Fibrosis In Chronic Hepatitis B Patients Research Articles

Prevalence and risk factors of significant fibrosis in chronic hepatitis B patients with concurrent metabolic dysfunction-associated steatotic liver disease

Introduction and objectivesSignificant fibrosis is an indicator of clinical intervention for both chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD). There remains a paucity of data regarding the clinical impact of biopsy-defined MASLD on significant fibrosis in CHB patients. The current study aims to elucidate whether patients with concomitant MASLD are at higher risk of significant fibrosis in patients with CHB. Patients and methodsThis retrospective research of two tertiary hospitals comprised 1818 patients between 2009 and 2021 with CHB and hepatic steatosis who had not received antiviral therapy. Pathologic findings by liver biopsy were contrasted between CHB group (n = 844) and CHB + MASLD (n = 974) group. METAVIR values of F≥2 were used to categorize significant fibrosis. ResultsPatients with CHB + MASLD had more significant fibrosis (35.5 % vs. 23.5 %, p < 0.001) than CHB group. The presence of MASLD [adjusted odds ratio (aOR) 2.055, 95 % confidence interval (CI) 1.635–2.584; p < 0.001] was strongly associated with significant fibrosis in all CHB patients. There was a trend for patients with more cardiometabolic risk factors (CMRFs) to have a higher prevalence of significant fibrosis: (25.7 % in CMRF1 subgroup v.s. 34.9 % in CMRF2 subgroup v.s. 53.7 % in CMRF≥ 3 subgroup, p < 0.001). Patients with CMRF≥3 had a three-fold higher significant fibrosis than those with just one CMRF. ConclusionsMASLD was associated with higher fibrosis stage in patients with CHB. Early detection and intervention are crucial to patients with three or more cardiometabolic risk factors.

Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B.

The progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent. Based on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests. Patients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively. Ultimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King's score, the model in the training cohort (AUC = 0.834, 95% CI 0.800-0.868, p < 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742-0.866, p < 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King's scores in all cohorts. This study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.

Plasma microRNA-15a/16-1 serves as a non-invasive indicator of liver fibrosis severity in individuals with chronic hepatitis B

BackgroundThe lack of effective non-invasive diagnostic methods for liver fibrosis hinders timely treatment for chronic hepatitis B (CHB) patients, leading to the progression of advanced liver disease. Circulating microRNAs offer a non-invasive approach to fibrosis assessment. MicroRNA-15a/16-1 (miR-15a/16) was reported to be implicated in fibrosis development, but the role of plasma miR-15a/16 in liver fibrosis assessment remains poorly understood. This study explored the importance of plasma miR-15a/16 in assessing liver fibrosis severity of CHB patients. MethodsQuantitative PCR was utilized to measure the levels of plasma miR-15a/16 in 435 patients with CHB and 74 healthy controls. We assessed the correlation between plasma miR-15a/16 levels and liver fibrosis and cirrhosis using Pearson correlation coefficients, multivariate linear and logistic regression models, and smooth curve fitting. Utilizing the receiver operating characteristic (ROC) curve, we examined the diagnostic potential of plasma miR-15a/16 in severe fibrosis and cirrhosis. ResultsPlasma levels of miR-15a/16 in patients with CHB were significantly reduced compared to those in healthy controls. In the CHB cohort, levels were notably decreased in individuals with severe fibrosis or cirrhosis compared to those without severe fibrosis or cirrhosis. Plasma miR-15a/16 levels exhibited a negative relationship with the severity of liver fibrosis, gradually decreasing as the histological fibrosis stage progressed from S0 to S4. Reduced levels of plasma miR-15a/16 were linked to an elevated risk of severe liver fibrosis (miR-15a: odds ratio [OR] = 0.243; 95 % confidence interval [CI]: 0.138, 0.427; miR-16: OR = 0.201; 95 % CI: 0.097, 0.417) and cirrhosis (miR-15a: OR = 0.153; 95 % CI: 0.079, 0.298; miR-16: OR = 0.064; 95 % CI: 0.025, 0.162). MiR-15a achieved an area under the ROC curve of 0.886 and 0.832 for detecting moderate-to-severe fibrosis (S2-S4) and cirrhosis, respectively. MiR-16 demonstrated similar diagnostic values. ConclusionPlasma miR-15a/16 levels were negatively correlated with the severity of liver fibrosis in CHB patients and could serve as a new non-invasive indicator in evaluating liver fibrosis.

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

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. 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. 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. 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.

A machine learning-based model analysis for serum markers of liver fibrosis in chronic hepatitis B patients

Early assessment and accurate staging of liver fibrosis may be of great help for clinical diagnosis and treatment in patients with chronic hepatitis B (CHB). We aimed to identify serum markers and construct a machine learning (ML) model to reliably predict the stage of fibrosis in CHB patients. The clinical data of 618 CHB patients between February 2017 and September 2021 from Zhejiang Provincial People's Hospital were retrospectively analyzed, and these data as a training cohort to build the model. Six ML models were constructed based on logistic regression, support vector machine, Bayes, K-nearest neighbor, decision tree (DT) and random forest by using the maximum relevance minimum redundancy (mRMR) and gradient boosting decision tree (GBDT) dimensionality reduction selected features on the training cohort. Then, the resampling method was used to select the optimal ML model. In addition, a total of 571 patients from another hospital were used as an external validation cohort to verify the performance of the model. The DT model constructed based on five serological biomarkers included HBV-DNA, platelet, thrombin time, international normalized ratio and albumin, with the area under curve (AUC) values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the training cohort were 0.898, 0.891, 0.907 and 0.944, respectively. The AUC values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the external validation cohort were 0.906, 0.876, 0.931 and 0.933, respectively. The simulated risk classification based on the cutoff value showed that the classification performance of the DT model in distinguishing hepatic fibrosis stages can be accurately matched with pathological diagnosis results. ML model of five serum markers allows for accurate diagnosis of hepatic fibrosis stages, and beneficial for the clinical monitoring and treatment of CHB patients.

Noninvasive models for the prediction of liver fibrosis in patients with chronic hepatitis B

ObjectiveTo evaluate the diagnostic accuracy of aspartate aminotransferase(AST)/ alanine transaminase (ALT), AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and gamma-glutamyl transpeptidase to platelet count ratio (GPR) for hepatic fibrosis in patients with chronic hepatitis B (CHB).MethodsA total of 1210 CHB patients who underwent liver biopsy were divided into two groups: patients with no significant fibrosis (control group) and patients with significant fibrosis, and routine laboratory tests were retrospectively included. Logistic regression models were used for the prediction, and the area under the receiver operating characteristic (AUROC) was used to assess the diagnostic accuracy.ResultsA total of 631 (52.1%) and 275 (22.7%) patients had significant fibrosis (≥ S2) and advanced fibrosis (≥ S3), respectively. The GPR showed significantly higher diagnostic accuracy than that of APRI, FiB-4, and AST/ALT to predict ≥ S2(significant fibrosis) and ≥ S3 fibrosis(advanced fibrosis), with an AUROC was 0.69 (95%CI: 0.66–0.71) and 0.72 (0.69–0.75), respectively. After stratified by the status of HBeAg ( positive or negative), GPR, APRI, and FiB-4 showed improved predicting performance for significant fibrosis and advanced fibrosis in HBeAg positive patients, with the most significant improvement was shown for GPR in predicting significant fibrosis (AUROC = 0.74, 95%CI: 0.70–0.78).ConclusionsAmong the four noninvasive models, GPR has the best performance in the diagnosis of hepatic fibrosis in CHB patients and is more valuable in HBeAg-positive patients.

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.

Effect of Concurrent Metabolic Dysfunction-Associated Steatotic Liver Disease on Serial Non-invasive Fibrosis Markers in Chronic Hepatitis B.

Concurrent hepatic steatosis has diverse effects on chronic hepatitis B (CHB), however the combined effects of metabolic dysfunction-associated steatotic liver disease (MASLD) and CHB on liver fibrosis progression remains unclear. The primary aim of this study was to utilize serial fibrosis measurements to compare the dynamic change in fibrosis in CHB patients with/without concurrent MASLD. The secondary aim was to investigate factors associated with steatosis development and regression in CHB patients. This was a retrospective cohort study of all non-cirrhotic CHB patients identified from 1/1/2011 to 31/12/2016. Hepatic steatosis was diagnosed by ultrasound. Fibrosis markers included liver stiffness (LSM) by transient elastography, APRI and FIB-4. General linear mixed effects modelling was used to fit polynomial and linear estimates. Of 810 CHB patients (n = 2,373 LSM measurements; median age 44.4y; 48% male; 24% HBeAg positive), 14% had concurrent MASLD. LSM was higher at baseline but decreased in MASLD patients over time, while LSM remained stable in non-MASLD patients, such that all patients had similar LSM beyond 4-5 years. MASLD patients had lower APRI compared to non-MASLD patients, which was predominately due to a higher platelet count and higher ALT over time. There was substantial discordance between LSM, APRI and FIB-4. Baseline BMI was the only factor that predicted steatosis development and regression. We found no evidence of an association between concurrent MASLD and fibrosis progression amongst CHB patients without baseline advanced liver disease. APRI and FIB-4 may have reduced accuracy in MASLD patients.

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 &lt;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 &lt; 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.

RDW Predicts Fibrosis in Patients with Chronic Hepatitis B Having Persistently Normal ALT Levels.

There are studies on the determination of hepatic fibrosis with noninvasive markers but data about liver biopsy results and noninvasive markers in patients with chronic hepatitis B (CHB) are limited. The aim of this study is to determine the relationship between pathological findings and noninvasive markers, and to determine the marker that predicts fibrosis in patients with consistently normal serum alanine aminotransferase (ALT) levels, diagnosed with CHB and undergoing liver biopsy. A total of 122 patients with CHB, 29 of them with HbeAg (+), aged 30 years and older, HBV DNA > 2000 IU / ml, and serum ALT levels measured four times in the last year, were consistently normal, and 93 of them with HbeAg (-) were included in the study. Demographic characteristics of patients, laboratory parameters, histological activity index (HAI) and fibrosis values obtained in liver biopsy, and noninvasive markers (AP (age-platelet) index, APRI (AST/Platelet ratio) and FIB-4 score, neutrophil/lymphocyte ratio, mean platelet volume (MPV) and erythrocyte distribution width (RDW) were recorded. The relationship between RDW value and fibrosis was statistically significant in the HbeAg (+) group (p<0.001). The relationship between AP index, APRI and FIB-4 score, neutrophil/lymphocyte ratio and MPV with fibrosis was not statistically significant (>0.05 for each). It has been shown that the RDW value can be used to predict fibrosis in CHB patients with normal ALT and HbeAg (+), and the cut-off value for RDW is 12.

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.

Performance of serum-based biomarkers in fibrosis prediction of chronic hepatitis B patients in real life practice.

Few studies have addressed the performance and diagnostic accuracy of laboratory-based markers for fibrosis prediction in chronic hepatitis B (CHB) patients yielding heterogeneous results. We aimed to study the performance of the FIB-4 and neutrophil-to-lymphocyte ratio (NLR) markers for the differentiation between significant and non-significant hepatic fibrosis in real-life practice. We prospectively recruited CHB patients attending the hepatology clinic to undergo shear wave elastography (SWE) and blood tests. The predictive accuracy of FIB-4 and NLR for liver fibrosis was assessed by receiver operating characteristics (ROC) analysis. Overall, 174 fully characterized CHB patients with an average age of 50.2±11.2 (29-86 years) and a male predominance (65.2%) were included. Of these, 23% had significant fibrosis (≥F2) per SWE (>7.1KPA). A significant and linear correlation was found between the SWE score and FIB-4 values (r=0.572; P<0.001). A lower cut-off of 1.43 has yielded an AUROC of 0.76, with a sensitivity of 68.8%, specificity of 79.8%, diagnostic accuracy of 78.5%, and NPV of 96%. On the contrary, NLR values were similar between significant and minimal fibrosis and were not found to be correlated with significant fibrosis (r=0.54, P=0.39). FIB4 has a moderate performance and may have a valuable role in excluding significant fibrosis in CHB patients in daily practice.

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.

Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

A novel non-invasive model for the prediction of advanced liver fibrosis in chronic hepatitis B patients with NAFLD.

Thereare still lack of non-invasive models to evaluate liver fibrosis in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). We aimed to establish a predictive model for advanced fibrosis in these patients. A total of 504 treatment-naive CHB patients with NAFLD who underwent liver biopsy were enrolled and randomly divided into a training set (n=336) and a validation set (n=168). Receiver operating characteristic (ROC) curve was used to compare predicting accuracy for the different models. One hundred fifty-six patients (31.0%) had advanced fibrosis. In the training set, platelet, prothrombin time, type 2 diabetes, HBeAg positivity and globulin were significantly associated with advanced fibrosis by multivariable analysis. A predictive model namely PPDHG for advanced fibrosis was developed based on these parameters. The areas under the ROC curve (AUROC) of PPDHG with an optimal cut-off value of -0.980 in predicting advanced fibrosis was 0.817 (95% confidence interval 0.772 to 0.862), with a sensitivity of 81.82% and a specificity of 66.81%. The predicting accuracy of PPDHG for advanced fibrosis was significantly superior to AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and NAFLD fibrosis score (NFS). Further analysis revealed that the AUROC of PPDHG remained significantly higher than FIB-4 and NFS indexes, while it was comparable with APRI for predicting advanced fibrosis in the validation set. PPDHG had a better predicting performance than established models for advanced fibrosis in CHB patients with NAFLD. The application of PPDHG can reduce the necessary for liver biopsy in these 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.

How effective are APRI, FIB-4, FIB-5 scores in predicting liver fibrosis in chronic hepatitis B patients?

Liver fibrosis is the most important factor in the prognosis and treatment plan of patients with chronic hepatitis B (CHB). Aspartate aminotransferase (AST)-to-platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4), and fibrosis index based on 5 factors (FIB-5) scores are noninvasive fibrosis markers, and previous comparative studies have shown that they are as effective as liver biopsy in detecting liver fibrosis in different liver diseases. The aim of our study is to investigate whether existing scoring systems are effective in demonstrating fibrosis in CHB patients and to compare the APRI, FIB 4, and FIB 5 scores in differentiating early and advanced fibrosis in 123 patients who underwent liver biopsy for CHB infection. APRI, FIB-4, and FIB-5 scores of patients who underwent liver biopsy due to CHB were calculated by means of calculators and recorded to be compared with liver biopsies in terms of fibrosis scoring. One hundred twenty-three patients who underwent liver biopsy due to chronic hepatitis B were included in the study. APRI (area under the receiver-operating characteristic [ROC] curve 0.728), FIB-4 (area under the ROC curve 0.693) and FIB-5 (area under the ROC curve 0.643) scores were evaluated as significant predictors of advanced fibrosis. The scoring system with the highest positive and negative predictive value was evaluated as FIB-4. APRI, FIB-4, and FIB-5 scoring systems are appropriate scoring systems in the assessment of advanced fibrosis in patients with CHB. Our study is the first to compare APRI, FIB-4, and FIB-5 values in CHB patients, and more comprehensive studies are needed.