Real-world study on the efficacy and safety of different treatment regimens in treatment-naïve CHB patients with high viral load.

Evaluate the real-world effectiveness and safety of different treatment regimens for treatment-naïve high viral load chronic hepatitis B (CHB) patients. Between January 2021 and August 2022, CHB patients with HBV DNA ≥ 107 IU/mL were collected from four medical centers in Shenzhen. Patients treated with mono or combine antiviral therapy. The primary endpoint was the cumulative incidence of virological response at 48 weeks, and other endpoints included changes in HBsAg, HBeAg, ALT, and eGFR at 48 weeks. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the bias. Weighted logistics regression was used to estimate the factors affecting virological response. A total of 391 patients were included in the study, with 296 patients undergoing statistical analysis after IPTW. The patients were distributed into four groups: ETV (n = 62), TDF (n = 89), TAF (n = 36), TDF + LdT/ETV (n = 109). The 48-week cumulative incidence of virological response was significantly lower in ETV group (52.3%) compared to TDF (71.7%), TAF (74.2%), and TDF + LdT/ETV groups (77.9%) (P < 0.05). There were no significant differences in HBsAg loss among the four groups, but the HBeAg seroconversion rate was significantly higher in the TAF group. The ALT normalization rate was significantly higher in the TAF group (72.2%) compared to the others at 48 weeks (P < 0.05). In treatment-naïve CHB patients with high viral load, combination therapy was not superior to TDF or TAF monotherapy in virological response. Patients treated with TDF or TAF showed superior virological response compared to those treated with ETV. The TAF group demonstrated superiority in terms of ALT normalization and HBeAg seroconversion.

Results of mother-to-child transmission in hepatitis B-positive mothers who underwent amniocentesis.

PURPOSE: This study aims to analyze whether undergoing amniocentesis during pregnancy in women diagnosed with hepatitis B virus (HBV) infection leads to HBV transmission to newborns. METHODS: Retrospective data collection was conducted from June 2019 to November 2022 on expectant mothers positive for hepatitis B surface antigen (HBsAg) who underwent amniocentesis at The Third Affiliated Hospital of Sun Yat-sen University, along with data on their newborns. The study summarized the HBV infection status of newborns born to mothers with different expressions of hepatitis B e antigen (HBeAg), antiviral treatment versus no treatment, and different HBV DNA viral loads before delivery. RESULTS: In this study, 346 expectant mothers tested positive for HBsAg, along with 351 newborns (including 5 sets of twins, with 8 infants (2.28%) testing HBsAg-positive at birth. All newborns received dual immunotherapy and were followed up. At 7-12 months, retesting for HBsAg positivity and HBV DNA positivity among infants revealed that out of the infants born with HBsAg positivity, 7 cases had seroconverted to negative, while the remaining infant, who was positive for both HBsAg and HBeAg at birth, tested positive for both HBsAg and HBV DNA at 7-12 months. Thus, one case of vertical transmission of hepatitis B from mother to child occurred in this study. The proportion of infants born with HBsAg + among newborns born to HBeAg-positive mothers (4 cases, 6.06%) was significantly higher than that among newborns born to HBeAg-negative mothers (4 cases, 1.41%) (P < 0.05). The proportion of infants born with HBsAg + showed no significant difference between newborns born to mothers receiving antiviral therapy (2 cases, 2.90%) and those born to mothers not receiving antiviral therapy (6 cases, 2.13%) (P > 0.05). Among expectant mothers with viral load ≥ 6 log 10 IU/mL before delivery, 3 newborns (30.00%) were manifesting HBsAg positivity at birth, significantly higher than the group with viral load < 6 log 10 IU/mL before delivery (5 cases, 1.47%) (P < 0.05). CONCLUSION: Among HBsAg-positive expectant mothers, only a small number of infants are infected with the hepatitis B virus at birth, the proportion of which is relatively low. Infants born to mothers who are HBeAg-positive or have a viral load ≥ 6 log10 IU/mL have a higher risk of being born positive.

Necessity of antiviral treatment for patients with chronic hepatitis B in the grey zone based on liver pathology analysis.

OBJECTIVE: 28-55% of chronic hepatitis B (CHB) patients belong to the grey zone (GZ). By analyzing the pathological characteristics of the liver of patients in the GZ, this study clarified whether the patients in the GZ need anti-hepatitis B virus treatment. METHOD: We reviewed 324 cases of liver pathology that underwent liver biopsy between 2011 and 2022. According to the total score of inflammation G, 0-6 points are classified as mild, 7-12 points are classified as moderate, and 13-18 points are classified as severe. According to the total score of fibrosis F, 0-2 is mild, 3-4 is moderate, and 5-6 is severe. Significant histological diseases (SHD) are defined as the presence of inflammation G ≥ 6 and/or fibrosis F ≥ 2 in liver biopsy specimens. RESULT: 324 GZ patients were scored using the Ishak method, with G7-18 accounting for 9%, F3-6 accounting for 19.2%, and SHD accounting for 37%. The inflammation, fibrosis, and SHD in the HBeAg (+) group were more pronounced than those in the HBeAg (-) group. Among the GZ-A ∼ GZ-D subgroups, the highest proportion of SHD in the GZ-B group was 58.35%. CONCLUSION: More than 1/3 of the patients in GZ need anti-hepatitis B virus treatment. More than half of GZ-B patients need anti-hepatitis B virus treatment. It is very necessary to carry out rescue anti-hepatitis B virus treatment for patients in GZ as soon as possible.

Determinants of HBeAg loss during follow-up of a multiethnic pediatric cohort.

Hepatitis B e antigen (HBeAg) loss is a key event in the natural history of chronic hepatitis B virus infection. The rate and determinants of HBeAg loss depend upon cohort characteristics at baseline. Few studies have examined the age-dependent rate, and none have examined the effect of patient sex and ethnicity on the age-dependant rate. The study of age-dependent rates requires the identification and long-term follow-up of a pediatric cohort. We have studied the age-dependent rate of HBeAg loss, and the rate of HBeAg loss measured from baseline, in a multi-ethnic cohort of 454 pediatric patients. During observation, HBeAg loss was observed in 121/303 (39.9%) HBeAg-positive patients. The rate of HBeAg loss was greater in the second versus the first and third decades of life. The age-related rate of HBeAg loss was clearly affected by patient sex and ethnicity, with earlier loss observed for males and for White versus both South Asian and Chinese ethnicities. When measured from baseline, Chinese patients had a slower rate of HBeAg loss in comparison with White patients. In multivariate analysis of HBeAg loss during prolonged follow-up, male sex, older age, and White ethnicity were associated with HBeAg loss, but antiviral treatment was not.

Association of hepatitis B core antibody level and hepatitis B surface antigen clearance in HBeAg-negative patients with chronic hepatitis B.

Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p < 0.001) and seroconversion (8.8 S/CO vs. 9.8 S/CO, p < 0.001) than those without. Anti-HBc level at week 12 was an independent predictor of HBsAg clearance and seroconversion. Patients with lower anti-HBc levels at week 12 showed a more significant decline in HBsAg levels during treatment. Combination of anti-HBc at week 12 and baseline HBsAg could identify over 70% of patients who achieved HBsAg clearance after 48 weeks of treatment. In addition to HBsAg, anti-HBc level could be used as a promising marker for selecting HBeAg-negative CHB patients who are more likely to respond to Peg-IFN-based therapy.

Effect of nucleos(t)ide analogue discontinuation on the prognosis of HBeAg-negative hepatitis B virus-related hepatocellular carcinoma after hepatectomy: A propensity score matching analysis.

BACKGROUND: Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. METHODS: This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS: Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348-3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537-4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). CONCLUSIONS: These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.

Age of hepatitis B e antigen loss in Aboriginal, Torres Strait Islander and non-Indigenous residents of tropical Australia; implications for clinical care.

Abstract: This study determined the hepatitis B e antigen (HBeAg) status of people living with chronic hepatitis B (CHB) in Far North Queensland (FNQ), Australia and their age of HBeAg loss. It was hoped that this would provide data to explain the stark difference in the incidence of hepatocellular carcinoma (HCC) between Aboriginal and Torres Strait Islander individuals living with CHB in FNQ, a finding that has been hypothesised to relate to differences in hepatitis B virus genotype. We identified every FNQ resident with CHB, determined their country of birth, their HBeAg status, the age they lost HBeAg and whether they identified as an Aboriginal, a Torres Strait Islander or a non-Indigenous individual. We then ascertained whether these demographic and virological variables were correlated. Of 1,474 individuals living with CHB in FNQ, 278 (19%) were Aboriginal, 507 (34%) were Torres Strait Islanders and 689 (47%) were non-Indigenous. Aboriginal individuals were less likely to be HBeAg positive (26/278, 9%) than Torres Strait Islander (91/507, 18%) and non-Indigenous (126/689, 18%) individuals, p < 0.0001. Aboriginal individuals lost HBeAg at an earlier age (median (interquartile range): 30 (23-39) years) than Torres Strait Islander (38 (29-49) years) and non-Indigenous (36 (29-47) years) individuals, p < 0.0001. Aboriginal individuals with CHB in FNQ are more likely to be HBeAg negative than Torres Strait Islander and non-Indigenous individuals and lose HBeAg at a younger age. This provides a biological basis for local clinicians' observation that Aboriginal individuals with CHB in FNQ are at a lower risk of HCC and data to support the principle of genotype-based care in the region.

Higher hepatitis B core-specific T cell response is associated with a lower risk of clinical relapse after discontinuation of oral antiviral treatment.

BACKGROUND: Hepatitis B virus (HBV)-specific T cell response is a major host immune response to control the virus. However, it is still unclear how it affects long-term outcomes of chronic hepatitis B patients, especially those who stop nucleos(t)ide analogue (NA) therapy. We aimed to explore whether the HBV-specific T cell response at the end of treatment (EOT) was associated with clinical outcomes. METHODS: In a prospective cohort study, 51 HBeAg-negative patients who discontinued NA therapy were enrolled. RESULTS: In a mean follow-up of 25.3 months, 25 patients developed clinical relapse. We found that a stronger hepatitis B core (HBc)-specific T cell response at EOT was associated with a lower risk of clinical relapse. Compared to the low-response group, the high-response group had a lower risk of clinical relapse with hazard ratio of 0.21 (95% CI: 0.05-0.88). The high HBc-specific T cell response was associated with reduced surge of HBV DNA and HBcrAg during the first year of follow-up. The T cell response at EOT was comparable between different NA treatments. Notably, the overall HBV-specific T cell response could be partially restored along with clinical relapse; however, such reinvigorated T cell response was not associated with HBsAg seroclearance. CONCLUSIONS: A higher HBc-specific T cell response at EOT was associated with lower risk of clinical relapse and reduced surge of HBV DNA and HBcrAg levels off NA therapy.

Histological Findings in Antigen E Positive and Negative in Chronic Hepatitis B.

OBJECTIVE: To determine the histopathological findings in patients with HBeAg-positive chronic HBV infection (immunotolerant phase in old terminology) and HBeAg-negative chronic HBV infection (inactive carrier phase in old terminology). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Gastroenterology, University of Health Sciences, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, Turkiye and Diyarbakir and Mersin University School of Medicine, Diyarbakir, Turkiye, from May 2014 to August 2022. METHODOLOGY: The difference between fibrosis and histological activity indices of 289 patients in the immunotolerant and inactive carrier phase who had liver biopsy was examined statistically. Additionally, the relationship of these data with age and gender was investigated. RESULTS: While 236 (81.7%) of the patients were in the inactive carrier phase, 53 (18.3%) patients were in the immunotolerant phase. The mean fibrosis score of patients in the immunotolerant stage was 2.0 ± 1.2, while it was 2.0 ± 1.0 in inactive carriers (p = 0.753). The number of patients with a fibrosis score of two and above was 21 (39.6%) in immunotolerant patients and 52 (22.0%) in inactive carrier patients (p = 0.004). In patients under 30 years of age, the mean fibrosis score was 1.7 ± 1.0. It was 2.0 ± 1.1 in those over 30 years of age (p = 0.016). CONCLUSION: Biochemical parameters or viral load cannot clearly reflect cellular damage in the liver. In the future, HBV DNA positivity alone may be the only criterion for the treatment. KEY WORDS: Chronic viral hepatitis B, Fibrosis, Immune tolerance phase, Inactive carrier phase.

A high functional cure rate was induced by pegylated interferon alpha-2b treatment in postpartum hepatitis B e antigen-negative women with chronic hepatitis B virus infection: an exploratory study.

Background and aims: Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure. Methods: A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks. Results: At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported. Conclusion: Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.

Diagnostic Significance of Serum Long Noncoding HOX Antisense Intergenic Ribonucleic Acid in Patients with Hepatitis B Virus Related Hepatocellular Carcinoma.

BACKGROUND/AIMS:  Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the third leading cause of cancer-related mortality. Extensive literature suggests that long noncoding RNAs play a role in the progression of HCC and hold potential as diagnostic biomarkers for this disease. MATERIALS AND METHODS:  We examined the serum levels of HOX antisense intergenic RNA (HOTAIR) in 49 hepatitis patients, 31 liver cirrhosis (LC), and 37 HCC patients using quantitative real-time polymerase chain reaction. Correlations between serum HOTAIR levels and clinical data were evaluated in HCC patients. The receiver operating characteristic curve was utilized to analyze the diagnostic potency of HOTAIR. RESULTS:  The HOTAIR levels in serum were significantly higher in HCC patients compared to those with hepatitis (P = .003) and LC patients (P = .048). There was a significant association between the serum levels of HOTAIR and positivity of hepatitis B e antigen (HBeAg) (P = .039) as well as portal vein tumor thrombus (P = .040) in HCC patients. The area under the curve (AUC) for HOTAIR for distinguishing HCC from hepatitis and LC was 0.697. The combined AUC for HOTAIR, HBeAg, and alpha-fetoprotein (AFP) was 0.777. CONCLUSION:  Serum HOTAIR functions as a potential diagnostic marker for hepatitis B virus-related HCC. Combining HOTAIR with clinical data and AFP can reinforce the diagnostic precision on HCC.

Functional cure induced by tenofovir alafenamide plus peginterferon-alpha-2b in young children with chronic hepatitis B: a case series study.

BACKGROUND AND AIMS: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.

Risk factors related to low-level viraemia in chronic hepatitis B patients receiving entecavir treatment.

Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.

MicroRNA levels in patients with chronic hepatitis B virus and HIV coinfection in a high-prevalence setting; KwaZulu-Natal, South Africa.

BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (microRNA) expression to support viral replication. The aim of this study was to describe the pattern of microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load. METHODS: Plasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with microRNA expression levels. RESULTS: Significantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients. CONCLUSION: This study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression.

Efficacy and safety of therapeutic vaccines for the treatment of chronic hepatitis B: A systematic review and meta-analysis of randomized controlled trials update.

BACKGROUND: Most people diagnosed with chronic hepatitis B (CHB) need treatment to help reduce the risk of liver disease and limit disease transmission. Therapeutic vaccine (TV) candidates have been under study for their clinical effects on inducing HBV-specific host immune responses. This review aimed to systematically synthesize updated evidence on the efficacy and safety of TVs in patients with CHB. METHODS: This systematic review was performed by searching different databases from January to February 2021. Completed randomized controlled trials that reported TVs' efficacy and/or safety for treating CHB compared with the standard of care (SOC) or placebo were included. Efficacy and safety estimates were reported as the logarithm of the odds ratio and risk differences, respectively. I2 > 50% was considered significant heterogeneity. Significant publication bias was considered when Egger's test P value < .10. The risk of bias was assessed using the Cochrane Risk of Bias tool. The GRADE methodology was used to assess the certainty of the evidence for each outcome. RESULTS: Twenty-four articles with 2889 pooled samples were included. TVs made a significant difference in hepatitis B envelope antigen (HBeAg) SC (log OR = 0.76, P = .01) and (log OR = 0.40, P = .03) compared to placebo and combination therapy, respectively. HBeAg SC was significantly affected by TVs at the end of follow up (log OR = 0.49, P = .01), with significant HBsAg mean difference (MD = -0.62, P = .00). At the end of treatment, the TVs had no significant effect on HBV DNA negativity over the SOC (log OR = 0.62, P = .09) or placebo (log OR = -0.07, P = .91). TVs do not significantly affect the risk of serious adverse events (RD 0.02, 95% CI 0.00-0.04). CONCLUSION: In patients with CHB, TVs had significant effects on HBeAg SC compared to the SOC or placebo. There was no significant difference between serious adverse events. TVs are promising treatment strategy to overcome CHB.

Characteristics analysis of hepatitis B core-related antigen in children with hepatitis B e antigen-positive chronic viral hepatitis B infection.

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups ( P  = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB ( R2  = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

Clinical trial: An open-label, randomised trial of different re-start strategies after treatment withdrawal in HBeAg negative chronic hepatitis B.

BACKGROUND: Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re-start strategies are lacking. AIM: To assess whether it is beneficial to undergo a prolonged flare after NA cessation. METHODS: One-hundred-and-twenty-seven patients with HBeAg negative, non-cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low-threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high-threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re-start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention-to-treat allocation with last observation carried forward. RESULTS: There was a numerical but not statistically significant difference in HBsAg loss between the low-threshold (3 of 64; 4.7%) and the high-threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: -2.3 to 19.6, p = 0.123). None of the patients with end-of-treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end-of-treatment HBsAg < 1000 IU/mL, 8 of 15 (53.3%) achieved HBsAg loss in the high-threshold group compared to 3 of 26 (11.5%) in the low-threshold group. CONCLUSIONS: We could not confirm our hypothesis that a higher threshold for restart of therapy after NA withdrawal improves the likelihood of HBsAg loss within 36 months in patients with HBeAg negative CHB. Further studies including only patients with HBsAg level <1000 IU/mL and/or larger sample size and longer follow-up duration are recommended.

HBcrAg values may predict virological and immunological responses to pegIFN-α in NUC-suppressed HBeAg-negative chronic hepatitis B.

OBJECTIVE: Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on. DESIGN: 53 HBeAg-negative NUC-treated patients with CHB were randomised at a 1:1 ratio to receive pegIFN-α-2a for 48 weeks, or to continue NUC therapy and then followed up for at least 6 months maintaining NUCs. Serum hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels as well as peripheral blood NK cell phenotype and function and HBV-specific T cell responses upon in vitro stimulation with overlapping HBV peptides were measured longitudinally before, during and after pegIFN-α therapy. RESULTS: Two cohorts of pegIFN-α treated patients were identified according to HBsAg decline greater or less than 0.5 log at week 24 post-treatment. PegIFN-α add-on did not significantly improve HBV-specific T cell responses during therapy but elicited a significant multispecific and polyfunctional T cell improvement at week 24 post-pegIFN-α treatment compared with baseline. This improvement was maximal in patients who had a higher drop in serum HBsAg levels and a lower basal HBcrAg values. CONCLUSIONS: PegIFN-α treatment can induce greater functional T cell improvement and HBsAg decline in patients with lower baseline HBcrAg levels. Thus, HBcrAg may represent an easily and reliably applicable parameter to select patients who are more likely to achieve better response to pegIFN-α add-on to virally suppressed patients.

Clinical performance of Circulating HBV RNA and iTACT-HBcrAg Assays in HBeAg-negative and HBsAg-cleared Chronic Hepatitis B Patients.

Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) have been reported to reflect the transcriptional activity of covalently closed circular HBV DNA. We retrospectively investigated the proportions of quantifiable serum HBV RNA and immunoassay for total antigen including complex via pretreatment-hepatitis B core-related antigen (iTACT-HBcrAg) in chronic hepatitis B patients negative for hepatitis B e antigen (HBeAg) and/or with hepatitis B surface antigen (HBsAg) seroclearance. This study included 246 HBeAg-negative HBV-infected patients, who comprised 13 with liver cirrhosis (LC, the LC group), 118 chronic hepatitis (CH, the CH group), and 115 inactive carriers (IC, the IC group), and 44 patients with HBsAg seroclearance. iTACT-HBcrAg and HBV RNA levels were determined using stored serum samples. Higher proportions of the patients had quantifiable iTACT-HBcrAg than HBV RNA in all groups of HBeAg-negative patients (iTACT-HBcrAg: 84.6%, 90.7%, 35.7%, HBV RNA: 23.1%, 26.3%, 14.8%, for the LC, CH, IC groups). With HBsAg seroclearance (HBsAg <0.05 IU/mL), the proportions of quantifiable samples for HBV RNA were also lower than iTACT-HBcrAg (0% for HBV RNA). Thus, iTACT-HBcrAg was more often detectable than circulating HBV RNA in this study population. Further long-term prospective evaluation of iTACT-HBcrAg is desirable for its utilization in clinical practice.

Detection technology and clinical applications of serum viral products of hepatitis B virus infection.

Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field.