High HBV DNA Research Articles

Risk factors for significant histological changes in both HBeAg positive and negative treatment-naive chronic hepatitis B with persistently normal alanine aminotransferase level

BackgroundChronic hepatitis B virus (HBV) infection remains a serious health issue, and determining the optimal time for antiviral therapy is challenging. We aimed to assess liver histological changes in patients with HBeAg-positive chronic hepatitis B (CHB) and those with HBeAg-negative CHB who had persistently normal alanine aminotransferase and to determine the association between significant liver injury and various clinical parameters.MethodsWe retrospectively included, in this study, 339 treatment-naïve patients with chronic HBV infections who had persistently normal alanine aminotransferase and underwent liver biopsy from 2013 to 2023. Histologic assessment was based on the Metavir scoring system to evaluate the association between clinical characteristics and the severity of liver inflammation and fibrosis.ResultsAmong the included participants, 138 were HBeAg-positive and 201 were HBeAg-negative. Lower hepatitis B surface antigen (HBsAg) (P = 0.003) and higher aspartate aminotransferase (AST) (P = 0.002) levels were associated with significant necroinflammation, whereas increasing age (P = 0.004) and lower HBV DNA (P < 0.001) levels were associated with significant fibrosis in HBeAg-positive patients with normal ALT levels. Higher HBV-DNA (P = 0.001) and AST levels(P < 0.001) were associated with significant necroinflammation, and higher AST(P < 0.001) levels were associated with significant fibrosis in HBeAg-negative patients.ConclusionsA substantial proportion of patients with HBV infection who had normal ALT presented significant liver injury. HBsAg and AST were independent predictive factors for evaluating inflammation, while HBV DNA load and age were independent predictive factors for evaluating fibrosis in the HBeAg-positive group. HBV DNA load and AST were independent predictive factors for evaluating inflammation, while AST were independent predictive factors for evaluating fibrosis in the HBeAg-negative group.

Preoperative Antiviral Therapy and Long-Term Outcomes for Hepatitis B Virus-Related Hepatocellular Carcinoma After Curative Liver Resection: A Multicenter Analysis.

To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing curative-intent hepatectomy. Patients who underwent curative-intent hepatectomy for HBV-related HCC between 2014 and 2019 at 4 Chinese hospitals were analyzed. Patients were categorized as having undergone preoperative antiviral therapy (AVT) > 1 year or without antiviral therapy (non-AVT). Patient clinical features, short-term outcomes, overall survival (OS), and time-to-recurrence (TTR) were also compared. Multivariate Cox regression analysis was performed to identify the impact of preoperative AVT on the OS and TTR. Among the 565 patients, 190 (33.6%) underwent continuous AVT > 1 year before surgery. Patients in the non-AVT group were more likely to have worse liver function and more advanced tumor pathological characteristics than those in the AVT group. Postoperative morbidity and mortality rates were comparable between the two groups. Multivariate analyses revealed that a preoperative HBV viral level ≥ 2000 IU/mL was independently associated with poorer TTR (hazard ratio, 1.328; 95% CI, 1.049-1.682) and preoperative AVT was a protective factor for OS (hazard ratio, 0.691; 95% CI, 0.484-0.986). A high preoperative HBV DNA level was an independent risk factor for tumor recurrence. Preoperative AVT > 1 year was associated with better OS and a reduced incidence of tumor recurrence by inhibiting the preoperative level of HBV DNA.

Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

The effect of intrahepatic cholestasis in pregnancy combined with different stages of hepatitis B virus infection on pregnancy outcomes: a retrospective study.

To investigate the impact of intrahepatic cholestasis of pregnancy (ICP) with hepatitis B virus (HBV) infection on pregnancy outcomes. We selected 512 pregnant women, collected the data including maternal demographics, main adverse pregnancy outcomes and maternal HBV infected markers HBeAg and HBV-DNA loads status, then have a comparative analysis. There were 319 solitary ICP patients without HBV infection (Group I) and 193 ICP patients with HBV infection. Of the latter, there were 118 cases with abnormal liver function(Group II) and 80 cases with normal liver function(Group III). All HBV-infected pregnant women with ICP were divided into hepatitis Be antigen (HBeAg)-positive group (102 cases) and HBeAg-negative group (91 cases), according to the level of the serum HBeAg status; and into high viral load group (92 cases), moderate viral load group (46 cases) and low viral load group (55 cases) according to the maternal HBV-DNA level. Group II had a higher level of serum total bile acids, transaminase, bilirubin as well as a higher percentage of premature delivery, neonatal intensive care unit (NICU) admission and meconium-stained amniotic fluid (MSAF) compared with the other two groups(P < 0.05), but there were no significant differences in the above indicators between the Group I and Group III. Among the HBV-infected patients with ICP, HBeAg-positive group had a higher level of serum transaminase, bilirubin and bile acid as well as earlier gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission than HBeAg-negative group (P < 0.05). Those with a high viral load (HBV-DNA > 106IU/ml) had a higher level of transaminase, bilirubin, and bile acid as well as shorter gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission compared with those with a low or moderate viral load (P < 0.05). HBV-infected pregnant women with ICP combined with abnormal liver function have more severe liver damage, a higher percentage of preterm birth and NICU admission. HBeAg-positive status and a high HBV-DNA load will increase the severity of conditions in HBV-infected pregnant women with ICP. HBV-infected patients with ICP who have abnormal liver function, HBeAg-positive or a high viral load should be treated more actively.

Predictors of Significant Histological Hepatic Abnormality in Treatment-Naive Patients Infected with HBeAg-Negative Chronic Hepatitis B.

This study aimed to determine the predictors for significant hepatic abnormality (SHA), a treatment indication, by assessing demographic, laboratory, and radiological results of chronic hepatitis B (CHB) patients who underwent liver biopsy. In this retrospective study, individuals with untreated hepatitis B e-antigen (HBeAg)-negative CHB infection were enrolled. Multivariate analysis modeling was conducted with parameters identified as predictors for SHA in univariate analysis. Optimal threshold levels for variables to predict SHA in patients with chronic hepatitis B were determined based on receiver operating characteristic (ROC) curve analysis. A total of 566 patients with untreated chronic hepatitis B were included in the cohort; 61% (345/566) were male, and the median age was 41 years (interquartile range [IQR]=34-50). Notably, 36.9% (209/566) had SHA. In the multivariate analysis, utilizing different models, age, gender, HBV-DNA, LDL, ALT, and platelet count were identified as the most reliable predictors for SHA in CHB patients. For predicting SHA, the area under the ROC curve values of HBV-DNA, AST, and ALT were 0.704 (sensitivity=62.8%, specificity=76.2%; p<0.0001), 0.747 (sensitivity=51.9%, specificity=88.9%; p<0.0001), and 0.737 (sensitivity=68.6%, specificity=68.4%; p<0.0001), respectively. In our study, age, male gender, ALT, AST, HBV-DNA, LDL cholesterol, platelet count, and FIB-4 score were independent predictors of SHA in HBeAg-negative chronic hepatitis B. The most sensitive parameters for SHA were LDL and ALT. The most specific parameters were age, AST, and APRI score. SHA may occur in patients with high HBV-DNA levels, even if ALT values are normal in HBeAg-negative patients.

Association of hepatitis B virus DNA levels with efficacy and safety outcomes in patients with hepatitis B virus-associated advanced hepatocellular carcinoma receiving tyrosine kinase inhibitor plus anti-PD-1 antibody: a multicenter propensity-matched study

BackgroundThe efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with anti-PD-1 antibodies (α-PD-1) in advanced hepatocellular carcinoma (HCC) with high hepatitis B virus (HBV) DNA levels (>500 IU/mL) remain unclear. MethodsWe retrospectively assessed patients from seven medical institutions diagnosed with HBV-related HCC, undergoing treatment with TKIs and α-PD-1 in conjunction with antiviral therapies. Based on HBV-DNA levels, patients were categorized into either high (HHBV-DNA, >500 IU/mL) or low HBV-DNA (LHBV-DNA, ≤500 IU/mL) cohorts Propensity score matching (PSM) was used to minimize baseline imbalance between groups. Results149 patients were included, with 66 patients exhibiting HBV-DNA > 500 IU/mL and 83 patients presenting HBV-DNA ≤ 500 IU/mL. Compared with the LHBV-DNA cohort, the HHBV-DNA cohort had a greater incidence of serum HBeAg positivity, tumor diameter ≥ 10 cm, and vascular invasion. Following PSM, 57 individuals were enrolled in each group. Oncological outcomes were comparable between HHBV-DNA and LHBV-DNA cohorts before and after PSM. Before PSM, the median PFS and OS were 6.1 months and 17.5 months in the HHBV-DNA cohort and 6.7 months and 19.3 months in the LHBV-DNA cohort (all P > 0.05). After PSM, the median PFS and OS were 6.0 months and 19.5 months in the HHBV-DNA cohort and 6.0 months and 17.1 months in the LHBV-DNA cohort, respectively (all P > 0.05). Safety profiles were equivalent across cohorts with no fatal incidents reported. Seven patients (4.7 %) had HBV reactivation.1 (0.7 %) from HHBV-DNA and 6 (4.0 %) from LHBV-DNA (P = 0.134). Only one patient developed HBV-related hepatitis. ConclusionsThe effectiveness and safety of TKIs plus α-PD-1 in advanced HCC with HBV-DNA > 500 IU/mL were not compromised in the context of concomitant antiviral therapy.

Effects of neonatal stimulator of interferon genes innate immune signaling pathway of HBsAg-positive mothers on non/hypo-response to hepatitis B vaccine in infants

Objective: To explore the effects of neonatal stimulator of interferon genes (STING) innate immune signaling pathway of HBsAg-positive mothers on non/hypo-response to hepatitis B vaccine (HepB) in their infants. Methods: From November 2019 to June 2022, HBsAg-positive mothers and their infants in the Third People's Hospital of Taiyuan were recruited as the study subjects. The epidemiological and clinical data were collected by questionnaire survey and medical records review. The key molecular proteins of STING innate immune signaling pathway (STING, pIRF3) and immune cells associated with vaccine response (DC, T and B and plasma cells) in neonatal cord blood were detected by flow cytometry. Follow up was conducted for infants for 1-2 months after the full vaccination of HepB. Serum hepatitis B surface antibody (anti-HBs) was detected by chemiluminescence microparticle immunoassay. Unconditional logistic regression model, nomogram and Bayesian network model were used to evaluate the effect of STING innate immune signaling pathway on non/hypo-response to HepB and related factors in infants, and the relationship between various factors. Results: A total of 195 pairs of HBsAg-positive mothers and infants were recruited, the rate of non/hypo-response to HepB in the infants was 12.31% (24/195). High maternal HBV DNA load, low expression of neonatal STING, low expression of pIRF3 and low percentage of plasma cells were risk factors for non/hypo-response to HepB in the infants (OR=4.70, 3.46, 3.18 and 2.20, all P<0.05). The nomogram constructed by these factors had good predictive efficacy (area under curve=0.81, 95%CI: 0.63-0.83). The results of Bayesian network model showed that the infants with a high maternal HBV DNA load had a higher conditional probability of low STING expression (62.50%) and a higher conditional probability of low pIRF3 expression (58.54%). The conditional probabilities of low expression of DC, T, B and plasma cells were 53.16%, 60.20%, 68.42% and 57.14%, respectively. Conclusion: Maternal HBV DNA might inhibit STING innate immune signaling pathways in infants and immune cells associated with HepB response, resulting in non/hypo-response to HepB in infants of HBsAg-positive mothers.

Factors affecting HBV DNA suppression in chronic hepatitis B patients treated with tenofovir disoproxil fumarate.

Background: This study aims to determine the factors affecting HBV DNA suppression in chronic hepatitis B patients with tenofovir disoproxil fumarate (TDF). Methods: A case-control was carried out from October 2021 to August 2022 on 182 chronic hepatitis B patients who had TDF therapy regularly for 24 weeks at H. Adam Malik and USU Hospitals in Medan, Indonesia. The history of the samples was obtained, followed by physical examination, and blood collection. CTLA-4 polymorphism examination was carried out using real-time PCR, while the serum CTLA-4 levels were assessed with ELISA. Results:The CTLA-4 -1661G>A polymorphism, genotype GG+AG, increased 1.52 times risk of not achieving HBV DNA suppression to TDF compared to genotype AA (p=0.041). High CTLA-4 levels increased 2.28 times risk, high HBV DNA levels increased 2.09 times risk, low ALT levels increased 1.95 times risk of not achieving HBV DNA suppression (p= 0.009, 0.026, 0.036, respectively). There was no relationship between gender, age, ethnicity, obesity, baseline AST, HBeAg, genotype, liver fibrosis and HBV DNA suppression after 24 weeks of treatment (p>0.05). Conclusions: The levels of CTLA-4, HBV DNA, ALT, and CTLA-4 -1661G>A polymorphism have a potential relationship with the suppression of HBV DNA in chronic hepatitis B patients with TDF.

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

BackgroundThe 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.Methods3163 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.ResultsThe 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.ConclusionsMaternal 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.

Primary non-response to antiviral therapy affects the prognosis of hepatitis B virus-related hepatocellular carcinoma

Background and aimAlthough antiviral treatments have been shown to affect the recurrence and long-term survival of patients with hepatocellular carcinoma (HCC) who have high viral loads, the effect of different responses to antiviral therapy on the clinical outcomes remains unclear. This study aimed to assess the effect of primary non-response (no-PR) to antiviral therapy on the survival or prognosis of patients with HCC with a high load of hepatitis B virus (HBV) DNA.MethodsA total of 493 HBV-HCC patients hospitalized at Beijing Ditan Hospital of Capital Medical University were admitted to this retrospective study. Patients were divided into two groups based on viral response (no-PR and primary response). Kaplan–Meier (KM) curves were used to compare the overall survival of the two cohorts. Serum viral load comparison and subgroup analysis were performed. Additionally, risk factors were screened and the risk score chart was created.ResultsThis study consisted of 101 patients with no-PR and 392 patients with primary response. In the different categories based on hepatitis B e antigen and HBV DNA, no-PR group had a poor 1-year overall survival (OS). In addition, in the alanine aminotransferase < 50 IU/L and cirrhosis groups, primary nonresponse was related to poor overall survival and progression-free survival. Based on multivariate risk analysis, primary non-response (hazard ratio (HR) = 1.883, 95% CI 1.289–2.751, P = 0.001), tumor multiplicity (HR = 1.488, 95% CI 1.036–2.136, P = 0.031), portal vein tumor thrombus (HR = 2.732, 95% CI 1.859–4.015, P < 0.001), hemoglobin < 120 g/L (HR = 2.211, 95% CI 1.548–3.158, P < 0.001) and tumor size ≥ 5 cm (HR = 2.202, 95% CI 1.533–3.163, P < 0.001) were independent risk factors for 1-year OS. According to the scoring chart, patients were divided into three risk groups (high-, medium-, and low-risk groups) with mortality rates of 61.7%, 30.5%, and 14.1%, respectively.ConclusionsThe level of viral decline at 3 months post-antiviral treatment may predict the OS of patients with HBV-related HCC, and primary non-response may shorten the median survival time of patients with high HBV-DNA levels.

Rapid viral suppression predicts good postoperative recurrence free survivals in patients with hepatocellular carcinoma with a high HBV-DNA titer

Rapid viral suppression predicts good postoperative recurrence free survivals in patients with hepatocellular carcinoma with a high HBV-DNA titer

Abstract 6019: Characteristics and impactof DNA methylationon prognosis in hepatitis B virus-related follicular lymphoma

Abstract Hepatitis B virus (HBV) infection (surface antigen positive, HBsAg+) has been linked to the increased risk and poor prognosis for B-cell lymphoma. Here, we aimed to discover distinctive potential factors to influence the prognosis in HBV-associated follicular lymphoma (FL). Retrospective investigation from multiple clinical centers showed that patients with HBsAg+ FL were featured with a higher incidence of disease progression within 24 months (POD24, P=0.031), shorter progression-free survival (PFS, P = 0.004) and overall survival (OS, P = 0.039). The patients with high HBV-DNA load (&amp;gt;10^5 copies/mL) had worse PFS (P &amp;lt;0.001) and OS (P = 0.007). Methylation detection identified that POD24 in HBsAg+ FL were contributed by pro-tumoral methylated KMT2A, EP300-AS1, and ARID1B. The majority of MHC I class molecular retained hypermethylated status with silencing expression to promote immune escape and progression in HBsAg+ FL. Hypermethylated TNFRSF1A significantly contributed to prevent the POD24 of HBsAg+ FL, whereas hypermethylated LTA promoted progression. Regarding the unsatisfactory prognosis guidance based on FLIPI in patients with HBsAg+ FL, we proposed new scoring combined with HBV-related clinical parameters, contributed gene methylation and FLIPI to define a high-risk group with worse prognosis than FLIPI in our study (mean OS, 67.7 vs 69.8). It exhibited good performances in internal cohort and external validation cohort from other three clinical centers. Taken together, chronic HBV infection may affect methylation of the immune-related genes to promote progression in FL. The combination of clinical features and genes methylation with FLIPI could provide a better prognostic model for HBV-related FL. Univariable and multivariable Cox regression analysis with respect to progression-free survival of c Univariate analysis Multivariate analysis HR 95%CI P value HR 95%CI P value Age(&amp;gt;60 vs ≤60) 1.457 0.963-2.205 0.073* 1.608 1.037-2.493 0.034 Sex(male vs female) 0.876 0.578-1.325 0.529 Grade(3A va 1-2) 1.315 0.847-2.042 0.221 Ann Arbor stage(III/IV vs I/II) 0.852 0.526-1.379 0.513 Number of extranodal sites≥5 0.732 0.483-1.110 0.141 B symptoms 1.679 1.028-2.741 0.036* 2.023 1.142-3.584 0.016 BM involvement 0.690 0.383-1.244 0.215 High FLIPI risk 3.081 1.740-5.454 &amp;lt;0.001* 1.972 1.023-3.803 0.043 Elevated LDH level 1.317 0.829-2.092 0.242 Serum albumin &amp;lt;3.5 g/dL 2.633 1.315-5.270 0.004* 1.465 0.649-3.309 0.358 ALC &amp;lt;1000/μL 1.581 0.641-3.898 0.316 HBsAg positivity 1.850 1.209-2.833 0.004* 1.184 0.705-1.991 0.523 HBeAg positivity 1.668 0.768-3.623 High HBV-DNA load(&amp;gt;10^5 copies/mL) 4.110 2.360-7.160 &amp;lt;0.001* 3.774 1.958-7.278 &amp;lt;0.001 Treatment (BR vs R-CHOP) 1.261 0.752-2.113 0.379 Citation Format: Jianli Ma, Yuwei Deng, Huilai Zhang, Xiaosan Zhang, Lihong Liu, Xianhuo Wang, Hongtao Song, Zirong Zhang, Caili Liu, Qingyuan Zhang, Jinming Yu. Characteristics and impactof DNA methylationon prognosis in hepatitis B virus-related follicular lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6019.

Inadequate Hospital Practices to Prevent Mother-to-Child Transmission of Hepatitis B Virus Infection: A European Survey.

Prevention of vertical transmission of Hepatitis B virus (HBV) infection is crucial to eliminate viral hepatitis as a major public health threat by 2030. We aimed to assess the current hospital policies and practices implemented before, at, and after birth, and to evaluate potential barriers to the full application of international guidelines. A web-based survey was supported by Penta Foundation and distributed across Europe from October to December 2021. Overall, 76 centers with delivery departments completed the survey. HBsAg maternal screening is performed in the first trimester of pregnancy in 53% of the centers and in the third in 46%. HBsAg positive pregnant women are tested for serologic HBV markers and HBV-DNA in 78% and 63% of the departments; 38% of the HBeAg positive women with high HBV-DNA levels are treated during the last trimester of pregnancy. At birth, 91% of the departments administer HBV vaccine to infants born to HBsAg positive mothers within 12 hours of birth; 74% test women with unknown HBsAg status and 78% of them wait for the maternal testing results before administering HBV vaccine to their newborns. After birth, 47% of the departments provide post-vaccination serological testing for infants born to HBsAg positive mothers. The timing of the HBV vaccine schedule varies greatly. There is significant heterogeneity in the hospital policies and correlated procedures. The implementation of a multidisciplinary clinical pathway is a must if a stronger connection between the prenatal, perinatal, and postnatal phases is to be established.

Assessment of Viral and Clinical Characteristics Among Patients With Chronic Hepatitis B Virus Infection in Georgia

Hepatitis B virus infection (HBV) is one of the major healthcare problems in Georgia. To achieve viral hepatitis elimination, gaps in diagnosis and management of chronic HBV infection need to be addressed. The aim of our study was to collect data on clinical and viral characteristics of patients with chronic HBV infection to estimate the proportion of patients who may need antiviral treatment. All relevant deidentified data about demographic, clinical, and viral characteristics were extracted from patients' medical records. Descriptive statistical analyses were done for univariate assessment of demographic, virologic, and clinical characteristics. Chi-square test was used to assess the associations between HBV-DNA level, HBeAg, alanine aminotransferase (ALT), and liver fibrosis. In total, 96% (124/129) of patients with chronic HBV infection are HBeAg-negative; 84% (145/173) had no or mild fibrosis, and 3% (6/162) had advanced liver fibrosis/cirrhosis. Sixty-five out of 126 (51%) patients were classified as HBeAg-positive or HBeAg-negative chronic HBV infection (without hepatitis); 11 (9%) as chronic hepatitis B; 46 (37%) had not classified in any of the known HBV phases, while 30 of them (24% out of total) had high viral load and normal ALT. Statistically significant association was seen between high HBV-DNA and HBeAg-positivity (P= .043). High ALT level was also associated with liver fibrosis (P= .015). Significant positive correlation between age and the presence of moderate or advanced liver fibrosis was observed (P= .002). This is the first study about the clinical and viral characteristics of patients with chronic HBV infection in Georgia. The vast majority were HBeAg-negative, only 3% had advanced liver diseases; about half of patients had inactive diseases. However, one out of four patients had a high viral load but normal ALT. By the evaluation of HBV phases, we estimated that 12%-36% of patients with chronic HBV monoinfection require antiviral treatment.

A Predictive Model to Evaluate the HbeAg Positivity of Chronic Hepatitis B Virus Patients in Clinics: A Cross-Sectional Study.

Background and Objective: The study aims to investigate the correlation between Hepatitis B ‘e’ antigen (HBeAg) and HBV DNA levels, and to find a convenient tool to estimate the HBV DNA level for clinicians. Materials and Methods: We enrolled 1020 patients in this cross-sectional study and divided them into four groups: an HbeAg-positive and -negative group, and high and low HBV DNA levels groups. Results: Alanine aminotransferase (ALT), Albumin (ALB) and HBeAg are independent risk factors for CHB patients. When the level of HBeAg is higher than 16.15 S/CO, it is four times more likely that the patients will have high levels of HBV DNA than those who do not. The ALT and TB are independent risk factors in HBeAg-negative patients with a high HBV DNA level. We have drawn three predictive models to estimate the HBV DNA levels for those with the chronic hepatitis B virus (CHB), and those that are HBeAg-positive and HBeAg-negative (Y1 = 0.004 × ALT(IU/L) + 1.412 × HBeAg (S/CO) − 0.029 × ALB (g/L) + 0.779, the AUC is 0.672, and the cutoff value is −0.072, there the sensitivity is 0.615, the specificity is 0.648, PPV is 65.182% and NPV is 60.837%; Y2 = 0.007 × HBeAg (S/CO) − 0.016 × HGB (g/L) + 3.070, the AUC is 0.724, and the cutoff value is 1.216, where the sensitivity is 0.626, the specificity is 0.897, PPV is 94.118% and NPV is 34.437%; Y3 = −0.005 × ALT(IU/L) + 0.006 × TB (umol/L) + 0.385, the AUC is 0.661, and the cutoff value is 0.263, where the sensitivity is 0.677, the specificity is 0.587, PPV is 66.820% and NPV is 40.774%, respectively). We propose that HBeAg is the most important risk factor for the patient with a high HBV DNA level, however, it is not as important in the HBeAg-positive group. Conclusions: HBeAg is an independent risk factor that reflects the level of HBV DNA with a strong correlation. Patient with HBeAg (−) should combine TB and ALT to estimate the level of HBV DNA.

A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Combination of IL-34 and AFP improves the diagnostic value during the development of HBV related hepatocellular carcinoma

IL-34 involves in host immunity regulated carcinogenesis. Alpha-fetoprotein (AFP) is related to the development of HCC. We explored if combination of IL-34 and APF could improve the diagnostic value in HBV related hepatocellular carcinoma (HBV-HCC). Serum was obtained from HBV patients or healthy control. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBV-HCC patients. Serum IL-34 and MCSF, or intrahepatic IL-34, MCSF and CD68+ tumor associate macrophages (TAMs) were determined using ELISA or immunohistochemistry. Serum IL-34 was 1.7, 1.3 or 2.3-fold higher in HBV-HCC than that of CHB, HBV related cirrhosis or healthy control, which was inhibited following trans-hepatic arterial chemoembolization (TACE) in HBV-HCC patients. Intra-hepatic IL-34 was higher in HBV-HCC than that of the other three groups. Intra-hepatic IL-34 was associated with high HBV-DNA, HBeAg−, poor differentiation and small tumor size of HBV-HCC patients. Intra-hepatic TAMs in HBV-HCC were increased 1.7 or 1.3-fold, compared to that from CHB or HBV-cirrhosis patients. Intra-hepatic TAMs were associated with high HBV-DNA, high tumor differentiation, small tumor size, abnormal AFP and more tumor number. AFP plus serum IL-34, showed the highest AUC (0.837) with sensitivity (0.632) and highest specificity (0.931), suggesting that AFP plus IL-34 enhances the reliability for prediction of the development of HBV-HCC among CHB patients. Circulating and intra-hepatic IL-34 was upregulated gradually in HBV disease progression from CHB, cirrhosis and HCC. IL-34 may be used as a diagnostic biomarker and potential therapeutic target for the management of HBV-HCC.

A long-term study of liver-related events in Caucasian hepatitis B patients with normal ALT values and high viremia.

There is ongoing debate whether antiviral therapy should be initiated in hepatitis B e antigen (HBeAg)-negative patients with normal alanine aminotransferase (ALT) levels but high HBV DNA levels >2,000 IU/mL. Since the need for antiviral therapy might be different between Asian and Caucasian patients, we studied the long-term disease outcome in Caucasian patients living in Western Europe. One hundred sixteen patients with high HBV DNA levels (>2,000 IU/mL) at diagnosis were included in the high viremia group, while those with HBV DNA <2,000 IU/mL were used as controls (n = 327). All patients were Caucasian, HBeAg negative, had normal ALT levels and had no significant liver disease at diagnosis. Median follow-up was 7 + 9.8 years in the high viremia group and this was 10 + 12.5 years in controls. The cumulative probability of a liver-related event over 10 years was 4.8% vs 0.0% in the control group (p=.008). In multivariable analysis, high viremia group was associated with the occurrence of a liver-related event (hazards ratio (HR) 95% confidence interval (CI): 1.20-11.98, p=.023). In this subgroup, older age at diagnosis (HR 95% CI: 1.01-1.16, p=.023) predicted a higher risk of liver-related event. In the high viremia group, liver-related mortality was 0.9% and none of the patients developed hepatocellular carcinoma. HBV DNA >2,000 IU/mL influences the long-term disease outcome in Caucasian HBeAg-negative patients living in Western Europe. Nevertheless, the risk of liver-related events is low.

Acute-Phase Serum Amyloid A May Predict Microvascular Invasion and Early Tumor Recurrence in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma Undergoing Liver Resection

Objective To elucidate the impact of acute-phase protein serum amyloid A (aSAA) on microvascular invasion (MVI) and early recurrence in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods HBV-related HCC patients (n = 192) undergoing liver resection were included in the study. The protein levels of aSAA were analyzed by immunohistochemical staining in 172 tumor specimens, and further detected via western blotting in HCC and their corresponding portal vein tumor thrombus (PVTT) (n = 20). Cox and logit regression analysis was performed. Exploratory subgroup analysis was used to balance the potential confounders. Results HBV-related HCC patients with high aSAA levels tended to have high HBV-DNA loads. Logit and Cox regression analyses revealed high expression of aSAA is an independent risk factor not only for MVI (OR 5.384, 95% CI 2.286–13.301, P < 0.001) but also for early recurrence (HR 6.040, 95% CI 1.970–18.540, P = 0.002), overall recurrence (HR 3.720, 95% CI 2.140–6.450, P < 0.001), and overall survival (HR 4.15, 95% CI 2.380–7.230, P < 0.001). Subgroup analysis showed that the effects of aSAA were consistent across all subgroups examined. Additionally, the aSAA protein level was significantly higher in PVTT than that in its corresponding tumor specimen. A high HBV-DNA level and large tumor size were the independent risk factors for early HCC recurrence in patients with high levels of aSAA. Conclusions High expression of aSAA was an independent risk factor for MVI and early tumor recurrence in HBV-related HCC patients after liver resection. The aSAA protein level could thus be a promising biomarker for predicting MVI and early recurrence in these patients.

Analysis on influencing factors of HBV intrauterine transmission based on integration of decision tree model and logistic regression model

Objective: To investigate the influencing factors of HBV intrauterine transmission and their interaction effects by integrating logistic regression model and Chi-squared automatic interaction detector (CHAID) decision tree model. Methods: A total of 689 pairs of HBsAg-positive mothers and their neonates in the obstetrics department of the Third People's Hospital of Taiyuan from 2007 to 2013 were enrolled, and the basic information of mothers and their neonates were obtained by questionnaire survey and medical record review, such as the general demographic characteristics, gestational week and delivery mode. HBV DNA and HBV serological markers of the mothers and newborns were detected by fluorescence quantitative PCR and electrochemiluminescence immunoassay respectively. The CHAID decision tree model and unconditional logistic regression analysis were used to explore the factors influencing HBV intrauterine transmission in neonates of HBsAg-positive mothers. Results: Among the 689 neonates, the incidence of HBV intrauterine transmission was 11.47% (79/689). After adjusted for confounding factors, the first and second logistic multivariate analysis showed that cesarean delivery was a protective factor for HBV intrauterine transmission (OR=0.25, 95%CI: 0.14-0.43; OR=0.27, 95%CI: 0.15-0.46); both models indicated that maternal HBeAg positivity and HBV DNA load ≥2×105 IU/ml before delivery were risk factors of HBV intrauterine transmission (OR=3.89, 95%CI: 2.32-6.51; OR=3.48, 95%CI: 2.12-5.71), respectively. The CHAID decision tree model screened three significant factors influencing HBV intrauterine transmission, the most significant one was maternal HBeAg status, followed by delivery mode and maternal HBV DNA load. There were interactions between maternal HBeAg status and delivery modes, as well as delivery mode and maternal HBV DNA load before delivery. The rate of HBV intrauterine transmission in newborns of HBeAg-positive mothers by vaginal delivery increased from 19.08% to 29.37%; among HBeAg-positive mothers with HBV DNA ≥2×105 IU/ml, the rate of HBV intrauterine transmission increased to 33.33% in the newborns by vaginal delivery. Conclusions: Maternal HBeAg positivity,maternal HBV DNA ≥2×105 IU/ml and vaginal delivery could be risk factors for HBV intrauterine transmission in newborns. Interaction effects were found between maternal HBeAg positivity and vaginal delivery, as well as vaginal delivery and high maternal HBV DNA load. Logistic regression model and the CHAID decision tree model can be used in conjunction to identify the high-risk populations and develop preventive strategies accurately.