Liver Fibrosis In Chronic Hepatitis B Patients Research Articles

Revisiting Mac-2-Binding Protein Glycosylation Isomer (M2BPGi) for Diagnosing High-Risk Liver Fibrosis in Chronic Hepatitis B Patients: A Stepwise Diagnostic Analysis

Abstract* Background The level of liver fibrosis is the basis for the treatment of chronic hepatitis B (CHB), and it is necessary to adapt non-invasive liver fibrosis modalities. We aimed to investigate the use of M2BPGi as a single or combined diagnostic modality for liver fibrosis in CHB patients through a stepwise diagnostic analysis. Methods Cross-sectional data were taken from patients between October 2021 and August 2022. Demographic data, blood profile, liver function, and liver stiffness were measured in CHB patients over 18 years old, willing to take part in the research, and had complete data. APRI, FIB-4, and AAR were calculated using the well-known formulas. Serum M2BPGi-levels were converted into a cut-off index (COI). The patients were divided into low-risk (LR) and high-risk fibrosis (HR) groups. A cut-off for each predictor variable to differentiate between the LR and HR groups was determined. The obtained cut-off was assessed for its association with the grouping of liver elastography results. Models to diagnose the liver stiffness measurement (LSM) ≥8 kPa were created and compared through multivariate and ROC analyses. Results The number of patients that met the inclusion and exclusion criteria was 143 (HR = 65, LR = 78). The cut-off for diagnosing LSM ≥8kPa was 0.311, 0.742, 0.635, and 1.434 for APRI, FIB-4, AAR, and M2BPGi, respectively. This cut-off was significantly associated with the results of the HR and LR groupings. A multivariate analysis found that FIB4, AAR, and M2BPGi added significantly to the model. Statistically, the most optimal use of M2BPGi was combined with FIB-4, with an AUC of 0.835. Conclusions The optimal cut-off of M2BPGi for diagnosing high-risk liver fibrosis in this study was 1.434. M2BPGi should be used with FIB-4 as a diagnostic tool for diagnosing liver fibrosis, especially in the absence of a liver biopsy or elastography.

Revisiting Mac-2-Binding Protein Glycosylation Isomer (M2BPGi) for Diagnosing High-Risk Liver Fibrosis: A Stepwise Diagnostic Analysis

Abstract* Background The level of liver fibrosis is the basis for the treatment of chronic hepatitis B (CHB), and it is necessary to adapt non-invasive liver fibrosis modalities. We aimed to investigate the use of M2BPGi as a single or combined diagnostic modality for liver fibrosis in CHB patients through a stepwise diagnostic analysis. Methods Cross-sectional data were taken from patients between October 2021 and August 2022. Demographic data, blood profile, liver function, and liver stiffness were measured in CHB patients over 18 years old, willing to take part in the research, and had complete data. APRI, FIB-4, and AAR were calculated using the well-known formulas. Serum M2BPGi-levels were converted into a cut-off index (COI). The patients were divided into low-risk (LR) and high-risk fibrosis (HR) groups. A cut-off for each predictor variable to differentiate between the LR and HR groups was determined. The obtained cut-off was assessed for its association with the grouping of liver elastography results. Models to diagnose the liver stiffness measurement (LSM) ≥8 kPa were created and compared through multivariate and ROC analyses. Results The number of patients that met the inclusion and exclusion criteria was 143 (HR = 65, LR = 78). The cut-off for diagnosing LSM ≥8kPa was 0.311, 0.742, 0.635, and 1.434 for APRI, FIB-4, AAR, and M2BPGi, respectively. This cut-off was significantly associated with the results of the HR and LR groupings. A multivariate analysis found that FIB4, AAR, and M2BPGi added significantly to the model. Statistically, the most optimal use of M2BPGi was combined with FIB-4, with an AUC of 0.835. Conclusions The optimal cut-off of M2BPGi for diagnosing high-risk liver fibrosis in this study was 1.434. M2BPGi should be used with FIB-4 as a diagnostic tool for diagnosing liver fibrosis, especially in the absence of a liver biopsy or elastography.

Serum ribonucleotide reductase M2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B patients.

It is known that ribonucleotide reductase M2 (RRM2) could be induced by hepatitis B virus (HBV) via DNA damage response. However, whether RRM2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B (CHB) patients is still unclear. In this study, CHB patients from GSE84044 (a transcriptome data from GEO data set) were downloaded and RRM2 was selected as a hub gene. Interestingly, a positive correlation was found between serum RRM2 and liver fibrosis stage. The similar results were found in CHB patients with normal alanine aminotransferase (ALT). Notably, RRM2 could effectively differentiate preliminary fibrosis from advanced fibrosis in CHB patients with/without normal ALT. In addition, RRM2 had a better performance in diagnosing liver fibrosis than two commonly used noninvasive methods (aspartate aminotransferase-to-platelet ratio index and fibrosis index based on the four factors), two classic fibrotic biomarkers (hyaluronic acid and type IV collagen) as well as Mac-2 binding protein glycosylation isomer, a known serum fibrosis marker. Moreover, CHB patients with high RRM2, who were associated with advanced fibrosis, had higher expressions of immune checkpoints. Overall, serum RRM2 may be a promising biomarker for diagnosing and monitoring liver fibrosis in CHB patients.

Perlemakan Hati Non-Alkoholik dan Risiko Fibrosis Hati pada Pasien Hepatitis B Kronik

Introduction. Prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing throughout the world due to sedentary lifestyle and dietary habit, including in patients with chronic hepatitis B (CHB). In several studies, advanced of liver disease were more likely observed among those CHB patients with NAFLD. NAFLD might increase the risk of liver disease progression in CHB patients, but prior investigations were still limited. This study aimed to determine the association between NAFLD and risk of liver fibrosis in CHB patients. Methods. All patients with positive serum hepatitis B surface antigen in the Hepatobilier Data Registry, Cipto Mangunkusumo Hospital, were included in this study. Based on abdominal ultrasonography, patients were divided into two group (group I: non-NAFLD – hepatitis B patients vs. group II: NAFLD – hepatitis B patients). Data demographic and clinical examination were collected. Significant liver fibrosis was defined as stage liver fibrosis above 7 kPa (≥ F2). Logistic regression was used to identify NAFLD as risk factor for significant fibrosis. Variables were expressed as prevalence odd ratio (POR) with 95% CI. P values <0.05 were considered statistically significant. Results. Among 130 hepatitis B patients, 45 patients (34.6%) were diagnosed with NAFLD. Of 45 patients in group II, 36 patients (80%) had significant liver fibrosis. It was observed that a higher percentage of patients in group II were HBeAg negative compared to those in group I (66.7% vs. 35.9%; p=0.038). Furthermore, group II also displayed higher levels of liver stiffness compared to group I (12.22 (8.6 kPa) vs. 8.57 (7.8 kPa); p 0.016). In multivariate analysis, NAFLD was significantly associated with significant liver fibrosis (POR: 5.87; CI95%: 2.48 – 13.86; p < 0.001) after adjusted with HBeAg status. Conclusion. NAFLD associated with the higher risk of liver fibrosis in patients with hepatitis B. Modification of lifestyle and potential therapeutic intervention may help in reducing the progression of liver fibrosis.

Interleukin-34 is more suitable than macrophage colony-stimulating factor for predicting liver significant fibrosis in patients with chronic hepatitis B

Aims Interleukin-34 (IL-34) and macrophage colony-stimulating factor (CSF-1) have similar functions, such as promoting the formation of liver fibrosis. This study aimed to evaluate and compare the diagnostic value of serum IL-34 and CSF-1 for significant liver fibrosis in patients with chronic hepatitis B (CHB). Methods A total of 369 CHB patients, consisting of 208 HBeAg-negative patients and 161 HBeAg-positive patients, were enrolled in this study. Additionally, 72 healthy individuals served as healthy controls (HCs). Serum levels of IL-34 and CSF-1 were measured using the enzyme-linked immunosorbent assay method. Liver fibrosis grades were assessed using the modified Scheuer scoring system. Results Serum IL-34 and CSF-1 levels exhibited significant elevation in both HBeAg-negative and HBeAg-positive patients in comparison to HCs (p < 0.001). IL-34 emerged as an independent factor linked to significant liver fibrosis, whereas CSF-1 did not exhibit such an association. Receiver operating characteristic (ROC) analysis indicated higher areas under the curves (AUCs) for IL-34 (0.814, p < 0.001 and 0.673, p < 0.001) when diagnosing significant liver fibrosis in HBeAg-negative and HBeAg-positive patients, respectively, as opposed to CSF-1 (0.602, p < 0.001; 0.619, p = 0.385). Within the HBeAg-negative patient subgroup, the AUC for IL-34 surpassed that of FIB-4 (p = 0.009) and APRI (p = 0.045). Conclusion Serum IL-34 has the potential to be a straightforward and practical biomarker that demonstrates superior performance to serum CSF-1 in the diagnosis of significant liver fibrosis in CHB patients, especially within the HBeAg-negative patients.

The informative value of noninvasive tools for assessment of liver fibrosis in chronic hepatitis B patients under antiviral treatment with nucleoside and nucleotide analogues

Background: Antiviral therapy (AVT) with nucleoside and nucleotide analogues (NAs) for chronic hepatitis B (CHB) is aimed at prevention of the development and progression of fibrosis, liver cirrhosis, and hepatocellular carcinoma. Therefore, monitoring of changes in liver fibrosis over time with noninvasive tests is a necessary prerequisite for the assessment of treatment efficacy. However, there are very few studies on changes of transient elastometry (TE) over time, the calculated indices APRI and FIB-4 under AVT in patients with CHB.&#x0D; Aim: To assess changes in noninvasive tests (TE, APRI, FIB-4) over time and to identify factors influencing the fibrosis severity in CHB patients treated with NAs.&#x0D; Materials and methods: This retrospective study was performed in 42 CHB patients, in whom noninvasive methods (TE, APRI and FIB-4) were used before and during NA-based AVT. The patients were divided into two groups: those with a significant reduction in liver density (SRLD, at least by 25% from their baseline TE) and those without a significant reduction ( 25%).&#x0D; Results: Virological response was achieved in 38/42 patients after NA-based AVT (mean duration, 21 months). TE values decreased significantly in the patients with severe fibrosis/cirrhosis (F3/F4) (from 14.2 to 8.3 kPa, p = 0.001), with minimal/moderate fibrosis (F1/F2) (from 5.9 to 5.1 kPa, p = 0.009), and in HBeAg-negative patients (from 6.9 to 5.2 kPa, p 0.001). The F3/F4, F1/F2, HBeAg-positive and HBeAg-negative patients demonstrated a significant reduction in APRI and FIB-4 indices (all p 0.05). Higher baseline TE values were independently associated with SRLD (odds ratio 1.324; 95% confidence interval (CI) 1.0291.702; p = 0.029). Baseline TE, APRI, and FIB-4 values positively correlated with their values on treatment (all p 0.05). The AUROC values of APRI and FIB-4 reduction as SRLD predictors were 0.632 (95% CI 0.4570.807; p = 0.160) and 0.578 (95% CI 0.3910.764; p = 0.408), respectively.&#x0D; Conclusion: NA-based AVT promoted the regression of fibrosis in CHB patients. A high baseline TE value was identified as an independent SRLD predictor. At the same time, despite moderate positive correlations between TE, APRI and FIB-4 parameters, the calculated indexes APRI and FIB-4 cannot be used to predict SRLD. The decrease in liver tissue density by at least 25% correlated only with TE parameters, which makes it possible to recommend TE for monitoring liver fibrosis in CHB patients treated with NA.

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B.

Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

AMAP Score and Its Combination With Liver Stiffness Measurement Accurately Assess Liver Fibrosis in Chronic Hepatitis B Patients

The changes in liver stiffness measurement (LSM) are unreliable to estimate regression of fibrosis during antiviral treatment for chronic hepatitis B (CHB) patients. The age-male-albumin-bilirubin-platelets score (aMAP), as an accurate hepatocellular carcinoma risk score, may reflect the liver fibrosis stage. Here, we aimed to evaluate the performance of aMAP for diagnosing liver fibrosis in CHB patients with or without treatment. A total of 2053 patients from 2 real-world cohorts and 2 multicentric randomized controlled trials in China were enrolled, among which 2053 CHB patients were included in the cross-sectional analysis, and 889 CHB patients with paired liver biopsies before and after 72 or 104 weeks of treatment were included in the longitudinal analysis. In the cross-sectional analysis, the areas under the receiver operating characteristic curve of aMAP in diagnosing cirrhosis and advanced fibrosis were 0.788 and 0.757, which were comparable with or significantly higher than those of the fibrosis index based on 4 factors and the aspartate aminotransferase-platelet ratio. The stepwise approach using aMAP and LSM further improved performance in detecting cirrhosis and advanced fibrosis with the smallest uncertainty area (29.7% and 46.2%, respectively) and high accuracy (82.3% and 79.8%, respectively). In the longitudinal analysis, we established a novel model (aMAP-LSM model) by calculating aMAP and LSM results before and after treatment, which had satisfactory performance in diagnosing cirrhosis and advanced fibrosis after treatment (area under the receiver operating characteristic curve, 0.839 and 0.840, respectively), especially for those with a significant decrease in LSM after treatment (vs LSM alone, 0.828 vs 0.748; P < .001 [cirrhosis]; 0.825 vs 0.750; P < .001 [advanced fibrosis]). The aMAP score is a promising noninvasive tool for diagnosing fibrosis in CHB patients. The aMAP-LSM model could accurately estimate fibrosis stage for treated CHB patients.

Fc receptor-like 5 gene polymorphisms and mRNA expression are associated with liver fibrosis in chronic hepatitis B.

Objective: To investigate the associations of Fc receptor-like 5 (FCRL5) gene polymorphisms and mRNA expression with liver fibrosis in chronic hepatitis B (CHB).Methods: A total of 114 CHB patients with liver fibrosis and 120 CHB patients without liver fibrosis were selected for this study. The gender, age, body mass index (BMI), alanine transaminase (ALT) value, aspartate aminotransferase (AST) value, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) were recorded. Two polymorphisms of the FCRL5 gene (rs6427384 and rs6692977) were genotyped. The mRNA expression level of FCRL5 in peripheral blood monocytes was determined.Results: ALT, AST, APRI, and FIB-4 in patients with fibrosis were significantly higher than those in non-fibrosis patients. There was statistically significant difference between fibrosis and non-fibrosis groups in the genotype distribution (χ2 = 7.805, p = 0.020) and allele frequencies (χ2 = 13.252, p < 0.001) at FCRL5 rs6692977. When compared with CC genotype, the genotype CT or TT at rs6692977 was significantly associated with a increased risk of liver fibrosis in CHB patients (CT vs. CC: OR = 1.921, 95% CI = 1.093–3.375, p = 0.023; TT vs. CC: OR = 2.598, 95% CI = 1.067–6.324, p = 0.031). The mRNA relative expression levels of FCRL5 in patients with liver fibrosis were significantly higher than those in the non-fibrosis group (t = 13.456, p < 0.001). The fibrosis patients carried TT or CT genotype of rs6692977 had significantly higher FCRL5 mRNA expression levels than those carried CC genotype (t = 2.859, p = 0.005). The mRNA expression levels of FCRL5, APRI, and FIB-4 index showed predictive efficacy in liver fibrosis with cut-off values of 0.75 (AUC = 0.896, 95% CI = 0.856–0.935), 0.45 (AUC = 0.852, 95% CI = 0.802–0.902) and 1.84 (AUC = 0.765, 95% CI = 0.703–0.826), respectively.Conclusion: FCRL5 gene rs6692977 polymorphisms and mRNA expression levels are associated with liver fibrosis in CHB patients.

Diagnostic Performance of Acoustic Radiation Force Impulse Imaging in Evaluating Liver Fibrosis in Patients with Chronic Hepatitis B Infection: A Cross-Sectional Study.

Background Acoustic radiation force impulse point shear wave elastography (ARFI-pSWE), measuring shear-wave velocity (SWV), has been utilized to examine the liver stiffness caused by different etiologies. However, information on its reliability in staging liver fibrosis in chronic hepatitis B (CHB) patients is scarce. Purpose The aim of the study is to examine the diagnostic performance of ARFI-pSWE and determine the optimal SWV cut-off values to predict significant fibrosis ( F ≥2) and cirrhosis (F4) in CHB patients. Material and Methods All 114 adult CHB patients visiting the University Medical Center, Ho Chi Minh City, Vietnam between February 2019 and March 2021 underwent liver stiffness measurement using ARFI-pSWE and FibroScan. SWV results were tested against FibroScan for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The area under the receiver operating characteristic (AUROC) curve was used to identify the optimal SWV cut-off values. Results There was a strong agreement between ARFI-pSWE and FibroScan ( r = 0.92, p <0.001). The optimal SWV cut-off value for detecting significant fibrosis was 1.37 m/s with an AUROC of 0.975, sensitivity of 83.3%, specificity of 100%, PPV of 100%, and NPV of 81%. The optimal cut-off value for predicting cirrhosis was 1.70 m/s with an AUROC of 0.986, sensitivity of 97%, specificity of 93%, PPV of 95%, and NPV of 96%. Conclusion ARFI-pSWE could be an effective technique for evaluating liver fibrosis in CHB patients. SWV cut-off values of 1.37 and 1.70 m/s could be used to diagnose significant fibrosis and cirrhosis, respectively.

The compound annual growth rate of the fibrosis-4 index in chronic hepatitis B patients.

Chronic hepatitis B (CHB) patients with low disease activity are at risk of liver fibrosis. The age-adjusted fibrosis-4 index (FIB4-AA), developed in our previous publication, and was implemented to evaluate the tendency of liver fibrosis in these patients. We aimed to investigate the rate of liver fibrosis in CHB patients with low disease activity. Resuming our previous study, the FIB-4 changes of 244 antiviral treatment-naïve CHB patients, with a total of 1243.48 person-years, were reviewed. Among the cohort, patients were categorized as FIB4-AA positive or negative according to the results of their last FIB4-AA minus their initial FIB-4 during at least 18 months of observation time. The compound annual growth rate (CAGR) of FIB-4 was calculated for the FIB4-AA positive and negative groups. The assumed healthy controls had an FIB-4 CAGR calculated to be 2.34% for both men and women, while the FIB-4 CAGR of the whole study cohort was 2.84% ± 6.01%. FIB4-AA positive effectively identifies CHB patients with higher mean FIB-4 CAGR (7.11% ± 3.88% vs. -2.36% ± 3.52%, p < 0.0001). Overweight CHB patients had 10 times smaller mean FIB-4 CAGR than lean ones (0.38% ± 10.35% vs. 3.83% ± 8.88%, p=0.009). An increase in FIB4-AA over at least 18 months in CHB patients with relatively low disease activity meant they were at greater risk of liver fibrosis, and these patients had a mean FIB-4 CAGR of 7.11%. The FIB-4 CAGR was compatible with the findings of previous studies on the collagen proportionate area in viral hepatitis patients.

Comparison of Non-Invasive Clinical Algorithms for Liver Fibrosis in Patients With Chronic Hepatitis B to Reduce the Need for Liver Biopsy: Application of Enhanced Liver Fibrosis and Mac-2 Binding Protein Glycosylation Isomer.

BackgroundNon-invasive clinical algorithms for the detection of liver fibrosis (LF) can reduce the need for liver biopsy (LB). We explored the implementation of two serum biomarkers, enhanced liver fibrosis (ELF) and Mac-2 binding protein glycosylation isomer (M2BPGi), in clinical algorithms for LF in chronic hepatitis B (CHB) patients.MethodsTwo clinical algorithms were applied to 152 CHB patients (1) transient elastography (TE) followed by biomarkers (TE/ELF and TE/M2GPGi); (2) biomarker test followed by TE (ELF/TE and M2BPGi/TE). Using the cut-off value or index for the detection of advanced LF (TE≥F3; 9.8 in ELF and 3.0 in M2BPGi), LB was expected to be performed in cases with discordant TE and biomarker results.ResultsIn both algorithms, the expected number of LBs was lower when using M2BPGi than when using ELF (TE/ELF or ELF/TE, 13.2% [N=20]; TE/M2BPGi or M2BPGi/TE, 9.9% [N=15]), although there was no statistical difference (P=0.398). In the TE low-risk group (TE≤F2), the discordance rate was significantly lower in the TE/M2BPGi approach than in the TE/ELF approach (1.5% [2/136] vs. 11.0% [15/136], P=0.002). In the biomarker low-risk group, there was no significant difference between the ELF/TE and M2BPGi/TE approaches (3.9% [5/126] vs. 8.8% [13/147], P=0.118).ConclusionsBoth ELF and M2BPGi can be implemented in non-invasive clinical algorithms for assessing LF in CHB patients. Given the lowest possibility of losing advanced LF cases in the low-risk group when using the TE/M2BPGi approach, this combination seems useful in clinical practice.

Prognostic Value of Inflammatory Indicators in Chronic Hepatitis B Patients With Significant Liver Fibrosis: A Multicenter Study in China.

Diagnosis of significant liver fibrosis is essential to facilitate the optimal treatment decisions and improve prognosis in patients with chronic hepatitis B (CHB). We aimed to evaluate the value of inflammatory indicators and construct a nomogram that effectively predicts significant liver fibrosis among CHB patients. 563 CHB patients from two centers in China from 2014 to 2019 were divided into three cohorts (development, internal validation, and independent validation cohorts), assigned into cases with significant fibrosis (liver fibrosis stages ≥2) and those without. Multiple biochemical and serological inflammatory indicators were investigated. Inflammatory indicators, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly associated with significant liver fibrosis in CHB patients but limited predictive performance, and then we combined them with prothrombin time activity percentage (PTA) and liver stiffness measurement (LSM) were identified by multivariate logistic regression analysis. Based on these factors, we constructed the nomogram with excellent performance. The area under the receiver operating characteristic curve (AUROC) for the nomogram in the development, internal validation, and independent validation cohorts were 0.860, 0.877, and 0.811, respectively. Our nomogram based on ALT and AST that had excellent performance in predicting significant fibrosis of CHB patients were constructed.

Epigenetically-regulated serum GAS5 as a potential biomarker for patients with chronic hepatitis B virus infection.

Long non-coding RNA-growth arrest specific transcript 5 (lncRNA-GAS5) plays a suppressive role in activated hepatic stellate cells (HSCs). LncRNAs could circulate in the blood in a cell-free form and serve as promising biomarkers for various human diseases. Herein, we investigated the feasibility of using serum GAS5 as a biomarker for liver fibrosis in chronic hepatitis B (CHB) patients and whether promoter methylation was responsible for GAS5 down-regulation. Serum GAS5 levels were quantified using quantitative real-time PCR in CHB patients and healthy controls. GAS5 promoter methylation was examined in LX-2 cells and cirrhotic tissues. Compared with the sera from healthy controls, lower GAS5 levels were found in the sera from CHB patients. Receiver operating characteristic curve analysis indicated that serum GAS5 had a significant diagnostic value for liver fibrosis in CHB patients. Serum GAS5 negatively correlated with HAI scores as well as ALT values in CHB patients. GAS5 was additionally reduced in cirrhotic tissues, associated with its hypermethylation promoter. In LX-2 cells, transforming growth factor-β1 treatment led to a reduction in GAS5 expression and an increase in promoter methylation. Hypermethylation of GAS5 was blocked down by DNA methyltransferase (DNMT) inhibitor and restored GAS5 inhibited HSC activation including proliferation and collagen production. Further studies confirmed that GAS5 methylation was mediated by DNMT1. We demonstrate that epigenetically-regulated serum GAS5 could serve as a potential biomarker in CHB patients. Loss of GAS5 is associated with DNMT1-mediated promoter methylation.

A Novel Non-invasive Model Based on GPR for the Prediction of Liver Fibrosis in Patients With Chronic Hepatitis B.

Background: Some controversy remains regarding conventional serum indices for the evaluation of liver fibrosis. Therefore, we aimed to combine the existing index with other serum parameters to discriminate liver fibrosis stages in patients with chronic hepatitis B (CHB).Methods: A total of 1,622 treatment-naïve CHB patients were divided into training (n = 1,211) and validation (n = 451) cohorts. Liver histology was assessed according to the Scheuer scoring scheme. All common demographic and clinical parameters were analyzed.Results: By utilizing the results of the logistic regression analysis, we developed a novel index, the product of GPR, international normalized ratio (INR), and type IV collagen (GIVPR), to discriminate liver fibrosis. In the training group, the areas under the ROCs (AUROCs) of GIVPR, APRI, FIB-4, and GPR for significant fibrosis were 0.81, 0.75, 0.72, and 0.77, respectively; the AUROCs of GIVPR, APRI, FIB-4, and GPR for advanced fibrosis were 0.82, 0.74, 0.74, and 0.78, respectively; and the AUROCs of GIVPR, APRI, FIB-4, and GPR for cirrhosis were 0.87, 0.78, 0.78, and 0.83, respectively. Similar results were also obtained in the validation group. Furthermore, the decision curve analysis suggested that GIVPR represented superior clinical benefits in both independent cohorts.Conclusion: The GIVPR constructed on GPR represents a superior predictive model for discriminating liver fibrosis in CHB patients.

LECT2, A Novel and Direct Biomarker of Liver Fibrosis in Patients With CHB.

Chronic hepatitis B (CHB) patients with severe liver fibrosis would be more likely to progress to a poorer prognosis. Treatment is considered once the liver fibrosis reaches significant liver fibrosis (≥S2). Leukocyte cell-derived chemotaxin-2 (LECT2) has been shown to contribute to liver fibrosis progression. No research has focused on the role of LECT2 in liver fibrosis in CHB patients. This study enrolled 227 CHB patients and divided them into the training group (n = 147) and validation group (n = 80), respectively. The expression of LECT2 in serum, protein and mRNA of the human liver tissues was detected to analyze the possible associations between LECT2 and liver fibrosis. A receiver operating characteristic curve (ROC) was used to estimate the efficacy of LECT2 for predicting liver fibrosis. The data showed that there was a positive relationship between LECT2 and the progression of liver fibrosis. In the training group, LECT2 was demonstrated to have better effectiveness than APRI and FIB-4. The AUC was 0.861, 0.698, and 0.734 for significant liver fibrosis, and 0.855, 0.769, and 0.752 for advanced liver fibrosis. Besides, the efficacy of LECT2 in different statuses of patients with CHB was examined and the effectiveness of LECT2 had also been confirmed in the validation group. All the results confirmed that LECT2 could act as a perfect predictor and thus offers a novel and direct biomarker to estimate liver fibrosis more accurately.

Comparison of Sound Touch Elastography, Sound Touch Quantify, and 4 Serum Fibrosis Indexes for the Diagnosis of Liver Fibrosis in Patients With Chronic Hepatitis B.

The aim of this research was to compare the use of shear wave elastography (sound touch elastography [STE] and sound touch quantify [STQ]) and serum liver fibrosis indexes in the evaluation and staging of chronic hepatitis B (CHB) liver fibrosis. Sound touch elastography is a form of 2-dimensional shear wave elastography, and STQ is a form of point shear wave elastography. Between June 2018 and March 2019, 122 patients with CHB were assessed using STE and STQ. Serum liver biomarkers tests were undertaken, and liver biopsy was performed, and these were used to assign a pathological stage based on the Scheuer scoring system. A receiver operating characteristic curve was used to analyze the diagnostic value of noninvasive methods for evaluating and staging liver fibrosis. The cutoff values of STE for liver fibrosis stages S2 to S4 were 8.85, 9.97, and 10.29 kPa, respectively, and the areas under the receiver operating characteristic (AUCs) curve were 0.703, 0.821, and 0.900, respectively. The cutoff values of STQ for liver fibrosis stages S2 to S4 were 11.31, 13.81, and 20.60 kPa, respectively, and the AUCs were 0.674, 0.807, and 0.893, respectively. The AUCs of STE and STQ in diagnosing fibrosis stage were significantly higher than those of liver serum biomarkers (P < 0.05). The AUCs for the ability of the aspartate transaminase-to-platelet ratio index, the fibrosis index based on the 4 factors, the King score, and the Forns index to diagnose S2 fibrosis were 0.502, 0.624, 0.542, and 0.616, respectively, and the AUCs for their ability to diagnose S4 fibrosis were 0.856, 0.861, 0.883, and 0.823, respectively. Both STE and STQ are noninvasive methods for the assessment of liver fibrosis in CHB patients, with better diagnostic performances than those of 4 serum fibrosis indexes.

INR-to-platelet ratio (INPR) as a novel noninvasive index for predicting liver fibrosis in chronic hepatitis B.

Objective: We aimed to investigate whether a novel noninvasive index, i.e., the international normalized ratio-to-platelet ratio (INPR), was a variable in determining liver fibrosis stage in patients with chronic hepatitis B (CHB).Methods: A total of 543 treatment-naïve CHB patients were retrospectively enrolled. Liver histology was assessed according to the Metavir scoring scheme. All common demographic and clinical parameters were analyzed.Results: Based on routine clinical parameters (age, sex, HBeAg status, HBV DNA, hematological parameters, coagulation index, and liver biochemical indicators), a novel index, i.e., the INR-to-platelet ratio (INPR), was developed to magnify the unfavorable effects of liver fibrosis on INR and platelets. The AUCs of INPR for predicting significant fibrosis, advanced fibrosis, and cirrhosis were 0.74, 0.76 and 0.86, respectively. Compared with APRI, FIB-4, and GPR, the INPR had comparable predictive efficacy for significant fibrosis and better predictive performance for advanced fibrosis and cirrhosis.Conclusion: INPR could be an accurate, easily calculated and inexpensive index to assess liver fibrosis in patients with CHB. Further studies are needed to verify this indicator and compare it with other noninvasive methods for predicting liver fibrosis in CHB patients.

Controlled attenuation parameter value-based diagnostic algorithm improves the accuracy of liver stiffness measurement in chronic hepatitis B patients.

Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis because of steatosis. However, the impact of the controlled attenuation parameter (CAP) on liver stiffness cutoff values remains unknown; CAP was used to quantify and diagnose the severity of hepatic steatosis. The study was conducted to determine the effect of CAP on liver stiffness cutoff values in chronic hepatitis B (CHB) patients. A retrospective cross-sectional study was performed in liver biopsy-proven CHB patients. The median LSM (kPa) in the elevated CAP group was higher than that in the normal CAP group at the same fibrosis stage. For S2-4, the area under the receiver operating characteristic (AUROC) curve of LSM was 0.78 and 0.72 in the normal and elevated CAP groups, respectively. When a cutoff value of 8.9 kPa was used, the diagnostic accuracy was 77.82% and 63.41% in the normal and elevated CAP groups, respectively. Compared with the alanine transaminase (ALT)-based LSM algorithm, the CAP-based LSM algorithm had a similar correct diagnosis rate (33.64% vs. 33.94%, respectively) but a lower misdiagnosis rate (16.97% vs. 20.30%, respectively). The new CAP-based LSM diagnostic algorithm will improve the diagnostic accuracy of liver fibrosis in CHB patients.

Noninvasive assessment of liver fibrosis in chronic hepatitis B carriers with sound touch elastography: study of surgical pathology specimens

ABSTRACT Purpose To evaluate the diagnostic performance of sound touch elastography (STE) for staging liver fibrosis in chronic hepatitis B (CHB) patients using pathological stage of surgical specimens as the reference standard. Method 239 CHB patients were included. Liver stiffness measurements (LSMs) on STE and Supersonic shear imaging (SSI), gamma glutamyl transferase-to-platelet ratio (GPR), aspartate aminotransferase-to-platelet ratio index (APRI) and four-factor Fibrosis-4 (FIB-4) index were obtained. Areas under the receiver operating characteristic (ROC) curves (AUCs) for the diagnosis of fibrosis stage were calculated and compared. Results The LSMs obtained by STE and SSI significantly correlated with the fibrosis stages (r = 0.757; r = 0.758, respectively, both p < 0.001). No significant differences in AUCs were observed between STE and SSI in identifying fibrosis ≥stage 1 (0.92 vs. 0.94), ≥stage 2 (0.89 vs. 0.91), ≥stage 3 (0.90 vs. 0.91) or stage 4 (0.92 vs. 0.91). Both STE and SSI had significantly higher AUCs in identifying each fibrosis stage than the GPR (0.68, 0.77, 0.76 and 0.79), APRI (0.53, 0.66, 0.74 and 0.69) and FIB-4 (0.61, 0.77, 0.79 and 0.74). Conclusions STE is an efficient tool for assessing liver fibrosis in CHB patients, with performance comparable to that of SSI and superior to that of biomarkers.