Fibrosis In Chronic Hepatitis Research Articles

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 tests maintain high accuracy for advanced fibrosis in chronic hepatitis B patients with different nomenclatures of steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a new nomenclature proposed in 2023. We aimed to compare the diagnostic efficacy of noninvasive tests (NITs) for advanced fibrosis under different nomenclatures in patients with chronic hepatitis B (CHB). A total of 844 patients diagnosed with CHB and concurrent steatotic liver disease (SLD) by liver biopsy were retrospectively enrolled and divided into four groups. The performances of fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio index (GPRI), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared among the four groups. The four NITs showed similar diagnostic efficacy for nonalcoholic fatty liver disease (NAFLD), MASLD, and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with CHB with advanced fibrosis. LSM showed the most stable accuracy for NAFLD (AUC = 0.842), MASLD (AUC = 0.846), and MAFLD (AUC = 0.863) compared with other NITs (p < 0.05). Among the four NITs, APRI (AUC = 0.841) and GPRI (AUC = 0.844) performed best in patients with CHB & MetALD (p < 0.05). The cutoff value for GPRI in patients with CHB & MetALD was higher than that in the other three groups, while further comparisons of NITs at different fibrosis stages showed that the median GPRI of CHB & MetALD (1.113) at F3-4 was higher than that in the CHB & MASLD group (0.508) (p < 0.05). Current NITs perform adequately in patients with CHB and SLD; however, alterations in cutoff values for CHB & MetALD need to be noted.

CCL20 and CD8A as potential diagnostic biomarkers for HBV-induced liver fibrosis in chronic hepatitis B

BackgroundThe main cause of the liver fibrosis (LF) remains hepatitis B virus (HBV) infection, especially in China. Histologically, liver fibrosis still occurs progressively in chronic hepatitis B (CHB) patients, even if HBV-DNA is negative or undetectable. The diagnosis of LF is beneficial to control the development of it, also it may promote the reversal of LF. Although liver biopsy is the gold standard of diagnosis in LF at present, it isa traumatic diagnosis. There are no diagnostic biomarkers as yet for the condition. It is badly in need of biomarkers clinically, which is simple to test, minimally invasive, highly specific, and sensitive. Early detection of HBV-LF development is crucial in the prevention, treatment, and prognosis prediction of HBV-LF. Cytokines are closely associated with both immune regulation and inflammation in the progression of hepatitis B virus associated-liver fibrosis (HBV-LF). In this bioinformatic study, we not only analyzed the relationship between HBV-LF and immune infiltration, but also identified key genes to uncover new therapeutic targets. ObjectivesTo find potential biomarkers for liver fibrosis in the development of chronic hepatic B patients. Materials and methodsWe obtained two sets of data including CHB/healthy control and CHB/HBV-LF from the Integrated Gene Expression (GEO) database to select for differential expression analysis. Protein-protein interaction (PPI) network was also generated, while key genes and important gene modules involved in the occurrence and development of HBV-LF were identified. These key genes were analyzed by functional enrichment analysis, module analysis, and survival analysis. Furthermore, the relationship between these two diseases and immune infiltration was explored. ResultsAmong the identified genes, 150 were individually associated with CHB and healthy control in the differential gene expression (DGE) analysis. While 14 with CHB and HBV-LF. It was also analyzed in the Robust rank aggregation (RRA) analysis, 34 differential genes were further identified by Cytohubba. Among 34 differential genes, two core genes were determined: CCL20 and CD8A. CCL20 was able to predict CHB positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.883, 95% confidence interval [CI] 0.786–0.963), while HBV-LF positivity ([AUC-ROC] = 0.687, 95% confidence interval [CI] 0.592–0.779). And CD8A was able to predict CHB positivity ([AUC-ROC] = 0.960, 95% confidence interval [CI] 0.915–0.992), while HBV-LF positivity ([AUC-ROC] = 0.773, 95% confidence interval [CI] 0.680–0.856). Relationship between CCL20 gene expression and LF grades was P < 0.05, as well as CD8A. ConclusionCCL20 and CD8A were found to be potential biomarkers and therapeutic targets for HBV-LF. It is instructive for research on the progression of LF in HBV patients, suppression of chronic inflammation, and development of molecularly targeted-therapy for HBV-LF.

Validation of FIB-6 score in assessment of liver fibrosis in chronic hepatitis B.

We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability.

The Potential Role of Autophagy in Progression of Liver Fibrosis in Chronic Hepatitis B Patients Receiving Antiviral Treatment: A Brief Report.

Despite antiviral treatment, some patients with chronic hepatitis B (CHB) progress to cirrhosis. Enhancement of autophagy was implicated in the proliferation of hepatitis B in hepatocytes. This study aimed to evaluate the potential role of autophagy in the progression of liver fibrosis in patients receiving antiviral treatments and having completely inhibited viral replication. This descriptive-analytical study was designed and conducted in 2020 at Mottahhari Hepatitis Clinic affiliated with Shiraz University of Medical Science (Shiraz, Iran). Patients who were on anti-hepatitis B nucleotide treatments for at least two years, and those who were not cirrhotic at baseline but later progressed to cirrhosis were identified to be included in the case group. Besides, for the control group, patients on the nucleotide regimens who did not have cirrhosis at baseline or during follow-up were randomly selected. Ultimately, 16 cases and 14 controls were included in the study. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Serum Beclin-1 and LC3 levels were compared between the two groups using enzyme-linked immunosorbent assays. The t test was used to assess the statistical differences between the case and control groups. Beclin-1 level was significantly higher in cirrhosis patients than the control group (1283±244 vs. 1063±257, P=0.024). However, there was no statistical difference between the level of LC3 in the cirrhotic group (168±31) and the control group (150±16) (P=0.065). Autophagy may have a role in the progression of cirrhosis in patients with CHB. Future larger prospective studies are required to determine the effect of blocking on the progression of liver disease in this population A preprint of this study was published at https://www.researchsquare.com/article/rs-1435490/v1.pdf.

Increased Levels of TNF-α, IL-6, and IL-10 are Associated with The Degree of Liver Fibrosis in Chronic Hepatitis B Patients with NUC Therapy

BACKGROUND: Liver fibrosis in chronic hepatitis B (CHB) involves the host immune responses mainly T-lymphocyte regulatory cells and cytokines production. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 have been reported to play a crucial role in the development of liver fibrosis. However, their association with liver fibrosis in treated CHB patients remains unclear. Therefore, this study was conducted to investigate the association between TNF-α, IL-6, and IL-10 with the degree of liver fibrosis in treated CHB patients.METHODS: This was a cross-sectional prospective study including 101 treated chronic hepatitis B subjects. TNF-α, IL-6, and IL-10 serum levels were measured with quantitative sandwich enzyme-linked immunosorbent assay (ELISA) kit. Transient elastography result was classified according to METAVIR score. Data was analyzed by the Spearman correlation test with a p&lt;0.05 was considered statistically significant.RESULTS: From 101 subjects, there were significant differences were seen in TNF-α, IL-6, and IL-10 between patients with mild, significant and advance fibrosis. TNF-α (r=0.292; p&lt;0.05), IL-6 (r=0.221; p&lt;0.05), and IL-10 (r=0.208; p&lt;0.05) were significantly correlated with the degree of fibrosis. After multivariate analysis, TNF-α was the only one cytokine parameter which significantly correlated with the degree of fibrosis.CONCLUSION: Levels of TNF-α, IL-6 and IL-10 are associated with the degree of liver fibrosis. These parameters may potentially be used to evaluate the development of liver fibrosis in treated CHB patients.KEYWORDS: chronic hepatitis B, liver fibrosis, cytokines, transient elastography

A study on outcome of hepatic fibrosis in chronic hepatitis B patients on anti-viral therapy

Background: Hepatitis B infection is a global public health problem. Chronic hepatitis B (CHB) infection leads to complications such as cirrhosis, liver failure, and hepatocellular carcinoma. Effective antiviral therapy significantly improves the stages of fibrosis in these patients. Hence, the liver stiffness measurement using transient elastography (Fibroscan) in CHB patients undergoing treatment is important to evaluate the effectiveness of the therapy and to predict the prognosis. Aims and Objectives: To see the outcome of Hepatic Fibrosis by non-invasive measurement in CHB patients after 6 months of oral anti-viral therapy. Materials and Methods: Seventy new CHB patients are included in a prospective hospital-based study and at the end of 6 months 53 patients were analysed. Results: Our study showed a significant statistical reduction in Liver Fibrosis as well as improvement of serological and biochemical parameters in CHB patients. Conclusion: There is liver fibrosis reversal in CHB patients after 6 months of anti-viral therapy and Fibroscan helps not only as a marker for initiation of treatment depending on the degree of fibrosis but also indicates the response or progression of the disease.

LiveBoost: A GB-based prediction system for liver fibrosis in chronic hepatitis B patients in China - A multi-center retrospective study

BackgroundThe aim of this study was to evaluate the accuracy of LiveBoost™, a gradient boosting (GB)-based prediction system based on standard biochemical values (AST, ALT, platelet count) and age, in Chinese patients with chronic hepatitis B (CHB) and compare its performance with FIB-4 (fibrosis-4 score) and APRI (the aspartate transaminase to platelet ratio index). MethodsThis retrospective trial enrolled 454 participants, including 279 CHB patients who underwent liver biopsy and 175 normal controls from 3 centers in China. All participants underwent laboratory blood testing. LiveBoost was constructed using GB and FIB-4 and APRI were calculated from laboratory data. ResultsLiveBoost outperformed APRI and FIB-4 in predicting hepatic fibrosis and cirrhosis. The GB model had an AUROC of 0.977 for CHB diagnosis, 0.804 for early and advanced fibrosis, and 0.836 for non-cirrhosis and cirrhosis, compared to AUROC of 0.554, 0.673 and 0.720 for FIB-4, AUROC of 0.977, 0.652 and 0.654 for APRI. ConclusionsLiveBoost is a more reliable and cost-effective method than APRI and FIB-4 for assessing liver fibrosis in Chinese patients with CHB.

How Successful Are APRI and FIB-4 Scores in Predicting Liver Fibrosis in Chronic Hepatitis B Patients?

We aimed to evaluate the correlation of fibrosis severity in liver biopsies, the gold standard for the diagnosis of patients with chronic hepatitis B (CHB), using noninvasive methods such as the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4). The study included patients who were followed and treated for CHB in 2018-2023. Biochemical markers and liver biopsy findings of the cases were retrospectively, and their correlations with APRI and FIB-4, which are noninvasive scores, were compared. The study included 202 patients. The biochemical markers and liver biopsy findings of the cases were examined retrospectively, and their correlations with the noninvasive scores APRI and FIB-4 were compared. According to liver biopsy results, 109 (54.0%) cases had no fibrosis (stage 0.1), 85 (42.1%) cases had mild fibrosis (stage 2, 3), and 8 (4%) cases had severe fibrosis (stage 4, 5, 6). The median FIB-4 score was 0.79 (0.25 -11.74), and the median APRI score was 0.29 (0.10-29.40). When the predictive power of the APRI score to discriminate between "without fibrosis" and "with fibrosis (mild and severe)" was evaluated by receiver operating characteristic (ROC) curve analysis, for the APRI score >0.408 as the ideal cut-off point, the sensitivity and specificity were found to be 34% and 79%, respectively. When the cut-off point for the FIB-4 score was >0.701, the sensitivity and specificity were 71% and 46%, respectively. Although the area under the curve (AUC) ratios ranged between 52% and 64% in the ROC analyses, the sensitivity ratios of the cut-off points calculated for FIB-4 were higher. The likelihood ratios of the cut-off point we found for the APRI score (1.61 and 1.75, respectively) were relatively better than those for FIB-4 (1.31 and 1.41, respectively). Noninvasive tests used to detect liver fibrosis in individuals with CHB do not eliminate the need for liver biopsy but may provide insight into the fibrosis status of patients.

Expert consensus on MRI diagnosis of liver fibrosis in chronic hepatitis B (version 2023)

Chronic hepatitis B is a common chronic inflammatory disease of the liver in China that frequently results in sustained damage to the liver parenchyma, followed by liver fibrosis, and ultimately progresses to unfavorable outcomes such as cirrhosis, liver failure, and liver cancer. Liver fibrosis reversal can be achieved through early and effective intervention. Therefore, timely and accurate assessment of the degree of liver fibrosis is of great clinical significance for the treatment and prognosis assessment of patients with chronic hepatitis B. MRI plays a crucial role in the early assessment and monitoring of the therapeutic efficacy of liver fibrosis in chronic hepatitis B. Currently, there is a lack of uniform consensus on MRI scanning protocols and related diagnostic thresholds for liver fibrosis in chronic hepatitis B, which is not conducive to practical clinical evaluation and application. This expert consensus is based on a full review of relevant domestic and international literature and the formulation of methodologies based on evidence-based medical guidelines and standards to develop recommendations for MRI scanning techniques and the diagnosis of liver fibrosis in chronic hepatitis B, with a view to providing a clear basis for the clinical diagnosis.

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.

Serum infrared spectral profile is predictive of the degree of hepatic fibrosis in chronic hepatitis C patients

Assessment of liver fibrosis is crucial to guide the therapeutic strategy in patients with chronic liver disease. We investigated the potential of serum Fourier transform infrared (FTIR) spectroscopy for assessing the degree of hepatic fibrosis in patients with chronic hepatitis C (CHC). The study was conducted on dried serum samples from 94 CHC patients at different histological stages of hepatic fibrosis: METAVIR F0 (n = 20), F1 (n = 17), F2 (n = 20), F3 (n = 20) and F4 (n = 17). Transmission FTIR spectra were acquired in the 4000–400 cm−1 range. Wavenumbers were selected by genetic algorithm (GA) according to their diagnostic performance as assessed by a partial least squares discriminant analysis (PLS-DA) model using a training and a validation set to differentiate severe stages of fibrosis from mild or moderate ones. The GA procedure was applied 50 times on randomly selected sets. Furthermore, the best set of wavenumbers was re-tested in 1000 randomly selected validation sets. Wavenumbers selected by GA corresponded to functional groups present in lipids, proteins, and carbohydrates. This model allowed to identify patients with cirrhosis (METAVIR F4), patients with advanced fibrosis (METAVIR F3 and F4), and patients with significant fibrosis (METAVIR F2, F3 and F4), with AUROC (Area Under the Receiver Operating Characteristic) of 0.88, 0.85 and 0.85, respectively. Thus, serum FTIR spectroscopy appears to have a strong potential as a new diagnostic tool for assessing the degree of fibrosis in patients with chronic liver disease.

NAFLD is associated with less severe liver fibrosis in chronic hepatitis B: A multi-center, retrospective study

Introduction and ObjectivesChronic hepatitis B (CHB) may progress to more serious liver diseases and it is often accompanied by non-alcoholic fatty liver disease (NAFLD). NAFLD and CHB share risk factors for liver fibrosis and cirrhosis, but the influence of NAFLD on fibrosis progression is controversial. This retrospective study evaluated the prevalence of NAFLD in patients with CHB and investigated associations between NAFLD and liver fibrosis in a large multi-center cohort of hepatitis B patients submitted to liver biopsy. Patients and MethodsTreatment-naïve patients with CHB who underwent liver biopsy were analyzed. Propensity score matching (PSM) was performed to adjust the confounders between patients with and without NAFLD. ResultsA total of 1496 CHB patients were included. Two hundred and ninety (19.4%) patients were diagnosed with NAFLD by liver biopsy. The proportions of significant liver fibrosis (52.8% vs. 63.9%, P<0.001), advanced liver fibrosis (27.2% vs. 36.5%, P=0.003), and cirrhosis (13.4% vs. 19.7%, P=0.013) was considerably lower in CHB patients with NAFLD compared to those without NAFLD. 273 patients were included in each group after PSM adjusted for age, sex, hepatitis B envelope antigen status, and hepatitis B virus DNA. Liver fibrosis remained less severe in CHB patients with NAFLD than those without NAFLD (P<0.05) after PSM. The presence of NAFLD was considered an independent negative factor of significant liver fibrosis (odds ratio (OR) 0.692, P=0.013) and advanced liver fibrosis (OR 0.533, P = 0.002) in CHB patients. ConclusionsNAFLD is not uncommon in CHB patients with the prevalence of 19.4%. The presence of NAFLD is associated with less severe liver fibrosis in CHB patients. Registration No. of the study/trialNCT03097952.

Accuracy of transient elastography in Identifying fibrosis among patients with Chronic hepatitis b: a cross-sectional Observational study

Background: Hepatitis B virus (HBV) infection is a significant global public health problem, affecting millions of people worldwide. Liver biopsy is the gold standard for assessing fibrosis but is invasive and carries post-procedural risks. Noninvasive tests to evaluate liver fibrosis are needed, and transient elastography is one such method. This cross-sectional observational study aimed to assess the accuracy of transient elastography in identifying fibrosis among patients with chronic hepatitis B.&#x0D; Methods: The study was conducted at the Department of Medicine and Hepatology, Sir Salimullah Medical College Mitford Hospital, Dhaka. The study subjects were patients diagnosed with chronic hepatitis B infection, both outpatient and inpatient cases. Data were collected from 25 patients using convenient and purposive sampling techniques. Demographic data, clinical examination, and relevant investigations were recorded in a structured case report form. Data were processed, registered, edited, computerized, and analyzed.&#x0D; Results: The study included 25 patients with a mean age of 26.8±6.5 years, predominantly male (80%). All patients were HBsAg positive, 12.0% were HBeAg positive, and 56.0% were antiHBe positive. The mean HBV DNA PCR was 1516293.4±7475976.3 IU/ml. The mean ALT level was 45.4±13.8 U/L. The mean liver stiffness measurement (LSM) was 7.5±2.3 kPa, with 64.0% of patients showing fibrosis stage F0-F1. The mean periportal +/- bridging necrosis was 2.92±1.58, intralobular degeneration and focal were 1.16±0.55, portal inflammation was 2.52±0.87, histological activity index was 6.6±2.2, and fibrosis score was 1.44±1.04. Positive correlations were observed between LSM and histological activity index (r=0.239; p=0.251) and between LSM and fibrosis score (r=0.107; p=0.612).&#x0D; Conclusion: Our study demonstrates that transient elastography provides a non-invasive, easy, and cost-effective method for identifying fibrosis in chronic hepatitis B patients, serving as a potential alternative to liver biopsy.&#x0D; Bangladesh J Medicine 2023; 34(3): 199-205

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.

Can We Accurately Assess Fibrosis in Chronic Hepatitis B Virus Patients?

Can We Accurately Assess Fibrosis in Chronic Hepatitis B Virus Patients?

Development of an in vitro Model to Study Hepatitis C virus-induced Fibrosis

Aim: To investigate the mechanism of liver fibrosis in chronic hepatitis C virus (HCV) infection we developed an in vitro model. Methods: Huh7 cells were transfected with HCV (JFH1 or Jc1) or sub-genomic replicons and expression of pro-fibrotic cytokines determined by qPCR. Media from infected cells was transferred onto LX2 cells or primary rat stellate cells and expression of pro-fibrotic genes measured by qPCR. Results: Replication competent HCV, but not sub-genomic replicons, induced expression of TGF-β1 and CTGF. Supernatant from infected cells induced α-SMA and COL1A1 expression and stellate cell migration, confirming functional activation. Conclusion: Infected cells produce pro-fibrogenic cytokines TGF-β1 and CTGF and activate stellate cells. This mechanism could be targeted to prevent or treat HCV-induced 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.

Immune response and treatment targets of chronic hepatitis B virus infection: innate and adaptive immunity.

Chronic hepatitis B virus (HBV) infection is a major global public health risk that threatens human life and health, although the number of vaccinated people has increased. The clinical outcome of HBV infection depends on the complex interplay between viral replication and the host immune response. Innate immunity plays an important role in the early stages of the disease but retains no long-term immune memory. However, HBV evades detection by the host innate immune system through stealth. Therefore, adaptive immunity involving T and B cells is crucial for controlling and clearing HBV infections that lead to liver inflammation and damage. The persistence of HBV leads to immune tolerance owing to immune cell dysfunction, T cell exhaustion, and an increase in suppressor cells and cytokines. Although significant progress has been made in HBV treatment in recent years, the balance between immune tolerance, immune activation, inflammation, and fibrosis in chronic hepatitis B remains unknown, making a functional cure difficult to achieve. Therefore, this review focuses on the important cells involved in the innate and adaptive immunity of chronic hepatitis B that target the host immune system and identifies treatment strategies.

WED-162 - Lower HBV DNA levels is associated more severe liver fibrosis in chronic hepatitis B with serological immune-tolerant phase

WED-162 - Lower HBV DNA levels is associated more severe liver fibrosis in chronic hepatitis B with serological immune-tolerant phase