Hepatitis B Research Articles

Prospect of emerging treatments for HBV functional cure.

Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is a favorable treatment endpoint in chronic hepatitis B (CHB). Nonetheless, functional cure is rarely attained with the current treatment modalities of nucleos(t)ide analogues (NUCs) and pegylated interferon alpha (Peg-IFNα). Multiple novel virus-targeting agents and immunomodulators are under development for HBV with functional cure as the treatment goal. Among virus-targeting agents, antisense oligonucleotides (ASOs) and small-interfering RNA (siRNAs) are the most advanced in the developmental pipeline, and can induce potent and sustainable HBsAg suppression. The other virus-targeting agents have varying effects on HBsAg and HBV DNA, depending on the drug mechanism. In contrast, immunomodulators have modest effects on HBsAg and have limited roles in monotherapy. Multiple combination regimens incorporating RNA interference agents with immunomodulators have been studied through many ongoing clinical trials. These combination strategies demonstrate synergistic effects in inducing functional cure, and will likely be the future direction of development. Despite the promising results, research is warranted to optimize treatment protocols and to establish criteria for NUC withdrawal after novel therapies. Functional cure is now an attainable target in CHB, and the emerging novel therapeutics will revolutionize CHB management.

HBeAg-positive CHB patients with indeterminate phase associated with a high risk of significant fibrosis.

The risk of liver fibrosis in HBeAg-positive chronic hepatitis B (CHB) patients with indeterminate phase is not well characterized. We aimed to compare the presence of liver fibrosis in HBeAg-positive CHB patients between indeterminate phase and immune-tolerant phase. This multi-center, retrospective cohort study included 719 treatment-naïve HBeAg-positive CHB patients with normal alanine aminotransferase (ALT). Patients with HBV DNA > 106 IU/mL were categorized into immune-tolerant phase, whereas those with HBV DNA ≤ 106 IU/mL were classified into indeterminate phase. Significant liver fibrosis and cirrhosis were determined by APRI, FIB-4, transient elastography, or liver biopsy. The median age of patients was 33.0 years and 59.8% of patients were male. 81.5% and 18.5% of patients were in the immune-tolerant phase and indeterminate phase, respectively. The APRI (0.33 vs. 0.27, P < 0.001), FIB-4 (1.07 vs. 0.72, P < 0.001), and liver stiffness values (7.80kPa vs. 5.65kPa, P = 0.011) were higher in patients with indeterminate phase than those with immune-tolerant phase. Patients in the indeterminate phase had significantly higher proportions of significant fibrosis (27.1% vs. 11.3%, P < 0.001) and cirrhosis (14.3% vs. 3.2%, P < 0.001) compared to those in the immune-tolerant phase. In the multivariate analysis, indeterminate phase (OR 2.138, 95% CI 1.253, 3.649, P = 0.005) was associated with a higher risk of significant fibrosis, especially for patients aged ≥ 30 years. HBeAg-positive CHB patients in the indeterminate phase had more severe liver fibrosis compared to those in the immune-tolerant phase.

Effect of dyslipidemia on HBsAg clearance in nucleos(t)ide analogues-experienced chronic hepatitis B patients treated with peginterferon alfa.

While previous reports have shown that hepatitis B virus (HBV) infection affects lipid metabolism and vice versa, the impact of dyslipidemia on the functional cure of HBV infection following peginterferon alfa (PegIFNα) therapy remains unknown. Hence, this study aimed to investigate the effect of dyslipidemia on hepatitis B surface antigen (HBsAg) clearance and develop a nomogram model for predicting patients for whom PegIFNα therapy is indicated. A total of 160 nucleos(t)ide analogues (NAs)- experienced chronic hepatitis B (CHB) patients treated with PegIFNα (180µg/week) were enrolled in this study. The relationship between serum lipid and HBsAg clearance was analysed. Univariate and multivariate COX analyses were used to construct and plot the nomogram model. The area under the receiver operating characteristic curve (AUC) and calibration curve were used to evaluate the discrimination and calibration of the model, respectively. After 48 weeks of PegIFNα therapy, a total of 33 patients in the cohort achieved HBsAg clearance. Univariate and multivariate COX analyses indicated that dyslipidemia was significantly associated with HBsAg clearance and was an independent predictor of HBsAg clearance (HR = 0.243, P = 0.001). Kaplan-Meier survival analyses show that cumulative HBsAg clearance was significantly higher in the normolipidemic group than in the dyslipidemia group (log-rank test, P = 0.007). During the treatment, triglyceride showed an increasing trend, while the levels of total cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein A1 and apolipoprotein B decreased. Dyslipidemia and other indicators independently associated with HBsAg clearance were used to construct the nomogram model. The AUC of the model at 36-week and 48-week were 0.879 and 0.856, and the model demonstrated good discrimination and calibration. Dyslipidemia can affect the antiviral efficacy of PegIFNα in NAs-experienced CHB patients. Our findings suggest that the nomogram model constructed using serum lipid has good predictive power and may help physicians to identify the superior patients for PegIFNα therapy.

Evaluation of genotype characteristics and drug resistance mutations in patients with chronic hepatitis B.

Hepatitis B is one of the public health priorities worldwide, especially in the Southwest China. Our study aimed to investigate the relationship between genotypes and drug resistance mutations among HBV patients in Southwest China, with the objective of providing guidance for clinical antiviral treatment. A total of 4266 chronic hepatitis B (CHB) patients treated in the Qianjiang Hospital of Chongqing University were included in our study from 2014 to 2020. Both genotypes and drug-resistant mutations of CHB patients were determined by polymerase chain reaction (PCR). Genotype B and genotype C were the main HBV genotypes in our study. We found 54 mutation patterns, including 9 single-site mutations and 45 multiple-site mutations, accounting for 57.64% and 42.36%, respectively. rtM204I/V/S (485/1936) was the most common single-site mutation type, and rtL180M + rtM204I/V (482/1936) was the most common multiple-site mutation type. 1372 CHB patients were resistant to LAM + LDT, and 342 CHB patients were resistant to ADV. There was only 1 CHB patient who exhibited resistance to LAM + LDT + ADV + ETV, with a specific mutation pattern of rtA181T + rtT184L + rtM204V. Our study demonstrated trends in genetic mutations and drug resistance in CHB patients to enable timely adjustment of antiviral treatment strategies.

Favourable Prognosis of Patients With Untreated HBeAg-Negative Chronic Hepatitis B Virus Infection With HBsAg < 100 IU/mL.

Serum hepatitis B surface antigen (HBsAg) < 100 IU/mL has been recently proposed as one of the key criteria of 'partial cure' in patients with chronic hepatitis B virus (HBV) infection. We analysed the clinical prognosis of hepatitis B e antigen (HBeAg)-negative untreated patients with HBsAg < 100 IU/mL and normal alanine aminotransferase (ALT) levels. Five hundred and twenty-one untreated patients with HBeAg negativity, HBsAg < 100 IU/mL and normal ALT levels were included from three hospitals. Spontaneous HBsAg seroclearance, phase transition, liver fibrosis progression and hepatocellular carcinoma (HCC) development were analysed. The median age was 43.0 years, and 62.2% of the patients were male. After a median follow-up of 25.0 months, 52 (10.0%) patients achieved spontaneous HBsAg seroclearance. The annual HBsAg seroclearance rate is 4.2%. Patients with baseline HBsAg ≤ 10 IU/mL (adjusted hazard ratio [aHR] = 3.490, p < 0.001) and male sex (aHR = 1.980, p = 0.041) were more likely to achieve HBsAg seroclearance. Only 4 (0.8%) and 23 (4.8%) patients transitioned to the immune escape phase and HBeAg-negative indeterminate phase, respectively. Baseline serum HBsAg > 10 IU/mL (aHR = 3.846, p = 0.034) and detectable HBV DNA (aHR = 2.672, p = 0.023) were associated with transition to the HBeAg-negative indeterminate phase. No patient developed HCC or had fatal outcomes. HBeAg-negative patients with serum HBsAg < 100 IU/mL and normal ALT levels had a favourable prognosis. HBsAg ≤ 10 IU/mL and male sex were associated with a higher rate of HBsAg seroclearance, while HBsAg > 10 IU/mL and detectable HBV DNA were associated with a higher risk of transition to the indeterminate phase.

Comparison of lipid profile alterations in chronic hepatitis b patients receiving tenofovir alafenamide or tenofovir disoproxil fumarate

This study aimed to compare the serum lipid profiles between tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in the long-term treatment of chronic hepatitis B (CHB). We analyzed data from treatment-naïve CHB patients administered with TDF or TAF, collected from electronic medical records between May 2017 and September 2022. Serum lipid indices, including total cholesterol (TC), triglycerides (TG), low-density (LDL) and high-density lipoprotein (HDL), and their ratios (TC/HDL, LDL/HDL), were assessed at baseline, and at 48 and 96 weeks. Propensity score matching (PSM) adjusted for baseline differences between groups. From 2344 patients initially screened, 418 were included for the 48-week analysis (265 on TDF, 153 on TAF) and 292 for the 96-week analysis (238 on TDF, 54 on TAF). At 48 weeks, comparing the serum lipid indicators between the pre- and post-treatment, TDF significantly reduced TC and TC/HDL, whereas TAF induced widespread dyslipidemia, characterized by elevated levels of TC, TG, LDL, LDL/HDL, and TC/HDL, and reduced HDL (P < 0.05). After PSM grouping, TAF remained significantly associated with higher TC, TG, LDL, LDL/HDL, and TC/HDL compared to TDF (P < 0.05). Over 48 weeks, TAF treatment was associated with significant increases in TC, TG, and LDL, whereas TDF treatment led to decreases (P < 0.05). TC/HDL and LDL/HDL increased in both groups, but more significant in TAF (P < 0.05). At 96 weeks, the TAF group continued to exhibit significantly higher levels of TC, LDL, and LDL/HDL compared to the TDF group (P < 0.05). Notably, LDL levels were 115.65 ± 28.07 mg/dL in TAF versus 96.07 ± 23.97 mg/dL in TDF. The increase in TC/HDL ratio in the TAF group was higher than in the TDF group, though not statistically significant. Furthermore, TAF treatment was associated with significant increases in LDL (18.58 ± 24.35 mg/dL) and LDL/HDL ratio (0.41 ± 0.95) over 96 weeks, while TDF treatment showed reductions in TC (-8.13 ± 30.86 mg/dL). Between 48 and 96 weeks, most lipid changes in the TDF group were not statistically significant, except for increases in LDL and LDL/HDL. In the TAF group, an increasing trend of LDL and TC/HDL was noted, although LDL showed a slight turnover after 48 weeks. This real-world study provides new evidence that TAF can induce dyslipidemia, while TDF exhibits a lipid-lowering effect in CHB. Patients at high risk for hepatic steatosis and cardiovascular diseases should consider these effects when choosing between TAF and TDF.

Exploring the active ingredients and mechanisms of Liujunzi decoction in treating hepatitis B: a study based on network pharmacology, molecular docking, and molecular dynamics simulations

Liujunzi decoction (LJZD) is commonly used to treat hepatitis B virus (HBV), though its active ingredients and mechanisms are not fully known. This study identified core targets and active components of LJZD for treating hepatitis B (HB) through network pharmacology, molecular docking, and molecular dynamics simulation. Screening from databases yielded 533 active components, 2619 targets for LJZD, and 2910 for HB, with 891 intersecting targets. STRING and CytoHubba analyses identified AR and VDR as core targets, with key pathways including PI3K-Akt and MAPK. The findings clarify LJZD’s multicomponent, multitarget mechanisms, supporting its clinical application for HB treatment.

Detection of equine parvovirus-hepatitis and efficacy of governmental regulation for equine biologics purity.

In 2018, a new virus, named equine parvovirus-hepatitis (EqPV-H), was discovered in a biologic product that had been administered to horses that subsequently developed clinical signs of equine serum hepatitis (Theiler disease). Further correlation of the virus with the disease sparked federal requirements that all equine biologics be free of EqPV-H. The initial quantitative real-time PCR (qPCR) test for EqPV-H has proved to be sensitive to co-extracted PCR inhibitors in template nucleic acids, causing false-negative results. We investigated the use of digital PCR (dPCR) as a more robust test. Examination of 227 equine biologic product lots available for purchase both before and after regulatory implementation using both detection methods indicated that dPCR is a more reliable platform. Nevertheless, use of the qPCR method for product screening had reduced the fraction of serials with EqPV-H detected from 39.6% prior to regulation to 6.8% after regulatory implementation. Adoption of dPCR testing is an opportunity to further decrease the prevalence of EqPV-H in equine biologics.

Host and Viral Factors Influencing Chronic Hepatitis B Infection Across Three Generations in a Family.

Chronic hepatitis B (CHB) infection is influenced by both virological and host factors. A total of 5,920 CHB patients were classified into four groups based on HBV seromarkers: three-generation families (CHB grandmother, mother, and child), two-generation families (CHB mother/child pairs), individuals recovered from HBV infection, and a control group. Serological markers, viral load, liver function tests (LFT), HBV mutations, HLA-DQ variations, cytokine polymorphisms, and liver stiffness measurements (LSM) were analyzed using FibroScan. Point mutations in genes such as core/pre-core (G1896A/G1899A), polymerase (H248N, H267Q, N263D), S (G145R, S143L), and X (C1500T, T1464C) were observed in 30% of three-generation pairs and 20% of two-generation pairs. The three-generation group exhibited the highest mean liver stiffness measurement (LSM) (4.94 ± 1.24kPa), which is considered a predictor for the development of hepatocellular carcinoma (HCC). Subsequent HLA allele analysis identified HLA-DQB105:01 (OR = 0.27) as a risk factor for treatment resistance, while HLA-DQB105 (OR = 0.98), HLA-DQB103 (OR = 0.80), and HLA-DQB104:01 (OR = 0.70) were associated with HBV persistence in both three- and two-generation groups. Higher frequencies of specific polymorphisms, including G/G (TNF-α: 75%; IL-18: 74%), A/A (IL-10: 74.28%), and C/C (IL-1ß: 80%), were significantly linked to persistent infection. Analysis of viral sequences, HLA-DQB1 variations, cytokine polymorphisms, and genetic relationships within the phylogenetic tree revealed that 40% of CHB patients from three-generation families were infected by a shared source of transmission, as indicated by the presence of the same HBV genotype. This study underscores the complex interplay of host and viral factors that influence hepatitis B infection outcomes and suggests potential familial transmission pathways.

Mex3a promoter hypomethylation can be utilized to diagnose HBV-associated hepatocellular carcinoma: a randomized controlled trial

BackgroundHepatocellular carcinoma remains a health challenge for humanity. Therefore, there is an urgent need to develop novel biomarkers with high efficiency yet fast ability to meet the requirements of hepatocellular carcinoma treatment.MethodsA total of 229 patients with HBV-associated hepatocellular carcinoma (HCC), 298 patients with chronic hepatitis B (CHB), and 96 healthy controls were retrospectively analyzed. Methylation levels of the Mex3a promoter in peripheral blood mononuclear cells (PBMCs) were measured using MethyLight to obtain clinical and laboratory parameters.ResultsThe Mex3a promoter methylation level in HCC patients (median: 0.289% and interquartile range: 0.126%–0.590%) was significantly lower than that in CHB patients (median: 0.999%, interquartile range: 0.417%–1.268%, and p &amp;lt; 0.001) and healthy people (median: 2.172%, interquartile range: 1.225%–3.098%, and p &amp;lt; 0.001). The Mex3a mRNA levels in HCC patients (median: 12.198 and interquartile range: 3.112–18.996) were significantly higher than those in CHB patients (median: 1.623 and interquartile range: 0.066–6.000, and p &amp;lt; 0.001) and healthy controls (median: 0.329, interquartile range: 0.031–1.547, and p &amp;lt; 0.001). MethyLight data were expressed as a percentage of the methylated reference (PMR) value. The Mex3a PMR value was negatively correlated with the mRNA expression level (Spearman’s R = −0.829 and p &amp;lt; 0.001). The Mex3a PMR value of HCC patients was significantly correlated with age (Spearman’s R = 0.113 and p = 0.044), and the mRNA level was significantly correlated with ALT (Spearman’s R = 0.132 and p = 0.046). The Mex3a promoter methylation levels and mRNA levels were also independent factors in the development of liver cancer. The Mex3a promoter methylation and mRNA levels were better at distinguishing HCC from CHB than AFP [area under the receiver operating characteristic curve (AUC) for predicting HCC vs. CHB: 0.915 vs. 0.715: p &amp;lt; 0.001]. The combined use of AFP and Mex3a methylation levels and mRNA levels further improved the area under the receiver operating characteristic curve.ConclusionThe presence of Mex3a promoter hypomethylation in hepatocellular carcinoma can be used as a non-invasive biomarker for the early detection of liver cancer.

HBV Transmission Knowledge Among Korean-American Chronic Hepatitis B Patients in the United States.

Chronic hepatitis B (CHB) is a condition that disproportionately affects Asian Americans in the United States. Knowledge of transmission is crucial for CHB patients to practice prevention methods to limit the spread of the hepatitis B virus (HBV), but also live their lives free from unwarranted fears or restrictions. Among Asian CHB patients, several misperceptions about HBV transmission have been identified. This analysis aims to assess the current state of HBV knowledge among a cohort of Korean-American CHB patients. This mixed-methods study includes 363 respondents who completed a survey in either Korean (N = 298) or English (N = 65) at two clinical care settings in Philadelphia (N = 161) and Los Angeles (N = 202); 30 participants also completed in-depth interviews. Knowledge was measured on a 10-point scale, asking patients yes or no transmission questions (n = 10, alpha = 0.87). The average knowledge score was 6.3. In multivariate analyses, older age was associated with lower knowledge (β=-0.25, p < 0.001). More years of formal education (β = 0.09, p = 0.076) and utilizing more sources for health information (β = 0.12, p = 0.023) were both independently associated with higher knowledge scores. Qualitative findings show that misperceptions about transmission through shared food still exist and that provider communication is an important part of knowledge acquisition. These results suggest that despite receiving specialized, culturally concordant medical care for their disease, some Korean-American CHB patients have an inadequate understanding of transmission and that opportunities exist to improve education in this population. Identifying additional factors that influence knowledge acquisition and retention is key to developing culturally effective education interventions for this population.

Screening of cancer-specific biomarkers for hepatitis B-related hepatocellular carcinoma based on a proteome microarray

Hepatocellular carcinoma (HCC) is associated with one of the highest mortality rates among cancers, rendering its early diagnosis clinically invaluable. Serum biomarkers, specifically alpha-fetoprotein (AFP), represent the most promising and widely used diagnostic biomarkers for HCC. However, its detection rate is low in the early stages of HCC progression, and distinguishing specific false positives for other liver-related diseases, such as cirrhosis and acute hepatitis, remains challenging. Therefore, this study was conducted to identify biomarkers for hepatitis B (HBV)-related liver diseases by screening differentially expressed autoantibodies against tumor-associated antigens (TAAbs). We designed a large-scale multistage investigation, encompassing initial screening, HCC-focused, and ELISA validation cohorts to identify potential TAAbs in HBV-related liver diseases, spanning from healthy control (HC) individuals to patients with chronic hepatitis B (CHB), hepatitis B-related cirrhosis (HBC), and HCC, using protein microarray technology. The differential biological characteristics of TAAbs were analyzed using bioinformatics analysis. Validation of tumor-specific biomarkers for HCC was performed using ELISA. In the screening cohort, 547 candidate TAAbs were identified in the HCC group compared to those in the HC group. In the HCC-focused cohort, 64, 61, and 65 candidate TAAbs were identified in the CHB, HBC, and HCC groups, respectively, compared to those in the HC group. Thirty-four proteins exhibited continuously elevated expression from HCs to patients with CHB, HBC, and HCC. Among these, nine were identified as cancer-specific proteins. In the validation cohort, UBE2Z, CNOT3, and EID3 were correlated with liver function indicators in patients with hepatitis B-related HCC. Overall, UBE2Z, CNOT3, and EID3 emerged as cancer-specific biomarkers for HBV-related liver disease, providing a scientific basis for clinical application.

HBV Antigen-Guided Switching Strategy From Nucleos(t)ide Analogue to Interferon: Avoid Virologic Breakthrough and Improve Functional Cure.

Little is known for factors associated with virologic breakthrough (VBT) after switching from nucleos(t)ide analogue (NA) to pegylated interferon alpha (Peg-IFN-α) for patients with chronic hepatitis B (CHB). Eighty patients who received 48-week Peg-IFN-ɑ and NA combination therapy followed by Peg-IFN-ɑ monotherapy for additional 48 weeks were included in this study. HBV-related markers including HBV DNA, HBsAg, HBcrAg, HBeAg, cccDNA, and immunological biomarkers were dynamically evaluated. Twelve (15.0%) patients experienced VBT after switching to Peg-IFN-ɑ and exhibited significantly lower rates of HBsAg loss after therapy completion (0% vs. 35.3%, p = 0.014). The patients with HBcrAg≥ 5 log10U/mL and HBsAg≥ 100 IU/mL had the highest risk of VBT and failed to achieve subsequent HBsAg clearance. Intrahepatic cccDNA level was significantly higher in patients with HBcrAg≥ 5 log10U/mL than those with HBcrAg< 5 log10U/mL. Notably, in contrast to patients with HBcrAg< 5 log10U/mL or with HBsAg< 100 IU/mL who had obviously restored HBV-specific CD8+T cell, Tfh or B cell responses before NA cessation, those with HBcrAg≥ 5 log10U/mL or with HBsAg≥ 100 IU/mL exhibited lackluster immunities before NA cessation and notable diminished immune responses thereafter. Monitoring HBcrAg and HBsAg levels, which correlated with poor immune responses during sequential Peg-IFN-ɑ strategy, may help to avoid VBT and improve functional cure of CHB.

Association Between IFN-λ4 rs12979860 And rs11322783 Polymorphisms with Spontaneous Clearance In Chronic Hepatitis B

Many studies have been published on the association between IFN-λ3 and IFN-λ4 polymorphisms and treatment related or spontaneous clearance of chronic hepatitis C. To date there is little known about the impact of IFN-λ4 polymorphisms on the natural history of chronic hepatitis B(CHB). This study aimed to investigate the role of IFN-λ4 polymorphisms on the course of CHB and to influence the presence of spontaneous clearance (SC) in CHB patients. One hundred and twenty-two patients who had CHB, and 81 subjects who had spontaneous resolution of HBV were analyzed regarding IFN-λ4 rs12979860 and rs11322783 single‑nucleotide polymorphisms. We couldn’t found any significant difference between CHB groups and SC groups in terms of IFN-λ4 rs12979860 polymorphisms and, the CC, C/T and TT genotypes represented 49%, 45% and 5% of CHB patients and, %46, 43% and 11% of SC group respectively (p=0.65). On the other hand, in IFN-λ4 rs11322783 polymorphisms analysis, recessive G/G allele was more common in SC group compared to CHB group (5% vs 16%, p=0.04; OR: 3,55). Moreover, non-G/G genotypes had significantly higher in CHB patients compared to SC group (95% vs 84%, p=0.013; OR:3.55). Our results suggest that IFN-λ4 rs11322783 polymorphism may be a predictor of spontaneous clearance in HBV infected patients. The role of IFN-λ4 polymorphisms needs to be investigated in the natural history of HBV.

The efficacy and safety of addition of pegylated interferon to long-term nucleos(t)ide analogue therapy on functional cure of chronic hepatitis B patient: a systematic review and meta-analysis.

This meta-analysis aims to assess the efficacy and safety of adding pegylated interferon (Peg-IFN) to long-term nucleos(t)ide analogs (NAs) treatment for achieving functional cure in patients with chronic hepatitis B (CHB). This meta-analysis was registered in PROSPERO (CRD42024519116). We searched PubMed, Embase, Cochrane Library and Web of Science for randomized controlled trials that compared adding Peg-IFN to long-term NAs with NAs alone for the treatment of CHB. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effects model. Seven trials with 692 participants were included. Compared to NAs monotherapy, sequential combination therapy significantly increased the HBsAg seroclearance rate (RR 4.37, 95%CI: 1.92-9.55; I2 = 0%) and HBsAg seroconversion rate (RR 3.98, 95%CI: 1.50-10.54; I2 = 0%), and the results reached statistical significance. Compared to NAs monotherapy, sequential combination therapy showed a significant increase in HBeAg seroclearance rate (RR 2.04; 95%CI: 0.47-8.82; I2 = 73%) and HBeAg seroconversion rate (RR 2.10; 95%CI: 0.41-10.71; I2 = 67%), but did not reach statistical significance. Sequential combination therapy was more likely to experience adverse events. Although most reactions are mild and reversible, vigilant monitoring for treatment-related adverse events is essential, with prompt intervention when needed. For CHB patients on long-term NAs treatment, sequential combination therapy boosts HBsAg seroclearance and HBsAg seroconversion rates compared to monotherapy. However, it may increase adverse events. Additional studies are needed to thoroughly evaluate its clinical effectiveness, given the current limited research available. PROSPERO, identifier CRD42024519116.

Comparison of Non-invasive Biochemical Fibrosis Markers According to Obesity-Based Metabolic Profile in Chronic Liver Disease with Chronic Hepatitis B Etiology

Aim: The aim of this study is to investigate the impact of obesity on fibrosis by comparing fibrosis markers between obese and non-obese patients with Chronic Hepatitis B (CHB). Material and Method: A total of 172 CHB (50.6±9.4 mean aged) patients were included in this retrospective study. The patients were divided into two groups: Obese (n=72) and Non-obese (n=100). Inclusion criteria were those diagnosed with chronic hepatitis B and ≤ 50 IU/mL or undetectable HBV-DNA, and exclusion criteria were other chronic diseases other than CHB and pregnancy. The height, body weight, and waist circumferences were measured. BMI ≥30 kg/m2 was classified as the obese group. Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl transferase, albumin, bilirubin, and prothrombin time were analyzed. Fibrosis-4 score (FIB-4) was calculated with the formula Age x AST / platelet count x √(ALT), and AST-Platelet Ratio Index (APRI) was calculated with the formula [AST/AST (upper limit of normal)]/ platelet count. Results: AST levels were significantly higher in obese patients (p

The value of serum Mac-2 binding protein glycosylation isomer in the diagnosis of liver fibrosis: a systematic review and meta-analysis

BackgroundThe early detection and intervention of liver fibrosis (LF) in patients with chronic liver disease is critical to their management. The accuracy of serum Mac-2 binding protein glycosylation isomer (M2BPGi) in the diagnosis of LF remains controversial. This study aimed to comprehensively assess the value of serum M2BPGi in diagnosing LF.MethodsThe PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases were searched. The effect values were combined using a random-effects model. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. In addition, publication bias assessment and sensitivity analysis were conducted.ResultsThis study includes 12 studies with 2,416 patients. The pooled sensitivity, specificity, and AUROC of M2BPGi in the diagnosis of significant fibrosis (≥F2) were 0.65 (95% CI: 0.57–0.71), 0.79 (95% CI: 0.72–0.84), and 0.78 (95% CI: 0.74–0.81), respectively, while those for predicting extensive fibrosis (≥F3) were 0.76 (95% CI: 0.71–0.80), 0.75 (95% CI: 0.68–0.81), and 0.81 (95% CI: 0.77–0.84). Sensitivity analysis indicated stable results in this study. The disease type, cut-off values, study country, average age, and male proportion were the sources of heterogeneity in diagnosing significant fibrosis of M2BPGi (p &amp;lt; 0.05). Sample size, disease type, study country, publication year, cut-off values, average age, and male proportion were important sources of heterogeneity in diagnosing extensive fibrosis (p &amp;lt; 0.05).ConclusionSerum M2BPGi has good diagnostic performance for significant fibrosis and extensive fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), or nonalcoholic fatty liver disease (NAFLD) and is an effective, non-invasive, and convenient marker.Systematic Review Registrationhttps://inplasy.com/inplasy-2023-10-0086/.

CHRONIC HEPATITIS B VIRUS INFECTION: SYSTEMATIC REVIEW OF EPIDEMIOLOGY, MECHANISMS OF VIRAL PERSISTENCE AND TREATMENT OF THE CONDITION

Objective: The general objective of this study is to analyze the scientific production on chronic infection by the Hepatitis B virus, seeking to identify the main methods used in the treatment of this pathology. Methodology: This is a systematic review focused on understanding the main aspects that permeate chronic infection by the Hepatitis B virus. The research was guided by the question: “What are the main aspects that permeate chronic infection by the Hepatitis B virus, as well as what are the diagnostic and therapeutic resources used in clinical practice?”. To find answers, searches were performed in the PubMed database using five descriptors combined with the Boolean term “AND”. This resulted in 408 articles. Twenty-four articles were selected for analysis and 15 articles were used to compose the collection. Results: The eradication of hepatitis B depends on the combination of preventive and therapeutic efforts. The persistence of cccDNA in the liver, even after viral suppression, makes complete functional cure difficult. Antivirals such as entecavir and tenofovir are effective in reducing viral load, but they fail to eradicate the virus in most patients, requiring prolonged treatments. Furthermore, the variability in treatment responses, influenced by factors such as viral genotype and disease stage, highlights the need for personalized approaches to improve clinical management. In summary, despite advances, there are still important challenges to be addressed in the search for a cure for chronic hepatitis B. Conclusion: The systematic review highlighted the main aspects of chronic hepatitis B (CHB), emphasizing its challenges and advances in clinical management. Chronic hepatitis B virus (HBV) infection remains a serious public health problem, with complications such as liver cirrhosis and hepatocellular carcinoma. Prevention strategies, such as universal vaccination and immunoprophylaxis, are effective in reducing vertical transmission, especially in newborns, but global adherence still needs to improve, especially in areas of high prevalence.

The expression of sICAM-1 influenced by Clonorchis sinensis co-infection in CHB patients.

Soluble Intercellular Adhesion Molecule-1 (sICAM-1) has emerged as an inflammatory biomarker of many essential functions. We investigated the level of sICAM-1 influenced by Clonorchis sinensis (C. sinensis) co-infection in chronic hepatitis B (CHB) patients to explore the degree of liver tissue inflammation and liver function damage after co-infection. The study included data from patients with C. sinensis mono-infection (n=27), hepatitis B virus (HBV) mono-infection (n=32), C. sinensis and HBV co-infection (n=24), post-hepatitis B liver cirrhosis (n=18), post-hepatitis B liver cirrhosis co-infected with C. sinensis (n=16), and healthy controls (n=39). The level of sICAM-1 was measured with specific enzyme-linked immunosorbent assay method. Compared to the healthy control group, all the experimental groups had significantly higher serum sICAM-1 levels. The levels of sICAM-1 in co-infected groups were significantly higher compared to the mono-infection groups and were positively correlated with the levels of glutamate aminotransferase (ALT) and aspartate aminotransferase (AST). Our research findings confirmed that co-infection could exacerbate liver tissue inflammation and liver function damage in patients, could raise the sICAM-1 level, and may lead to the chronicity of HBV infection. These results provide clues for pathological mechanism study and formulating treatment plans.

Asiatic acid inhibits HBV cccDNA transcription by promoting HBx degradation

BackgroundHepatitis B virus (HBV) infection is a persistent global public health problem, and curing for chronic hepatitis B (CHB) through the application of existing antiviral drugs is beset by numerous challenges. The viral protein HBx is a critical regulatory factor in the life cycle of HBV. Targeting HBx is a promising possibility for the development of novel therapeutic strategies.MethodsThe Nano-Glo® HiBiT Lysis Detection System was used to screen the herbal monomer compound library for compounds that inhibit HBx expression. Western blotting was used to examine proteins expression. Southern blotting or Northern blotting were used to detect HBV DNA or HBV RNA. ELISA was performed to detect the HBsAg level. The effect of asiatic acid on HBV in vivo was investigated by using recombinant cccDNA mouse model.ResultsAsiatic acid, an extract of Centella asiatica, significantly reduced the HBx level. Mechanistic studies demonstrated that asiatic acid may promote the degradation of HBx in an autophagy pathway-dependent manner. Subsequently, asiatic acid was found to reduce the amount of HBx bound to covalently closed circular DNA (cccDNA) microchromosomes, and repressive chromatin modifications then occurred, ultimately inhibiting cccDNA transcriptional activity. Moreover, in HBV-infected cells and a mouse model of persistent HBV infection, asiatic acid exhibited potent anti-HBV activity, as evidenced by decreased levels of HBV RNAs, HBV DNA and HBsAg.ConclusionsAsiatic acid was identified as a compound that targets HBx, revealing its potential for application as an anti-HBV agent.