Hepatitis B Virus Deoxyribonucleic Acid Levels Research Articles

Assessment of liver fibrosis by transient elastography among human immunodeficiency virus/hepatitis B virus and hepatitis B virus-mono-infected patients on tenofovir therapy in Jos, Nigeria

Objectives: Chronic hepatitis B (CHB) infection, both in human immunodeficiency virus (HIV) coinfection and hepatitis B virus (HBV)-mono-infection, is associated with a risk of progression to chronic liver disease. In Nigeria, there is a paucity of data on transient elastography (TE) in HIV/HBV and HBVmono-infected patients. This study aimed at assessing liver fibrosis using TE in relation to liver function biomarkers and HBV deoxyribonucleic acid (DNA) among HIV/HBV and HBV-mono-infected patients on long-term antiviral therapy. Material and Methods: This was a cross-sectional study among HBV–HIV and HBV-mono-infected adult’s patients receiving a tenofovir-containing antiretroviral and mono-tenofovir ≥12 months at three selected tertiary hospitals in Jos Metropolis from February 2018 to May 2019, after obtaining ethical approval from the Institutional Review Boards and informed consents. The patients’ HBV DNA, platelet count, hematological, and biochemical parameters were assessed, and liver stiffness was measured by TE in kilopascals (kPa), and valid TE measurements were interpreted as: normal (F0– 1 0–4), minimal fibrosis (F2 5–7.4), moderate (F3 7.5.9.4), and severe fibrosis and cirrhosis (F4 ≥9.5). Results: A total of 101 (50 HIV/HBV and 51 HBV-mono-infected) were enrolled during the study period, comprising 42.6% males and 57.4% females. The median age interquartile range among HIV/HBV coinfected was 40.5 years (36.0–45.3) and HBV-mono-infected was 41.0 years (35.0–49.0). The median platelet count was low in the HBV-mono-infected group 195 × 109/L (168–257), P = 0.034. The overall prevalence of severe liver fibrosis (≥9.5 kPa) was 13/101 (13.0%), and among HIV/HBV-coinfected and HBV-mono-infected patients, the prevalence was 4/50 (8.0%) and 9/51 (17.6%), respectively. The plasma HBV DNA was <20 copies/mL in 38/50 (76.0%) HIV/HBV coinfected individuals and in 30/51 (58.8%) of HBV-mono-infected patients. In addition, 10/50 (20.0%) HIV/HBV coinfected and 19/50 (37.3%) HBV-mono-infected patients had plasma HBV DNA levels of 20–20,000 copies/mL. In the case of HIV/HBV coinfection, the prevalence of severe fibrosis (≥9.5) was 4/50 (8.0%), while in HBV-mono-infected patients, the prevalence was was 9/51 (17.6%). The overall prevalence of thrombocytopenia was observed in 4/101 cases (3.9%): 1/50 (2.0%) in HIV/HBV coinfected individuals and 3/51 (5.9%) in HBV-mono-infected patients. Conclusion: Severe liver fibrosis as observed among HIV/HBV-coinfected and HBV-mono-infected patients in this study affirmed the necessity of routine HBV screening in clinics and it highlights the immense potentials of tenofovir therapy in the treatment of CHB patients.

Effectiveness and Safety of Tenofovir Alafenamide Fumarate in the Prevention of Perinatal Hepatitis B Transmission: A Meta-Analysis.

This study aimed to assess the effectiveness and safety of tenofovir alafenamide fumarate (TAF) in the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). We performed a meta-analysis of studies from the Cochrane Library, PubMed, ClinicalTrials.gov, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), China Medical Information Network, and Wanfang databases. The databases were searched from inception to January 7, 2023, for cohort studies and randomized controlled trials (RCTs) comparing the use of TAF antivirals to other antivirals during pregnancy. We combined the data by means of a random-effect DerSimonian-Laird model and risk ratios (RRs) or a random-effect inverse variance model and standardized mean differences (SMDs) to determine the influence on mothers and infants. Our primary outcomes were infant weight, height, head size, birth defects, and Apgar scores. Additionally, we assessed whether newborns tested positive for hepatitis B surface antigen (HBsAg) at birth and at six months of age. The secondary outcomes of our investigation were alterationsin levels of HBV deoxyribonucleic acid (DNA), alanine aminotransferase (ALT), total bilirubin (TBIL), blood creatinine, and urine β2-microglobulin (β2-M)in mothers. An extensive literature search identified 216 relevant publications; three cohort studies and two RCTs were included in this study. A total of 341 mothers were treated with TAF, and 342 were treated with other antiviral agents. TAF was as effective as other antiviral medications at lowering HBV MTCT rates at birth and at 6months of age and ALT, TBIL, and HBV DNA levels. Moreover, compared with other antiviral drugs, TAF did not affect infant weight, height, head size, Apgar scores, and birth defects or maternal blood creatinine or β2-M levels. TAF antiviral therapy during pregnancy was found to be safe for both mothers and fetuses.

Use of serum Golgi protein 73 for screening chronic hepatitis B virus infection patients needing antiviral therapy in the community.

Use of serum Golgi protein 73 for screening chronic hepatitis B virus infection patients needing antiviral therapy in the community.

346.1: Hepatitis B virus Suppression Predicts Better Recurrencefree Survivals in Liver Transplant Patients With Hepatocellular Carcinoma

Introduction: High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is known to be a strong risk factor of hepatocellular carcinoma (HCC) development. The aim of study was to investigate the predictive role of HBV DNA levels in recurrence of HCC after liver transplantation (LT). Methods: From June 2006 to May 2020, 729 recipients underwent LT for HBV-related HCC in Seoul National University Hospital. The risk factors for HCC recurrence after LT were analyzed including serum HBV DNA load. Results: Recurrence-free survival at 1, 3, 5, and 10 years were 99.6%, 98%, 95.1%, and 87.8%, respectively. Detectable HBV DNA level (higher than 10 IU/mL) before transplant was significant predictors of HCC recurrence in univariate analysis (P=0.027). Further subgroup analysis was performed to demonstrate the significance of HBV DNA level according to the risk of HCC recurrence. Based on the score of the predicted survival after liver transplantation for HCC (SALT), patients were divided in three groups. In high risk group of recurrence with SALT score more than 2.44, detectable HBV DNA level were significantly associated with recurrence free survival (57.9 % vs. 78.7 %, P<0.0001). Conclusion: There is a close relationship between HBV DNA level and HCC recurrence after transplant. High HBV DNA levels before transplant are associated with HCC recurrence after transplant, especially in high recurrence risk group.

Liver histology of treatment-naïve children with chronic hepatitis B virus infection in Shanghai China

ObjectivesChronic hepatitis B (CHB) is associated with high morbidity and mortality. We aimed to investigate associations between hepatic histology and clinical characteristics in treatment-naïve children with CHB in Shanghai, China. MethodsThe liver biopsy specimens of 278 treatment-naïve children with CHB virus infection were scored for inflammation and fibrosis, and correlations with clinical and laboratory data were determined. ResultsCHB clinical, virologic, and pathologic features were studied in 278 treatment-naïve children (177 [63.7%] males) in Shanghai, China. Maternal sera were positive for hepatitis B surface antigen for 277 children. At biopsy, 87.4% of patients were hepatitis B e antigen–positive. The median age at biopsy was 5.1 years (interquartile range 2.8-8.4 years). Hepatitis B virus (HBV) deoxyribonucleic acid levels were generally high (mean 7.4 log10 IU/ml), as were levels of serum alanine aminotransferase (ALT, median 105 U/l). Using the Metavir histology activity index scoring system, no, mild, moderate, and severe inflammation were seen in 2.9%, 22.3%, 73.4%, and 1.4% of patients, respectively. No fibrosis, mild fibrosis, moderate fibrosis, and cirrhosis were seen in 11.5%, 32.7%, 47.5%, and 8.3% of patients, respectively. When the serum ALT level was ≤80 (two times the upper limit of normal) and >80 U/l, the inflammation score (P <0.0001) was significantly different, and the fibrosis score was also significantly different (P <0.0001). Inflammation and fibrosis were aggravated with increasing ALT levels. Fibrosis scores were significantly higher in children aged ≤3 than aged >3 years (P <0.0001). The rates of moderate fibrosis and cirrhosis were higher in children aged ≤3 years at biopsy. No correlations were found between histologic changes and sex, HBV genotype, or HBV deoxyribonucleic acid level. ConclusionSubstantial heterogeneity in inflammatory and fibrotic levels was observed in treatment-naïve children with CHB in Shanghai, China. Serum ALT levels >80 U/l may be a strong indicator of the degree of hepatic inflammation and fibrosis severity. Moderate fibrosis and cirrhosis can appear in children aged 3 years or younger.

Big Data Information under Proportional Hazard Mathematical Model in Analysis of Hepatitis B Virus Infection Data of Patients with Interventional Liver Cancer through Antiviral Therapy of Entecavir.

The objective of this study was to analyze the application of proportional hazard mathematical model (PHMM) in Hepatitis B Virus (HBV) infection analysis of interventional liver cancer patients treated with entecavir, so as to provide data support for clinical diagnosis and treatment. Based on the survival analysis, the treatment factor x was undertaken as an independent variable to perform linear regression. The regression model took the hazard rate function as the dependent variable to establish an exponential regression equation to construct a PHMM. 136 patients with primary liver cancer receiving interventional chemoembolization combined with the drug (entecavir) were selected as the experimental group, who were in the computer gene expression omnibus (GEO). 87 patients with primary liver cancer who underwent interventional chemoembolization therapy without antiviral treatment were taken as the control group. The PHMM was adopted for comprehensive analysis. In addition, the factors affecting the virological response to antiviral therapy were analyzed using the multiple logistic regression. The results revealed that HBV deoxyribonucleic acid (DNA) negative conversion rate, Hepatitis B e-Antigen (HBeAg) negative conversion rate, and HBeAg serological conversion rate in the experimental group were much higher than those in the control group (P < 0.05). HBV DNA level and proportion of HBsAg <100 IU/mL in the experimental group were much lower than those in the control group (P < 0.05). The virological breakthrough rate and incidence of adverse events at week 24 in the experimental group were greatly lower than those in the control group (P < 0.05). The adverse virological response of patient was positively correlated with HBV DNA load and HBeAg status and negatively correlated with alanine aminotransferase (ALT) level (P < 0.05). Therefore, entecavir can significantly inhibit HBV DNA replication in patients with liver cancer, showing high antiviral effect. High baseline HBV DNA load, positive HBeAg, and low baseline alanine aminotransferase levels were independent risk factors for adverse virology response to entecavir antiviral therapy, which provided a reference for the selection of antiviral drugs for HBV infection.

Interaction between hepatitis B virus infection and the efficacy of camrelizumab in combination with apatinib therapy in patients with hepatocellular carcinoma: a multicenter retrospective cohort study.

BackgroundThe interaction between hepatitis B virus (HBV) load and anti-programmed cell death (PD)-1 in combination with (+) antiangiogenic therapy remains controversial, especially for hepatocellular carcinoma (HCC) patients. This study sought to explore the effects of HBV load and antiviral therapy on anti-PD-1+ antiangiogenic therapy, and the rate of HBV reactivation during anti-PD-1+ antiangiogenic treatment.MethodsWe performed a multicenter retrospective cohort study of camrelizumab combined with apatinib (C+A) therapy between January 1, 2019 and January 1, 2021 in patients with unresectable HCC who were seropositive for hepatitis B surface antigen (HBsAg) and received antiviral therapy before C+A involvement. The effects of HBV load and antiviral therapy on C+A and the rate of HBV reactivation during C+A treatment were examined.ResultsEighty-six patients were included in the analysis. The patients had a mean age of 55 years, and 72 (83.7%) were male. The objective response rates (ORRs) in patients with low (<2,000 IU/mL) and high (≥2,000 IU/mL) baseline HBV deoxyribonucleic acid (DNA) levels were 34.5% and 32.2%, respectively (χ2=0.046; P=0.829), while the disease control rates (DCRs) were 67.3% and 80.6%, respectively (χ2=1.762; P=0.184). The results of the univariate and multivariate analyses showed that the baseline HBV DNA level did not affect PD. Additionally, none of the 86 patients suffered from HBV reactivation or HBV-related hepatic impairment with continuous antiviral treatment, regardless of nucleos(t)ide analogue (NA) type (F=1.473; P=0.228).ConclusionsBaseline HBV loads did not affect the tumor responses of HCC patients receiving anti-PD-1+ antiangiogenic therapy. Thus, HBV reactivation should not be a contradiction for anti-PD-1+ antiangiogenic therapy among patients undergoing continuous and effective antiviral treatment.

East Asia expert opinion on treatment initiation for chronic hepatitis B.

Globally, chronic hepatitis B (CHB) is a major public health concern. Timely and effective management can prevent disease progression to cirrhosis and reduce the risk of hepatocellular carcinoma (HCC). Currently, there is no consensus on the clinical management of CHB in East Asia. To establish an East Asia expert opinion on treatment initiation for CHB based on alanine aminotransferase (ALT) level, hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, cirrhosis and HCC risk scores. A meeting was held online with a panel of 10 experts from East Asia to discuss ALT, HBV DNA, cirrhosis and HCC risk scores. Indications for CHB treatment in the latest international guidelines were reviewed. Consensus was summarised to provide recommendations on the initiation of treatment for CHB. Anti-viral therapy is recommended for CHB patients with (a) HBV DNA≥2000IU/mL and ALT≥1× upper limit of normal (ULN); (b) HBV DNA≥2000IU/mL, ALT<1× ULN and≥F2 fibrosis and/or≥A2 necroinflammation occurs; (c) cirrhosis and detectable HBV DNA; or (d) HBV DNA≥2000IU/mL, ALT<1× ULN and a family history of cirrhosis or HCC, extrahepatic manifestations or age>40years. Patients with cirrhosis and/or HCC should be treated regardless of ALT levels if HBV DNA level is detectable. Initiating anti-viral therapy or close monitoring at 3-month intervals is recommended for CHB patients with at least two HCC risk factors. These expert recommendations will contribute to a new standard of daily clinical practice in East Asia.

Virological activity in treatment-naïve HBeAg-negative HBV-infected adult patients: A community-based study in Jiangsu, China.

Nowadays most of the hepatitis B virus (HBV) infected population are adults, among which hepatitis B e antigen (HBeAg) negative infection occupied the largest proportion of HBV infection in China. HBeAg-negative patients are heterogeneous, and the corresponding interventions are different. Therefore, it is worth researching the infection characteristics of HBeAg-negative patients to help guide the interventions.A total of 11,738 treatment-naïve HBeAg-negative adult patients were randomly selected, and their demographic and medical history information were collected. The liver biochemistry, and HBV infection biomarkers including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg, hepatitis B e antibody (anti-HBe), hepatitis B core antibody (anti-HBc), and hepatitis B virus deoxyribonucleic acid (HBV-DNA) levels were tested. The infection characteristics and their influencing factors were explored.Sixty percent of the patients presented HBV-DNA-positive, of which 31.2% had HBV-DNA level higher than 2000 IU/mL, and 16.5% had HBV-DNA level higher than 20,000 IU/mL. HBV-DNA levels tended to increase along with the increasing of age, and the male patients had significant higher HBV-DNA levels than the female patients. Twenty-four percent of the patients had abnormal transaminase. The male patients were more vulnerable to abnormal transaminase (30.0%) than the female patients (18.4%). Fifty-five percent patients with HBV-DNA ≥20,000 IU/mL presented abnormal alanine aminotransferase (ALT) or aspartate transaminase (AST), which was significantly higher than that of patients with HBV-DNA levels below 20,000 IU/mL (19.0–21.7%). Multivariate logistic regression analyses revealed that the male patients and the patients with higher viral load had higher risk of having abnormal liver function.A considerable number of HBeAg-negative patients were virological active and had liver damage. It is necessary and urgent to carry out regular active interventions for the chronic HBV-infected patients.

Incidence of hepatitis B virus infection among human immunodeficiency virus-infected treatment naïve adults in Botswana.

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection is highest in sub-Saharan Africa and results in accelerated clinical outcomes compared with HBV or HIV mono-infection. HBV clearance rates are higher in healthy adults; however, in sub-Saharan Africa, there are limited data on clearance of incident HBV in HIV-infected adults. Therefore, we sought to estimate HBV incidence and HBV surface antigen (HBsAg) clearance in HIV-infected adults in Botswana.This was a retrospective longitudinal study of 442 HIV-1C infected treatment naïve patients enrolled in a previous Botswana Harvard AIDS Institute Partnership study. Archived plasma samples from 435 HIV-infected treatment naïve participants were screened for HBsAg and HBV core antibody (anti-HBc). HBsAg was evaluated annually over a 4-year period, and HBV deoxyribonucleic acid (DNA) levels of HBsAg-positive chronic and incident patients were quantified.Baseline median CD4+ T-cell count was 458 cells/μL [Q1, Q3: 373, 593], and median HIV viral load was 4.15 copies/mL [Q1, Q3: 3.46, 4.64]. Twenty two HBV incident cases occurred, representing an incidence of 3.6/100 person-years [95% CI: 2.2–5.6]. All incident HBV cases with a follow-up sample available for screening (13/22) cleared HBsAg. Detectable HBV viral loads among chronic and incident cases ranged between 5.15 × 101 to 1.4 × 107 IU/L and 1.80 × 101 to 1.7 × 108 IU/mL, respectively.We report high HBV incidence associated with elevated HBV DNA levels despite high CD4+ T-cell counts in HIV-infected patients in Botswana. These incidence cases represent a potential source of HBV transmission in the population. Scaling-up of HIV treatment strategies utilizing antiretroviral therapy regimens with anti-HBV activity coupled with screening for HBV infections in households of the HBsAg-positive cases is recommended.

Correlation of liver function with intestinal flora, vitamin deficiency and IL-17A in patients with liver cirrhosis.

The aim of this study was to investigate the correlation of liver function, intestinal flora, vitamin D and interleukin-17A (IL-17A) levels in patients with liver cirrhosis. A total of 52 patients diagnosed with posthepatitic cirrhosis and admitted into Yantai Infectious Disease Hospital (Yantai, China) from January to December in 2012 (liver cirrhosis group), and 52 patients with chronic hepatitis B (hepatitis group), and 40 healthy volunteers receiving physical examination in the hospital (normal control group) were selected into the study. The liver function, hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, intestinal flora distribution, vitamin D and IL-17A levels of all patients were detected, and the correlation among them was analyzed via Pearson's analysis. The number of Enterobacteriaceae, Enterococcus, Staphylococcus aureus and Saccharomyces in hepatitis and liver cirrhosis groups was significantly greater than in the normal control group (P<0.05), but the number of Lactobacillus, Bacteroides, Bifidobacterium and Clostridium was significantly decreased (P<0.05); the serum IL-17A levels in hepatitis and liver cirrhosis were obviously higher than that in the normal control group (P<0.05), but the serum vitamin D 25(OH) D and 1,25(OH)2D levels were obviously lower than that in the normal control group (P<0.05). In patients with liver cirrhosis, Enterobacteriaceae was positively correlated with prothrombin time (PT), Enterococcus was positively correlated with alanine aminotransferase and aspartate aminotransferase (AST) levels, Bifidobacterium was negatively correlated with AST, alkline phosphatase (AKP) and HBV DNA levels, and Bacteroides was negatively correlated with AST level and PT. There was a significant negative correlation between serum IL-17A and total bilirubin in patients with liver cirrhosis, and 25(OH) D was negatively correlated with AST, AKP and HBV DNA levels. In patients with liver cirrhosis, there was significant positive correlation between Enterococcus and IL-17A, and between Lactobacillus and 25(OH)D, but other bacteria were not obviously associated with IL-17A and vitamin D. Intestinal flora imbalance, vitamin D deficiency and IL-17A imbalance play an important role in the evolution of liver cirrhosis.

Effect of indigenous interferon - alpha on Hepatitis B virus deoxyribonucleic acid level in hepatitis b e antigen-positive chronic Hepatitis B patients

&lt;p class="ABS"&gt;&lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Background and Objective:&lt;/span&gt; HBeAg-positive chronic hepatitis B patients have high serum HBV DNA level showing high viral replication. Goal of treatment of hepatitis B is to prevent cirrhosis, hepatic failure and hepatocellular carcinoma by serum alanine transaminase (ALT) normalization, decrease in serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and loss in hepatitis B e antigen (HBeAg). Interferons (IFNs) have antiviral, anti-proliferative, and immunomodulatory effects. IFN-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; is effective in suppressing HBV replication and in inducing remission of liver disease. &lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Materials and Methods:&lt;/span&gt; In this prospective, single treatment arm study, HBeAg-positive chronic hepatitis patients without decompensated liver disease were enrolled to receive indigenous recombinant IFN-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; 2b in the dose of 5 MU daily for 6 days a week subcutaneously for 16 weeks. Quantitative HBV-DNA, HBeAg, and hepatitis B surface antigen (HBsAg) were assessed at baseline and at the end of treatment. ALT level assessment was done at baseline and during therapy at week 1, week 2, week 8, week 12, and week 16. &lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Res&lt;/span&gt;&lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;ults:&lt;/span&gt; Out of 37 patients enrolled in the study, 8 patients (21.62%) did not complete study due to lost to follow-up (3 patients), discontinuation due to adverse event (3 patients), and consent withdrawal (2 patients). Among 29 patients who completed the study, 10 patients (34.48%) had clearance of HBeAg and 1 patient (3.44%) had lost HBsAg after 16 weeks of therapy. Mean ALT level started decreasing after 4 weeks of therapy but did not come to normal range till 16 weeks of therapy. At least 2 log decreases in HBV DNA was observed in 9 (31.03%) patients and at least 1 log decrease in 18 (62.06%) patients. Overall decline in HBV DNA level was observed in 62% patients after 16 weeks of therapy. &lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Conclusion:&lt;/span&gt; IFN-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; treatment does result in HBeAg and HBsAg loss and decreases HBV-DNA levels in chronic hepatitis B patients. Most of adverse events were mild to moderate in intensity. So, interferon-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; therapy was well tolerated, safe, and efficacious to treat HBeAg-positive chronic hepatitis B patients without decompensated liver disease.&lt;/p&gt;

Detection of HBV DNA and antigens in HBsAg-positive patients with primary hepatocellular carcinoma

Hepatitis B virus (HBV) markers include HBV deoxyribonucleic acid (DNA) and HBV antigens. The former involves HBV covalently closed circular DNA (cccDNA) as well as total HBV DNA, whereas the latter involves HBsAg, HBcAg, and HBx. Samples of tumor and adjacent non-tumor liver tissue were collected from 28 HBV-associated HCC patients. Intrahepatic total HBV DNA and cccDNA were measured using the real-time PCR Taqman assay. HBV antigens in hepatocytes were detected using immunohistochemical staining. Intrahepatic levels of total HBV DNA or cccDNA in HCC patients with different intrahepatic HBV antigen expression patterns were compared, and the correlation between serum HBV DNA and intrahepatic HBV DNA was analyzed. No significant differences in intrahepatic cccDNA levels were observed between tumor and non-tumor liver tissue (median -3.00 vs. -2.30 log copies/cell, P=0.298). However, the tumor tissue had significantly higher levels of total HBV DNA (median -0.60 vs. -1.24 log copies/cell, P=0.045) but significantly lower proportion of intrahepatic HBV DNA in the form of cccDNA (median 0.25% vs. 4%, P=0.023) than the corresponding values in the non-tumor tissue. Also, HBV antigen levels were lower in the tumor tissue than in the non-tumor tissue. Analysis of the correlation between serum HBV DNA and intrahepatic HBV DNA indicated that the viral status in the tumor tissue was more complicated in HBV-HCC patients-the detected serum HBV DNA failed to accurately reflect intrahepatic viral load. HBV DNA may play an important role in hepatocarcinogenesis, and cccDNA was not the predominant form of HBV DNA in the tumor tissue.

Role of quantitative hepatitis B surface antigen in predicting inactive carriers and HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients.

To evaluate quantitative hepatitis B surface antigen (qHBsAg) as a diagnostic marker for inactive carriers (ICs) and hepatitis B surface antigen (HBsAg) seroclearance in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. We retrospectively studied 300 HBeAg-negative CHB patients with initial serum hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) levels <2000 IU/mL. Serum HBV DNA and alanine aminotransferase (ALT) levels were monitored every 6 months for 24 months. ICs were identified as having persistent HBV DNA levels <2000 IU/mL and normal ALT levels, whereas active carriers (ACs) were identified as having HBV DNA levels ≥2000 IU/mL, with or without elevated ALT levels. The serum qHBsAg level was defined at baseline and evaluated as a diagnostic predictor using a receiver-operating characteristic curve. The study group comprised 134 men and 166 women with a median age of 41.5 years. At baseline, 200 ICs displayed lower levels of qHBsAg (1492 IU/mL) compared with 100 ACs (2936 IU/mL) (P = 0.005). The qHBsAg level was independently associated with the IC state and HBsAg seroclearance. Baseline qHBsAg levels <1000 IU/mL and HBV DNA levels <2000 IU/mL, when detected simultaneously, allowed for identification of ICs with 41% sensitivity and 72% specificity. Fifteen patients (5%) displayed HBsAg seroclearance after 24 months. A qHBsAg cutoff value of <50 IU/mL provided 100% sensitivity and 92% specificity in predicting HBsAg seroclearance. The qHBsAg level at a single timepoint among HBeAg-negative CHB patients with low HBV DNA levels at baseline was not a predictive marker for ICs; however, it accurately predicted spontaneous HBsAg seroclearance at 24 months.

Is Serum Angiotensin-Converting Enzyme Level Useful For Determining Necroinflammatory Activity In Chronic Hepatitis B Infection?

The purpose of this study was to investigate the relationship between the findings from liver biopsy and the serum angiotensin-converting enzyme (ACE) level to determine whether ACE might serve as a potential noninvasive sign of necroinflammatory activity in patients with Chronic Hepatitis B (CHB) infection. A total of 54 CHB patients referred for liver biopsy were enrolled in the study. Serum ACE levels were determined photometrically with a kinetic test. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatitis B virus-deoxyribonucleic acid (HBV-DNA), histological activity index (HAI), and white blood cell counts were higher in patients with severe fibrosis, while albumin levels were low. The serum ACE levels showed a statistically significant correlation with HBV-DNA, HAI score, and ALT-AST levels. In this study, a statistically significant relation between serum ACE levels and HAI scores was observed. This represents the first analysis to compare necroinflammation of the liver and serum ACE levels. There may be some explanations that the suppression of hepatocyte growth factor (HGF) by Angiotensin II and increased inflammatory damage might be a reason for the correlation between HAI and ACE. Serum ACE levels, HBV-DNA levels, and serum transaminase levels might be used together as noninvasive markers for the prediction of necroinflammation in CHB patients.

Kinetic Changes of Viremia and Viral Antigens of Hepatitis B Virus During and After Pregnancy.

Whether pregnancy may influence the replication of hepatitis B virus (HBV) remains unknown. The authors aimed to clarify this issue by observing the kinetics of HBV deoxyribonucleic acid (DNA) and viral antigens in women during and after pregnancy.Total, 371 pregnant women with positive hepatitis B surface antigen (HBsAg) were enrolled. Serial sera collected during and after pregnancy were quantitatively measured for HBV DNA, HBsAg, and hepatitis B e antigen (HBeAg).Total, 34 HBeAg-positive women underwent alanine aminotransferase (ALT) elevation during or after pregnancy; levels of HBV DNA and HBsAg in them showed no obvious change between second trimester or delivery and 7 to 12 months postpartum (P > 0.05). The 337 others had normal alanine aminotransferase levels during pregnancy and postpartum. In 147 HBeAg-positive women with follow-up 7 to 12 months postpartum, the average levels of HBV DNA (>7.0 log10 IU/mL), HBsAg (>4.0 log10 IU/mL), and HBeAg (>3.0 log10 S/CO) were longitudinally constant during pregnancy and postpartum, respectively. In 173 women with follow-up 4.8 years postpartum, neither HBV DNA levels nor antigen titers showed significant difference between second trimester and 4.8 years postpartum, regardless of the HBeAg status. In addition, levels of HBV DNA and viral antigens in second trimester, around delivery, 6 to 8 weeks and 7 to 12 months postpartum showed no marked fluctuations, respectively.Serum levels of HBV DNA and viral antigens in HBsAg-positive women are highly constant during pregnancy and postpartum, regardless of the HBeAg status and alanine aminotransferase levels. This demonstrates that pregnancy has little influence on the HBV replication and antigen expression.

Influence of a 100-km Ultra-Marathon on Hepatitis B Carrier Runners

This study compares the serological markers between runners who are hepatitis B virus carries (HBVc) and runners who are non-HBVc in a 100-km ultra-marathon race. Blood samples of 8 HBVc and 18 non-HBVc runners were drawn 1 week before, immediately following, and 24 h after the race. Samples were analyzed and compared between the 2 groups for liver function tests, muscle damage markers and oxidative stress cytokines. For HBVc runners, HBV-DNA (hepatitis B virus-deoxyribonucleic acid) levels were also evaluated for virus reactivation. The results demonstrate a statistically significant increase in both immediate and 24-h post-race values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), compared with pre-race values. No statistically significant difference was observed between the 2 groups for the values of AST, LDH, CK, hs-CRP, IL-6 and TNF-α either before or after the race. There was also no statistically significant change in the levels of HBV-DNA in HBVc runners. These findings suggest that HBVc runners do not have higher risks of liver function impairment, muscle breakdown and inflammatory response compared to non-HBVc runners in such endurance races.

Liver Function Tests in Viremic and Nonviremic Chronic Hepatitis B Virus–Infected Pregnant Women

The major risk factor of perinatal transmission of Hepatitis B virus (HBV) infection is the level of maternal HBV-deoxyribonucleic acid (DNA) during the third trimester of pregnancy. The primary aim of this study was to evaluate the hematological and biochemical status in Hepatitis B e-antigen (HBeAg)-negative chronic HBV-infected pregnant women and to correlate the findings with the presence or absence of viremia. Ninety-five consecutive chronic HBV-infected pregnant women were evaluated between the 28th and 32nd week of gestation. Viral load was determined by using the COBAS TaqMan HBV test. Sixty-nine women were evaluated and 14 of them exhibited HBV-DNA levels higher than 2000 IU·ml. In this study, viremic women exhibited significantly higher alanine aminotransferase (ALT), creatinine, and uric acid values as well as significantly lower white blood cell count compared with nonviremic women. There was also a significant statistical difference concerning ALT/sodium ratio between viremic and nonviremic women (0.20 ± 0.22 vs. 0.10 ± 0.09, respectively, p= .024). The optimal cutoff points discriminating those women with a high probability to have detectable serum HBV-DNA were 0.092 for ALT/sodium ratio (sensitivity = 73.0%, specificity = 61.5%, area under the receiver operating characteristic curve [AUC] = 71.05%) and 12.8 IU/L for ALT (sensitivity = 73.0%, specificity = 63.0%, AUC = 72.2%). Chronic HBV-infected pregnant women with ALT/sodium ratio ≥ 0.11 had the higher probability of having serum HBV-DNA levels higher than 2000 IU/ml (sensitivity = 76.92%, specificity = 58%, AUC = 62.38%). Presence of HBV-DNA in maternal blood during the third trimester of pregnancy is significantly associated with maternal serum ALT levels in HBeAg-negative chronic HBV-infected pregnant women. Women with an ALT/sodium ratio greater than 0.092 have the higher probability of HBV-DNA presence in maternal blood whereas an ALT/sodium ratio greater than 0.11 could discriminate those women with HBV-DNA levels higher than 2000 IU/ml.

The clinical significance of the detection of hepatitis B virus large surface protein for the diagnosis and treatment

Objective To explore the correlation between hepatitis B virus large surface protein(HBV-LP)and hepatitis B virus deoxyribonucleic acid(HBV-DNA),analyze the clinical significance of detecting the two index dynamically for diagnosis and treatment of hepatitis B.Methods Enzyme linked immunosorbent assay(ELISA)and fluorescent quantitation polymerase chain reaction(FQ-PCR)were used to detect the levels of HBV-LP and HBV-DNA in serum specimen of 230 hepatitis B patients.Results There was a positive correlation between the content of HBV-LP and copy numbers of HBV-DNA in serum of hepatitis B positive cases(r=0.84,P＜0.01).The positive rate was 84.78％ in HBV-LP and 84.35％ in HBV-DNA of 230 HBV positive cases.As a result there was no significant difference(P＞0.05)in this study.Therefore,the positive rate was 63.63 ％(35/55)in HBV-LP and 58.18％(32/55)in HBV-DNA of 55 HBV negative cases.There was also no significant difference(P＞0.05)in this study.However,the positive rate of HBV-LP(82.47％)was higher than HBE(52.06％)in the 194 HBV-DNA positive cases.There was significantly different(P＜0.01).Conclusion HBV-LP and HBV-DNA are the significant index of the degree of hepatitis B virus replication in hepatitis B positive cases,especially in determining the virus replication and prognosis of treatment in HBe Ag negative,providing the reliable laboratory data for the clinical diagnosis and treatment. Key words: Hepatitis B large surface protein; Hepatitis B virus; Virus replication

YMDD motif mutations in chronic hepatitis B antiviral treatment naïve patients: a multi-center study

OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.