Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments.

In this editorial, we discussed the apparent discrepancy between the findings described by Colapietro et al, in their case report and data found in the literature. Colapietro et al reported a case of hepatitis B virus (HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton's tyrosine kinase (BTK) inhibitor therapy. First of all, we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response, focusing our attention on the protective role of anti-HBs. We then carefully analyzed literature data on the risk of HBV reactivation (HBVr) in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies. Based on literature data, we suggested that several factors may contribute to the different risks of HBVr: The type of hematologic malignancy; the type of therapy (BTK inhibitors, especially second-generation, seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors); previous exposure to an anti-CD20 as first-line therapy; and ethnicity and HBV genotype. Therefore, the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Seroepidemiology of hepatitis B virus (HBV) and relationship to serum transaminase levels in Indian population.

Background: Hepatitis B virus (HBV) infection is a serious public health issue that must be addressed. Aim: The goal of this study was to investigate the correlation between serological status for hepatitis Be antigen (HBeAg)/anti-HBe, serum transaminase levels, and serum HBV-DNA in patients with chronic HBV infection. Methods: A retrospective observational study with 620 patients with persistent HBV infection (mean age, 36.35 years; 506 men) was conducted. All patients tested positive for hepatitis B surface antigen (HBsAg). Liver profile, HBeAg, and anti-HBe antibody tests were conducted for all patients. Additionally, serum HBV DNA was examined using a DNA assay in these individuals. Results: Of 620 patients, 114 (18.39%) were HBeAg-positive and 506 (81.61%) HBeAg-negative. A detectable level of HBV DNA was found in 89.79% of HBeAg-positive/anti-HBe negative patients compared to HBeAg-negative/anti-HBe positive carriers 33.69% (P value <0.0001). The median viral load was significantly higher in HBeAg-positive cases (4.72 log10 copies/mL) than in HBeAg-negative individuals (4.23 log10 copies/mL; P = 0.997). Additionally, a higher proportion of HBeAg-positive samples (P = 0.0001) had HBV-DNA levels above 10,000 copies/mL.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection: How to achieve a better outcome.

BACKGROUND: Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. AIM: To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. METHODS: A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. RESULTS: Kaplan-Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). CONCLUSION: In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.

[Association between HBV viral load and severity of liver inflammation in patients with chronic hepatitis B virus infection].

Objective: To explore the relationship and dynamic changes between virological markers and hepatic pathological damage due to host anti-hepatitis B virus (HBV) immunity in the natural course of disease in chronic HBV infected patients. Methods: Two hundred and thirty-eight adult chronic HBV-infected patients who underwent liver biopsy from January 2016 to June 2022 in Taizhou Hospital, Zhejiang Province, were retrospectively selected. General clinical data such as age, gender, platelets, ALT, AST, albumin, HBV DNA, qHBsAg, HBeAg, and liver pathology diagnostic indexes such as the grade of liver necroinflammation and liver fibrotic stages of the patients were collected. The patients were grouped according to HBeAg status, and subgrouped according to different grades of liver necroinflammation and different HBV DNA loads. Statistical analyses were performed to compare the differences in HBV virologic marker levels between the groups, and the correlation between them and the indicators of hepatic inflammatory injury, such as ALT,AST, and the grade of liver necroinflammation in the patients. Results: The levels of HBV virological markers in HBeAg-positive patients with moderate or higher liver necroinflammatory grade (G≥2) were significantly lower than those with mild (no) liver necroinflammatory grade (G < 2) (P < 0.01); whereas the opposite trend was observed in HBeAg-negative patients, with the levels of HBV DNA, and qHBsAg in the G≥2 subgroup being significantly higher than those in the G < 2 subgroup (P < 0.01). Correspondingly, HBV DNA level and qHBsAg showed weak to moderately strong negative correlation with liver necroinflammatory grade and AST which was an indicator of hepatic inflammatory injury in HBeAg-positive patients (P < 0.05); whereas in HBeAg-negative patients, they showed weak to moderately strong positive correlation with hepatic inflammatory activity and ALT, AST (P < 0.001), in which qHBsAg showed only a weak positive correlation with patients' liver necroinflammatory grade (P = 0.003). Further subgroup analyses of HBeAg-positive patients according to whether the HBV DNA level was > 2×10(6) IU/ml showed weak to moderate negative correlations between HBV virological markers and liver necroinflammatory grade as well as ALT and AST in the subgroup of patients with HBV DNA > 2×10(6) IU/ml (P < 0.05); however, the negative correlation disappeared in patients who were still HBeAg positive and had HBV DNA ≤ 2×10(6) IU/ml. Moreover, HBV DNA and ALT, HBeAg and AST showed moderate positive correlation (P < 0.05). Conclusion: We speculate that the activation of host anti-HBV immunity can efficiently inhibit HBV replication by targeting the infected hepatocytes, but only in the early phase of disease progression in HBeAg positive patients with HBV DNA high (> 2×10(6) IU/ml).

The relationship of maternal hepatitis B e antigen and response to vaccination of infants born to women with chronic infection.

BACKGROUND: The relationship of maternal HBeAg and infants' response to hepatitis B vaccine remains controversial. This study aims to observe the dynamic changes in infant birth HBV markers and study the time-varying effects of maternal HBeAg on vaccination response of infants born to women with chronic HBV infection. METHODS: 3163 infants born to HBsAg positive mothers including 1737 with maternal HBeAg positive in group A and 1426 negative in group B were enrolled eventually. Demographic information and laboratory tests were collected at birth, 7-12th and 24th month. The dynamic changes of infant HBV markers and HBsAb titers at different time points were compared between the two groups. RESULTS: The infant HBV markers at birth displayed different modes. During the follow-up, we observed a significant downward trend in the positive rates of HBsAg, HBeAg, HBeAb and HBcAb. The HBsAg of two groups switched to negative at 7-12 months and HBeAg in Group A became negative at 24 months. The HBsAb titers of the infants in the two groups were 576.91(192.8-1000.0) vs 719.67(208.1-1000.0) at 7-12 months (Z = -3.049, P = 0.002) and 783.5(227.8-1000.0) vs 891.4(234.0-1000.0) at 24 months (Z = -0.853, P = 0.394). High HBV DNA viral load (OR 1.260, 95% CI 1.139-1.395, P < 0.001) and maternal HBeAg level (OR 1.003, 95% CI 1.002-1.003, P < 0.001) were associated with the higher HBeAg positive rate of infants. CONCLUSIONS: Maternal HBeAg did affect the infants' immune response to vaccination and reduce the anti-response at 7-12th month temporarily, but these influences were negligible by 24th months after birth, which proved that the maternal HBeAg would not induce immune tolerance of infants from a long-term perspective.

Liver histopathological lesions is severe in patients with normal alanine transaminase and low to moderate hepatitis B virus DNA replication.

BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major global public health problem. Chronic hepatitis B (CHB) patients can be divided into treatment indication and non-treatment indication individuals according to alanine transaminase (ALT), HBV DNA, serum hepatitis B e antigen status, disease status [liver cirrhosis, hepatocellular carcinoma (HCC), or liver failure], liver necroinflammation or fibrosis, patients' age, and family history of HCC or cirrhosis. For example, normal ALT patients in 'immune-tolerant' phase with HBV DNA higher than 107 or 2 × 107 IU/mL, and those in 'inactive-carrier' phase with HBV DNA lower than 2 × 103 IU/mL do not require antiviral therapy. However, is it reasonable to set the defined values of HBV DNA as the fundamental basis to estimate the disease state and to determine whether to start treatment? In fact, we should pay more attention to those who do not match the treatment indications (gray-zone patients both in the indeterminate phase and in the 'inactive-carrier' phase). AIM: To analyze the correlation of HBV DNA level and liver histopathological severity, and to explore the significance of HBV DNA for CHB with normal ALT. METHODS: From January 2017 to December 2021, a retrospective cross-sectional set of 1299 patients with chronic HBV infection (HBV DNA > 30 IU/mL) who underwent liver biopsy from four hospitals, including 634 with ALT less than 40 U/L. None of the patients had received anti-HBV treatment. The degrees of liver necroinflammatory activity and liver fibrosis were evaluated according to the Metavir system. On the basis of the HBV DNA level, patients were divided into two groups: Low/moderate replication group, HBV DNA ≤ 107 IU/mL [7.00 Log IU/mL, the European Association for the Study of the Liver (EASL) guidelines] or ≤ 2 × 107 IU/mL [7.30 Log IU/mL, the Chinese Medical Association (CMA) guidelines]; high replication group, HBV DNA > 107 IU/mL or > 2 × 107 IU/mL. Relevant factors (demographic characteristics, laboratory parameters and noninvasive models) for liver histopathological severity were analyzed by univariate analysis, logistics analysis and propensity score-matched analysis. RESULTS: At entry, there were 21.45%, 24.29%, and 30.28% of the patients had liver histopathological severities with ≥ A2, ≥ F2, and ≥ A2 or/and ≥ F2, respectively. HBV DNA level (negative correlation) and noninvasive model liver fibrosis 5 value (positive correlation) were independent risk factors for liver histopathological severities (liver necroinflammation, liver fibrosis, and treatment indication). The AUROCs of the prediction probabilities (PRE_) of the models mentioned above (< A2 vs ≥ A2, < F2 vs ≥ F2, < A2 and < F2 vs ≥ A2 or/and ≥ F2) were 0.814 (95%CI: 0.770-0.859), 0.824 (95%CI: 0.785-0.863), and 0.799 (95%CI: 0.760-0.838), respectively. HBV DNA level (negative correlation) was still an independent risk factor when diagnostic models were excluded, the P values (< A2 vs ≥ A2, < F2 vs ≥ F2, < A2 and < F2 vs ≥ A2 or/and ≥ F2) were 0.011, 0.000, and 0.000, respectively. For the propensity score-matched pairs, whether based on EASL guidelines or CMA guidelines, the group with significant liver histology damage (≥ A2 or/and ≥ F2) showed much lower HBV DNA level than the group with non- significant liver histology damage (< A2 and < F2). Patients in the moderate replication group (with indeterminate phase) had the most serious liver disease pathologically and hematologically, followed by patients in the low replication group (with 'inactive-carrier' phase) and then the high replication group (with 'immune-tolerant' phase). CONCLUSION: HBV DNA level is a negative risk factor for liver disease progression. The phase definition of CHB may be revised by whether the level of HBV DNA exceeds the detection low limit value. Patients who are in the indeterminate phase or 'inactive carriers' should receive antiviral therapy.

Reappraisal of screening strategy in hepatitis B surface antigen-negative blood donors: Correlation with hepatitis B virus-DNA quantification.

BACKGROUND: In spite of screening for hepatitis B surface antigen (HBsAg), transfusion-associated hepatitis B virus (TAHBV) infection remains a serious public health problem due to transmission of HBV in window period and occult HBV infection. To avoid TAHBV infection, some health-care facilities have started Hepatitis B core antibody test along with HBsAg, but this leads to a lot of potential donor rejection who are not HBV infected. Our aim is to find a new protocol of donor screening to prevent TAHBV without compromising blood availability. MATERIALS AND METHODS: A total of 88 HBsAg-negative anti-HBc total positive blood donors were included in this study. All samples were also tested for anti-HBs by enzyme immunoassay and for the presence of HBV-DNA viral load by real-time polymerase chain reaction. RESULTS: A total of 88 HBsAg negative and anti-HBc, total positive blood donors were tested for anti-HBs and HBV-DNA (Qn.). Among them, 76 donors (86.4%) (males 73 and females 3) were found to be positive for anti-HBs, while rest 12 (13.6%) showed no detectable antibody against HBsAg. HBV-DNA was found to be positive in 4 (7.7%) donor samples among 52 (60%) who have anti-HBs level <100 mIU/ml, while 36 (40%) donor samples were found to have >100 mIU/ml anti-HBs antibody with no detectable HBV-DNA. CONCLUSION: HBV-DNA should be implemented as a screening test of the blood donors to prevent TAHBV infection without potential donor rejection.

Hepatitis B core-related antigen: Are we near a treatment endpoint?

Different serological and virological markers in chronic hepatitis B patients guide staging of viral infection, and initiation and response to therapy. Due to the persistence of intrahepatic covalently closed circular DNA (cccDNA) in the hepatocyte nucleus, hepatitis B is not curable. Even after undetectable hepatitis B virus DNA levels, the persistence of hepatitis B surface antigen and novel markers such as hepatitis B core-related antigen (HBcrAg) indicate the persistence of intrahepatic cccDNA. In this study, HBcrAg levels at baseline and after 24 and 48 wk of antiviral therapy predicted hepatitis B e antigen seroconversion. Due to the poor sensitivity of assays and detectable levels in HBsAg-negative patients, the long-term utility of HBcrAg needs future research.

Dried blood spot is the feasible matrix for detection of some but not all hepatitis B virus markers of infection.

OBJECTIVE: Use of dried blood spots (DBS) for detection of hepatitis B virus (HBV) markers of infection has the potential to facilitate diagnosis of HBV infection especially in resource-limited countries. The aim of this study was to evaluate the feasibility of DBS for detection of various markers of HBV infections. RESULTS: Fifty-four DBS samples were engineered from well-characterized plasma samples. All DBS samples were tested for HBsAg, total anti-HBc and HBV DNA, 20 of 54 samples were also tested for HBeAg using commercially available assays. HBsAg was detected in 24 of 25 (96%), HBV DNA in 22 of 25 (88%), total anti-HBc in all 9 (100%), and HBeAg in all 7 (100%) DBS samples. The average difference in HBV DNA levels between DBS eluates and corresponding plasma samples was 2.7 log10 IU/mL. Fifteen DBS eluates positive for HBV DNA were sequenced and all of them belonged to HBV genotype A. Thirteen samples which were negative for all HBV markers showed HBeAg false positivity. Therefore, DBS is a reliable sample matrix for detection of HBsAg, total anti-HBc and HBV DNA, but not HBeAg. Further feasibility studies of DBS for diagnostic purposes and epidemiologic studies are warranted.

Effects of Let-7c on the processing of hepatitis B virus associated liver diseases.

BACKGROUND: The most common type of cancer of the digestive system is hepatocellular carcinoma. In China, many patients harbour HBV. The lin28B/Let-7c/MYC axis is associated with the occurrence of many cancers. Therefore, we aimed to illuminate the function of the lin28B/Let-7c/MYC axis in hepatocellular carcinoma. We aimed to evaluate the critical involvement of lin28B and Let-7c in the carcinogenesis of human hepatocellular carcinoma (B-HCC). METHODS: Data from the GEO database were used to analyse differentially expressed genes and IRGs. A protein - protein interaction (PPI) network and Venn diagram were generated to analyse relationships. Real-time RT-PCR, Western blotting, and cell counting kit-8 assays were used to examine the association of lin28B, Let-7c, and MYC with cell proliferation. RESULTS: A total of 2552 functionally annotated differentially expressed RNAs were analysed in HBV patients from the GSE135860 database. In addition, 46 let-7c target genes were screened in HBV patients, and the interactions were analysed through PPI network analysis. The results confirmed that Let-7c and its target genes play a key role in HBV-related diseases. Next, we discovered a gradual decrease in Let-7c expression during the progression from HBV-associated chronic hepatitis (B-CH) and HBV-associated liver cirrhosis (B-LC) to B-HCC. We found evidence for a negative association between lin28B expression and Let-7c expression. The expression of MYC was obviously upregulated when Let-7c was inhibited. CONCLUSION: Our results highlight that Let-7c and lin28B participate in the carcinogenesis of HBV-associated diseases through the lin28B/Let-7c/MYC axis.

Incidence of mother-to-child transmission of hepatitis B in relation to maternal peripartum antiviral prophylaxis: A systematic review and meta-analysis.

INTRODUCTION: Mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) is a serious public health challenge. Estimating HBV MTCT incidence by region under different prophylaxis regimens is critical to understanding the regional disease burden and prioritizing interventions. This study aimed to calculate HBV MTCT incidence under different prophylaxis regimens globally and regionally and identify the HBV DNA threshold for maternal peripartum antiviral prophylaxis. MATERIAL AND METHODS: This review was registered in advance in PROSPERO (CRD 42019120567). We searched PubMed, Embase, China National Knowledge Infrastructure, ClinicalTrials.gov, and Cochrane Library databases for studies on MTCT in pregnant women with chronic HBV infection from their inception until June 13, 2022. MTCT was defined as hepatitis B surface antigen (HBsAg) or HBV DNA seropositivity in infants aged 6-12 months. We calculated the pooled HBV MTCT incidence using the DerSimonian-Laird random-effects model. RESULTS: Among 300 studies, 3402 of 63 293 infants had HBV due to MTCT. Without prophylaxis regimens, the pooled HBV MTCT incidence was 31.3%, ranging from 0.0% (95% confidence interval [CI] 0.0%-6.0%; European Region) to 46.1% (95% CI 29.7%-63.0%; Western Pacific Region). Following the introduction of the hepatitis B vaccine, the HBV MTCT incidence decreased from 82.9% to 15.9% in HBeAg-positive women and from 10.3% to 2.3% in HBeAg-negative women. Maternal peripartum antiviral treatment alongside infant immunoprophylaxis further decreased MTCT incidence to 0.3% (95% CI 0.1%-0.5%). Despite infant immunoprophylaxis, the incidences of MTCT at maternal HBV DNA levels of <2.30, 2.00-3.29, 3.00-4.29, 4.00-5.29, 5.00-6.29, 6.00-7.29 and ≥7.00 log10  IU/ml were 0.0% (95% CI 0.0%-0.0%), 0.0% (95% CI 0.0%-0.0%), 0.0% (95% CI 0.0%-0.5%), 0.6% (95% CI 0.0%-2.6%), 1.0% (95% CI 0.0%-3.1%), 4.3% (95% CI 1.8%-7.5%), and 9.6% (95% CI 7.0%-12.5%), respectively. CONCLUSIONS: HBV MTCT incidence varies across regions. The Western Pacific Region bears the heaviest burden. Peripartum antiviral prophylaxis plus infant immunoprophylaxis is promising for interrupting HBV MTCT. Regarding the HBV DNA threshold for peripartum antiviral prophylaxis, maternal HBV DNA of 4.00 log10  IU/ml or greater seems justified.

Effectiveness of antiviral treatment in HBeAg-negative chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase: a retrospective study.

BACKGROUND: There are inadequate data and no histological evidence regarding the effects of antiviral treatment for hepatitis B e-antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT). This study investigated the effects of antiviral treatment on these patients. METHODS: We retrospectively analysed the outcomes of antiviral treatment for HBeAg-negative CHB patients with normal or mildly elevated ALT who were treated with nucleoside/nucleotide analogues (NAs) for up to 96 weeks. RESULTS: A total of 128 patients were enrolled; 74 patients had normal ALT and 54 patients had mildly elevated ALT. The total cumulative rates of viral suppression were 64.06%, 81.97%, and 96.39%, at weeks 24, 48, and 96, respectively. The cumulative rates of viral suppression for the normal and mildly elevated ALT groups were 67.85% and 58.97%, 86.39% and 76.31%, and 93.13% and 97.04% at weeks 24, 48, and 96, respectively. The serum HBV DNA levels at week 12 and hepatitis B surface antigen (HBsAg) levels at week 24 were significant predictors of the 96-week virological response. Of the 128 patients, 54 with normal ALT and 33 with mildly elevated ALT underwent FibroScan at baseline. Significant fibrosis (F ≥ 2) was found in 44.4% (n = 24) and 51.5% (n = 17) of the patients in the normal ALT group and mildly elevated ALT group, respectively. Compared with the values at baseline, liver stiffness values significantly decreased at week 48 (8.12 kPa vs. 6.57 kPa; p < 0.001) and week 96 (8.87 kPa vs. 6.43 kPa; p < 0.001), respectively. CONCLUSIONS: HBeAg-negative CHB patients with normal ALT could benefit from antiviral therapy with NAs, similar to patients with mildly elevated ALT. Antiviral treatment is strongly recommended for HBeAg-negative CHB patients with normal ALT. Additionally, significant liver fibrosis is not rare in HBeAg-negative CHB patients with ALT less than two-times the upper limit of normal, and FibroScan should be performed regularly for these patients.

Preoperative serum hepatitis B virus DNA was a risk factor for hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND: Tumour characteristics and orthotopic liver transplantation (OLT) criteria are risks for recurrence of hepatocellular carcinoma (HCC). In Asia, most HCC is caused by chronic hepatitis B infection. Whether hepatitis B virus DNA (HBV DNA) is a risk factor for HCC recurrence after OLT is not clear. PATIENTS AND METHODS: In this retrospective study, we classified patients into groups of detectable and undetectable HBV DNA, non-HCC recurrence, and recurrence and performed analyses on differed characteristics between groups and risk factors for HCC recurrence after OLT. RESULTS: Among patients who underwent OLT for HCC, 117 were secondary to CHB infection. CHB was not a risk, but advanced tumour characteristics were risk factor for HCC recurrence. In patients with CHB-HCC, 24 (20.5%) of 117 patients had HCC recurrence. Compared to patients with HBV DNA undetectable (n = 75), patients with detectable HBV DNA (n = 42) had higher AFP concentration (p < .001), higher proportion of macrovascular invasion (p = .014), greater tumour diameter (p < .001), poorer TNM stage (p = .017), and higher proportion of extended OLT criteria (p = .011) and HCC recurrence (p = .036). Preoperative HBV DNA >2000 IU/mL was an independent risk factor for HCC recurrence (OR = 8.35, 95% CI 1.40, 50.00, p = .020). HBV DNA detectable was not a risk for HCC-related death. CONCLUSION: Individuals with preoperative undetectable HBV DNA had advanced tumour characteristics and a higher proportion of HCC recurrence. Antiviral treatment for HCC should be performed, and HBV DNA undetectable should be obtained before OLT. But for an urgent OLT, preoperative detectable HBV DNA may not affect long-term survival.KEY MESSAGESPatients with HBV DNA detectable had advanced tumour characteristics, a higher proportion of extended OLT criteria, and HCC-recurrence.HBV DNA >2000 IU/mL was a risk factor for HCC recurrence.HBV DNA detectable was not a risk for HCC related death; extended OLT criteria affected long-term survival.

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China.

BACKGROUND: Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative HCC patients to allow for improved clinical management and prognostication of the disease. METHODS: This study observed a cohort of HCC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods. RESULTS: Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child-Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR). CONCLUSIONS: The are significant differences in clinical pathologic characteristics between AFP positive and negative HCC patients which may be helpful for the management and prognostication of the disease.

Detection of occult hepatitis B virus infection among subjects with isolated hepatitis B core antibodies: Results from a 3-year survey in an Italian tertiary-care hospital.

BACKGROUND: Hepatitis B virus (HBV) infection causes hepatitis, liver cirrhosis, hepatocellular carcinoma, and death. This study examines the subjects with isolated anti-HBV core antigen antibody (anti-HBcAg), a pattern characterized by the persistent HBV carriage in the absence of HBV surface antigen (HBsAg) and anti-HBsAg antibody. METHODS: Based on medical orders, from 2017 to 2019, serological and molecular assays were performed on serum/plasma samples of 33,048 subjects (71.4% Italians, 28.6% foreigners), who referred to the Virology Unit of the University-Hospital of Parma (Northern Italy) for the laboratory diagnosis of HBV infection. RESULTS: The seroprevalence was 4.6% for HBsAg and 11% for anti-HBcAg. The occurrence of the isolated anti-HBcAg status was 3.1%, with higher frequency in males than in females (66.3% vs. 33.7%, P < 0.0001), in Italians than in foreigners (54.8% vs. 45.2%, P < 0.001), and in outpatients than in inpatients (57.4% vs. 42.6%, P < 0.0001). Foreigners with isolated anti-HBcAg came mostly from Africa (67.9%) and Eastern Europe (26.2%). Among subjects with isolated anti-HBcAg, 14.8% had occult HBV infection, 26.3% hepatitis C virus co-infection, 2% human immunodeficiency virus co-infection, and 3.3% both of these latter co-infections. CONCLUSIONS: The anti-HBcAg assay accurately evaluates the HBV exposure; subjects with isolated anti-HBcAg antibody should be further analysed for HBV DNA. The HBV infection prevalence in Italy is increasing, due to growing migratory flows from endemic areas.

CRISPR-Cas12a-regulated DNA adsorption and metallization on MXenes as enhanced enzyme mimics for sensitive colorimetric detection of hepatitis B virus DNA.

Hepatitis B virus (HBV) infection is closely associated with the high risk of evolving into human hepatitis diseases including chronic hepatitis, liver fibrosis and cirrhosis, as well as hepatoma. Although various methods have been developed for HBV DNA detection, most of them either rely on expensive instruments or laborious procedures involving professional personnel. In this study, we for the first time established the CRISPR-Cas12a based colorimetric biosensor for target HBV detection by utilizing probe DNA regulation of the catalytic behaviors of Mxene-probe DNA-Ag/Pt nanohybrids. In the presence of HBV target, the Cas12a trans-cleavage activity could be efficiently activated to degrade the DNA probes, which led to the inhibition of DNA metallization and enzyme activity enhancer DNA adsorbed on Mxene, resulting in significantly reduced catalytic activity. The Mxene-probe DNA-Ag/Pt nanohybrids exhibited excellent sensitivity and specificity with subpicomolar detection limits, as well as good accuracy and stability for the determination of target HBV DNA in human serum samples. Moreover, this colorimetric sensing strategy could be integrated with the smartphone platform to allow the visible sensitive detection of target DNA. Taken together, the proposed colorimetric method provides a novel approach for HBV DNA diagnosis, especially suitable for the high endemic, developing countries with limited instrumental and medical supports.

The relationship between hepatitis B virus serum DNA, RNA and quantitative hepatitis B surface antigen, and the predictive value for mother-to-child transmission: an observational cohort study.

OBJECTIVE: To explore the relationships between hepatitis B virus (HBV) DNA, HBV RNA and hepatitis B surface antigen (HBsAg) and to evaluate their predictive value for mother-to-child transmission of HBV. DESIGN: An observational cohort study. SETTING: First Hospital of Jilin University. POPULATION: HBsAg-positive and hepatitis B e antigen (HBeAg) -positive pregnant women were recruited. METHODS: Blood samples were collected from mothers before delivery, and HBV infection of infants was evaluated at 7 months of age. RESULTS: Overall, 268 mothers and 271 infants were enrolled. HBV DNA and HBsAg levels were correlated (rs = 0.699; P < 0.001), and HBV DNA (rs = 0.500; P < 0.001) and HBsAg (rs = 0.372; P < 0.001) were both correlated with HBV RNA. The areas under the curve for HBV DNA, HBsAg and HBV RNA for prediction of infection were 0.69 (95% CI 0.57-0.82), 0.63 (95% CI 0.51-0.76) and 0.65 (95% CI 0.52-0.78), respectively. Higher HBV DNA (odds ratio [OR] 4.77, 95% CI 1.44-15.86), higher HBsAg (OR 4.13, 95% CI 1.12-15.25) and higher HBV RNA (OR 3.19, 95% CI 1.09-9.32) were risk factors for HBV infection. Analysis of the HBV DNA-RNA-HBsAg Score revealed that it was an independent predictive factor for mother-to-child transmission (the OR of Score 3 was 8.81, 95% CI 2.79-27.82). CONCLUSION: HBV DNA, HBV RNA and HBsAg were correlated in HBeAg-positive pregnant women. HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. We should pay special attention to pregnant women with high levels of all three markers. TWEETABLE ABSTRACT: HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. Special attention should be given to pregnant women with high levels of all three markers (HBV DNA, HBV RNA and HBsAg).

Frequency of hepatitis B virus-DNA among hepatitis B surface-Ag negative, anti-hepatitis B core antibody-positive blood donors in Yazd, Iran.

BACKGROUND: The diagnosis of hepatitis B infection in most blood transfusion centers is based on hepatitis B surface (HBs) antigen detection by an enzyme immunoassay method. This study aimed to determine the frequency of hepatitis B core (HBc) antibody, HBs antibody, and hepatitis B virus (HBV) DNA among HBs antigen-negative healthy blood donors of Yazd province, Iran. MATERIALS AND METHODS: This cross-sectional study was conducted on 1500 healthy blood donor samples negative for HBs antigen, hepatitis C virus antibody, human immunodeficiency virus antigen/antibody, and rapid plasma regain tests. All samples were screened for HBc antibody test. HBs antibody and real-time polymerase chain reaction were performed for HBc antibody-positive samples. RESULTS: HBc antibody was positive in 74 (4.9%) samples and 11 (14.9%) of 74 positive samples for HBc antibody were negative for HBs antibody. Sixty-three (85.1%) positive samples for HBc antibody had HBs antibody titer over 10 IU/L, and 43 (58.1%) had HBs antibody titer over 100 IU/L. There was no hepatitis B DNA-positive sample in the present study. CONCLUSIONS: The study results suggest that there is a very low risk for transmission of HBV through blood donors of Yazd, Iran.

Quantitative HBsAg versus HBV DNA in Predicting Significant Hepatitis Activity of HBeAg-Positive Chronic HBV Infection.

(1) Background: As specialparameters in predicting significant hepatitis activity of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection, the quantitative standard of HBV DNA has not been agreed and that of hepatitis B surface antigen(HBsAg) has not been formed. Our objective is to evaluate the validity of HBsAg and HBV DNA in predicting the significant hepatitis activity of HBeAg-positive patients. (2) Methods: A population of 516 patients with HBeAg-positive chronic HBV infection was enrolled. Serum ALT was measured using an Abbott Architect c16000 autoanalyzer; diagnoses of liver pathological grade and stage referred to the Scheuer standard. Three levels of significant hepatitis activity were preset, which were successively "ALT ≥ 20 IU/L or Grade > G1 or Stage > S1", "ALT ≥ 30 IU/L or Grade > G1 or Stage > S1" and "ALT ≥ 40 IU/L or Grade > G1 or Stage > S1". (3) Results: A subpopulation of 288 patients with possible high HBV replication was selected based on locally weighted scatterplot smoothing regression curves between ALT and HBsAg, HBeAg and HBV DNA. In the subpopulation with possible high HBV replication, areas under receiver operating characteristic curves of HBsAg for predicting the three levels of significant hepatitis activity were successively 0.868, 0.839 and 0.789, which were all significantly greater than those of HBV DNA, as those were successively 0.553, 0.550 and 0.574 (p = 0.0002, p < 0.0001 and p < 0.0001). With the standard of HBsAg ≤ 4.699 log10 IU/mL, the sensitivity and specificity of HBsAg for predicting the three levels of significant hepatitis activity were successively 75.81% and 81.82%, 79.23% and 78.57% and 80.82% and 67.44%. (4) Conclusion: Quantitative HBsAg instead of HBV DNA is valuable in predicting significant hepatitis activity of HBeAg-positive chronic HBV infection.

A Study of Prevalence of Occult Hepatitis B Virus Infection, Knowledge and Preventive Practices Against Hepatitis B Virus in Barbers Serving the Armed Forces.

OBJECTIVE: Hepatitis B virus (HBV) infection is a major health problem in the world. Barbers deal with frequent abrasions/lacerations due to sharp equipment, making them a high-risk group. Determination of HBsAg positive status excludes most reservoirs of transmission in the population. However, Occult Hepatitis B continues to be a source of transmission. The aim of this study was to study the prevalence of occult HBV infection in barbers serving the armed forces clientele and evaluate their knowledge and preventive practices against HBV transmission. METHODS: Seventy-nine HBsAg negative barbers were included in this study and interviewed for the status of immunisation and preventive practices. Anti-HBc total and HBV DNA levels were measured along with a complete haemogram, LFT, PT INR, ultrasound abdomen and Fibroscan of the liver. RESULTS: The prevalence of occult Hepatitis B status was 3.79%. Among barbers who were anti-HBc total positive, 100% were found to have replicative HBV DNA status. All barbers (100%) were unaware of the existence and modes of HBV transmission and were never screened for HBV; 98.73% of barbers followed improper disinfection practices and were never immunised. CONCLUSION: The prevalence of occult HBV infection in barbers, absence of immunisation, unawareness and improper disinfection practices are significantly at risk for transmission to the unaware clients. It is important to educate barbers, establish a universal disinfection procedure and implement a system of compulsory Hepatitis B vaccination before the commencement of their trade work.