Liver Fibrosis In Chronic Hepatitis B Research Articles

The role of сhemokine CX3CL1/Fractalkine in chronic viral hepatitis B

Hepatitis B is an infectious disease resulting from infection with the hepatitis B virus. Chronic hepatitis B (CHB) is characterized by prolonged inflammation in the liver, the development of fibrosis, liver cirrhosis and hepatocellular carcinoma. Factors of the immune system play a critical role in the pathogenesis of CHB. Thanks to chemokines, immune cells migrate to the site of inflammation to implement their effector functions. The CX3CL1/Fractalkine chemokine is the only member of the CX3C family of chemokines with unique structural and functional properties. Its receptor CX3CR1 is expressed mainly on the surface of cytotoxic effector lymphocytes such as NK cells, TNK and cytotoxic T lymphocytes. The purpose of our study was to analyze the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB and the analysis of this chemokine with liver fibrosis. The concentration of CX3CL1/Fractalkine was determined in the blood plasma of patients with CHB using a multiplex assay based on xMAP technology. Blood plasma from patients with chronic viral hepatitis C (CHC) and autoimmune liver diseases (AILD) was used as a comparison group. The control group consisted of healthy individuals. For statistical analysis of data, nonparametric statistics methods were used: Kruskal–Wallis test, Spearman correlation coefficient ROC-analysis. It was shown a reduced level of CX3CL1/Fractalkine in patients with CHB compared with the control group (p = 0.0003) and with the comparison groups of CHC (p 0.0001) and AILD (p = 0.0005). A reduced concentration of CX3CL1/Fractalkine was shown in the blood plasma of CHB patients with initial fibrosis (p = 0.0092) and severe fibrosis/cirrhosis (p = 0.0009), while in patients with severe fibrosis/cirrhosis, a significantly reduced level of this chemokine was established compared with the initial degree of liver fibrosis (p = 0.0081). Correlation analysis revealed a highly significant inverse relationship between the severity of liver fibrosis and the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB (Spearman r = –0.33; p = 0.02). Thus, the chemokine CX3CL1/Fractalkine is included in the immunopathogenesis of CHB; its reduced content is characteristic only of CHB and does not change in other chronic liver diseases. It is involved in the processes of liver fibrosis during infection with the hepatitis B virus. The concentration of the chemokine CX3CL1/Fractalkine depends on the stage of liver fibrosis in CHB, and a decrease in the level of CX3CL1/Fractalkine in the blood plasma can serve as a negative factor in the development of CHB.

Diagnostic Performance of Mac 2–Binding Protein Glycosylation Isomer in Chronic Hepatitis B

Chronic Hepatitis B (CHB) is a concern for Chronic Liver Disease (CLD) and causes a 74% mortality rate in Asia Pacific. World Health Organization (WHO) showed Indonesia is the highest second country of Hepatitis B (HB) in the South East Asian Region, Central Java is the highest in Java and Dr. Moewardi Hospital (RSDM) Surakarta in 2019 increased to 15%. Liver biopsy is fibrosis gold standard staging. It has limitations and requires invasive procedure pain in 40% of patients. This study aimed to determine M2BPGi diagnostic test against to transient elastography (TE) Fibroscan® (sensitivity 85.7%, specificity 81.6%) as a predictor of significant liver fibrosis of CHB in RSDM. Fibroscan® examination was performed on patients diagnosed with CHB by a clinician performed at the endoscopy department of RSDM, whereas laboratory tests were carried out from December 2020 to January 2021. Plasma M2BPG-I cut-off value was determined using Receiving Operating Characteristic (ROC) curve, M2BPGi levels were measured sandwich ELISA using spectrophotometry at a wavelength of 450 ± 2 nm. A total of 70 subjects was divided into 35 subjects with significant and 35 subjects with non-significant fibrosis. The results of the statistical calculation showed that plasma M2BPGi levels had a cut-off of 12.939 ng/mL (mean value of 17.841 ng/mL with significant fibrosis at 16.74 ng/mL and non-significant fibrosis at 10.14 ng/mL) had a moderate performance as a marker of liver fibrosis in CHB (71.4% sensitivity; 68.6% specificity; 69.4% PPV; 70.6% NPV and PLR 2.273), NR 0.417 with AUC of 0.727, CI 96% (0.681-0.0906). M2BPGi plasma levels at a cut-off of 12.939 ng/mL had a moderate performance as a predictor of significant liver fibrosis in chronic hepatitis B patients.

1236. Baseline liver stiffness and alanine transaminase predicts reduction in liver stiffness in people with chronic hepatitis B on tenofovir alafenamide

Abstract Background Globally, 296 million people are infected with chronic hepatitis B (CHB) and at risk for cirrhosis and hepatocellular carcinoma. Suppressive therapy with a nucleos(t)ide analogue (NUC) such as tenofovir alafenamide (TAF) reduces risk of cirrhosis and cancer. Transient elastography measures liver stiffness and is used to monitor liver fibrosis in CHB. This study evaluates liver stiffness change among people taking NUC and determines correlates with improvement in liver stiffness. Methods Participants enrolled at the University of Maryland, Baltimore were treated with TAF 25mg daily for 2 years. Liver stiffness (FibroScan©) was measured at baseline and year 2. Mild (F0/F1) and advanced (≥ F2) fibrosis, was defined as ≤ 7.4kPa and ≥ 7.5kPa, respectively. Correlates of liver stiffness change from baseline to year 2 was evaluated with multiple linear regression. P-value of < 0.05 was considered statistically significant. Results Since 2017, 60 have completed the study. Twenty-nine were switched from another NUC to TAF and 31 were off NUC treatment at baseline (“No NUC”: 17 treatment naïve, 14 prior NUC). Baseline alanine transaminase (ALT) was higher in the "No NUC" group (53.5 IU/ml ± 42.7 versus 30.2 IU/ml ± 15.5, p = < 0.007). Most (67.2%) participants had mild fibrosis at baseline. Nineteen had advanced fibrosis. Among those with advanced fibrosis, fibrosis stage improved by at least 1 stage in 14 with no change in 5. Liver stiffness improved in the No NUC group (mean change in stiffness -1.2161 kPa, p = 0.02), but not in the switch group. Subgroup analysis of those with advanced fibrosis also showed reduction in liver stiffness in the No NUC group only. Increased baseline ALT and baseline liver stiffness were predictive of reduction in liver stiffness (rho= - 0.3, p= 0.005 and rho= - 0.7, p < 0.0001, respectively). Baseline liver stiffness predicts change in liver stiffness with NUC therapy Increased liver stiffness, and therefore fibrosis, at baseline was associated with greater reductions in liver stiffness, and therefore liver stiffness, after 2 years of NUC therapy (rho = -0.7, p< 0.0001). Conclusion Liver stiffness improved with 2 years of NUC treatment in people with CHB, including those with advanced liver fibrosis. Either baseline ALT or liver stiffness can predict reduction in liver stiffness. This may reflect an overestimation of fibrosis stage in the presence of liver inflammation at NUC initiation. Repeating FibroScan after initiation of NUC treatment would therefore be useful, especially in people with elevated ALT, for guiding CHB care. Disclosures Lydia Tang, MBChB, Gilead Sciences: Grant/Research Support Shyam Kottilil, MD, PhD, Arbutus Pharmaceuticals: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Regeneron Pharmaceuticals: Advisor/Consultant|Silverback Therapeutics: Advisor/Consultant|The Liver Company: Advisor/Consultant|Yufan Biotechnologies: Advisor/Consultant.

Evaluating the clinical value of MRI multi-model diffusion-weighted imaging on liver fibrosis in chronic hepatitis B patients.

To explore the value of various diffusion parameters obtained from monoexponential, biexponential, and stretched exponential in assessing liver fibrosis in chronic hepatitis B (CHB). DWI and intravoxel incoherent motion (IVIM) MRI were performed prospectively on liver for 146 patients with CHB and 21 healthy volunteers. ADC values were obtained from monoexponential model imaging. Diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) obtained by biexponential model imaging, and stretched exponential model to obtain diffusion distribution coefficient (DDC) and diffusion heterogeneity index (α). Blood draw were performed on patients to obtain AST, ALT, and PLT, and then APRI and FIB-4 index were determined based on the serological diagnostic models. The fibrosis stage was staged (S0-S4) according to the pathology of liver puncture. Independent sample t test was used to compare the parameter values between liver fibrosis group and control group. One-way ANOVA was used to compare the parameters of different liver fibrosis grades. Bonferroni test was used for correcting multiple comparisons. Spearman correlation was used to analyze the correlation between each parameter and liver fibrosis grades. ROC was used to predict the diagnostic power of each parameter for liver fibrosis stages ≥ S2 and ≥ S3. ADC, D, D*, f, and DDC values were significantly different between normal control group and hepatic fibrosis group (P < 0.05). There were significant differences in ADC, D*, f, and DDC value among liver fibrosis groups (P < 0.05). D* and DDC values were moderately negatively correlated with the grades of liver fibrosis (r = - 0.483, P < 0.001; r = - 0.622, P < 0.001). ADC and f values were slightly negatively correlated with the grades of liver fibrosis (r = - 0.295, P < 0.001; r = - 0.312, P < 0.001). DDC values have the highest diagnostic efficiency in liver fibrosis stages ≥ S2 and ≥ S3. The areas under ROC curve (AUC) were 0.813 and 0.832 for ≥ S2 and ≥ S3, respectively, the sensitivity is 83.72% and 73.53%, and the specificity of 83.33% and 66.04%, which were better than APRI and FIB-4. D* obtained from biexponential and DDC obtained from stretched exponential DWI have better value in evaluating the degree of liver fibrosis in CHB.

A New Visual Transient Elastography Technique for Grading Liver Fibrosis in Patients With Chronic Hepatitis B.

Liver fibrosis is evaluated to assess the prognosis and guide the treatment of chronic hepatitis B (CHB). To compare the efficiency of 2 transient elastography techniques for grading liver fibrosis in CHB: visual transient elastography (ViTE) with real-time image guidance and FibroScan (FS) with no image guidance. All of the CHB patients in this study underwent both FS and ViTE examinations. The final diagnosis was based on the histological findings of a liver biopsy. According to the severity of liver fibrosis (based on the Scheuer criteria), the area under the receiver operating characteristic curve values for diagnostic efficiency were calculated for the 2 elastography techniques. This study enrolled 227 patients (79 [39.1%] women; mean age, 45.8 ± 16.8 years). The ViTE and FS liver elasticity measurements were highly correlated with liver fibrosis stage (r = 0.852 and r = 0.813, respectively). The area under the receiver operating characteristic curve value was larger for ViTE compared with FS, with respect to differentiating liver fibrosis stage, but not significantly (P > 0.05). The ViTE and FS can be used to detect and stage liver fibrosis. ViTE, easier and quicker to perform with superior interoperator reproducibility, is a stable and reliable elastography technique that benefits from real-time visual guidance.

Serum rheumatoid factor is correlated with liver fibrosis in patients with chronic hepatitisB.

Non-invasive methods are being developed to evaluate liver fibrosis. In this study, we aimed to evaluate the diagnostic performance of rheumatoid factor (RF) to predict liver fibrosis in chronic hepatitisB (CHB). Atotal of 235 non-arthritic, treatment-naive patients with hepatitis B virus (HBV) were enrolled in this study. The RF level was analyzed concurrently with HBV-DNA and routine biochemical tests. The liver biopsies were scored by using the Knodell modified histology activity index (HAI) and the Ishak fibrosis score. Mean age, ALT, AST, ALP, GGT, INR, and HBV-DNA levels were significantly higher, and mean albumin and platelet levels were significantly lower in the RF positive group than the RF negative group. Liver biopsy was performed in 112 (47.66%) patients, and the RF positivity rate was 18 (15.38%) in the infection subgroup and 73 (61.86%) in the hepatitis subgroup. Along with the RF positivity rate, the fibrosis and HAI scores were also increased. Ahigh fibrosis score is associated with ahigh RF positivity rate. In the current study, we found that there was asignificant positive correlation between RF and liver fibrosis stage in patients with CHB. The RF that is easily obtained with low cost may be considered as an alternative biomarker for predicting liver fibrosis in CHB.

Fibrosis evolution in chronic hepatitis B e antigen-negative patients across a 10-year interval.

The degree of liver fibrosis in chronic hepatitis B (CHB) infection influences outcome and management. Existing data describing the long-term dynamic changes of liver fibrosis are limited. This study aimed to evaluate the evolution of liver fibrosis in CHB across a 10-year period. CHB patients with liver stiffness measurement (LSM) by transient elastography 10years ago were recruited for follow-up LSM. Fibrosis stages were classified according to EASL-ALEH guidelines. Fibrosis progression/regression was arbitrarily defined as ≥1 fibrosis stage change from baseline. A total of 459 hepatitis B e antigen (HBeAg)-negative patients (224 untreated, 235 treated with nucleos(t)ide analogues [NAs]) were recruited. The mean age at baseline LSM was 41.7±9.0years (56.2% male). Over 10years, the proportion of patients with advanced fibrosis/cirrhosis significantly reduced from 16.3% to 5.7% (P<0.001). Fibrosis progression and regression were observed in 8.7% and 37.5%, respectively. No treatment with NAs (OR 2.259, 95% confidence interval [CI]: 1.032-4.945), metabolic syndrome (OR 4.379, 95% CI: 1.128-16.999) and hepatic steatosis (OR 7.799, 95% CI: 2.271-26.776) was associated with fibrosis progression. Liver stiffness decline demonstrated positive correlation with the time after HBsAg seroclearance (r=-0.50, P<0.001). Median liver stiffness was higher both at baseline (14.0 vs 6kPa, P<0.001) and 10years (9.1 vs 4.9kPa, P<0.001) in patients with cirrhosis-related complications/hepatocellular carcinoma compared with those without. In conclusion, CHB-related liver fibrosis changed dynamically across 10years. Metabolic syndrome and hepatic steatosis were associated with fibrosis progression, while antiviral therapy was associated with fibrosis regression. Patients with HBsAg seroclearance demonstrated time-dependent decline in liver stiffness.

Gamma-glutamyl-transpeptidase to platelet ratio is not superior to APRI,FIB-4 and RPR for diagnosing liver fibrosis in CHB patients in China

The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

A novel predictive model using routinely clinical parameters to predict liver fibrosis in patients with chronic hepatitis B.

ObjectivesNoninvasive models have been established for the assessment of liver fibrosis in patients with chronic hepatitis B(CHB). However, the predictive performance of these established models remains inconclusive. We aimed to develop a novel predictive model for liver fibrosis in CHB based on routinely clinical parameters.ResultsPlatelets(PLT), the standard deviation of red blood cell distribution width(RDW-SD), alkaline phosphatase(ALP) and globulin were independent predictors of significant fibrosis by multivariable analysis. Based on these parameters, a new predictive model namely APRG(ALP/PLT/RDW-SD/globulin) was proposed. The areas under the receiver-operating characteristic curves(AUROCs) of APRG index in predicting significant fibrosis(≥F2), advanced fibrosis(≥F3) and liver cirrhosis(≥F4) were 0.757(95%CI 0.699 to 0.816), 0.763(95%CI 0.711 to 0.816) and 0.781(95%CI 0.728 to 0.835), respectively. The AUROCs of the APRG were significantly higher than that of aspartate transaminase(AST) to PLT ratio index(APRI), RDW to PLT ratio(RPR) and AST to alanine aminotransferase ratio(AAR) to predict significant fibrosis, advanced fibrosis and cirrhosis. The AUROCs of the APRG were also significantly higher than fibrosis-4 score (FIB-4) (0.723, 95%CI 0.663 to 0.783) for cirrhosis(P=0.034) and better than gamma-glutamyl transpeptidase(GGT) to PLT ratio(GPR) (0.657, 95%CI 0.590 to 0.724) for significant fibrosis(P=0.001).Materials and Methods308 CHB patients who underwent liver biopsy were enrolled. The diagnostic values of the APRG for liver fibrosis with other noninvasive models were compared.ConclusionsThe APRG has a better diagnostic value than conventionally predictive models to assess liver fibrosis in CHB patients. The application of APRG may reduce the need for liver biopsy in CHB patients in clinical practice.

Serum S100 calcium binding protein A4 improves the diagnostic accuracy of transient elastography for assessing liver fibrosis in hepatitis B

The diagnostic performance of Fibroscan might be improved when combined with other serum fibrosis related markers. Previous study has demonstrated that S100A4 expression is associated with liver fibrosis in humans with hepatitis. This study aimed to clarify diagnostic accuracy of serum S100A4 levels for significant liver fibrosis in patients with chronic hepatitis B (CHB), and develop a combined algorithm of liver stiffness measurement (LSM) and S100A4 to predict significant liver fibrosis in CHB. One hundred and seventy-five CHB patients who had performed liver biopsy were consecutively included. We evaluated serum S100A4 levels, LSM values and other clinically-approved fibrosis scores. Serum S100A4 level was higher in CHB patients with significant fibrosis, compared to those without [199.58 (33.31-1971.96) vs. 107.15 (2.10-1038.94), P<0.001]. Using receiver-operating characteristic (ROC) analyses, the area under the curves (AUC), sensitivity, specificity and accuracy of S100A4 were found to be 0.749, 62.7%, 75.9% and 0.70 for significant fibrosis (≥Stage 2), respectively. Although not superior to LSM, these results were better than the fibrosis index based on the 4 factor (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI) for significant fibrosis detection. An algorithm consisting of S100A4 and LSM was derived. The AUC, sensitivity, specificity and accuracy of model based on serum S100A4 level and LSM were 0.866, 86.6%, 77.8% and 0.79 for significant fibrosis detection, superior to those based on LSM alone (0.834, 76.1%, 80.7% and 0.76, P=0.041). Serum S100A4 level was identified as a fibrosis marker of liver fibrosis in patients with CHB. Combining serum S100A4 with LSM improved the accuracy of transient elastography for hepatitis B significant fibrosis detection.

Assessment of liver fibrosis in chronic hepatitis B via multimodal data

Assessing liver fibrosis with chronic hepatitis B (CHB) in patients is quite important. Some non-invasive approaches for evaluating liver fibrosis include blood tests and ultrasound elastography. How to effectively combine multiple methods to improve the diagnostic performance remains a challenging problem. The main goal of this paper is to assess and stage liver fibrosis in CHB using feature selection and machine learning methods based on multimodal data. Popular machine learning approaches (e.g., support vector machine (SVM)) and feature selection (FS) were explored to stage the CHB. 16 volunteers and 92 patients with CHB were investigated for liver fibrosis staging based on transient elastography (TE) and acoustical radiation force impulse imaging (ARFI) data. The accuracy of the staging result using FS and a SVM classifier was an accuracy of 90.68% for significant fibrosis (≥F2) and an accuracy of 93.52% for cirrhosis (F4), respectively. The proposed method also increased the sensitivity, specificity, and area under curve (AUC) values for both significant fibrosis and cirrhosis diagnosis, which is very promising for staging liver fibrosis from multimodal information. It outperforms any single method and their linear combination and also achieves a state-of-the-art performance.

APRI Score as a Predictor of Significant Liver Fibrosis in Chronic Hepatitis B

Background Chronic hepatitis B (CHB) is a global public health problem. Histologic staging of liver fibrosis is crucial to identify patients who need antiviral treatment. As an alternative to percutaneous liver biopsy (PLB), Aminotransferase Platelet Ratio index (APRI) score was recently validated by the WHO. We aimed to evaluate the performance of APRI score in predicting significant fibrosis (SF) in patients with CHB.Methods We conducted a retrospective study including 179 patients aged ≥ 15 years with documented CHB and who underwent a PLB during the period 2008-2016. A SF was defined according to Metavir score (≥ F2). ROC curves assessed the performance of APRI score in predicting SF. We estimated PLB cost of 60 Dollars in our institution.ResultsMean age of patients was 37.6 ± 10 years and sex ratio was 1.48. There were 93 patients with SF (52%) who had a high level of aspartate aminotransferase (ASAT) (71.4 ± 38 vs. 34 ± 16 IU/L; P < 0.001) but a low level of platelet count (195 ± 53 vs. 208 ± 52 G/L; P = 0.04). APRI score was significantly higher in patients with SF (1.1 ± 0.7 vs. 0.48 ± 0.26; P < 0.001). Multivariate analysis using logistic regression showed that only APRI score was independently predictive of a SF (HR = 3.78, CI95% 1.23-11.6; P = 0.02). APRI predicted accurately SF with an Area Under the Receiving Operating Curve (AUROC) of 0.7 (CI 95% 0.62–0.77; P < 0.001). At a threshold of 0.5, APRI had a sensitivity of 62%, a specificity of 68%, a positive predictive value of 64.4% and a negative predictive value of 60.7%. The number of avoided PLB with APRI score was 112 PLB with a diagnostic accuracy of 62.5%. Subsequently, the saved cost was estimated to be around 6720 Dollars.Conclusion APRI score was well performing in predicting SF in patients with CHB. This could be of paramount importance particularly in developing countries given that this non-invasive score may help to assess liver fibrosis in CHB. Larger scale and analytic prospective studies are required in order to strengthen the accuracy of this score.Disclosures All authors: No reported disclosures.

Serum ceruloplasmin levels correlate negatively with liver fibrosis in males with chronic hepatitis B: a new noninvasive model for predicting liver fibrosis in HBV-related liver disease.

AimsThis study aimed to investigate associations between ceruloplasmin (CP) levels, inflammation grade and fibrosis stages in patients with chronic hepatitis B (CHB) and to establish a noninvasive model to predict cirrhosis.MethodsLiver biopsy samples and sera were collected from 198 CHB patients randomized into a training group (n=109) and a validation group (n=89). CP levels were determined using nephelometric immunoassays. Relationships between CP and liver inflammation and fibrosis were analyzed by Spearman rank correlation. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of CP for determining liver fibrosis in CHB. The liver pathology-predictive model was built using multivariate logistic regression analysis to identify relevant indicators.ResultsCP levels were lower in males than in females, lower in patients with inflammation stage G4 compared to other stages and lower in cirrhotic compared to non-cirrhotic patients. Using area under the curve (AUC) values, CP levels distinguished different stages of inflammation and fibrosis. Multivariate analysis showed that CP levels were all significantly associated with cirrhosis in males. A model was developed combining routine laboratory markers APPCI (alpha-fetoprotein [AFP], prothrombin time, and platelets [PLT] with CP) to predict fibrosis in CHB patients. The APPCI had a significantly greater AUC than FIB-4 (aspartate aminotransferase [AST]/ alanine aminotransferase [ALT]/PLT/age), APRI (AST/PLT ratio index), GPI (globin/PLT), and APGA (AST/PLT/gammaglutamyl transpeptidase [GGT]) models (all P-values<0.001).ConclusionsCP levels correlate negatively and indirectly with inflammation and fibrosis stages in male CHB patients. The APPCI model uses routine laboratory variables with CP to accurately predict liver fibrosis in CHB.

APRI, the FIB-4 score, and Forn’s index have noninvasive diagnostic value for liver fibrosis in patients with chronic hepatitis B

The aim of this study was to evaluate the potential use of serum transforming growth factor-β1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1), fetuin-A, and fibroblast growth factor 21 (FGF21) in the detection of liver fibrosis in patients with chronic hepatitis B (CHB). The value of the noninvasive fibrosis models - that is, the aspartate aminotransferase to platelet ratio index (APRI), the fibrosis index based on the four factors (FIB-4) score, and Forn's index - was also examined. CHB patients who underwent liver biopsy for the evaluation of fibrosis were included in the study. A total of 73 patients were divided into two groups according to their METAVIR scores (F0-1, no/minimal fibrosis; F2-4, significant fibrosis). Serum levels of TGF-β1, TIMP-1, fetuin-A, and FGF21 were measured besides APRI, FIB-4, and Forn's scores. The area under the receiver operating characteristic curve was measured for each parameter, followed by calculation of sensitivity, specificity, and positive and negative predictive values. APRI, FIB-4, and Forn's index scores were significantly higher in patients with significant fibrosis (P<0.05). There was no difference between no/minimal fibrosis and significant fibrosis groups in terms of serum levels of TGFβ-1, TIMP-1, fetuin-A, and FGF21 (P>0.05). The areas under the receiver operating characteristic curve for TGF-β1, TIMP-1, fetuin-A, FGF21, APRI, FIB-4, and Forn's index were 0.445, 0.483, 0.436, 0.585, 0.662, 0.687, and 0.680, respectively. Our results suggest that serum TGF-β1, TIMP-1, fetuin-A, and FGF21 are not useful for the assessment of the extent of liver fibrosis in CHB in this patient group. However, APRI, FIB-4, and Forn's index have a better diagnostic value in patients with significant fibrosis than in those with no/minimal fibrosis.

Magnetic resonance elastography for the detection and staging of liver fibrosis in chronic hepatitis B

We measured the accuracy of magnetic resonance elastography (MRE) for the detection and staging of liver fibrosis in chronic hepatitis B (CHB) and compared it with serum fibrosis markers. Prospective comparison of MRE and routine serum fibrosis markers, namely serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), ALT/AST ratio (AAR), AST to platelet ratio index (APRI) and prothrombin index (PI), was performed in 63 consecutive CHB patients who underwent MRE and histological confirmation of liver fibrosis within a 6-month interval. Diagnostic performance of MRE and serum markers for staging fibrosis (≥F1), significant fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4) was compared. The study group comprised 63 patients (19 female; mean age ± SD, 50 ± 11.9years). MRE (ρ = 0.94, P < 0.0001), APRI (ρ = 0.42, P = 0.0006), PI (ρ = 0.42, P = 0.0006) and AST (ρ = 0.28, P = 0.028) results correlated significantly with fibrosis stage. MRE was significantly more accurate than serum fibrosis markers for the detection of significant fibrosis (0.99 vs. 0.55-0.73) and cirrhosis (0.98 vs. 0.53-0.77). Sensitivity, specificity, positive predictive and negative predictive values for MRE for significant fibrosis and cirrhosis were 97.4%, 100%, 100% and 96%, and 100%, 95.2%, 91.3% and 100%, respectively. MRE is an accurate non-invasive technique for the detection and staging of liver fibrosis in CHB. • Magnetic resonance elastography is accurate for liver fibrosis detection and staging. • MR elastography is more accurate than serum tests for staging liver fibrosis. • MR elastography can potentially replace liver biopsy in chronic hepatitis B.

Noninvasive assessment of liver damage in chronic hepatitis B

To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index (APRI) and neutrophil-lymphocyte (N/L) ratio to predict liver damage in chronic hepatitis B (CHB). 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. 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 1.01 with 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). N/L ratio was negatively correlated with HAI. APRI score may be useful to exclude cirrhosis in CHB patients.

Diagnostic accuracy of transient elastography (FibroScan) versus the aspartate transaminase to platelet ratio index in assessing liver fibrosis in chronic hepatitis B: The role in primary care setting

BackgroundA non-invasive method to assess liver fibrosis by measuring liver stiffness with transient elastography (TE) has been recently introduced. The role of TE among chronic hepatitis B (CHB) patients in...

Clinical expression of insulin resistance in hepatitis C and B virus-related chronic hepatitis: Differences and similarities

To investigate the prevalence of the clinical parameters of insulin resistance and diabetes in patients affected by chronic hepatitis C (CHC) or chronic hepatitis B (CHB). We retrospectively evaluated 852 consecutive patients (726 CHC and 126 CHB) who had undergone liver biopsy. We recorded age, sex, ALT, type 2 diabetes and/or metabolic syndrome (MS), body mass index (BMI), and apparent disease duration (ADD). Age, ADD, BMI, prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC. However, the degree of steatosis and liver fibrosis evaluated in liver biopsies did not differ between CHC and CHB patients. At multivariate analysis, age, sex, BMI, ALT and diabetes were independent risk factors for liver fibrosis in CHC, whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis (>30%) and age, sex, BMI, diabetes, MS and liver fibrosis. Diabetes, BMI and liver fibrosis were associated with steatosis >30% in CHC, whereas only age and BMI were related to steatosis in CHB. These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.

Serum hyaluronic acid: A promising marker of hepatic fibrosis in chronic hepatitis B

Serum hyaluronic acid: A promising marker of hepatic fibrosis in chronic hepatitis B