Fibrosis In Chronic Hepatitis B Research Articles

Fetuin A and fetuin B as an indicator of liver fibrosis in hepatitis B

Abstract Objectives The aim of this study is to investigate the diagnostic and prognostic characteristics of fetuin A and fetuin B in chronic hepatitis B (CHB) and HBe Ag-negative chronic infection (HCI) and the relationship between the levels of these proteins and fibrosis in CHB. Methods In this study, we examined 98 patients with CHB, 58 with HCI and 42 control groups. Fetuin A and B levels were determined via ELISA. Results Serum fetuin A and B levels were significantly higher in the control group than the hepatitis B cases (p=0.001). No significant difference in fetuin A and B levels between patients in the CHB and HCI. In the CHB, fetuin A level was significantly lower in patients with significant fibrosis than those with mild fibrosis (p=0.007). Fetuin B was lower in patients with significant fibrosis than in with mild fibrosis; however, this difference was not significant. In predicting the absence of significant fibrosis, the area under the curve was estimated as 0.855 for fetuin A and 0.866 for fetuin B using the ROC curve. Conclusions Fetuin A and B were lower in CHB and HCI compared to the control group and there was no difference between the two groups suggests that these proteins may be effective in the pathogenesis of hepatitis B-induced liver damage. Fetuin A and B, which are found to be lower in patients with significant fibrosis in CHB, can be used as non-invasive markers in the early detection of fibrosis and in the follow-up of progression to significant fibrosis.

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.

Withdrawn: Bing‐Tian Dong, Yu‐Ping Chen, Guo‐Rong Lyu, Hua‐Ming Wang, Guo‐Fu Lin and Jiong‐Hui Gu; Diagnostic accuracy of two‐dimensional shear wave elastography and magnetic resonance elastography for staging liver fibrosis in patients with chronic hepatitis B: A systematic review and meta‐analysis

An accurate assessment of liver fibrosis is critical for the management of chronic hepatitis B (CHB) patients. Two-dimensional shear wave elastography (2D-SWE) and magnetic resonance elastography (MRE) have recently been proposed to diagnose liver fibrosis. To determine the optimal noninvasive method for diagnosing fibrosis in CHB, we conducted a meta-analysis to compare the performance of 2D-SWE and MRE for diagnosing fibrosis in patients with CHB. Literature databases were searched until January 1st 2021. Three measures, the summary area under the receiver operating characteristic curve (AUSROC), the summary diagnostic odds ratios, and the summary sensitivities and specificities, were used to assess the performance of 2D-SWE and MRE for detecting liver fibrosis. Twenty-four studies with 5126 CHB patients were included. The summary sensitivities and specificities of 2D-SWE and MRE were 82% and 81%, 91% and 94%, respectively, for detecting significant fibrosis, 88% and 85%, 93% and 93%, respectively, for detecting advanced fibrosis, and 89% and 87%, 92% and 92%, respectively, for detecting cirrhosis. The AUSROC value of MRE (0.97) in predicting significant fibrosis was significantly higher than those of 2D-SWE (0.88, P < 0.001). The AUSROC values of 2D-SWE and MRE were 0.93 and 0.98, respectively, for the diagnosis of advanced fibrosis, and 0.94 and 0.97, respectively, for the diagnosis of cirrhosis. MRE and 2D-SWE are excellent tools for staging fibrosis in patients with CHB. MRE probably exhibit the better diagnostic accuracy in detecting significant fibrosis as compared to 2D-SWE.

Assessment of liver fibrosis with liver and spleen stiffness measured by sound touch elastography, serum fibrosis markers in patients with chronic hepatitis B.

To evaluate the performance of liver stiffness (LS) and spleen stiffness (SS) by using the sound touch elastography (STE) technique and compare with those of the splenic index, aspartate transaminase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) index, King's score and combined models for diagnosing and staging fibrosis in chronic hepatitis B (CHB). One hundred patients with CHB underwent STE and serological tests. LS and SS values were measured with STE technique, and splenic index was calculated. Staging of fibrosis was determined with liver biopsy. Correlations between the individual parameters and the stage of fibrosis were evaluated with the Spearman correlation analysis. The area under the receiver operating characteristic curve (AUROC) was calculated to analyze the performance of all methods. Among all individual parameters, LS showed the highest AUROC for diagnosing fibrosis of ≥S2, ≥S3, and S4 stages (AUROC: 0.70, 0.86, and 0.96, respectively; all P < 0.05). The AUROC of combined model 1 (LS and SS) and 2 (LS, SS, APRI, FIB-4 index, King's score) for diagnosing ≥S2, ≥S3, and S4 fibrosis were 0.70, 0.86, 0.97, and 0.70, 0.86, 0.96, respectively, which were higher than those of APRI, FIB-4 index and the King's score (P < 0.05). No significant differences were found between two combined models and LS for staging fibrosis (P > 0.05). LS measurement is reliable for diagnosing and staging fibrosis in CHB, with a better performance than SS, splenic index and serum biomarkers. It is also comparable with the performance of combined models.

The Importance of Serum Leptin Level in Chronic Viral Hepatitis B and C

OBJECTIVE: Leptin plays an important role in inflammation and liver fibrogenesis in viral liver diseases. In this study, determination of serum leptin level and the effect of leptin levels on liver inflammation and fibrosis in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) cases were evaluated.MATERIALS AND METHODS: In this prospective clinical research study, a total of 75 CHB patients, 36 CHC patients, and a 51 control group were included. Liver biopsy specimens were scored using Ishak histological scoring system. Serum leptin levels were determined by ELISA method.RESULTS: Overall, 39 of CHB cases were female while 36 was male, there were 18 female and 18 male cases of CHC, while the control group consisted of 26 female and 25 male. Serum leptin levels were statistically significantly higher in CHB (2.81±0.38) and CHC (2.97±0.35) cases than in the control group (1.39±0.08) (p: 0.001). However, there was no statistically significant difference in serum leptin level between CHC and CHB cases. There was no statistically significant difference between serum leptin levels and age, gender, and biochemical parameters (P&amp;gt; 0.05). Serum leptin levels were statistically significantly higher in patients with significant fibrosis in chronic hepatitis B and KHC patients compared to those with mild fibrosis (P&amp;lt;0.05).CONCLUSION: Leptin plays a role in liver inflammation and fibrosis in CHB and CHC. In CHB and CHC patients, leptin levels can be used to evaluate the degree of advanced fibrosis and in clinical follow-up, but larger studies are needed.

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.

Are adropin, apelin, elabela, asprosin and betatrophin biomarkers for chronic hepatitis and staging of fibrosis?

ABSTRACTChronic viral hepatitis affects nearly one half billion people; it can result in hepatic fibrosis and cirrhosis if untreated. We investigated whether the polypeptides, adropin, apelin, elabela, asprosin and betatrophin, could be useful biomarkers for diagnosing chronic hepatitis and for the staging fibrosis. Patients 18−60 years old who underwent a liver biopsy for chronic hepatitis B (CHB) or C (CHC) from January 2014 to January 2019 were included in our study. The patients were divided into three groups: control group, CHB group, and CHC group. The CHB group comprised four subgroups based on the severity of the hepatic fibrosis. Liver biopsy specimens of all groups were evaluated for adropin, apelin, elabela, asprosin and betatrophin immunoreactivity by light microscopy. Adropin, apelin, elabela and betatrophin were immunoreactive in the hepatocytes, while asprosin was not in any group. In the CHB group, adropin and elabela immunoreactivity was increased significantly in stages III and IV patients compared to the other subgroups, whereas stages I and II patients were comparable to the control group. The CHC group exhibited decreased betatrophin immunoreactivity and increased elabela immunoreactivity compared to the control group. We suggest that adropin and elabela can provide clues for staging and monitoring fibrosis in CHB, and may be potentially useful biomarkers.

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.

Expressions and roles of three inflammatory cytokines in chronic hepatitis B patients with nonalcoholic fatty liver disease

Objective To investigate the roles of cytokeratin 18 (CK18) M30 and M65, thymosin beta 4 (Tβ4) and tumor necrosis factor (TNF)-α in hepatic steatosis and development of inflammatory and fibrosis in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). Methods A total of 46 CHB patients with NAFLD and 42 CHB patients were collected. Serum CK-18 M30, M65, Tβ4 and TNF-α levels were measured by enzyme linked immunosorbent assay (ELISA) in two groups. The associations between inflammatory factors levels and biochemical or pathological indicators were analyzed. The statistical analysis was conducted by t test and chi square test of two independent samples. The correlation analysis was performed by Pearson and Logistic regression analysis. Results The mean serum CK-18 M30 level in CHB with NAFLD group was (614.48±471.43) U/L, which was significantly higher than that in CHB group (374.50±231.04) U/L (t=2.988, P 0.05). In CHB with NAFLD patients, the CK-18 M30 level was positively correlated with alanine aminotransferase, triglyceride, fasting blood glucose, histology inflammation score, fibrosis score and steatosis (r=0.507, 0.456, 0.384, 0.551, 0.458 and 0.457, respectively, all P<0.01). Tβ4 level was negatively correlated with inflammation and fibrosis score (r=-0.371 and -0.308, respectively, P<0.05). TNF-α level was positively correlated with inflammation score and steatosis (r=0.570 and 0.441, respectively, P<0.01). CK-18 M30, Tβ4 and TNF-α were independent predictors of CHB combined with NAFLD, progressive inflammatory fibrosis and severe steatosis. Conclusions Serum CK-18 M30, Tβ4 and TNF-α levels are associated with hepatic steatosis, development of inflammation and fibrosis in CHB with NAFLD patients. Key words: Hepatitis B, chronic; Non alcoholic fatty liver disease; Cytokeratin 18; Thymosin beta4; Tumor necrosis factor-alpha

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.

Diagnostic Estimation of Noninvasive Tests for Hepatic Fibrosis in Chronic Hepatitis B Patients Without a Gold Standard.

Background:Assessment of hepatic fibrosis stage in patients with chronic hepatitis B (CHB) is indispensable for prognosis evaluation and therapeutic regime. Noninvasive tests are fast, safe and cheap and need low technical requirements for diagnosing hepatic fibrosis in CHB patients.Objectives:Using the latent class model with a random-factor to estimate relative accuracy of noninvasive tests for the diagnosis of hepatic fibrosis without a gold standard in a large population with CHB.Patients and Methods:A total of 544 patients with CHB were assessed for fibrosis stage by four noninvasive tests containing liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4) and globulin and platelet (GP). The diagnostic evaluation was made by the latent class method with random effect which analyzed the clinical data above to assess the accuracy of four ways of noninvasive diagnosis.Results:The latent class model with random effect permitted to conciliate the observed data and estimates of test performances. For significant fibrosis, the specificity/sensitivity were 83.24%/91.59% (APRI), 90.05%/95.57% (FIB-4), 75.11%/66.01% (LSM) and 71.13%/98.33% (GP), respectively. For cirrhosis, the specificity/sensitivity were 84.04%/17.91% (APRI), 89.86%/17.09 (FIB-4), 78.64%/37.07% (LSM) and 82.28%/37.07% (GP), respectively.Conclusions:FIB-4 confirmed the best value for diagnosis of significant fibrosis. APRI had a sub-optimal diagnosis accuracy for significant fibrosis. LSM showed the most balance diagnosis value for cirrhosis with the highest sensitivity and moderate specificity.

Aberrant serum immunoglobulin G glycosylation in chronic hepatitis B is associated with histological liver damage and reversible by antiviral therapy.

Aberrant serum immunoglobulin G (IgG) glycosylation and its immunomodulatory effect are rarely addressed in chronic hepatitis B virus (HBV) infection. Serum IgG-Fc glycosylation profiles in 76 patients with HBV-related liver cirrhosis and 115 patients with chronic hepatitis B (CHB) before and after 48 weeks of anti-HBV nucleos(t)ide analogue treatment were analyzed using high-throughput liquid chromatography-mass spectrometry and were compared to profiles in 108 healthy controls. The level of aberrant serum IgG-Fc glycosylation ,: particularly galactose deficiency, was higher in patients with CHB and those with cirrhosis (P < .001 for both) than in healthy controls. IgG galactose deficiency was correlated with the severity of liver necroinflammation and fibrosis in CHB. Multivariate logistic regression analyses showed that the IgG-Fc glycoform with fucosylation and fully galactosylation was an independent factor for a total Knodell necroinflammation score of ≥ 7 (odds ratio, 0.74; 95% confidence interval, .56-.97) and an Ishak fibrosis score of ≥ 3 (odds ratio, 0.69; 95% confidence interval, .49-.97). Administration of antiviral therapy for 48 weeks reversed aberrant IgG-Fc glycosylation in patients with CHB from week 12 onward but did not reverse glycosylation in patients with cirrhosis. Attenuated IgG opsonization in patients with CHB, which was correlated with aberrant Fc-glycosylation, was reversed after treatment as well. Aberrant serum IgG-Fc glycosylation in CHB, which is highly associated with histological liver damage, affects IgG opsonizing activity and can be reversed by antiviral therapy.

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.