Quantitative Hepatitis Research Articles

Comparison of Anti-Hepatitis A Antibody Pharmacokinetics in Healthy Australian Subjects Receiving Standard or Weight-Based Dosing of Polyvalent Immunoglobulin.

This randomized controlled trial compared two dosing regimens of the polyvalent immunoglobulin available for hepatitis A post-exposure prophylaxis in Australia. Participants were randomized to receive either 270 IU (standard dose) or 3.375 IU/kg (dose by weight). Quantitative serial serum hepatitis A antibody concentrations were measured at baseline and then on days 1, 3, 7, 28, and 50. Fifteen participants completed the trial. Serum hepatitis A antibody concentrations were not different between the study groups at any time point. Pharmacokinetic parameters estimated from participant data were not different between the study groups. The hepatitis A antibody level of all participants exceeded 10 mIU/mL at day 50. While no difference between dosing regimens was found in this study, further research should examine dosing at the lower limit of current Australian recommendations before making policy decisions.

Overview of HbsAg Testing Results for Chronic Kidney Disease Patients Undergoing Hemodialysis at Ciamis Hospital

Background & Objective: Chronic renal failure is a slow and incurable disease. Regular treatment can halt the deterioration of kidney function, with kidney transplantation and hemodialysis being the most common options. However, hemodialysis patients are at risk of contracting the Hepatitis B virus due to the use of repeated vascular access and high frequency of hemodialysis. This study aims to describe the results of HBsAg examination in patients with chronic renal failure who undergo hemodialysis. Method: The research is a descriptive study that used a purposive sampling technique and was conducted in May-June 2022. The study included 44 chronic renal failure patients who underwent HBsAg examination using the Immunochromatography method. Result: The study's results showed that all 44 respondents (100%) who underwent hemodialysis had negative HBsAg examination results, indicating that they were not exposed to the Hepatitis B virus. Conclusion: In conclusion, the study indicates that chronic renal failure patients undergoing hemodialysis are not at risk of contracting the Hepatitis B virus. Further research could include quantitative Hepatitis B antibody examinations.

Evaluating the relationship between hepatitis B viral activity and gestational diabetes mellitus: A prospective cohort study.

Hepatitis B infection has been associated with the development of gestational diabetes but the underlying mechanism is not known. To examine associations between viral activity, gestational diabetes mellitus (GDM), and insulin resistance in pregnant people with chronic hepatitis B infection (HBV). Prospective cohort study across three tertiary maternity centres in Melbourne, Australia, between May 2021 and April 2023. Participants were followed prospectively through pregnancy to evaluate subsequent GDM diagnosis. Demographics, pregnancy outcomes, and markers of viral activity were compared between those with GDM versus those without. Logistic regression analysis was performed pre- and post-adjustment for known confounders. Sub-group analysis of participants from South East Asia (SEA) was performed. Outcome measures included GDM diagnosis, insulin resistance (Homeostatic Model Assessment Insulin Resistance score (HOMA-IR) score), HBV activity as measured by liver function tests, HBV viral load, hepatitis B e antigen, and quantitative hepatitis B surface antigen (quantHBsAg). A total of 113 women were recruited. One third (38/112, 33.9%) developed GDM, mostly diagnosed on isolated postprandial hyperglycaemia (25/38, 65.8%). Over half were born in SEA (66/113, 58.4%). Mean quantHBsAg was significantly lower in those with GDM (p = 0.044). No other associations were identified between GDM or HOMA-IR and markers of hepatic activity on multivariate logistic regression analysis and on sub-group analysis of those born in SEA. QuantHBsAg was significantly lower in those with GDM; otherwise, no association between GDM and measures of HBV viral activity was found. QuantHBsAg may be useful as an early pregnancy marker for GDM risk and warrants further research.

Higher end-of-treatment HBsAg levels is associated with later onset but not severe relapse in HBeAg-negative chronic hepatitis B patients stopping antivirals.

Quantitative hepatitis B surface antigen (qHBsAg) level at end-of-treatment (EOT) predict clinical relapse (CR) after nucleos(t)ide analogues (Nuc) in chronic hepatitis B(CHB) patients. It is unclear if higher EOT qHBsAg leads to earlier onset or more severe off-Nuc CR. This large cohort study investigates the association between EOT qHBsAg and CR onset/severity. This study enrolled HBeAg-negative CHB patients who had achieved undetectable HBV DNA for over 1 year after receiving Nuc therapy before discontinuation. The EOT qHBsAg level was categorised into three groups: <100, 100-999, ≥1000 IU/mL. The study assessed the predictability of qHBsAg levels for CR, and analysed and compared the incidence, time to onset and severity of CR among these three groups. Patients with higher EOT qHBsAg showed a higher incidence of CR (≥1000, 100-999, <100 IU/mL: 73%, 65%, and 38%, p < 0.01) but a later onset of CR (median time to CR: 35, 33 and 27 weeks, p < 0.01). The predictabilities of EOT qHBsAg for CR were greater in patients aged <50-year-old or with genotype C than in those aged ≥50-year-old or with genotype B. There's no correlation between EOT qHBsAg level and ALT folds at CR (Pearson correlation coefficient: r = -0.03, p = 0.35). EOT qHBsAg was neither a predictor for severe hepatitis flare nor a predictor for hepatic decompensation. Predictability using EOT qHBsAg levels for CR differed in subgroups of age and genotypes. Higher EOT qHBsAg levels correlate with higher incidence but later onset of CR. No correlation between EOT qHBsAg and relapse severity was observed.

Steady Decline of HBV DNA Load under NAs in Lymphoma Patients and a Higher Level of qAnti-HBc Predict HBV Reactivation.

Background: Patients with lymphoma and chronic hepatitis B virus infection need to be treated with both chemotherapy and nucleotide analogue (NA) therapy. However, dynamic changes in HBV DNA loads with increasing chemotherapy cycles are lacking. It is unknown whether HBV replication markers, namely, the quantitative hepatitis B core antibody (qAnti-HBc), HBV RNA, and the hepatitis B virus core-related antigen (HBcrAg), are also markers for predicting HBV reactivation (HBVr). Methods: From 29 June 2010 to 6 December 2021, the data of patients with single-site diffuse large B-cell lymphoma and HBV infection (HBsAg+ and HBsAg-/anti-HBc+) were collected from a hospital medical record system, retrospectively. Serum HBV DNA loads (using real-time fluorescent quantitative PCR tests), qAnti-HBc levels (using a newly developed chemiluminescent particle immunoassay), HBV RNA levels (using the simultaneous amplification testing method based on real-time fluorescence detection), and HBcrAg levels (using a Lumipulse G HBcrAg assay) were tested, and factors related to HBVr were analyzed. Results: Under NAs, the HBV DNA loads of 69 HBsAg+ lymphoma patients declined from 3.15 (2.13-4.73) lg IU/mL to 1.00 (1.00-1.75) lg IU/mL, and further declined to 1.00 (1.00-1.04) lg IU/mL at the end of a 24-month follow-up. The qAnti-HBc levels decreased gradually during chemotherapy in HBsAg+ lymphoma patients (F = 7.090, p = 0.009). The HBV RNA and HBcrAg levels remained stable. A multivariate analysis revealed that higher qAnti-HBc levels (1.97 ± 1.20 vs. 1.12 ± 0.84 lg IU/mL, OR = 6.369, [95% CI: 1.523-26.641], p = 0.011) and higher HBV RNA levels (1.00 ± 1.13 vs. 0.37 ± 0.80 lg copies/mL, OR = 3.299, [95% CI: 1.229-8.854], p = 0.018) were related to HBVr in HBsAg-/anti-HBc+ lymphoma patients. Conclusions: HBV DNA loads declined under NAs during chemotherapy in lymphoma patients. In HBsAg-/anti-HBc+ lymphoma patients, a higher level of baseline serum qAnti-HBc and HBV RNA levels can predict the likelihood of HBVr during chemotherapy.

Comparison between Quantitative Hepatitis B DNA and HBeAg Positivity to Detect Active Viral Replication among Patients with Hepatitis B infection in a Tertiary Care Hospital

To study the correlation between quantitative Hepatitis B DNA and HBeAg positivity among HBsAg positive patients in a tertiary care hospital. To detect HBsAg, HBeAg levels by CMIA (Chemiluminescent microparticle immunoassay). To perform quantitative Hepatitis B virus DNA assay using Real Time Polymerase Chain Reaction. The study took place between July and December 2022 for 6 months. Sixty four patients were included in the study for whom HBsAg was positive by CMIA and for whom HBeAg (detected by CMIA) and Hepatitis B Virus DNA by quantitative Real Time PCR was performed. Of the 64 HBsAg reactive patients, the ‘e’ antigen of Hepatitis B virus was positive in six patients. In all the six HBeAg positive patients, HBV DNA was detected with a range of 78-10,288 IU/ml with 66% having levels more than 2000 IU/ml and requiring treatment. Among the 58 patients who were negative for the ‘e’ antigen of Hepatitis B virus, the Hepatitis B Viral DNA was detected in 27 patients with a range of 10-1,76,000 IU/ml, with 21% of patients having levels more than 2000 IU/ml. HBeAg is a good serological test to detect viral replication. However, it alone might not be sufficient as quantitative HBV DNA levels are more accurate and it does identify more patients who may require treatment.

Interpreting Serogical Markers in Hepatitis B Virus Infection

Abstract Hepatitis B virus (HBV) is considered a global health-related problem. The World Health Organization estimates an incidence of approximately 1.5 million new cases annually despite an available effective vaccine, and approximately 296 million people worldwide are living with chronic hepatitis B. This large number of patients require continuous monitoring of the treatment efficacy, disease progression, and screening for the HBV-related liver complications. Recently, it has become more evident that we need better predictive markers to allow treatment cessation when there is a reduced risk of viral reactivation, in addition to the present need to predict disease outcome and improve the management of people living with chronic hepatitis B. Novel HBV biomarkers are focused on in this minireview. These new markers include quantification of serum HBV RNA, hepatitis B core–related antigen, quantitative hepatitis B surface antigen, quantitative anti–hepatitis B core antigen, and detection of HBV nucleic acid–related antigen. The target of finding new markers for HBV replication is to provide crucial clinical data in a noninvasive way for detecting the replicative and transcriptional activity of the virus. This may support better management of patients compared with the criterion-standard invasive marker for detecting the intrahepatic replication and transcription of HBV, which is the quantification of covalently closed circular DNA.

Role of HBsAg levels in guiding hepatitis B virus prophylaxis in pregnancy: Insights from a multi-ethnic cohort.

Pregnant mothers with chronic hepatitis B infection (CHB) need peri-partum antiviral prophylaxis (PAP) to reduce the risk of mother-to-child-transmission. Currently, PAP is recommended in those with high viral load (VL) that is, HBV DNA >200,000 IU/mL. Quantitative hepatitis B surface antigen (qHBsAg) >10,000 IU/mL, a cut-off derived primarily from hepatitis B e-antigen (HBeAg) positive antenatal cohorts in Chinese populations, is advocated as a surrogate marker of VL for guiding PAP. We investigated the utility of qHBsAg to predict high-VL in a multi-ethnic urban cohort with CHB. A consecutive cohort of women with CHB was identified from Barts Health NHS Trust databases in the United Kingdom. We included women with paired HBV DNA and qHBsAg during pregnancy. Women already on antiviral at conception were excluded. A total of 769 pregnancies in 678 CHB pregnant mothers (median age 31 years-old, 8.6% HBeAg+) were included. At median gestational age of 15.3 weeks, HBV DNA was 336 (IQR 44-2998) IU/mL, with 65 (8.5%) being high-VL. Serum qHBsAg was most useful in Black/Black-British/Caribbean/African (AUROC 0.946) with 100% sensitivity and 80.6% specificity to predict high-VL; but it performed less well for other ethnicities: Asian (AUROC 0.877), White (AUROC 0.797) and mixed ethnicities (AUROC 0.742). In conclusion, for settings where healthcare resources are not limited, HBV DNA remains the optimal marker to identify highly viraemic pregnancies for guiding PAP. For resource-limited settings where the prevailing cost is treatment, serum qHBsAg can be used in Black/Black British/Caribbean/African sub-cohorts, but not for other ethnicities.

Efficacy of Lactococcus lactis strain Plasma on clearance of anal HPV infection in men who have sex with men: A single-center, double-blinded, randomized placebo-controlled trial (CLEAR HPV study)

Background: Anal cancer is a human papillomavirus-related cancer; specifically, it is preceded by high-grade squamous intraepithelial lesions, which are less likely to regress spontaneously than low-grade intraepithelial lesions. Although most human papillomavirus (HPV) infections are thought to clear spontaneously, anal HPV infection persists, especially in people living with HIV. Preliminary results from a recent small randomized placebo-controlled trial of oral bacteriotherapy using a high dose of probiotics demonstrated clearance of anal high-risk HPV (hr-HPV) infection and lower onset of new high-grade squamous intraepithelial lesions among people living with HIV. Lactococcus lactis strain Plasma is a lactic acid bacterium directly activating plasmacytoid dendritic cells and inducing release of type I and III interferons via Toll-like receptor 9 stimulation. Based on these findings, oral bacteriotherapy with LC-plasma may contribute to clearing anal hr-HPV infection and reducing anal precancerous lesions by activating innate and acquired immune responses. This randomized placebo-controlled trial aims to investigate the efficacy and safety of LC-plasma therapy in clearing anal hr-HPV infection and reducing anal precancerous lesions among men who have sex with men with or without HIV infection. Methods: Participants with anal hr-HPV infection will be included and receive test capsules. A total of 150 patients will be included in the intervention group with follow-up, which will consist of HPV genotype test, cytology by anal pap smear, and biopsy with high-resolution anoscopy. The primary endpoint will be the clearance rate of the hr-HPV genotype infection at the anal site at 180 days. The secondary endpoints will be changes in anal epithelial neoplasia detected using high-resolution anoscopy at 180 days; change in abnormal cytology by anal pap smear at 180 days; change in hr-HPV genotype at the anal site at 180 days; change or percentage change in peripheral blood CD4 positive T-lymphocyte numbers in HIV-infected participants at 180 days; changes in quantitative hepatitis B surface antigen levels at 180 days in the HBV-infected participants; and adherence to the study drugs. Conclusion: This randomized controlled study will provide data on the efficacy and safety of LC-plasma as a treatment for anal HPV infection and grade 2 or 3 anal intraepithelial neoplasia.

Effectiveness and Safety of Tenofovir Alafenamide in Treatment-Naïve and Treatment-Experienced Patients with Chronic Hepatitis B: Results of a Real-World Study from China

Background: Tenofovir alafenamide (TAF) has been effective against naïve patients with chronic hepatitis B (CHB) in phase 3 clinical trials. However, its real-world data are still limited. Objectives: This study aimed to investigate the effectiveness and safety of TAF in real-life situations in treatment-naïve (TN) and treatment-experienced (TE) CHB patients in China. Methods: This retrospective study enrolled TAF-treated patients between January 2019 and October 2020 at the outpatient clinic of West China Hospital. The primary endpoint was the rates of virologic response (VR), and the secondary endpoints were the proportion of normal alanine aminotransferase (ALT) and quantitative hepatitis B surface antigen (qHBsAg) levels. Safety endpoints comprised serum lipid profiles, changes in estimated glomerular filtration rate (eGFR), and serum creatinine (Scr). Results: A total of 161 TAF-treated patients were enrolled, including 49 TN patients and 112 TE patients. In the TN group, the VR rate at week 96 was 91.7% (22/24), and the proportion of normal ALT at week 96 was 95.8% (23/24). In the TE group, the VR rate at week 96 was 97.2% (69/71), and the proportion of normal ALT at week 96 was 90.1% (64/71). Serum qHBsAg levels decreased from 2930 to 1292 IU/mL in the TN group and 1158 to 533IU/mL in the TE group during 96 weeks of treatment (P = 0.05). For patients in the TN and TE groups, when compared to baseline measurements, serum creatinine increased (+7.91 vs. +6.62 mL/min/1.73 m2, P = 0.52) while eGFR decreased (-11.46 vs. -10.90 µmol/L, P = 0.82) at week 96. Simultaneously, triglycerides (TG) (+ 0.39 vs. + 0.31 mmol/L, P = 0.32), total cholesterol (TC) (+0.65 vs. +0.52 mmol/L, P = 0.02), and low-density lipoprotein cholesterol (LDL-C) (+0.25 vs. +0.25 mmol/L, P = 0.60) increased over time. Conclusions: TAF was highly effective in TN and TE CHB patients. However, there are potential risks in eGFR decrease and a continuous increase in lipidemia with the prolongation of medication time.

Long-term quantitative hepatitis B surface antigen (HBsAg) trajectories in persons with and without HBsAg loss on tenofovir-containing antiretroviral therapy.

Improving the understanding of the patterns of quantitative hepatitis B surface antigen (qHBsAg) trajectories associated with HBsAg loss is important in light of novel anti-hepatitis B virus agents being developed. We evaluated long-term qHBsAg trajectories in persons with HIV and HBV during tenofovir-containing antiretroviral therapy in the Swiss HIV Cohort Study. We included 29 participants with and 29 without HBsAg loss, defined as qHBsAg <0.05 IU/mL. We assessed qHBsAg decline during therapy in both groups and used agglomerative hierarchical clustering to identify different qHBsAg trajectory profiles in persons with HBsAg loss. The median follow-up time was 11.9 years (IQR 8.4-14.1), and the median time to HBsAg loss was 48 months (IQR 12-96). Among participants with HBsAg loss, 79% had a qHBsAg decline ≥1 log10 IU/mL 2 years after starting tenofovir. The trajectories in qHBsAg levels during tenofovir therapy were heterogeneous, characterized by five distinct profiles. Among participants without HBsAg loss, only 7% had a qHBsAg decline ≥1 log10 IU/ml after 2 years. Most persons with HIV who experienced HBsAg loss had an early decline in qHBsAg levels, with diverse trajectories during long-term tenofovir therapy. In persons without HBsAg loss, qHBsAg levels remained remarkably stable over time.

Optimization and Application of Quantitative In-House ELISA for Diagnosis of HBsAg and its Correlation with Commercial ELISA and Molecular Kits

Background: Several studies have indicated the role of quantitative hepatitis B surface antigen (HBsAg) evaluation in managing and prognosis of hepatitis B virus (HBV) infection. Thus, quantitative evaluation of HBsAg using cost-effective assays can be an important approach to managing HBV patients. Objectives: This study aimed to set up and apply an in-house quantitative enzyme-linked immunosorbent assay (ELISA) to evaluate HBsAg in research and diagnosis. Methods: New Zealand white rabbits were immunized with HBsAg. Sera were collected 28 days after immunization, and polyclonal HBsAb (antibody to hepatitis B surface antigen) were purified and evaluated. Then, the in-house quantitative ELISA was optimized. Finally, the functional characteristics of the assay were evaluated using 200 plasma samples compared to commercial ELISA and quantitative TaqMan real-time PCR. Results: The assay has a limit of detection (LOD) of 0.5 ng/mL with a specificity and sensitivity of 94% and 97%, respectively. The assay's highest coefficient of variation (CV) values for intra- and inter-assays were 7.23% and 8.59%, respectively. The correlation of the developed assay with commercial ELISA was 0.987 (P-value = 0.024). The correlations of the developed assay and commercial ELISA with quantitative TaqMan real-time PCR were 0.739 and 0.658, respectively (P-value = 0.017). Conclusions: The developed assay has a suitable sensitivity and specificity. It is also reproducible and well-correlated with commercial assays. Most importantly, it is cost-effective and, thus, can be used for detecting and quantifying HBsAg in research and diagnosis.

Evaluation and Determination of Quantitative Hepatitis B Surface Antigen Diagnostic Performance in Chronic Hepatitis B Virus-Infected Patients.

Background Hepatitis B virus DNA (HBV-DNA) assessment is recommended for diagnosing and monitoring chronic hepatitis B (CHB) patients. Quantitative hepatitis B surface antigen (qHBsAg) estimation adjunct to HBV-DNA is vital for assessing HBV chronicity and therapeutic prognosis. This study aimed to estimate the qHBsAg and compare its diagnostic performance with that of the HBV-DNA levels in CHB patients from Bangladesh. Methodology A total of 148 CHB patients were enrolled in this study. qHBsAg and hepatitis B e-antigen (HBeAg) were estimated using chemiluminescent and enzyme immunoassays, respectively, and HBV-DNA was quantified using real-time polymerase chain reaction. The parameters and diagnostic performances were analyzed by receiver operating characteristic (ROC) curve analysis. Results The overall levels (mean ± SD) of qHBsAg, HBV-DNA, and alanine aminotransferase (ALT) among the total population (n = 148) were 3.45 ± 0.80 log10 IU/mL, 4.40 ± 2.44 log10 IU/mL, and 86.17 ± 39.06 IU/L, respectively. Significant differences were observed in the levels of both qHBsAg (p = 0.004) and HBV-DNA (p < 0.0001) in cases with HBeAg positivity. qHBsAg levels showed a weak positive correlation with the levels of HBV-DNA and ALT in HBeAg-positive CHB patients, but no such relationship was observed in HBeAg-negative CHB patients. ROC curve analysis showed that the area under the curve for the qHBsAg level to distinguish high HBV-DNA levels (>5 log10 IU/mL) was 0.653 (p = 0.002), which indicated an acceptable diagnostic performance. The best cut-off of qHBsAg for predicting high HBV-DNA levels was 3.469 log10 IU/mL. Conclusions Our results indicated that qHBsAg might be a useful marker for monitoring HBV-DNA in CHB patients throughout treatment and follow-up.

Correlation Between Quantitative Hepatitis B Surface Antigen and Hepatitis B Virus Deoxyribonucleic Acid Levels in Hepatitis B e Antigen-Positive and Hepatitis B e AntigenNegative Chronic Hepatitis B Patients.

This study aimed to analyze the relationship between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid in hepatitis B e antigen-positive and hepatitis B e antigen-negative chronic hepatitis B patients and to determine the best cut-off value for quantitative hepatitis B surface antigen to predict high hepatitis B virus deoxyribonucleic acid levels (≥2000 IU/mL). Ninety-seven sera from chronic hepatitis B patients were collected in this study. Hepatitis B virus deoxyribonucleic acid levels were quantified by real-time polymerase chain reaction. Quantitative hepatitis B surface antigen and hepatitis B e antigen levels were determined by two-site sandwich chemiluminescence immunoassay. Alanine transaminase levels were measured by the International Federation of Clinical Chemistry-approved methods. A significant correlation between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid levels was observed in hepatitis B e antigen-positive group (r = 0.453, P = .002), but not in hepatitis B e antigen-negative group (r = 0.117, P = .454). No significant correlation between quantitative hepatitis B surface antigen and alanine transaminase was found in the hepatitis B e antigen-positive group (r = 0.521, P = .241). However, a significant correlation was shown between quantitative hepatitis B surface antigen and alanine transaminase levels in the hepatitis B e antigen-negative group (r = 0.455, P = .001). The best cut-off value of quantitative hepatitis B surface antigen for predicting high hepatitis B virus deoxyribonucleic acid levels was 3.422 × 103 IU/mL. Correlation between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid levels is significant in the hepatitis B e antigen-positive group. Quantitative hepatitis B surface antigen can be used to predict high hepatitis B virus deoxyribonucleic acid levels in the hepatitis B e antigen-positive group.

A real-world retrospective single-centre study of the cost-effectiveness and long-term outcomes of pegylated interferon for chronic hepatitis B.

Pegylated interferon (Peg-IFN) is recommended as first-line therapy for chronic hepatitis B (CHB) but has significant side effects and is rarely used compared to oral nucleos(t)ide analogues (NA). There are limited recent clinical efficacy or economic analysis data comparing approved CHB therapy in North America. This retrospective study examined clinical outcomes, off-treatment durability, and cost-effectiveness of Peg-IFN versus NA for CHB. Demographic (age, sex, ethnicity), clinical data (i.e., liver tests, hepatitis B virus DNA, serology, transient elastography) and documented side effects were collected by retrospective chart review of patients followed in the University of Calgary Liver Unit who received Peg-IFN therapy from January 2007 to December 2020. The cost-effectiveness of Peg-IFN versus NA therapy was modelled over a 10-year time horizon. Sixty-eight CHB patients were treated with Peg-IFN (median age 45.65, 74% male, 84% Asian); 50/68 (74%) completed 48 weeks of treatment with a median follow-up of 6.54 years (interquartile range 5.07). At the last known follow-up, 23/68 (34%) have not required NA treatment and one had HBsAg loss; 27 have been started on NA. Predictors of obtaining a sustained virological response included being hepatitis B e antigen-negative at treatment end and a quantitative hepatitis B surface antigen <1000 IU/mL. Economic modelling showed that finite Peg-IFN was not cost-effective versus NA at a 10-year time horizon. PEG-IFN remains a potential treatment for CHB although there is a significant intolerance/failure rate. Using PEG-IFN based on patient preference is reasonable and optimal patient selection may improve treatment cost-effectiveness.

Evaluation of Quantitative Hepatitis C Virus Core Antigen Testing as a Tool for Screening and Confirmation of HCV Infection.

Hepatitis C is a common viral infection worldwide. Finding the most effective diagnostic methods with low cost is always needed for laboratory improvement. In this study, we evaluated the performance of a quantitative chemiluminescent hepatitis C virus core antigen (HCV cAg) test by comparing it with the HCV confirmatory antibody line immunoblot assay (HCV Ab-LIA) test as well as the HCV quantitate reverse transcription-polymerase chain reaction (qRT-PCR) test. A total of 394 samples were enrolled in the retrospective study. Of these, 225 samples were tested using HCV Ab screening and confirmatory Ab-LIA along with chemiluminescent HCV core Ag testing, while 169 samples were tested using qRT-PCR for HCV RNA and chemiluminescent HCV core Ag testing. Out of these, 225 positive samples tested by HCV Ab screening test were analyzed using the confirmatory Ab LIA and HCV cAg assays, a total of 183 samples (81.3 %) were confirmed to be Ab-positive, and among those, 77 samples (42.1%) were also positive for HCV cAg. Thirty-eight samples (20.76%) were HCV Ab indeterminate, and all of them were HCV cAg negative. Four samples (1.8%) were HCV Ab LIA-negative and negative for HCV cAg. Moreover, 169 samples were measured for qRT-PCR HCV viral load and quantitative HCV cAg test. One hundred and three samples were positive for HCV RNA, while 66 were negative. Among the positives, 96/103 samples were HCV cAg positive and 7/103 samples were negative. Out of the negatives, 4/66 samples were HCV cAg positive but 62/66 samples were negative. The HCV cAg results were concordant with the qRT-PCR results in 158 samples (93.5%); however, 11 samples (6.5%) were found to be discrepant. The sensitivity, specificity, positive predictive value, and negative predictive value of the quantitative HCV cAg were found to be 93%, 94%, 96%, and 90%, respectively. The overall coefficient of correlation between the HCV RNA levels and HCV cAg data was determined to be r2 = 0.9. The HCV cAg test showed a high correlation with the HCV RNA levels and may potentially be used as a more cost-effective alternative to the HCV RNA qRT-PCR test.

Correlation between serum quantitative HBsAg and HBV DNA levels in chronic hepatitis B patients

Background/Aim. Quantitative hepatitis B virus (HBV) surface antigen (qHBsAg) has become increasingly wide-spread in the last few years in both diagnostic and therapeutic protocols for HBV infection. Numerous studies have proposed it as a surrogate marker for covalently closed circular DNA (cccDNA). The aim of the study was to determine the correlation between qHBsAg and HBV DNA viremia in untreated patients. Methods. The study included 112 untreated patients diagnosed with chronic HBV infection. Demographic and other data from medical records and laboratory analyses, taken as part of routine chronic HBV infection diagnosis with the determination of qHBsAg and HBV DNA viremia, were recorded for all patients. Results. The average age of the patients included in the study was 48.27 ? 15.14 years; males (58%) were more represented. qHBsAg levels had a high-intensity positive correlation with HBV DNA viremia. The concentration of qHBsAg, HBV DNA viremia, and the concentrations of alanine aminotransferase and aspartate aminotransferase showed statistically significantly higher values in HBV e antigen (HBeAg)-positive than in HBeAg-negative patients. Conclusion. Our study showed that qHBsAg has a high-intensity positive correlation with HBV DNA viremia. The use of qHBsAg is essential for determining the phase of chronic HBV infection, assessment of the success and length of treatment, as well as for safe discontinuation of antiviral therapy with a lower risk of relapse.

Acute Hepatitis B Virus Infection in North American Adults

Acute hepatitis B virus (aHBV) is thought to be self-limited with clearance of hepatitis B surface antigen (HBsAg) within 6 months. There are limited reports of the presenting features and outcomes of adults with symptomatic aHBV in the United States. Demographics, clinical features, and 12-month outcomes of patients with adjudicated aHBV were captured prospectively and compared with a contemporaneous cohort of chronic HBV (cHBV) patients enrolled in the Hepatitis B Research Network. Between 2011 and 2018, 60 adjudicated patients with aHBV were compared with 1534 cHBV untreated controls. Although similar in age, other features were dissimilar: aHBV patients were more often male (72% vs 51%), single (72% vs 30%), and non-Hispanic whites or blacks (75% vs 24%). They also were frequently genotype A2 (65% vs 9%), having different risk factors: sexual exposure (75% vs 16%) or injection drug use (10% vs 2%), compared with the cHBV controls. In addition to higher serum aminotransferase and bilirubin levels, acute patients had higher HBV DNA levels (4.8 vs 3.6 log10 IU/mL), whereas quantitative hepatitis B e antigen (HBeAg) levels were lower (1.4 vs 3.0 log10 IU/mL), despite higher rates of HBeAg (73% vs 25%). The median time to HBsAg clearance was 27 weeks and to anti-HBs appearance, 41 weeks. In the current era, caucasian men infected with genotype A2 as a result of sexual exposure or injection drug use were the predominant group in aHBV, suggesting a potential strategy for adult vaccination in North America. Strikingly, only an estimated 36% of subjects cleared HBsAg by month 6; the definition of resolution in acute hepatitis B may need to be modified. ClinicalTirals.gov number NCT01263587.

An improved method for rapid identification of hook effect samples in HBsAg quantitative assay

Quantitative hepatitis B surface antigen assay is widely used for diagnosis of hepatitis B virus infection; however, specimens with high levels of the antigen can cause false-negative results (Hook effect), which needs to be resolved. The hook effect samples and non-hook effect samples were detected on the LiCA® 500 instrument using three methods, viz., 1, 2, and 3. Method 1, the currently used procedure, was performed in two steps with a total reaction time of 25 min in a final volume of 250 µL: first incubation was with two reagents for 15 min and then with one other reagent for 10 min. In Method 2, all three reagents were added in one step with a final volume of 250 µL, and the total reaction time was still 25 min. In Method 3, the improved method, all three reagents were added in one step while the final volume was only 130 µL and the total reaction time was only 1 min. Signal values of the non-hook effect samples obtained using Method 2 were significantly lower than those with Method 1, showing competitive inhibition. The hook effect samples tested with Method 2 approximated those obtained using Method 1. Method 3 took 1 min and differentiated hook effect samples successfully, similar to the results with Method 2 which took 25 min. Changing the timing of one reagent addition and incubation time in Method 3 provided a rapid and effective method for the identification of hook effect. The results were more clearly distinguishable due to the phenomenon of competitive inhibition. Method 3 can be considered an improvement on the chemiluminescence platform.

Quantitative anti-HBc combined with quantitative HBsAg can predict HBsAg clearance in sequential combination therapy with PEG-IFN-α in NA-suppressed chronic hepatitis B patients.

Background and aimsPrecise predictors are lacking for hepatitis B surface antigen (HBsAg) clearance under the combination therapy of nucleos(t)ide analogs (NA) and pegylated interferon-alpha (PEG-IFN-α) in patients with chronic hepatitis B (CHB). This study aimed to determine the quantitative anti-hepatitis B core antibody (qAnti-HBc) and quantitative hepatitis B core-related antigen (qHBcrAg) as predictors for HBsAg clearance in NA-suppressed patients with CHB receiving PEG-IFN-α add-on therapy.MethodsSeventy-four CHB patients who achieved HBV DNA suppression (HBV DNA < 20 IU/ml) and quantitative HBsAg (qHBsAg) < 1,500 IU/ml after ≥1 year of NA treatment were enrolled. Fifteen patients continued on NA monotherapy, while 59 patients received PEG-IFN-α add-on therapy. Serum qAnti-HBc and qHBcrAg levels were detected every 12 or 24 weeks for add-on and NA-alone groups, respectively.ResultsSerum qAnti-HBc but not qHBcrAg levels at baseline were negatively correlated with the duration of prior NA therapy. After 48-week treatment, both qAnti-HBc and qHBcrAg levels declined further, and 17/59 (28.81%) and 0/15 (0%) achieved HBsAg clearance in add-on and NA groups, respectively. In the add-on group, the rate of HBsAg clearance was significantly higher in patients with baseline qAnti-HBc < 0.1 IU/ml (52.63%). Logistic regression analysis identified baseline qAnti-HBc but not qHBcrAg, which was an independent predictor for HBsAg loss. Receiver operating characteristic curve analysis showed that the combination of qAnti-HBc and qHBsAg had a better predictive value for HBsAg clearance.ConclusionsA combination of qHBsAg and baseline qAnti-HBc levels may be a better prediction strategy for HBsAg clearance in NA-suppressed CHB patients receiving PEG-IFN-α add-on therapy.