HBV Viral Load Research Articles

Efficacy of antiviral treatment on patients with acute-on-chronic hepatitis B liver failure with low viral load.

To investigate the efficacy of antiviral treatment on patients with acute-on-chronic hepatitis B liver failure with low viral load. 352 patients with acute-on-chronic hepatitis B liver failure including 175 cases of low HBV viral load and 177 cases of high HBV viral load were enrolled into this study. The patients were divided into the antiviral group which received antiviral therapy (Lamivudine, Entecavir or Telbivudine) plus routine supportive therapy and the control group which received supportive therapy only. The clinical features and the 24-week short-term efficacy of antiviral therapy were assessed. At week 24,total survival rate in antiviral group was higher than that in control group (P = 0.010). The survival rate of patients with low viral load in the antiviral group was higher than that in the control group (P = 0.001). But there was no significant difference between the antiviral group and the control group with high viral load (P = 0.856). But in the antiviral group, there was no significant difference in survival rate between the patients with high HBV viral load and those with low viral load (P = 0.755). Antiviral therapy can significantly improve survival rate of patients of acute-on-chronic hepatitis B liver failure with low viral load. Liver failure;

Liver Fibrosis Changes in HIV–HBV-Coinfected Patients: Clinical, Biochemical and Histological Effect of Long-Term Tenofovir Disoproxil Fumarate Use

Data on liver fibrosis evolution in HIV-HBV-coinfected patients treated with tenofovir disoproxil fumarate (TDF) are scarce. The effect of TDF on liver fibrosis in 148 HIV-HBV-coinfected patients was prospectively evaluated using Fibrometer∆ scores and liver biopsies in a subset of patients. The mean change from baseline (Δ) in Fibrometer score was modelled using a generalized estimating equation. Homogeneous continuous-time Markov models were used to study risk factors for regression or progression of liver fibrosis. Median follow-up of patients treated with TDF was 29.5 months (25th-75th percentile 20.9-38.1). The distribution of scored fibrosis at TDF initiation was F0-F1 n=65, F2 n=37 and F3-F4 n=46. In patients with a baseline fibrosis score of F3-F4, Fibrometer score decreased with a triphasic shape (Fibrometer Δ at 12, 24 and 36 months after TDF initiation was -0.079, -0.069 and -0.102, respectively). Despite duration on TDF, higher fibrosis scores were noted in F3-F4 patients with high HBV viral load and HDV coinfection, and in F0-F2 patients who had high HBV viral load and low CD4(+) T-cell count. Progression in fibrosis score over time was influenced by age, alcohol consumption, low CD4(+) T-cell count and HCV coinfection, whereas HDV coinfection and longer duration of HBV infection prevented fibrosis regression. No influence of antiretrovirals other than TDF was found. The use of TDF in HIV-HBV-coinfected patients led to a decrease in liver fibrosis score in patients with advanced fibrosis or cirrhosis. Sustainability of its direct antiviral and indirect antifibrotic effects on the liver need to be studied further.

Serological and molecular expression of Hepatitis B infection in patients with chronic Hepatitis C from Tunisia, North Africa

BackgroundThis study reports the prevalence and the viral aspects of HBV infection in HCV-positive patients from Tunisia, a country with intermediate and low endemicity for hepatitis B and C, respectively.ResultsHBV infection was assessed in the serum samples of 361 HCV-positive patients and compared to a group of HCV negative individuals. Serological markers were determined by ELISA tests and HBV DNA by real-time PCR. HBV serological markers were found in 43% and 44% of patients and controls, respectively. However, the serological and molecular expression of HBV infection differed in the two groups: The group of patients included more individuals with ongoing HBV infection, as defined by the presence of detectable HBsAg and or HBV DNA (17% and 12%, respectively). Furthermore, while most of the controls with ongoing HBV infection expressed HBsAg, the majority of HCV and HBV positive patients were HBsAg negative and HBV DNA positive. Genotyping of HCV isolates showed large predominance of subtype 1b as previously reported in Tunisia. Comparison of the replicative status of the two viruses found low HBV viral load in all co-infected patients as compared to patients with single HBV infection. In contrast, high levels of HCV viremia levels were observed in most of cases with no difference between the group of co-infected patients and the group with single HCV infection.ConclusionsThis study adds to the knowledge on the prevalence and the virological presentation of HCV/HBV dual infection, providing data from the North African region. It shows that, given the local epidemiology of the two viruses, co-infected patients are likely to have low replication levels of HBV suggesting a suppressive effect of HCV on HBV. In contrast, high replication levels for HCV were fond in most cases which indicate that the presence of circulating HBV-DNA does not necessarily influence HCV replication.

The prevalence of “anti‐HBc alone” and HBV DNA detection among anti‐HBc alone in Korea

The "anti-HBc alone" is a frequent serological finding in clinical laboratories, making it difficult to determine whether the HBV infection has resolved. The objectives of this study were to investigate the prevalence of anti-HBc alone and HBV DNA detection (occult HBV infection) among anti-HBc alone, and to describe the demographic and clinical characteristics of anti-HBc alone. A total of 17,677 sera referred from the Health Promotion Center (HPC group, 4,014 sera) as well as all the hospital clinical departments (Patient group, 13,663 sera) were tested for HBs Ag, anti-HBc, and anti-HBs. HBV DNA test using real-time PCR was performed on 230 anti-HBc alone. The prevalence of anti-HBc alone was 8.9%, significantly higher in the Patient group than in the HPC group. The prevalence of anti-HBc was higher in men than women and was increased with age. Very low levels of HBV DNA were found in only 4 (1.7%) out of 230 subjects with anti-HBc alone. They were patients with conditions unrelated to chronic liver disease. Considering the high prevalence of anti-HBc alone, the frequency of occult HBV infection among anti-HBc alone was unexpectedly low. In addition, HBV viral load was low in these patients. Further studies are required to determine the clinical significance and infectivity of anti-HBc alone, in conjunction with very low levels of HBV DNA and to standardize the detection methodology for both anti-HBc alone and HBV DNA.

Hepatitis B virus BCP, precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India

The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient's age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P < 0.001 for all comparisons). HBV/D was the predominant genotype associated with HCC cases seen in India. The presence of different types of HBV mutations, age, sex, HBeAg status, and viral load was found to increase significantly the risk of HCC development in India.

Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: A perspective on Asia

Data from clinical trials suggest a potential role for on-treatment monitoring of serum HBsAg titres during interferon-alpha (pegIFN) therapy in predicting virological responses. However, baseline HBsAg titres during the natural history of chronic hepatitis B (CHB) have not been well-characterized. We aimed to define the serum HBsAg titres during the different phases of CHB in a cohort of Asian patients infected with either genotype B or C HBV. Two-hundred and twenty patients were classified into immune-tolerant (IT), immune-clearance (IC), non/low-replicative (LR) or hepatitis B e antigen negative hepatitis (ENH) phases. Serum HBsAg was quantified using the ARCHITECT platform (Abbott Laboratories, Chicago, USA). Correlation of HBsAg titre with HBV DNA and serum ALT within each phase of infection was performed. Median HBsAg titres were different between each phase of CHB (p=0.001): IT (4.53 log(10)IU/ml), IC (4.03 log(10)IU/ml), LR (2.86 log(10)IU/ml), and ENH (3.35 log(10)IU/ml). HBsAg titres were highest in the IT phase, and lowest in the LR phase. In general, median HBsAg titres were similar between genotypes B and C HBV. Serum HBsAg titres only correlated with HBV viral load in the IC phase. No correlation between the serum HBsAg level and ALT was observed. This study demonstrated significant differences in median baseline serum HBsAg titres across the different phases of CHB. These results provide further insight into the HBV viral life cycle in the setting of the various phases of CHB. Baseline HBsAg quantification may help refine future treatment algorithms for both immune-modulator therapy and oral nucleos(t)ide analogue therapy.

Acute hepatitis B virus infection with simultaneous high HBsAg and high anti-HBs signals in a previously HBV vaccinated HIV-1 positive patient

We present a case of a clinical manifest hepatitis B virus infection and a potentially misleading HBV serological profile in an HIV-1 positive patient despite previous HBV vaccination. The patient presented with an acute hepatitis B and there was no indication of chronic HBV infection or the presence of a mutation in the ‘a’ determinant. Remarkably, simultaneously with high HBV surface antigen and HBV viral load, high anti-HBs antibodies were present. If, due to previous HBV vaccination only anti-HBs was tested in this patient, the result of the high anti-HBs antibodies could be very misleading and offering a false sense of security. Our findings contribute to the ongoing discussion on how to assess HBV specific immunological memory and determining the role of HBV booster vaccinations in immunocompromised individuals.

Schönlein-Henoch purpura: a case observation

A 58 year old male with chronic obstructive lung disease came to the clinic due to confluent purpuric lesions which tended to ulcerate, which began during the days prior on the lower limbs; they increased in number and extended to the buttocks, trunk, upper limbs and face an were accompanied by joint pain of the hands and feet. No other gastrointestinal problems, fever or clinical data suggesting connective tissue disease existed. Upon examination, the patient presented pitting edema of the lower limbs and a universally distributed palpable purpura which did not affect mucosal tissue, with ulcers due to the loss of epidermis on the lower limbs (Figure 1, Figure 2). Laboratory analysis showed: normal urea and creatinine; an erythrocyte sedimentation rate of 95 mm/h; C reactive protein of 5.8 mg/dl; microhematuria; 24 h urine proteins 2,859 mg en orina de 24 h; normal complement and elevated IgA. Autoantibodies were negative. Serology for HBV was compatible with a chronic infection and the viral load was negative. Rheumatoid factor was positive at a low titer and was interpreted as secondary to HBV infection. Skin biopsy was compatible with purpuric leukocytoclastic vasculitis, with an absence of immunofluorescnet deposits. Renal biopsy showed non-hyaline glomeruli and no half moons, with a mild increase in the mesangial matrix and some areas of cellularity, in addition to granular IgA and C3 deposits, detected through immunofluorescence, in the mesangium. Suspecting Schonlein-Henoch purpura (HSP), oral prednisone was started (1 mg/kg/day for 2 weeks, reduced at a rate of 2.5 mg every 14 days, reaching 5 mg per day); losartan, atorvastatine and weekly alendronate plus cholecalcipherol. After one year, the patient has not developed new symptoms and is maintained with low dose steroids, and is being treated with low dose steroid, has good renal function, proteinuria under 500mg/dl and the HBV viral load is still negative. Discussion

核酸アナログ未使用のB型慢性肝炎症例へのエンテカビル治療中にrtA181T変異ウイルスが増殖した1症例

A 51-year-old Japanese woman with chronic hepatitis B who had never treated with nucleotide analogues was admitted to our hospital and treated with entecavir. In this patient, entecavir successfully reduced the HBV level, but viral and biochemical breakthrough was observed at 10 months after the beginning of therapy. The HBV viral load reached up to 8.2 log copies/ml, but direct sequence analysis showed no LAM and ETV resistant-related mutation (rtT184, S202, M204, M250). Comparison by clonal analysis of samples obtained before and after the viral breakthrough showed the increase of the rtA181T mutant strains (8.5% versus 39.5%). It was considered that the rtA181T mutant strain in this case might be related to entecavir resistance.

Description of liver disease in a cohort of HIV/HBV coinfected patients

Background Factors associated with advanced liver disease have been incompletely explored in HIV/HBV coinfected patients. Objectives To describe liver-related morbidity, mortality, and related risk factors, in HIV/HBV coinfected patients. Study design We followed-up 107 consecutive HIV/HBV coinfected patients. Clinical, biological and virological data were collected every 3 months. Liver-related mortality and a composite score were used to define advanced liver disease. Results The patients were mainly sub-Saharan Africans (61%) or Europeans (33%). Forty-four percent of patients had liver biopsy, 78% of patients received lamivudine. Advanced liver disease (ALD) was diagnosed in 19/107 patients during follow-up (mean 4.8 years): 10 extensive fibrosis, 5 cirrhosis, 3 hepatocellular carcinoma resulting from cirrhosis, and 1 fulminant hepatitis following lamivudine withdrawal. Eleven patients died, 4 from HBV-related liver disease. In univariate analysis, male gender, mean HIV and HBV viral loads, and raised AST/ALT transaminases were associated with increased risk of ALD. The strongest associations, in a multivariate model, were mean AST transaminase and cumulated time receiving lamivudine, with a favourable effect. 39% of patients with increased mean AST presented with ALD, versus 7% when normal mean AST (Relative Risk 5.5). Conclusions During HIV/HBV coinfection, transaminase levels are strongly associated with ALD. Normal mean AST has a high negative predictive value, contrary to previously reported data in HIV/HCV patients.

HD-03/ES: A promising herbal drug for HBV antiviral therapy

Introduction The present study was designed to study the genotypes associated with different groups of chronic liver disease and to see their response to HD-03/ES (an antiviral herbal molecule) on chronic HBV patients. Methods A total of 51 patients of chronic liver disease were recruited in the study and were given HD-03/ES, two capsules twice daily for 6 months. Liver function tests were done every month after initiating treatment. Serum was analyzed for HBsAg, HBeAg and HBV DNA and quantitative estimation of HBV at baseline, 4 and 6 months after therapy. The genotype of all the cases was also determined by PCR-RFLP method. Results After 6 months of therapy with HD-03/ES, a significant reduction of ALT values from 71.2 ± 16.3 to 36.4 ± 6.8 and a significant HBeAg loss (27.4%) and HBV DNA loss (27.4%) was observed. Adverse effects were mild. Genotype D was found in 39 (76.5%) while genotype A was found in 12 (33.5%) cases, respectively. The mean reduction in viral load was observed from log 10 7.1 ± 1.8 copies/ml to log 10 4.4 ± 1.1 copies/ml. However, a sharp decline in viral load was observed in patients infected with genotype A (log 10 6.8 ± 2.5 to log 10 4.9 ± 1.8; P < 0.01) compared to genotype D (log 10 7.0 ± 2.6 to log 10 5.9 ± 3.5; P = 0.074). Conclusion The study had shown that majority of the patients of chronic HBV related liver disease had genotype D. In additional, the molecule HD03/ES had a better therapeutic capability of lowering the HBV viral load in patients with genotype A, which needs to be validated in larger studies.

Negative correlation between viral load and HBsAg levels in chronic HBV-infected patients

The objective of this study is to reveal the relationship between viral load (as HBV DNA) and HBsAg levels. Ninety-two chronically HBV-infected patients were included in the study. The patients were divided in two different groups: the cirrhotic group (n = 32) and the non-cirrhotic group (n = 60). The correlation between study groups was also examined with regard to HBeAg status. Hepatitis B viral markers (HBsAg, HBeAg, Anti-HBs, anti-HBc and anti-HBe) and HBV viral load of the patients were measured. A significant negative correlation between HBV DNA and HBsAg levels was found in the non-cirrhotic group (p < 0.01). The anti-HBc level was higher in the non-cirrhotic group than in the cirrhotic group (p < 0.016). The viral load was significantly higher in HBeAg (+) patients in comparison with HBeAg (-) cases (p < 0.0001). The HBsAg level was low in HBeAg (+) patients, whereas it was higher in HBeAg (-) cases (p < 0.001). In conclusion, a significant negative correlation between viral load and HBsAg levels was detected in the non-cirrhotic chronically HBV-infected group. Therefore, concomitantly low HBsAg and HBV DNA levels may indicate a better prognosis compared to high HBsAg and low HBV DNA levels.

Hepatitis B virus reactivation in a large haemodialysis unit: Virological and infection control issues

A 60-year-old Asian man, originally from Pakistan but presently UK resident had been on long-term haemodialysis for end stage enal disease secondary to diabetic nephropathy.Hewasbeingdialsed three times a week at the various dialysis units at the Heart of ngland NHS Trust and was not on any immunosuppressive treatent. He had no history of recent travel. He was “negative” for BV, HCV and HIV by routine screening. In late September 2007 BsAgwasweaklypositive (signal/cut-off ratio3.337)by theMonoisa Ultra assay (Bio-Rad Laboratories) and strongly positive (s/co 37.77) by the Vidas Ultra assay (BioMerieux). The results of the idas assay were confirmed by a specific HBsAg neutralisation test Vidas Ultra assay). He was also found to be weakly reactive for epatitis B e antigen (HBeAg), antibody to HBeAg (anti-HBe) postive, anti-HBc positive, and anti-HBc IgM negative. His HBV viral oad reached a peak of 1,667,360 IU/ml (Roche Cobas Taqman HBV ssay). The patient had mild transaminitis (peak aspartate aminoransferase 124 IU/ml). Retrospective testing of stored sera showed hat 4 months previously he was anti-HBc positive and HBV DNA ositive but HBsAg negative (HBV viral load 848 IU/ml) (Fig. 1).

Biologic Agents in the Treatment of Rheumatic Diseases with Chronic Viral Infection. Where Are We?

Biologic agents have increased the therapeutic armamentarium against immune-mediated disorders, and particularly rheumatic diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Nevertheless, infectious side effects are a major concern in the use of these biologics, especially anti-tumor necrosis factor (TNF) agents1. In this context, the use of TNF blockers in patients with chronic viral infection seems hazardous, and represents an unresolved issue2. In this issue of The Journal , Zingarelli, et al 3 report 3 cases of patients with RA positive for HBsAg, in which anti-TNF therapies (etanercept, infliximab then etanercept, adalimumab) under prophylactic use of lamivudine were not associated with hepatitis reactivation, even after anti-TNF discontinuation with prolonged lamivudine therapy. In one of their cases, an increase in HBV viral load occurred after discontinuation of methotrexate. Methotrexate was reported to induce subfulminant hepatitis B virus reactivation after its withdrawal4,5. This illustrates the interactions of the underlying condition and the associated immunosuppressive therapy that may confuse our interpretation of the responsibility of … Address reprint requests to Dr. Wendling. E-mail: dwendling{at}chu-besancon.fr

Rapid HBV DNA decrease (week 12) is an important prognostic factor for first-line treatment with adefovir dipivoxil for chronic hepatitis B

The aim of the study was to estimate the effect of viral factors (HBV genotype, viral load and kinetics) to treatment response in chronic hepatitis B (CHB) and first-line therapy with adefovir dipivoxil (ADV). Sixty-six patients (60% males, 65% HBeAg negative) were treated with 10 mg ADV QD. Quantitative HBV DNA and ALT levels were determined at weeks 4, 12, 24, 48, 72 and 96. Nonresponse or viral resistance to ADV was assessed in patients with either persistent elevated HBV DNA levels (week 24) or with an increase in HBV DNA of at least 1 log after initial decline. Most patients were infected with genotype D (66.7%; genotype A: 27.3%; genotype E: 6%); 86.4% achieved a virological (VR) and 54.5% a biochemical response (BR) in week 48, more often in patients with genotype A (P < 0.01). In week 96, BR increased to 60.5%, whereas a negative HBV DNA was observed in 83.3%. In 3% an ADV-induced viral resistance was detected. As an important predictive parameter for VR, a rapid decline of viral load at week 12 was observed. Of the patients with a negative PCR or drop of viral load of at least 3 log, 96% were still HBV DNA negative at the end of week 96; 77% of patients with a partial response achieved a VR. In contrast, no patient with nonresponse (week 12) reached a negative PCR at week 96 (P < 0.0001). These results underline the importance of early viral kinetics to assess treatment response in CHB. In ADV nonresponders (week 12), an advanced antiviral therapy or switch to another nucleoside analogue should be considered.

Immunosuppressive effect of IDO on T cells in patients with chronic hepatitis B*

Recently indoleamine 2,3-dioxygenase (IDO) has drawn considerable attention as a mechanism of immune regulation. Our study was to observe the role of IDO in immune tolerance of chronic hepatitis B (CHB), so as to provide a novel approach for reestablishment of active immunity. Peripheral venous blood samples were taken from 50 CHB patients and HBV viral load, T lymphocyte subsets as well as the mRNA, protein and activity of IDO were detected. The correlations between HBV viral load, T lymphocyte subsets and IDO were statistically analyzed. Blood samples from 50 healthy people were tested as a control group. In CHB patients, the mRNA, protein and activity of IDO were all significantly more than those in control group (mRNA:[2.11 +/- 0.615] x 10(3) vs. [0.143 +/- 0.026] x 10(3); protein: 0.22 +/- 0.06 vs. 0.02 +/- 0.0017; activity: 26.07 +/- 8.12 vs. 4.98 +/- 1.65; P < 0.05) and IDO mRNA was positively correlated with HBV viral load (r = 0.502, P < 0.001) and alanine aminotransferase (ALT) (r = 0.65, P < 0.01). Furthermore, IDO mRNA, protein and activity were negatively correlated with CD4(+) T cells (r = -0.622, -0.682, -0.549 respectively, P < 0.05), CD8 (+) T cells (r = -0.487, -367, -294 respectively, P < 0.05) and the ratio of CD4/CD8 (r = -0.426, -0.533, -0.397 respectively, P < 0.05). IDO closely correlates with HBV viral load and is responsible for immunotolerance against HBV. Suppression of IDO could be a novel approach to break tolerance in CHB.

Performance evaluation of the QIAGEN EZ1 DSP Virus Kit with Abbott RealTi me HIV-1, HBV and HCV assays

Background Automated sample preparation systems must meet the demands of routine diagnostics laboratories with regard to performance characteristics and compatibility with downstream assays. Objectives In this study, the performance of QIAGEŃs EZ1 DSP Virus Kit on the BioRobot EZ1 DSP was evaluated in combination with the Abbott RealTi me HIV-1, HCV, and HBV assays, followed by thermalcycling and detection on the Abbott m2000 rt platform. Study design The following performance characteristics were evaluated: linear range and precision, sensitivity, cross-contamination, effects of interfering substances and correlation. Results Linearity was observed within the tested ranges (for HIV-1: 2.0–6.0 log copies/ml, HCV: 1.3–6.9 log IU/ml, HBV: 1.6–7.6 log copies/ml). Excellent precision was obtained (inter-assay standard deviation for HIV-1: 0.06–0.17 log copies/ml (>2.17 log copies/ml), HCV: 0.05–0.11 log IU/ml (>2.09 log IU/ml), HBV: 0.03–0.07 log copies/ml (>2.55 log copies/ml)), with good sensitivity (95% hit rates for HIV-1: 50 copies/ml, HCV: 12.5 IU/ml, HBV: 10 IU/ml). No cross-contamination was observed, as well as no negative impact of elevated levels of various interfering substances. In addition, HCV and HBV viral load measurements after BioRobot EZ1 DSP extraction correlated well with those obtained after Abbott m2000 sp extraction. Conclusions This evaluation demonstrates that the QIAGEN EZ1 DSP Virus Kit provides an attractive solution for fully automated, low throughput sample preparation for use with the Abbott RealTi me HIV-1, HCV, and HBV assays.

Peripheral NK and NKT cell in pediatric subjects with chronic HBV infection

To investigate the characteristic of NK cells and NKT cells in HBV infected pediatric subjects for evaluation of their clinical implication. Fresh peripheral blood samples were obtained from 42 HBV-infected pediatric cases and 15 healthy counterparts. NK cells and NKT cells were analyzed by flow cytometry assay. The clinical data such as serum ALT level and HBV viral load was simultaneously recorded from each HBV carrier. HBV-infected children had an obviously increasing percentage of NK cells 12.071% +/- 7.100%, there were significant differences between the children with chronic B hepatitis and the healthy children (P <0.05). As far as percentage of NKT 3.048% +/- 1.937% was concerned, there were not differences. Furthermore the association was not found between serum HBV viral load level and the NK lymphocyte. Our data may provide valuable information of NK and NKT lymphocyte for evaluation of disease progression of HBV infected children NKI cells.

Pharmacotherapy of Chronic Hepatitis B in Adults: Focus on Tenofovir Disoproxil Fumarate

Treatment for hepatitis B (HBV), a global disease affecting over 400 million persons, has changed over the past 15 years. Many of the current treatments are oral therapies which suppress HBV viral load and improve liver-related outcomes. However, differences exist in the currently available therapies both in terms of potency and resistance. The newest HBV nucleotide to be approved for the treatment of hepatitis B is tenofovir disoproxil fumarate that when phosphorylated to its active form leads to DNA chain termination. Tenofovir is active against human immunodeficiency virus (HIV) and was approved for its treatment in 2001. It is also active against HBV and was approved for its treatment in 2008. Tenofovir has emerged as an effective and potent therapy against lamivudine resistant strains as well as wild type HBV. Tenofovir resistance to HBV is rare. Long-term use of tenofovir has been associated with renal and bone marrow toxicity in some HIV-infected patients. To date, this is the only oral therapy which is both potent and does not lead to viral resistance in both treatment naïve and experienced patients. Further studies in HBV mono-infected persons are needed to evaluate long-term impact of tenofovir use.

Impact of viral replication inhibition by entecavir on peripheral T lymphocyte subpopulations in chronic hepatitis B patients

BackgroundTo investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy.MethodsFifty-five patients received entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly, every four weeks and every eight weeks during weeks 1–12, 13–24 and 24–48, respectively. Multilevel modelling was used to analyse the relationship between these variables.ResultsOf the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 107 copies per milliliter. HBV viral load dropped sharply during the first two weeks. In 28 and 43 patients, the level became undetectable from week 24 and 48, respectively. Using pre-therapy level as the reference, a significant decrease in CD8+ T cells and increase in CD4+ T cells were found from week 12. Both parameters and CD4+/CD8+ ratio steadily improved throughout the 48 weeks. Multilevel analyses showed that the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities only in the later period (4–48 week). After 4 weeks of therapy, for each log10 scale decrement of HBV DNA, the percentage of CD4+ lymphocyte was increased by 0.49 and that of CD8+ decreased by 0.51.ConclusionT-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.