Chronic Hepatitis Research Articles

Portocaval shunts' role in gut microbiota and hepatic encephalopathy: The gut-to-brain pathway

I read the study by Zhao et al with great interest. Although the study design was quite complicated, it was successful in raising awareness of science and relevant researchers. Thirty patients with liver cirrhosis and portal hypertension secondary to chronic hepatitis B were included in the study. They were treated for variceal bleeding and underwent trans-jugular intrahepatic portosystemic shunt to prevent the recurrence of variceal bleeding and to reduce portal pressure. The authors evaluated the effects of changes in gut microbiota (GM) on hepatic encephalopathy secondary to portocaval bypass. The GM is greatly affected by local and general factors, including herbal and medical drugs, a person's dietary characteristics (carnivorous, vegan, vegetarian), supplementary foods, drinking water sources, and living in a city center or town. Therefore, I congratulate Zhao et al for their concise and comprehensive study on a multifactorial subject.

Unlocking CD8+ T cell potential in chronic hepatitis B virus infection

Unlocking CD8+ T cell potential in chronic hepatitis B virus infection

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.

Assessment of Glecaprevir/Pibrentasvir Treatment’s Influence on Biochemical and Metabolic Markers in Patients with Chronic Hepatitis

Background/Objectives: Liver function tests (LFT) are essential for diagnosing and monitoring liver status in patients with chronic hepatitis. In addition, tracking the systemic implications reflected in the changes in metabolic parameters is essential for correctly managing the cases. This study addresses the critical gap in the literature by evaluating the effects of glecaprevir/pibrentasvir on key liver function markers (AST, ALT, GGT, TB) and metabolic parameters (TC, TG, HbA1c) in patients with chronic hepatitis C (CHC). Moreover, this study will evaluate the impact of glecaprevir/pibrentasvir on A2MG, which provides insights into its effects on liver fibrosis. Awareness of these effects is critical for the optimal management of patients during and following antiviral therapy to ensure that therapeutic success does not come at the expense of overall liver and metabolic health. These parameters should be monitored as they supply clinicians with essential data, informing treatment more accurately and ensuring a holistic approach in CH patients. Methods: This study consists of 104 patients with chronic hepatitis C treated with glecaprevir/pibrentasvir and monitored from January to June 2024. Assessments comprised standard liver markers, lipid profiles, glycated hemoglobin, and alpha-2-macroglobulin, as well as specific non-invasive tests of liver injury. Results: 95.2% of the patients experienced a sustained virologic response. Biochemical markers and total cholesterol values were significantly decreased with glecaprevir/pibrentasvir therapy. Non-significant elevations in total bilirubin and glycated hemoglobin support the drug’s favorable tolerability profile. Conclusions: In the treatment of chronic hepatitis C patients, glecaprevir/pibrentasvir therapy leads to normalization in biochemical markers (AST, ALT, and GGT), as well as in total cholesterol.

Clinical- and Cost-Effectiveness of Liver Disease Staging in Hepatitis C Virus Infection: A Microsimulation Study.

Liver disease assessment is a key aspect of chronic hepatitis C virus (HCV) infection pre-treatment evaluation but guidelines differ on the optimal testing modality given trade-offs in availability and accuracy. We compared clinical outcomes and cost-effectiveness of common fibrosis staging strategies. We simulated adults with chronic HCV receiving care at US health centers through a lifetime microsimulation across five strategies: (1) no staging or treatment (comparator), (2) indirect serum biomarker testing (Fibrosis-4 index [FIB-4]) only, (3) transient elastography (TE) only, (4) staged approach: FIB-4 for all, TE only for intermediate FIB-4 scores (1.45-3.25), and (5) both tests for all. Outcomes included infections cured, cirrhosis cases, liver-related deaths, costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We used literature-informed loss to follow-up (LTFU) rates and 2021 Medicaid perspective and costs. FIB-4 alone generated the best clinical outcomes: 87.7% cured, 8.7% developed cirrhosis, and 4.6% had liver-related deaths. TE strategies cured 58.5%-76.6%, 16.8%-29.4% developed cirrhosis, and 11.6%-22.6% had liver-related deaths. All TE strategies yielded worse clinical outcomes at higher costs per QALY than FIB-4 only, which had an ICER of $12 869 per QALY gained compared with no staging or treatment. LTFU drove these findings: TE strategies were only cost-effective with no LTFU. In a point-of-care HCV test-and-treat scenario, treatment without any staging was most clinically and cost-effective. FIB-4 staging alone resulted in optimal clinical outcomes and was cost-effective. Treatment for chronic HCV should not be delayed while awaiting fibrosis staging with TE.

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.

Abstract 4134309: From Heartache to Headache: Cryptococcal Meningitis Post-Heart Transplant in a Chronic Hepatitis B and Sarcoidosis Patient

Introduction: We report the case of a heart transplant patient on chronic immunosuppression diagnosed with cryptococcal meningitis. Up to 5% of solid organ transplant patients develop cryptococcosis, carrying a 50% mortality rate in central nervous system involvement. Case Presentation: This is a 57-year-old male with a past medical history of heart failure with reduced ejection fraction (HFrEF) status post orthotopic heart transplantation (on prednisone 7.5 mg daily, mycophenolate, tacrolimus and sirolimus), pulmonary sarcoid, and chronic hepatitis B (on tenofovir and entecavir) who presented with headache, nausea, vomiting and seizure-like activity. The patient’s heart rate was 129 beats per minute, blood pressure 188/92 mmHg, but was afebrile. He eventually underwent a lumbar puncture with the cerebrospinal fluid (CSF) positive for cryptococcal antigen (1:2560). The patient was started on liposomal amphotericin B and flucytosine. Mycophenolate and sirolimus were held in the setting of his infection. The patient’s hospital course was complicated by acute kidney injury likely secondary to elevated tacrolimus levels while on fluconazole. He was ultimately discharged with plans to repeat CSF studies as an outpatient. Discussion: Here we report a case of cryptococcal meningitis in a heart transplant patient in the context of pulmonary sarcoidosis, chronic hepatitis B and quadruple immunosuppression. Of note, as part of rejection surveillance, the patient undertook serial AlloSure and AlloMap testing. Sirolimus was added to his regimen due to persistently elevated AlloSure scores. Indeed, immunosuppressive agents are the leading risk factor for cryptococcosis in organ transplant patients. Our patient also has two important risk factors for cryptococcal infection. Firstly, sarcoidosis is associated with T-cell dysregulation, compromising cell-mediated immunity. Additionally, hepatitis B carriers have an increased predisposition for cryptococcal infections, notwithstanding that our patient had been on dual antiviral therapy. Conclusion: Quadruple immunosuppression in heart transplant patients, especially in the context of risk factors such as sarcoidosis and hepatitis B infection, can result in cryptococcal meningitis and should be considered in patients with suggestive symptoms. Effective prophylactic regimens for such higher risk patients may be a potential area for further investigation.

Direct Antivirals Can Achieve a Cure in All Patients With Chronic Hepatitis C due to Genotype 5: A French Multicentre Study.

Hepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%. Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure. HCV-GT-5 patients treated with a DAA regimen had a 99% SVR12 in intention-to-treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real-world HCV-GT-5 patients.

Suspected hepatic hydrothorax secondary to cirrhosis in a dog

AbstractAn 8‐year‐old, entire, female labrador retriever presented with a 2‐week history of abdominal distension. Biochemistry identified hepatic dysfunction (elevated hepatobiliary markers, hypocholesterolaemia). Abdominal ultrasonography documented an irregular liver and a large volume of anechoic peritoneal effusion, which laboratory analysis confirmed as a protein‐poor transudate. Thoracic computed tomography identified a moderate volume of pleural effusion with a similar composition to the peritoneal fluid. Hepatic histopathology was consistent with cirrhosis secondary to chronic hepatitis and, in the absence of another cause for the pleural effusion, hydrothorax secondary to the hepatic disease was suspected. The patient was started on ciclosporin for treatment of the underlying liver disease, but developed signs consistent with disseminated intravascular coagulopathy 24 hours later and was humanely euthanased. As reported in humans, hydrothorax may therefore occur secondary to cirrhosis in dogs and should be considered as a differential diagnosis for pleural effusion in patients with advanced hepatic disease and concurrent peritoneal effusion.

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.

Letter to the Editor Clinical and Molecular Hepatology Correspondence on the Editorial regarding "The use of transient elastography for predicting hepatocellular carcinoma in chronic hepatitis B patients".

Letter to the Editor Clinical and Molecular Hepatology Correspondence on the Editorial regarding "The use of transient elastography for predicting hepatocellular carcinoma in chronic hepatitis B patients".

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.

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.

Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT-V Study.

The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH. In the US multicentre SHUNT-V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy. Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut-off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%. SHUNT-V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child-Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%-100% for LEV and 97.3%-100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%-35% of EGDs could have been avoided with 0%-3.7% of LEV and 0%-2.7% of all significant PH lesions missed. HepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal-systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child-Pugh A cirrhosis. The SHUNT-V study was registered at ClinicalTrials.gov (NCT03583996).

Fanconi Syndrome Due to Tenofovir Disoproxil Fumarate in a Patient with Chronic Hepatitis B Induced Cirrhosis: A Case Report

We present a 63-year-old woman with chronic hepatitis B. The patient has a history of cirrhosis due to chronic hepatitis B and is under treatment with Tenofovir disoproxil fumarate. The patient presented to our center with nausea, vomiting, and severe metabolic acidosis. After initial evaluation, along with the typical course of events and the exclusion of differential diagnoses of normal anion gap metabolic acidosis, we determined that the cause of illness was related to Tenofovir disoproxil fumarate. All our practical and laboratory data supported a diagnosis of proximal tubular acidosis. After discontinuing the drug for two weeks and providing supportive management, metabolic acidosis and electrolyte imbalance improved. The other isoform of Tenofovir (Tenofovir alafenamide) was initiated for the patient, and after two months of follow- up, there were no signs of acidosis or electrolyte imbalance

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.

Outcomes following use of hepatitis B surface antigen positive liver allografts in hepatitis B surface antigen negative recipients.

The use of positive hepatitis B surface antigen (HBsAg+) liver allografts has been increasing globally and is gaining wider acceptance within the United States. However, most of the data supporting the use of HBsAg+ organs has been in the setting of recipients with chronic hepatitis B. We aim to describe our institutional experience using HBsAg+ liver donors in HBsAg-negative recipients via case series. Between 2019 and 2021, 10 HBsAg-negative recipients received a HBsAg+ liver transplant. Kaplan-Meier survival analysis showed no difference in survival when compared to all other liver transplants performed at the institution during the same period (p=0.5, HR=1.6, CI=0.4-6.5). Based on these findings, the use of HBsAg+ liver donors appears to be safe; however, continued follow-up is required to understand further risks associated with the use of HBsAg+ liver allografts.

ANXA4 restricts HBV replication by inhibiting autophagic degradation of MCM2 in chronic hepatitis B

BackgroundHepatitis B virus (HBV) is an enveloped DNA virus that causes chronic hepatitis B (CHB) infection. Annexin, a Ca2+-activated protein, is widely expressed in various organs and tissues and has potential utility in disease diagnosis and treatment. However, the relationship between the annexin family and CHB remains unclear.MethodsClinical samples from hepatitis patients and donors or healthy individuals were collected. Transcriptome sequencing in CHB liver tissues and HBV-infected cells were performed. HepG2.2.15 cells with the full-length HBV genome and HBV-infected HepG2-NTCP cell models were established. HBV-infected mouse model was constructed and adeno-associated virus was utilized.ResultsANXA4 expression was elevated during CHB infection. ANXA4 knockdown promoted HBV replication and aggravated liver injury, while ANXA4 overexpression alleviated that. Mechanistically, autophagy pathway was activated by ANXA4 deficiency, promoting autophagic degradation of minichromosome maintenance complex component 2 (MCM2). MCM2 inhibition activated HBV replication, while MCM2 overexpression attenuated ANXA4 deficiency-induced HBV replication and liver injury. Clinically, the expression of hepatitis B viral protein was negatively correlated with the ANXA4 levels, and CHB patients with high ANXA4 levels (> 8 ng/ml) showed higher sensitivity to interferon therapy.ConclusionsANXA4 functions as a protective factor during HBV infection. ANXA4 expression is elevated under HBV attack to restrict HBV replication by inhibiting autophagic degradation of MCM2, thereby alleviating liver injury and suppressing the CHB infection process. ANXA4 also enhances the sensitivity of CHB patients to interferon therapy. Therefore, ANXA4 is expected to be a new target for CHB treatment and prognostic evaluation.Graphical

ZNF350 gene polymorphisms promote the response to Peg-IFNα therapy through JAK-STAT signaling pathway in patients with chronic hepatitis B

ZNF350 gene polymorphisms promote the response to Peg-IFNα therapy through JAK-STAT signaling pathway in patients with chronic hepatitis B

HBsAg trajectories and key thresholds toward functional cure of hepatitis B

Chronic hepatitis B virus (HBV) infection remains a pivotal global health challenge. The pursuit of a functional cure for hepatitis B remains an ardent and intricate issue in clinical settings, as the current arsenal of nucleos(t)ide analogues (NAs) primarily achieves sustained suppression of HBV DNA but falls short in fully addressing clinical needs. The standalone use of Peg-interferon (PEG-IFN) or its combination with NAs still fails to satisfy the pressing clinical demands for functional cure. However, groundbreaking advancements in hepatitis B treatment have emerged through the research and development of antiviral agents with novel mechanisms, notably small nucleic acid drugs, which have ushered in a new era for functional cure prospects. Leveraging longitudinal data spanning multiple time points of HBsAg levels, we can now delineate the trajectory leading towards HBV functional cure and devise predictive models that refine clinical treatment protocols. Two pivotal thresholds of HBsAg levels emerge as crucial milestones, facilitating the selection of eligible participants for clinical trials. This refinement in screening enhances the personalized management of hepatitis B, tailoring interventions to individual patient needs and maximizing outcomes.