Hepatitis B Virus DNA (hepatitis + b_virus_dna)

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Terms modified by Hepatitis B Virus DNA

  • hepatitis b virus dna level

  • Selected Abstracts

    Occult hepatitis B virus infection in patients with autoimmune liver diseases

    Sarah P. Georgiadou
    Abstract Background: Occult hepatitis B virus (HBV) infection is characterized by undetectable serum HBV surface antigen (HBsAg) but detectable HBV-DNA in serum or liver. Aims: To determine the prevalence and clinical impact of occult HBV in autoimmune liver diseases as similar data are missing. Methods: One hundred and ninety-six sera samples from HBsAg-negative patients, including 66 autoimmune hepatitis (AIH), 93 primary biliary cirrhosis (PBC) and 37 primary sclerosing cholangitis (PSC), were investigated for HBV-DNA using the polymerase chain reaction (PCR) before treatment initiation. One hundred and three serial samples from 38 AIH patients under immunosuppression and 282 selected blood donors (HBsAg negative; antibodies to HBV-core antigen positive) were also investigated. Fourteen available paraffin-embedded AIH liver samples were also investigated for HBV-DNA by nested-PCR. Results: Hepatitis B virus DNA was detected in the serum of 24/196 patients (12.2%) and 0/282 donors (P=0.0000). Nine patients had AIH (13.6%), eight had PBC (8.6%) and seven had PSC (18.9%) (P=0.0000 vs healthy). HBV-DNA detection in AIH livers was higher than in serum. HBV-DNA was associated neither with HBV markers nor with epidemiological, laboratory and clinical data. Serial testing of AIH patients revealed two HBV-DNA-negative patients before treatment becoming positive during treatment, while all HBV-DNA-positive patients before immunosuppression became negative. Conclusion: Based mainly on serum HBV-DNA, we found a significant proportion of autoimmune liver disease patients with occult HBV compared with donors. However, taking into account our results in a small number of liver tissues, it should be emphasized that occult HBV could be even higher when both serum and liver specimens are investigated. Occult HBV does not seem to affect the clinical and laboratory features of the diseases, while AIH patients with occult HBV under immunosuppression do not deteriorate during follow-up. [source]

    Correlation of YMDD mutation and breakthrough hepatitis with hepatitis B virus DNA and serum ALT during lamivudine treatment

    Mariko Kobayashi
    Aim:, Continuous lamivudine treatment is associated with high frequency of drug resistance. We analyzed the incidence of tyrosine-methionine-aspartate-aspartate (YMDD) motif mutant and breakthrough hepatitis (BTH) in hepatitis B virus (HBV) DNA positive patients receiving lamivudine for > 1 year and correlated it with HBV DNA and alanine aminotransferase (ALT) levels to evaluate if these measurements can provide a practical option for monitoring patients in clinical practice and define early switch from lamivudine therapy. Methods:, Of the 929 patients receiving lamivudine for > 1 year, 359 patients who maintained an ALT level of , 40 IU/L during the course of lamivudine treatment were stratified into two groups based on the duration of lamivudine treatment , one receiving lamivudine for < 3 years and the other for , 3 years. Results:, The incidence of YMDD motif in patients receiving lamivudine for < 3 years was 27% in patients with ALT , 20 IU/L, 58% with ALT , 30 IU/L, and 63% with ALT , 40 IU/L, (P = 0.002). The corresponding incidence of BTH was 2%, 7%, and 48% (P < 0.001). The incidence of YMDD motif and BTH in these patients was 7% and 2% with HBV DNA < 2.6 (log copies/mL) and ALT , 20 IU/L, while with ALT at 21,30, the YMDD motif mutant was 16% and BTH was 0%. Conclusion:, Correlation of ALT and HBV DNA levels with YMDD motif mutant and BTH indicates that these measurements can be used in clinical practice for deciding early switch from lamivudine to other suitable antiviral therapies. [source]

    Spontaneous HBeAg seroconversion and loss of hepatitis B virus DNA after acute flare due to development of drug resistant mutants during entecavir monotherapy

    Ri-Cheng Mao
    Aims:, Patients with chronic hepatitis B virus (HBV) infection under entecavir (ETV) treatment develop resistant mutants with viral rebound. Here, we report an interesting case of spontaneous loss of HBV-DNA and seroconversion following an acute flare after the development of ETV-resistant mutants. This patient received ETV after lamivudine breakthrough. Methods:, Cloning and sequence analysis of the HBV reverse transcriptase (RT) region were performed with seven samples during ETV therapy. In addition, two full-length HBV genomes derived from samples before and after the emergence of ETV resistance were sequenced. Results:, ETV resistant mutants appeared at week 228, with virological and biochemical rebound at the same time. Unexpectedly, HBeAg seroconversion occurred 8 weeks later. The viral load decreased and became undetectable from week 252. Analysis of HBV isolates in the patient at week 124 revealed that wild-type HBV was predominant at that time and ETV resistant mutants were not found among 20 clones. Interestingly, a new mutant type with rtL180M+rtT184L was found alongside rtL180M+rtT184L+rtM204V/I at week 228 and appeared to develop independently, according to the sequence analysis. In contrast to the previously identified ETV resistant mutants, it did not carry the rtM204V/I mutations. Conclusion:, The data presented here indicates that the flare following the emergence of ETV resistant mutants may reflect immune-mediated control of HBV infection, leading to a spontaneous loss of HBV-DNA and seroconversion. [source]

    Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients,

    L.Y. Lin
    Abstract Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-nave patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40,IU/L and a serum HBV DNA >10,000,copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r,=,0.41, P,=,0.018) and log total intrahepatic HBV DNA (r,=,0.71, P,<,0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P,=,0.15) or log total intrahepatic HBV DNA (P,=,0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/106 cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P,=,0.03 and 5.46 vs. 4.64, P,<,0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B. J. Med. Virol. 82:1494,1500, 2010. 2010 Wiley-Liss, Inc. [source]

    Prevalence of hepatitis B virus DNA polymerase mutations in treatment-nave patients with chronic hepatitis B

    M. H. NGUYEN
    Summary Background, One of the most important factors in treatment failure using nucleos(t)ide analogues in chronic hepatitis B is anti-viral resistance. Primary drug resistance refers to amino acid changes in the hepatitis B virus polymerase/reverse transcriptase (rt) that result in reduced susceptibility to anti-viral agents. Pre-existing drug resistance mutations may occur in untreated patients and may affect their treatment outcomes. Aim, To determine the prevalence of hepatitis B DNA polymerase mutations in treatment-nave patients. Methods, We used a direct PCR sequencing test to detect DNA polymerase mutations in 472 consecutive treatment-nave patients at two community gastroenterology clinics in Northern California. Results, A majority of patients were Asians (>95%), had either genotype B or C (95%) and had no evidence of cirrhosis or liver cancer (94%). Mean age was 45 13 and mean hepatitis B virus DNA was 5.3 1.8 log10 IU/mL. Most patients did not have any detectable mutations (82.4%). Some (16.7%) had mutations of unknown clinical significance (rtV207M/L/I) and only 4 patients had rtA181A/S, rtA194S or M250I. Conclusions, No rtM204V/I or rtN236T mutations were observed in our study. Less than 1% of our patients had mutations that can be associated with primary resistance to existing anti-viral therapies for hepatitis B virus. [source]

    Virological response to antiviral therapy at week 12 indicates a great reduction of intrahepatic hepatitis B virus DNA and cccDNA in HBeAg-positive chronic hepatitis B patients

    H. Y. Lu
    Summary., Early virological response is considered to be a predictor for the outcome of anti-hepatitis B virus (HBV) therapy. To analyze its correlation to intrahepatic HBV DNA and covalently closed circular DNA (ccc)DNA, 71 hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B patients were recruited: 34 patients were treated with lamivudine; 13 with interferon-,2b; and 24 with sequential therapy of lamivudine,interferon-,2b for 48 weeks. Intrahepatic HBV DNA and cccDNA load were measured at the baseline and at Week 48. Fifty-seven patients had virological response at Week 12. Median decreases of serum HBV DNA in patients with or without virological response at Week 12 were 4.0 log10 (max. 6.2, min. 2.2) and 1.1 log10 (max. 2.1, min. 0) (Z = ,5.766, P = 0.0000), respectively. At Week 48 they were 4.1 log10 (max. 7.4, min. 1.0) and 2.3 log10 (max. 7.5, min. 0.3) (Z = ,2.760, P = 0.006), respectively. For intrahepatic HBV DNA load they were 1.3 log10 (max. 4.3, min. ,1.2) and 0.6 log10 (max. 3.5, min. ,0.8), respectively, and for HBV cccDNA load they were 1.1 log10 (max. 4.8, min. ,0.5) and 0.5 log10 (max. 3.0, min. ,0.8) (Z = ,2.097, P = 0.036), respectively at Week 48. Step-wise logistic regression analysis indicated that the baseline intrahepatic HBV DNA load effected virological response at Week 12 [odds ratio (OR) 0.405; 95% confidence interval (CI) 0.174,0.944; P = 0.036] and HBeAg seroconversion at Week 48 (OR 0.292; 95% CI 0.131,0.649; P = 0.003). In conclusion, virological response at Week 12 indicated a great reduction of intrahepatic DNA and cccDNA load in HBeAg-positive CHB patients. The baseline intrahepatic HBV DNA load affected virological response at Week 12 and HBeAg seroconversion at Week 48. [source]

    Quantitative detection of hepatitis B virus DNA in serum by a new rapid real-time fluorescence PCR assay

    R. Jardi
    A sensitive and accurate HBV DNA quantification assay is essential for monitoring hepatitis B virus (HBV) replication. This study evaluated a real-time PCR method performed in the LightCyclerTM analyser for quantitative HBV DNA assay. HBV DNA results with this method were compared with those obtained using a branched-chain DNA (bDNA) solution hybridization assay. Real-time PCR was performed using two adjacent fluorescently labelled probes and primers corresponding to the HBV core gene. The same standard employed in the bDNA assay was used for calibration. Serum samples came from 193 HBV surface antigen (HBsAg)-positive patients (34 HBV e antigen (HBeAg)-positive and 93 with antibody to HBeAg (anti-HBe)), and 66 asymptomatic HBV carriers. In addition, we analysed serum samples from 8 anti-HBe-positive patients who had been receiving lamivudine treatment for more than three years. A linear standard curve was seen in the range from 103 to 108 copies/mL. In the reproducibility analysis, intra-assay coefficient of variation (CVs) at two known HBV DNA concentrations were 4% and 2% and interassay CVs were 6% and 4%. The median of serum HBV DNA by real-time PCR was 9.2 108 copies/mL in HBeAg-positive patients with persistently elevated alanine aminotransferase (ALT) levels, 1.3 107 copies/mL in anti-HBe-positive cases with persistently elevated ALT levels, 3.7 104 copies/mL in anti-HBe-positive patients with fluctuating ALT levels and 104 copies/mL in asymptomatic HBV carriers. The differences in HBV DNA levels among the various groups studied were statistically significant (P < 0.05). The cut-off between chronic hepatitis patients and asymptomatic carriers was found to be at a serum HBV DNA concentration of 5 104 copies/mL. Of the 109 serum samples with a viral load < 7.5 105 (negative by bDNA assay) 44 (40%) were positive by real-time PCR: 24 (56%) chronic hepatitis and 20 (33%) asymptomatic carriers. There was a positive association between HBV DNA levels determined by real-time PCR and ALT levels (P < 0.05), which was not observed with the bDNA assay for HBV DNA quantification. At 12 months of lamivudine treatment, 6 patients (75%) showed HBV DNA levels < 5 104 copies/mL (range < 103,2 103), significantly lower than at baseline. At 36 months, 2 of 8 (25%) showed HBV DNA levels persistently lower than 5 104 copies/mL (1.7 103, 6 103). The LightCycler quantitative real-time PCR is a practical, sensitive, reproducible single-tube assay with a wide dynamic range of detection. The assay is automatic except for DNA extraction and the running time is only 70 min. The LightCycler real-time PCR is useful for identifying different states of HBV infection and for evaluating the efficacy of viral therapy. [source]

    48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection

    C.-K. HUI
    Summary Background/aim, Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown. Method, We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated interferon alpha-2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <105 copies/mL at week 72. Results, Twenty-nine patients were treated with 48 weeks of pegylated-interferon-alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <105 copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated-interferon-alpha-2a was independently associated with sustained virological response (P = 0.04 adjusted hazards-ratio 9.37). Conclusion, Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B. [source]

    Clinical course after stopping lamivudine in chronic hepatitis B patients with lamivudine-resistant mutants

    V. W.-S.
    Summary Background :,The efficacy of lamivudine therapy in chronic hepatitis B is well established. However, drug-resistant YMDD mutants emerge with extended therapy. This may result in the resurgence of viral replication, the return of hepatitis and histological deterioration. Aim :,To study the safety of stopping lamivudine when the drug is no longer effective. Methods :,In the 5-year Asian Lamivudine Study, 34 patients from a single centre were included in this study. They had harboured YMDD mutants for at least 2 years. Lamivudine was discontinued and they were followed up at regular intervals. Clinical symptoms, liver biochemistry and viral serology were monitored. Results :,In a median follow-up of 20 months after stopping lamivudine (range, 7,39 months), 20 of the 34 patients (58.8%) had elevated alanine aminotransferase (ALT), 13 patients (38.2%) had elevated ALT one to five times the upper limit of normal and seven patients (20.6%) had an ALT flare (ALT more than five times the upper limit of normal with detectable hepatitis B virus DNA). There was no liver decompensation. ALT flare could be predicted by ALT over twice the upper limit of normal at the time of stopping lamivudine (P = 0.037). Conclusions :,It is relatively safe to stop lamivudine after YMDD mutants have emerged. ALT levels greater than or equal to twice the upper limit of normal at the time of stopping lamivudine have a higher risk for ALT flare. [source]

    Expression of cyclooxygenase-2 in chronic hepatitis B and the effects of anti-viral therapy

    A. S. L. Cheng
    Backgound: Cyclooxygenase-2 may play a role in the development of hepatocellular carcinoma, but the relationship between cyclooxygenase-2 and chronic hepatitis B is unknown. Aim: To investigate the expression and cellular localization of cyclooxygenase-2 in chronic hepatitis B patients and the effects of anti-viral therapy. Methods: Using immunohistochemistry, in situ hybridization, Western blot and reverse transcription polymerase chain reaction, protein and messenger RNA expression and cellular localization of cyclooxygenase-2 in 35 chronic hepatitis B patients were assessed. Fourteen histologically normal and non-viral-infected livers were used as controls. The cyclooxygenase-2 immunoreactivities of paired liver biopsies from 12 patients receiving anti-viral therapy were compared. Results: Immunohistochemistry and in situ hybridization revealed that cyclooxygenase-2 expression was confined to hepatocytes. Patients with chronic hepatitis B had significantly higher cyclooxygenase-2 expression compared with controls. The cyclooxygenase-2 expression of hepatitis B e antigen-positive and -negative chronic hepatitis B patients was not significantly different, although the necro-inflammatory activity of the latter group was significantly lower. Over-expression of cyclooxygenase-2 in patients with chronic hepatitis B was further confirmed by Western blot and reverse transcription polymerase chain reaction. Twelve hepatitis B e antigen-positive chronic hepatitis B patients received anti-viral therapy: lamivudine in seven and interferon in five. Despite hepatitis B e antigen seroconversion, disappearance of hepatitis B virus DNA in serum, normalization of liver enzymes and a significant reduction in necro-inflammatory activity in all 12 patients, no significant change in cyclooxygenase-2 expression was found. Conclusions: Chronic hepatitis B is associated with elevated cyclooxygenase-2 levels in hepatocytes, and the over-expression of this enzyme does not reflect inflammatory activity. Up-regulation of cyclooxygenase-2 persists after successful anti-viral therapy. [source]

    Lamivudine treatment in maternally transmitted chronic hepatitis B virus infection patients

    Yen-Hsuan Ni
    Abstract, Background:,Lamivudine treatment in chronic carriers who acquired hepatitis B virus through maternal transmission were investigated. Methods:,A total of 29 subjects (Male : Female, 24:5; mean age, 14.7 5.6 years) who were hepatitis B e antigen (HBeAg) seropositive for >6 months, alanine aminotransferase (ALT) was >1.3 times of upper limit of normal value, and receiving a 52 week-long treatment, received open-label lamivudine (3 mg/kg per day, maximum 100 mg/day). Another 29 subjects matched for gender, age, liver function, and HBeAg status followed up before the introduction of lamivudine served as the control group. The control group did not receive any treatment and were evaluated at week 52 after the onset of abnormal ALT. Mothers of all study subjects were hepatitis B surface antigen (HBsAg) carriers. A successful treatment response at week 52 was defined as: (i) undetectable hepatitis B virus DNA by real time polymerase chain reaction; (ii) normal ALT; and (iii) HBeAg/anti-HBe seroconversion. Lamivudine-resistant YMDD mutants were checked at week 52. Results:,The lamivudine group did not reach a better successful treatment response rate than the control group (17 vs 10%, P = 0.44), except in patients with a baseline ALT >5 times of the upper limit of normal value. YMDD mutants developed in 34% of patients in the lamivudine group. Conclusion:,Lamivudine treatment is effective for maternally transmitted subjects with high ALT. [source]

    Does Cerumen Have a Risk for Transmission of Hepatitis B?,

    THE LARYNGOSCOPE, Issue 3 2004
    M. Tayyar Kalcioglu MD
    Abstract Objectives/Hypothesis Chronic hepatitis B virus infection is a significant worldwide health problem. It affects 350 to 400 million people. The patients with chronic hepatitis B virus infection have a significant risk for the development of cirrhosis or hepatocellular carcinoma. Full awareness of the mechanisms of transmission can allows susceptible individuals to refrain from this infection. Cerumen has never been studied as a route for hepatitis B transmission. The aim of the study was evaluate the importance of cerumen in transmission of hepatitis B virus infection. Study Design This study was performed on forty patients with confirmed hepatitis B virus infection. Methods Forty cerumen specimens collected from the patients with hepatitis B virus DNA in their sera were prospectively analyzed for the presence of hepatitis B virus DNA by real-time polymerase chain reaction. Results Eleven of 40 cerumen specimens (27.5%) were positive for hepatitis B virus DNA, with counts ranging from 4.2 102 to 4.7 106 copies per sample. There was positive correlation between hepatitis B virus DNA concentrations of serum and cerumen. Half of hepatitis B e antigen (HBeAg),positive patients had detectable hepatitis B virus DNA levels (5.7 102 to 4.7 106 copies) in cerumen specimens, whereas 12.5% of cerumen specimens from anti-HBe,positive patients had hepatitis B virus DNA levels (4.2 102 to 7.0 103 copies). Conclusion Cerumen can be a potential source of transmission. Therefore, this route should be investigated in further studies for horizontal, nosocomial, and occupational transmission of hepatitis B. [source]