, total bilirubin and platelet count were significant relevant indices for early liver cirrhosis, and their sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 31.5%, 94.4%, 60.7%, 83.3% and 80.7%, respectively. CONCLUSIONS: Single examination of serum ALT and AST does not help much to predict the status of liver test in patients with chronic hepatitis B. Serum AST, total bilirubin, WBC and platelet count are associated with the degree of liver inflammation. The patients' age, serum total bilirubin, AST and platelet count are relevant indices for liver fibrosis, and patients' age, serum total bilirubin, PT, and platelet count provide valuable assistance in confirmation of early liver cirrhosis with high specificity, but not so for screening purpose.

[Screening and evaluation of non-invasive diagnosis markers for compensated liver cirrhosis in patients with chronic hepatitis B].

OBJECTIVE: To evaluate the diagnostic value of liver fibrosis markers and ultrasonic examination for determining compensated liver cirrhosis in patients with chronic hepatitis B, and screen applicable non-invasive diagnostic marker for compensated liver cirrhosis. METHODS: Serum hyaluronic acid (HA), Type III procollagen (PCIII), laminin (LN) and Type IV collagen (CIV) were measured from 350 patients with chronic hepatitis B, who were also detected with liver biopsy and ultrasonography. To determine the cut-off value of every serum liver fibrosis marker for diagnosing compensated liver cirrhosis, data was analysed with clinical epidemiology methods. Then evaluated and compared all the markers. RESULTS: 85 out of 350 patients were diagnosed as compensated liver cirrhosis by liver biopsy, and 81 had liver cirrhosis images by ultrasonic examination. HA achieved the biggest area under the ROC curve. The cut-off values with best sensitivity and accuracy of HA, PCIII, LN and CIV were 154.35 microg/L, 198.44 microg/L, 137.58 microg/L and 100.80 microg/L respectively. The related diagnostic sensitivities of HA, PCIII, LN and CIV were 82.4%, 63.5%, 57.3% and 70.6%, specificities were 79.3%, 54.0%, 56.8%, 68.3%, and accuracies were 80.0%, 56.3%, 56.9%, 68.9%, respectively. Parallel tests could increase the diagnostic sensitivity, but decreased specificity and accuracy accordingly. Compared with other non-invasive diagnostic methods, HA was the best marker (mu > or =1.814, P<0.05). The level of HA at 119.17 microg/L was suitable for determining compensated cirrhosis, with a 87.1% sensitivity, 67.6% specificity, 72.3% accuracy, 46.25% positive predictive value and 94.7% negative predictive value. CONCLUSION: Among the non-invasive serum diagnostic markers for liver fibrosis and ultrasonic examination for cirrhosis image, HA is the best marker for diagnosing compensated liver cirrhosis.

Non-invasive assessment of liver fibrosis in patients with chronic hepatitis B.

In patients with chronic hepatitis B (CHB), liver fibrosis assessment is essential not only for determining prognosis but also for identifying patients who should receive treatment. Liver biopsy is limited by its invasiveness and sampling error. To explore effective non-invasive methods for liver fibrosis assessment, we reviewed international literature published over the past decade that focused on patients with CHB. Biomarker panels such as API, FIB-4, Forns Index, HepaScore, FibroMeter, FibroTest, Zeng Index and Hui Index detect advanced fibrosis and cirrhosis with fairly satisfactory accuracy with area under the receiver-operating characteristics curve higher than 0.85. However, most panels and the suggested cutoffs have not been independently validated. Transient elastography is accurate in detecting advanced fibrosis and cirrhosis, and the relative cutoffs have been defined. False-positive results may, however, occur in cases of active necroinflammation and cholestasis. Other promising imaging methods such as acoustic radiation force impulse and magnetic resonance elastography still require further validating studies. We conclude that transient elastography, FibroTest and API are the most widely validated. Transient elastography has been validated as the most useful non-invasive method for liver fibrosis assessment. To improve non-invasive performance of detecting liver fibrosis, a combined application of transient elastography and biomarkers may be the preferred course of action.

Improving transient elastography performance for detecting hepatitis B cirrhosis.

BACKGROUND: Transient elastography is a well-established method for detecting cirrhosis. AIM: To improve the performance of transient elastography in detecting hepatitis B cirrhosis by alanine aminotransferase (ALT)-stratified cutoffs, bilirubin normalization and transient elastography-based algorithms. METHODS: A total of 315 compensated patients were analysed following liver biopsies, transient elastography, ultrasonography and blood tests. RESULTS: The area under the receiver operating characteristics (ROC) curve of transient elastography for predicting cirrhosis was 0.88 (95% confidence interval 0.84-0.92). The cutoffs to exclude and confirm cirrhosis were 10.4 kPa and 17.3 kPa in patients with ALT <5 × upper limit of normal range, 13.7 kPa and 25.0 kPa in ALT ≥5 × upper limit of normal range, respectively. With ALT-stratified cutoffs, 68.6% of patients did not require liver biopsies. Areas under the ROC curve in patients with normal or abnormal bilirubin was 0.90(0.85-0.95) and 0.84(0.77-0.92), respectively. In patients with normal bilirubin, the cutoffs for excluding and confirming cirrhosis were 10.6 kPa and 16.9 kPa, respectively. By transient elastography screening, 78.3% of patients with normal bilirubin would not need a liver biopsy. Areas under the ROC curves between transient elastography and transient elastography-based algorithm including transient elastography-splenomegaly-platelet index [0.90(0.86-0.94)] and ultrasonic score-transient elastography index [0.91(0.86-0.96)] were not significantly different. CONCLUSIONS: Amongst ALT-stratified cutoffs, bilirubin normalization and transient elastography-based algorithm, bilirubin normalization was especially important for improving performance of transient elastography for compensated hepatitis B cirrhosis detection.