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HBV DNA Levels (hbv + dna_level)
Kinds of HBV DNA Levels Selected AbstractsHepatitis B viral load predicts survival of HCC patients undergoing systemic chemotherapy,HEPATOLOGY, Issue 6 2007Winnie Yeo HCC is a common cause of morbidity and mortality. For patients who are not candidates for curative surgery, systemic chemotherapy is one of the standard treatments. In parts of China and the Far East, over 80% of HCC patients have chronic HBV infection. In this study, we aimed to assess the relationship between pre-chemotherapy HBV viral load and the survival of HCC patients. HBV infection status was determined prior to chemotherapy in 188 patients, 170 of whom had evidence of HBV chronic infection/exposure (160 hepatitis B surface antigen [HBsAg]-positive, 10 HBsAg-negative/hepatitis B core antibody,positive). Of these, 125 had pretreatment HBV DNA levels determined via real-time PCR. Virological data were analyzed using conventional clinical variables to identify factors that influenced survival. Multivariate analysis revealed that high total bilirubin (P = 0.0016; hazard ratio = 1.040 per 1 ,M increase; 95% CI 1.015,1.065), HCV infection (P = 0.0095; hazard ratio = 6.955; 95% CI 1.606,30.129), and high HBV DNA level (P = 0.0217; hazard ratio = 1.650; 95% CI 1.076,2.531) affected survival significantly. Exploratory analysis revealed that high levels of pretreatment HBV DNA had a significantly higher incidence of severe hepatitis during chemotherapy. Conclusion: For HCC patients with HBV chronic infection/exposure, a high viral load prior to treatment is an adverse factor for survival and may be associated with a higher incidence of severe hepatitis during chemotherapy. Future strategies to improve the prognosis of HCC patients undergoing chemotherapy should consider supportive therapy that incorporates antiviral therapies to reduce HBV viral load. (HEPATOLOGY 2007;45:1382,1389.) [source] Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipientsHEPATOLOGY, Issue 5 2002Tak Mao Chan Hepatitis B surface antigen (HBsAg)-positive kidney transplant recipients have increased liver-related mortality. The impact of lamivudine treatment on patient survival, the optimal time to start treatment, and the feasibility of discontinuing treatment have not been determined. This study examined these issues with a novel management protocol. Serum hepatitis B virus (HBV) DNA levels were measured serially in HBsAg-positive kidney transplant recipients, and lamivudine was administered preemptively to patients with increasing HBV DNA levels with or without elevation of aminotransferase levels. Outcomes of patients who underwent transplantation before or after institution of this preemptive management strategy (in January 1996) were compared. Eleven de novo patients (91.7%) who underwent transplantation between 1996 and 2000 and 15 existing patients (39.5%) who underwent transplantation between 1983 and 1995 received preemptive lamivudine therapy for 32.6 ± 13.3 months. The treatment criteria were met by de novo patients at 8.4 ± 6.2 months (range, 1-18 months) after transplantation. Suppression of HBV DNA and normalization of aminotransferase levels were achieved in all treated patients, and 21.4% had hepatitis B e antigen (HBeAg) seroconversion. The survival of preemptively managed de novo transplant patients was similar to that of HBsAg-negative controls, whereas HBsAg-positive patients who underwent transplantation before January 1996 had inferior survival (relative risk of death, 9.7 [P < .001]; relative risk of liver-related mortality, 68.0 [P < .0001]). Eleven patients (40.7%) developed lamivudine resistance. Discontinuation of lamivudine was attempted in 12 low-risk patients after stabilization and was successful in 5 (41.7%). In conclusion, preemptive lamivudine therapy based on serial HBV DNA levels and clinical monitoring improved the survival of HBsAg-positive renal allograft recipients. Treatment can be discontinued safely in selected patients after stabilization to minimize the selection of drug-resistant HBV mutants. [source] Lamivudine monoprophylaxis and adefovir salvage for liver transplantation in chronic hepatitis B: A seven-year follow-up study,,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2009Jenny L. Limquiaco Abstract In Asia Pacific countries, lamivudine is used frequently as the sole prophylaxis for hepatitis B virus (HBV) recurrence after liver transplantation due to financial consideration. The aim was to evaluate the long-term outcome of lamivudine monoprophylaxis with adefovir salvage for liver transplantation in chronic hepatitis B. Consecutive chronic hepatitis B patients who received liver transplantation from 1999 to 2003 and with at least 12 months follow up were studied. Lamivudine monotherapy was used for antiviral prophylaxis and adefovir was added as salvage treatment for recurrence of HBV. Twenty-four patients were followed up for 272 (76,372) weeks post-liver transplantation. HBV recurrence developed in seven patients with cumulative probabilities of 8%, 13%, 28%, 35%, 35%, and 49% in 1, 2, 3, 4, 5, and 6 years. At the time of recurrence of HBV, the HBV DNA level was 910,244 (363 to 9,×,108) copies/ml. On direct sequencing, four patients had rtM204I mutation and three patients HBV DNA levels were too low for sequencing. Six patients had elevated ALT (two patients had ALT >1,000 IU/L and jaundice) but none had hepatic encephalopathy. After adefovir treatment for 150 (91,193) weeks, six (86%) patients had normal ALT. HBV DNA was undetectable in two (29%) patients, 100,1,000 copies/ml in two (29%) patients and 10,000,100,000 copies/ml in three (43%) patients on last visit. No genotypic resistance to adefovir was detected. Lamivudine followed by adefovir salvage is effective for prophylaxis of recurrence of HBV after liver transplantation up to 7 years. J. Med. Virol. 81:224,229, 2009. © 2008 Wiley-Liss, Inc. [source] Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinomaJOURNAL OF MEDICAL VIROLOGY, Issue 4 2008Yuehua Huang Abstract Identification of risk factors for recurrence and metastasis of HCC is important for the prognosis of HCC surveillance in chronic HBV infection. In this article, 125 HCC patients recruited were followed up prospectively for tumor metastasis and recurrence for a median of 104 (10,130) weeks. HBV DNA level was detected by LightCycler-based real-time fluorescence quantitative polymerase chain reaction-restriction system. HBV genotypes were determined by using PCR restriction-fragment length polymorphism. BCP and PC mutations were performed by PCR and direct sequencing of amplified products. Among 125 HCC patients, 19 patients were excluded because of the lack of follow-up data and the remaining 106 patients were followed up of 2 years and entered into analysis. Sixty-nine patients had tumor metastasis or recurrence during the follow-up and the cumulative probability of HCC metastasis or recurrence was 65.1%. On multivariate analysis, genotype C and HBV DNA level were the risk factors for HCC recurrence or metastasis. The incidence of recurrence or metastasis increased with baseline HBV DNA level in a dose-response relationship ranging from 22% for HBV DNA level of less than 3 log10 copies/ml to 80% for HBV DNA level of 5 log10 copies/ml or greater (P,=,0.012). Fifty-seven (74.0%) and 12 (41.4%) patients had metastasis or recurrence in patients with genotype C and B, respectively. The adjusted OR of recurrence or metastasis for genotype C compared with genotype B was 9.755 (P,=,0.009). In conclusion, elevated HBV DNA level and genotype C are strong risk predictors of HCC metastasis or recurrence. J. Med. Virol. 80:591,597, 2008. © 2008 Wiley-Liss, Inc. [source] Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinomaJOURNAL OF VIRAL HEPATITIS, Issue 3 2007F.-C. Tsai Summary., Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (,40 years of age) and old (>40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 ± 24.1 vs 58.4 ± 65.4 IU/L, P = 0.006) and HBV DNA levels (log10 titre: 4.20 ± 1.33 vs 4.80 ± 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log10 titre: 4.79 ± 1.34 vs 3.27 ± 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075,2.333] rather than in young patients (OR 0.848, 95% CI 0.645,1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC. [source] Hepatitis B virus DNA levels, precore mutations, genotypes and histological activity in chronic hepatitis BJOURNAL OF VIRAL HEPATITIS, Issue 4 2000Lindh The present study aimed to clarify how viraemia levels reflect the clinical stages of chronic hepatitis B virus (HBV) infection, in particular studying whether ,healthy carriers' can be identified by analysing HBV DNA levels with a highly sensitive quantitative assay. Histology activity index (HAI), alanine aminotransferase (ALT) level, genotype and precore mutations were compared with the HBV DNA level, as measured using the Amplicor HBV Monitor assay in a prospective study. In 124 hepatitis B e antigen-negative (HBeAg,) patients, the majority with mild liver disease, log HBV DNA levels showed a Gaussian distribution around a geometric mean of 33 000 genome copies ml,1, and increasing HBV DNA level was associated with significantly higher inflammation (HAIinfl) and fibrosis (HAIfibr) scores and higher ALTi (ALT ÷ the upper reference value). Severe inflammation (HAIinfl , 7) was seen in 83% (five of six), 36% (eight of 22) and 3% (one of 37) of HBeAg, patients with HBV DNA > 107, > 2 × 105 and < 104 copies ml,1, respectively. In severe HBeAg, hepatitis, patients with precore wild-type infection had lower HBV DNA levels than those with precore mutants. In 36 HBeAg-positive (HBeAg+) patients, no correlation between HBV DNA level and liver damage was seen. Ninety-six per cent of HBeAg, patients with ALTi < 0.5 had HAIinfl , 3. In HBeAg, carriers with ALTi 0.5,1.0, the relative risk for severe inflammation, comparing HBV DNA > 2 × 105 copies ml,1vs < 2 × 105 copies ml,1, was 14.7. In conclusion, in HBeAg, carriers, HBV DNA < 104 copies ml,1 or ALTi < 0.5 indicates mild inflammation, while > 2 × 105 copies ml,1 of HBV DNA may justify further investigations. Precore status may be relevant for the interpretation of viraemia. [source] Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistanceLIVER INTERNATIONAL, Issue 1 2006Eiji Tanaka Abstract: Objective: The clinical usefulness of hepatitis B virus core-related antigen (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the occurrence of lamivudine resistance in patients with chronic hepatitis B. Patients: Of a total of 81 patients who were treated with lamivudine, 25 (31%) developed lamivudine resistance during a median follow-up period of 19.3 months. Results: The pretreatment positive rate of HBe antigen, or pretreatment levels of HBVcrAg or HBV DNA did not differ between patients with and without lamivudine resistance. Levels of both HBVcrAg and HBV DNA decreased after the initiation of lamivudine administration; however, the level of HBVcrAg decreased significantly more slowly than that of HBV DNA. The occurrence of lamivudine resistance was significantly less frequent in the 56 patients whose HBV DNA level was less than 2.6 log copy/ml at 6 months of treatment than in the remaining 25 patients. The cumulative rate of lamivudine resistance was as high as 70% within 2 years in the latter group, while it was only 28% in the former group. Lamivudine resistance did not occur during the follow-up period in the 19 patients whose HBVcrAg level was less than 4.6 log U/ml at 6 months of treatment, while it did occur in 50% of the remaining patients within 2 years. Conclusion: These results suggest that measurement of HBV DNA is valuable for identifying patients who are at high risk of developing lamivudine resistance, and that, conversely, measurement of HBVcrAg is valuable for identifying those who are at low risk of lamivudine resistance. [source] Evolution of hepatitis B virus precore/basal core promoter gene in HBeAg-positive chronic hepatitis B patients receiving lamivudine therapyLIVER INTERNATIONAL, Issue 1 2004Chih-Lin Lin Abstract: Aim: Lamivudine is effective in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, but the relapse rate after cessation of treatment is high. The evolution of viral genome may contribute to the viral replication under antiviral pressure of lamivudine. We therefore determined the evolution of hepatitis B virus (HBV) precore/basal core promoter and polymerase genes in HBeAg-positive chronic hepatitis B patient during lamivudine therapy. Method: Thirteen patients with HBeAg-positive chronic hepatitis who had received short-term lamivudine therapy (mean, 30 weeks) during 1999,2001 were enrolled. The precore/basal core promoter region and polymerase gene were amplified and directly sequenced before, during and post lamivudine treatment. Result: HBeAg loss or seroconversion occurred in 11, but eight relapsed after stopping therapy and five had reversion of HBeAg. Before treatment, basal core promoter mutation was found in 1. In the first 3 months of therapy, a rapid decline of serum HBV DNA level accompanied with basal core promoter mutation appeared in 11 of 13 patients (vs. before therapy; P=0.003). However, this mutant was replaced by wild-type virus in four of eight patients who relapsed after treatment. There was no significant change of precore sequences before and during therapy. Conclusions: Lamivudine therapy may result in the rapid development of basal core promoter mutation of HBV, but this mutation may revert to wild type gradually after cessation of therapy. [source] Impact of Virologic Breakthrough and HBIG Regimen on Hepatitis B Recurrence After Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010B. Degertekin The availability of hepatitis B immune globulin (HBIG) and several oral antiviral therapies has reduced but not eliminated hepatitis B virus (HBV) recurrence. We aimed to determine the rate of HBV recurrence after orthotopic liver transplantation (OLT) in relation to virologic breakthrough pre-OLT and HBIG regimens post-OLT. Data from the NIH HBV-OLT database were analyzed. A total of 183 patients transplanted between 2001 and 2007 followed for a median of 42 months (range 1,81) post-OLT were studied. At transplant, 29% were hepatitis B e antigen (HBeAg) (+), 38.5% had HBV DNA > 5 log10 copies/mL, 74% were receiving antiviral therapy. Twenty-five patients experienced virologic breakthrough before OLT. Post-OLT, 26%, 22%, 40% and 12% of patients received intravenous (IV) high-dose, IV low-dose, intramuscular low-dose and a finite duration of HBIG, respectively as maintenance prophylaxis. All but two patients also received antiviral therapy. Cumulative rates of HBV recurrence at 1 and 5 years were 3% and 9%, respectively. Multivariate analysis showed that listing HBeAg status and HBV DNA level at OLT were the only factors associated with HBV recurrence. In conclusion, low rates of HBV recurrence can be accomplished with all the HBIG regimens used when combined with antiviral therapy including patients with breakthrough pre-OLT as long as rescue therapy is administered pre- and post-OLT. [source] Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels,HEPATOLOGY, Issue 2 2010Vincent Rijckborst Peginterferon alfa-2a results in a sustained response (SR) in a minority of patients with hepatitis B e antigen (HBeAg),negative chronic hepatitis B (CHB). This study investigated the role of early on-treatment serum hepatitis B surface antigen (HBsAg) levels in the prediction of SR in HBeAg-negative patients receiving peginterferon alfa-2a. HBsAg (Architect from Abbott) was quantified at the baseline and during treatment (weeks 4, 8, 12, 24, 36, and 48) and follow-up (weeks 60 and 72) in the sera from 107 patients who participated in an international multicenter trial (peginterferon alfa-2a, n = 53, versus peginterferon alfa-2a and ribavirin, n = 54). Overall, 24 patients (22%) achieved SR [serum hepatitis B virus (HBV) DNA level < 10,000 copies/mL and normal alanine aminotransferase levels at week 72]. Baseline characteristics were comparable between sustained responders and nonresponders. From week 8 onward, serum HBsAg levels markedly decreased in sustained responders, whereas only a modest decline was observed in nonresponders. However, HBsAg declines alone were of limited value in the prediction of SR [area under the receiver operating characteristic curve (AUC) at weeks 4, 8, and 12 = 0.59, 0.56, and 0.69, respectively]. Combining the declines in HBsAg and HBV DNA allowed the best prediction of SR (AUC at week 12 = 0.74). None of the 20 patients (20% of the study population) in whom a decrease in serum HBsAg levels was absent and whose HBV DNA levels declined less than 2 log copies/mL exhibited an SR (negative predictive value = 100%). Conclusion: At week 12 of peginterferon alfa-2a treatment for HBeAg-negative CHB, a solid stopping rule was established with a combination of declines in serum HBV DNA and HBsAg levels from the baseline. Quantitative serum HBsAg in combination with HBV DNA enables on-treatment adjustments of peginterferon therapy for HBeAg-negative CHB. (HEPATOLOGY 2010) [source] Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection,HEPATOLOGY, Issue 6 2004Florian van Bömmel Adefovir dipivoxil was recently approved for the treatment of wild-type and lamivudine-resistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender of adefovir that is used in the treatment of HIV infected patients, has recently been shown to also be effective in patients with lamivudine-resistant HBV infection. We therefore compared the two substances in a study of 53 patients defined by high HBV DNA (>6 log10 copies/mL) levels and genotypic evidence of lamivudine resistance. Thirty-five patients received tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80 weeks. Changes in HBV DNA levels were followed for the complete period of 48 weeks. Early viral kinetics were compared on matched subgroups of 5 patients each. Individually, all tenofovir-treated patients showed a strong and early suppression of HBV DNA within a few weeks whether they were coinfected with HIV or were without comorbidity. In contrast, considerable individual variations in HBV DNA decline were observed in the adefovir group. Thus at week 48, only 44% of these patients had HBV DNA levels below 105 copies/mL in contrast to 100% of the tenofovir-treated patients (P = .001). No severe side effects were noticed in either group. No evidence of phenotypic viral resistance could be demonstrated in the tenofovir-treated patients in the long term (up to 130 weeks). In conclusion, tenofovir may become an effective alternative for the treatment of patients with lamivudine-resistant HBV infection. (HEPATOLOGY 2004;40:1421,1425.) [source] Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipientsHEPATOLOGY, Issue 5 2002Tak Mao Chan Hepatitis B surface antigen (HBsAg)-positive kidney transplant recipients have increased liver-related mortality. The impact of lamivudine treatment on patient survival, the optimal time to start treatment, and the feasibility of discontinuing treatment have not been determined. This study examined these issues with a novel management protocol. Serum hepatitis B virus (HBV) DNA levels were measured serially in HBsAg-positive kidney transplant recipients, and lamivudine was administered preemptively to patients with increasing HBV DNA levels with or without elevation of aminotransferase levels. Outcomes of patients who underwent transplantation before or after institution of this preemptive management strategy (in January 1996) were compared. Eleven de novo patients (91.7%) who underwent transplantation between 1996 and 2000 and 15 existing patients (39.5%) who underwent transplantation between 1983 and 1995 received preemptive lamivudine therapy for 32.6 ± 13.3 months. The treatment criteria were met by de novo patients at 8.4 ± 6.2 months (range, 1-18 months) after transplantation. Suppression of HBV DNA and normalization of aminotransferase levels were achieved in all treated patients, and 21.4% had hepatitis B e antigen (HBeAg) seroconversion. The survival of preemptively managed de novo transplant patients was similar to that of HBsAg-negative controls, whereas HBsAg-positive patients who underwent transplantation before January 1996 had inferior survival (relative risk of death, 9.7 [P < .001]; relative risk of liver-related mortality, 68.0 [P < .0001]). Eleven patients (40.7%) developed lamivudine resistance. Discontinuation of lamivudine was attempted in 12 low-risk patients after stabilization and was successful in 5 (41.7%). In conclusion, preemptive lamivudine therapy based on serial HBV DNA levels and clinical monitoring improved the survival of HBsAg-positive renal allograft recipients. Treatment can be discontinued safely in selected patients after stabilization to minimize the selection of drug-resistant HBV mutants. [source] Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infectionHEPATOLOGY, Issue 3 2001Ph.D., Robert A. de Man M.D. Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log10 reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P < .05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients. (HEPATOLOGY 2001;34:578-582.) [source] Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in KoreaHEPATOLOGY, Issue 4 2000Byung-Cheol Song It has been suggested that hepatitis B e antigen (HBeAg) seroconversion after lamivudine therapy is durable in Caucasians with chronic hepatitis B (CHB). However, little is known whether it is also durable in endemic areas of hepatitis B virus (HBV) infection. We evaluated the posttreatment durability of lamivudine-induced HBeAg seroconversion and the predictive factors for relapse in Korean patients with CHB. We retrospectively analyzed 98 HBeAg-positive patients with CHB who were treated with lamivudine between August 1996 and December 1997. Lamivudine was given at a dose of 150 mg per day. After HBeAg seroconversion, lamivudine was continued for an additional 2 to 4 months, and posttreatment monitoring continued for up to 24 months. HBeAg seroconversion was achieved in 34 of the 98 patients (34.7%). The mean duration of treatment in these seroconverters was 9.3 ± 3.0 months. During the follow-up period, the cumulative relapse rates at 1 year and 2 years posttreatment were 37.5% and 49.2%, respectively. Most relapses were accompanied by elevation of serum alanine transaminase (94%) and reappearance of HBeAg (81%). Pretreatment serum HBV DNA levels and the duration of additional lamivudine therapy after HBeAg seroconversion were 2 independent predictive factors for posttreatment relapse. In conclusion, lamivudine-induced HBeAg seroconversion was not durable in this endemic area. And the duration of additional lamivudine therapy after HBeAg seroconversion significantly affected the posttreatment relapse. Further studies are needed to determine the duration of lamivudine and to elucidate the cause of high relapse after HBeAg seroconversion in endemic areas of HBV. [source] Correlation of YMDD mutation and breakthrough hepatitis with hepatitis B virus DNA and serum ALT during lamivudine treatmentHEPATOLOGY RESEARCH, Issue 2 2010Mariko 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] Long-term outcome of tenofovir disoproxil fumarate use against hepatitis B in an HIV-coinfected cohortHIV MEDICINE, Issue 5 2009G Alvarez-Uria Objectives Tenofovir disoproxil fumarate (TDF) is active against hepatitis B virus (HBV) and HIV. However, the long-term efficacy of tenofovir disoproxil fumarate (TDF) is not well known and the appearance of resistance is a major concern. We have studied the efficacy of TDF against HBV in patients treated at an Infectious Diseases Unit. Methods We carried out a retrospective observational study of the efficacy of TDF against HBV replication in a cohort of 52 HIV-coinfected patients who received TDF for at least 6 months. Results The median duration of follow-up of TDF treatment was 34 months. Forty-one patients (79%) were positive for HBV envelope antigen (HBeAg) and 35 had received previous lamivudine monotherapy for a median duration of 32 months. Virological breakthrough was observed in nine cases (17%). At the end of the follow-up period, HBV DNA levels were <1000 copies/mL in 42 patients (81%) and <200 copies/mL in 31 patients (60%). There were no significant differences between the lamivudine-naïve and lamivudine-experienced groups. In the lamivudine-experienced group, the duration of previous lamivudine monotherapy was associated with failure to achieve HBV DNA levels <200 copies/mL (P=0.036). Adding lamivudine or emtricitabine to TDF did not improve virological suppression. In 39 patients who achieved <200 HBV DNA copies/mL during TDF treatment, virological breakthrough was seen only in two patients (5%) after a median follow-up duration of 39.7 months. Conclusions TDF was able to control HBV replication in most HIV-coinfected patients after a median follow-up duration of 34 months, regardless of previous lamivudine treatment. However, a sizeable proportion of patients developed virological breakthrough. [source] Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2010Marion Levast Abstract The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real-time PCR techniques are available commercially and can detect more reliably low HBV DNA levels. The aim of this study was to determine the prevalence of occult hepatitis B virus infection using the COBAS Taqman assay (Roche Diagnostics, Meylan, France) in the serum and liver of HBsAg negative patients with chronic hepatitis C and to evaluate its clinical consequences on liver pathology and its impact on the response to treatment with peg-IFN, and Ribavirin. HBV DNA detection was assessed retrospectively on 140 sera and 113 liver biopsies of HCV positive/HBsAg negative patients before treatment. A 4.4% (5/113) prevalence of occult hepatitis B was recorded in liver samples and in none of the sera. Anti-HBc was not detected in one, three of whom were sustained virological responders to treatment, one was relapsed responder and one was non-responder. Furthermore, in this cohort composed of 12% anti-HBs negative/anti-HBc positive and 20% anti-HBs positive/anti-HBc positive patients, anti-HBc was not associated with pre-therapeutic viral load, ALT serum levels, and histological activity or fibrosis. Using a commercial real-time PCR assay, we observed a low prevalence of occult B hepatitis. This, just as anti-HBC status, had no clinical impact in a large cohort of hepatitis C patients. It therefore does not appear useful to screen for occult hepatitis B in these patients with this test before beginning HCV treatment. J. Med. Virol. 82: 000,000, 2010. © 2010 Wiley-Liss, Inc. J. Med. Virol. 82: 747,754, 2010. © 2010 Wiley-Liss, Inc. [source] Lamivudine monoprophylaxis and adefovir salvage for liver transplantation in chronic hepatitis B: A seven-year follow-up study,,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2009Jenny L. Limquiaco Abstract In Asia Pacific countries, lamivudine is used frequently as the sole prophylaxis for hepatitis B virus (HBV) recurrence after liver transplantation due to financial consideration. The aim was to evaluate the long-term outcome of lamivudine monoprophylaxis with adefovir salvage for liver transplantation in chronic hepatitis B. Consecutive chronic hepatitis B patients who received liver transplantation from 1999 to 2003 and with at least 12 months follow up were studied. Lamivudine monotherapy was used for antiviral prophylaxis and adefovir was added as salvage treatment for recurrence of HBV. Twenty-four patients were followed up for 272 (76,372) weeks post-liver transplantation. HBV recurrence developed in seven patients with cumulative probabilities of 8%, 13%, 28%, 35%, 35%, and 49% in 1, 2, 3, 4, 5, and 6 years. At the time of recurrence of HBV, the HBV DNA level was 910,244 (363 to 9,×,108) copies/ml. On direct sequencing, four patients had rtM204I mutation and three patients HBV DNA levels were too low for sequencing. Six patients had elevated ALT (two patients had ALT >1,000 IU/L and jaundice) but none had hepatic encephalopathy. After adefovir treatment for 150 (91,193) weeks, six (86%) patients had normal ALT. HBV DNA was undetectable in two (29%) patients, 100,1,000 copies/ml in two (29%) patients and 10,000,100,000 copies/ml in three (43%) patients on last visit. No genotypic resistance to adefovir was detected. Lamivudine followed by adefovir salvage is effective for prophylaxis of recurrence of HBV after liver transplantation up to 7 years. J. Med. Virol. 81:224,229, 2009. © 2008 Wiley-Liss, Inc. [source] Characterization of viral kinetics in patients with hepatitis B e antigen-positive chronic hepatitis BJOURNAL OF MEDICAL VIROLOGY, Issue 6 2007I-Chin Wu Abstract A study was conducted during a 1 year follow-up to characterize the viral kinetics in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and to develop a model of predicting the probability of spontaneous HBeAg seroconversion. Fifty-seven patients with HBeAg-positive chronic hepatitis B were enrolled with monthly follow-ups from three Phase III clinical trial placebo groups. According to serial viral loads, 30 patients (52.6%) with the stationary pattern maintained stable HBV DNA levels with fluctuations of less than 1.5 log copies/ml. Twenty patients (35.1%) with the declining pattern exhibited a spontaneous decline of more than 1.5 log copies/ml without a following rebound of at least 1.5 log copies/ml. The remaining seven patients (12.3%) had the wavering pattern. Both declining and wavering patterns, when compared with the stationary pattern, had significantly higher hepatic necroinflammation in terms of ALT and Knodell scores at the baseline and peak ALT levels during the follow-up period. The declining pattern had a significantly better clinical outcome in terms of the lowest final HBV DNA and a reduction in the necroinflammatory score after 1 year. Furthermore, the declining pattern had a favorable HBeAg seroconversion rate (40%) compared with the wavering (14.3%) and stationary patterns (0%). A regression equation, incorporating simultaneous serum bilirubin, ALT, and HBV DNA levels, predicted the probability of HBeAg seroconversion with a sensitivity of 76.8% and a specificity of 74.7%. In conclusion, different viral kinetic patterns in patients with chronic hepatitis B implicate distinct clinical significance and immunologic perspective. J. Med. Virol. 79: 663,669, 2007. © 2007 Wiley-Liss, Inc. [source] Differences of YMDD mutational patterns, precore/core promoter mutations, serum HBV DNA levels in lamivudine-resistant hepatitis B genotypes B and CJOURNAL OF VIRAL HEPATITIS, Issue 11 2007X. P. Pan Summary., The aims of this study were to investigate the viral differences among lamivudine-resistant hepatitis B virus (HBV) genotypes B and C in vivo. Fifty-three patients carrying lamivudine-resistant HBV were enrolled in this study. HBV genotypes, Levels of alanine aminotransferase (ALT), HBV DNA levels were monitored during therapy. The polymerase and precore/core promoter genes were amplified by polymerase chain reaction and their products were sequenced directly. Among 53 patients resistant HBV genotypes B and C accounted for 41.50% and 58.50%, respectively. The occurrence of reverse transcriptase rt204I mutants was lower in genotype B (36.36%) than that in genotype C (87.10%), whereas rt204V mutants was higher in genotype B (63.64%) than that in genotype C (12.90%). The occurrence of precore mutation (nt1896A) was higher in genotype B (77.27%) than that in genotype C (32.26%). Serum HBV DNA levels after emergence of lamivudine resistance were higher in genotype C (7.71 ± 0.80 Log copies/mL) compared with genotype B (6.97 ± 0.77 Log copies/mL). Multivariate analysis identified pretreatment HBV DNA levels, HBeAg status and HBV genotype as independent factors associated with a shorter time to lamivudine resistance(P = 0.035, P = 0.006 and P = 0.001, respectively). Multivariate analysis showed that HBV genotype (P = 0.004) and pretreatment ALT levels (P = 0.01) was independently associated with YMDD mutational patterns. The results showed that the YMDD mutational patterns, precore mutation and serum HBV DNA levels differ between lamivudine-resistant HBV genotypes B and C in vivo. It is valuable for treatment of lamivudine-resistant HBV in clinic. [source] Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinomaJOURNAL OF VIRAL HEPATITIS, Issue 3 2007F.-C. Tsai Summary., Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (,40 years of age) and old (>40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 ± 24.1 vs 58.4 ± 65.4 IU/L, P = 0.006) and HBV DNA levels (log10 titre: 4.20 ± 1.33 vs 4.80 ± 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log10 titre: 4.79 ± 1.34 vs 3.27 ± 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075,2.333] rather than in young patients (OR 0.848, 95% CI 0.645,1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC. [source] Hepatitis B virus (HBV) DNA levels and the management of HBV-infected health care workersJOURNAL OF VIRAL HEPATITIS, Issue 1 2006A. A. Van Der Eijk Summary., Different guidelines exist for the management of hepatitis B virus (HBV)-infected health care workers (HCWs). Various HBV DNA levels are used as a cutoff level to determine whether an HBV-infected HCW is allowed to perform exposure-prone procedures (EPPs) or not. In this paper we discuss the factors that determine HBV DNA levels and the implications of different HBV DNA cutoff levels for EPP performing HCWs. If the level of HBV DNA in the serum of HCWs is used to determine acceptability for the conduct of EPPs, it is necessary to take into account the variability in time of HBV DNA levels in HBV carriers and the reliability and reproducibility of the molecular diagnostic test involved. The issue of standardization has to be addressed, before a universal, maximum level of viraemia for EPP performing HCWs can be introduced. [source] Quantitative detection of hepatitis B virus DNA in serum by a new rapid real-time fluorescence PCR assayJOURNAL OF VIRAL HEPATITIS, Issue 6 2001R. 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] Hepatitis B virus DNA levels, precore mutations, genotypes and histological activity in chronic hepatitis BJOURNAL OF VIRAL HEPATITIS, Issue 4 2000Lindh The present study aimed to clarify how viraemia levels reflect the clinical stages of chronic hepatitis B virus (HBV) infection, in particular studying whether ,healthy carriers' can be identified by analysing HBV DNA levels with a highly sensitive quantitative assay. Histology activity index (HAI), alanine aminotransferase (ALT) level, genotype and precore mutations were compared with the HBV DNA level, as measured using the Amplicor HBV Monitor assay in a prospective study. In 124 hepatitis B e antigen-negative (HBeAg,) patients, the majority with mild liver disease, log HBV DNA levels showed a Gaussian distribution around a geometric mean of 33 000 genome copies ml,1, and increasing HBV DNA level was associated with significantly higher inflammation (HAIinfl) and fibrosis (HAIfibr) scores and higher ALTi (ALT ÷ the upper reference value). Severe inflammation (HAIinfl , 7) was seen in 83% (five of six), 36% (eight of 22) and 3% (one of 37) of HBeAg, patients with HBV DNA > 107, > 2 × 105 and < 104 copies ml,1, respectively. In severe HBeAg, hepatitis, patients with precore wild-type infection had lower HBV DNA levels than those with precore mutants. In 36 HBeAg-positive (HBeAg+) patients, no correlation between HBV DNA level and liver damage was seen. Ninety-six per cent of HBeAg, patients with ALTi < 0.5 had HAIinfl , 3. In HBeAg, carriers with ALTi 0.5,1.0, the relative risk for severe inflammation, comparing HBV DNA > 2 × 105 copies ml,1vs < 2 × 105 copies ml,1, was 14.7. In conclusion, in HBeAg, carriers, HBV DNA < 104 copies ml,1 or ALTi < 0.5 indicates mild inflammation, while > 2 × 105 copies ml,1 of HBV DNA may justify further investigations. Precore status may be relevant for the interpretation of viraemia. [source] Tenofovir plus lamivudine as rescue therapy for adefovir-resistant chronic hepatitis B in hepatitis B e antigen-positive patients with liver cirrhosisLIVER INTERNATIONAL, Issue 6 2008Won Hyeok Choe Abstract Background/Aims: There is no consensus on the management of patients with adefovir (ADV)-resistant hepatitis B virus (HBV) infection. The aim of this study was to investigate whether tenofovir disoproxil fumarate (TDF) combined with lamivudine (LMV) is effective and safe in patients with resistance to or non-response to ADV. Methods: Six patients with HBV-related cirrhosis, viral breakthrough during LMV therapy and viral breakthrough or non-response during ADV therapy were treated daily with TDF plus LMV for at least 6 months. The HBV DNA level, alanine aminotransferase (ALT), the Child,Pugh score and serum creatinine were monitored. Genotypic LMV- or ADV-resistant mutations were measured in stored samples. Results: In five of six patients, ADV-resistant mutations at rt181 or rt236 were detected during ADV therapy. At 6 months of starting TDF/LMV combination, HBV DNA levels became undetectable (detection limit, 400 copies/ml) in four of six patients. Within 12 months, HBV DNA levels became undetectable in all patients, and ALT levels were normalized in four of six patients. These responses persisted up to the end of the observation period (median duration 16.5 months, range 6,21 months). The Child,Pugh scores improved in two of three patients with hepatic decompensation. No significant changes in serum creatinine were observed. Conclusion: Our data demonstrated that TDF plus LMV safely and markedly suppressed HBV replication in patients with resistance to or non-response to ADV. This study suggests that this combination may be a promising rescue therapy for these patients, particularly those with liver cirrhosis or pre-existing LMV resistance. [source] Prognostic analysis in chronic hepatitis B patients: a retrospective study of 216 cases about Scheuer scores, in situ expression of viral antigens and tissue hepatitis B virus DNA levelsLIVER INTERNATIONAL, Issue 1 2006Rong Zhu Abstract: Background: Most of the previous studies of patients with chronic hepatitis B virus (HBV) infection concentrated on serum samples. Liver biopsy specimens for HBV have not been systematically analyzed. This study was performed to analyze some histopathological indicators (Scheuer scores, the expression of HBV antigens in situ, HBV DNA quantification) in the biopsy samples and showed the relationship among them and the prognosis of chronic hepatitis. Methods: A total of 216 consecutive chronic HBV-infected patients were followed up by clinical and laboratory data and classified into two groups at first: carcinogenesis and non-carcinogenesis. The non-carcinogenesis also included two groups: cirrhosis and non-cirrhosis. The non-cirrhosis was still divided into fluctuation and normalization at last. Histological activity index was described by Scheuer scores. Two-step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV DNA levels were determined by fluorescence quantitative real-time PCR. Results: Regression analysis revealed significant positive correlations between the expression of hepatitis B e antigen (HBeAg) and grading, as well as between hepatitis Bx (HBx) protein and grading or staging of Scheuer scores. Positive correlations between grading or staging and prognosis were statistically significant. The expressions of HBeAg and HBx protein were higher in patients with cirrhosis than those without cirrhosis. Scheuer score was the most important indicator of prognosis. Conclusions: HBeAg and HBx protein can be used as indicators of hepatitis activity and their positive expressions increase the risk for cirrhosis remarkably. In addition to be a marker of liver damage, Scheuer score is the most reliable indicator of the prognosis. [source] Adefovir dipivoxil for wait-listed and post,liver transplantation patients with lamivudine-resistant hepatitis B: Final long-term resultsLIVER TRANSPLANTATION, Issue 3 2007Eugene Schiff Wait-listed (n = 226) or post,liver transplantation (n = 241) chronic hepatitis B (CHB) patients with lamivudine-resistant hepatitis B virus (HBV) were treated with adefovir dipivoxil for a median of 39 and 99 weeks, respectively. Among wait-listed patients, serum HBV DNA levels became undetectable (<1,000 copies/mL) in 59% and 65% at weeks 48 and 96, respectively. After 48 weeks, alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 77%, 76%, 60%, and 84% of wait-listed patients, respectively. Among posttransplantation patients, serum HBV DNA levels became undetectable in 40% and 65% at weeks 48 and 96, respectively. After 48 weeks, ALT, albumin, bilirubin, and prothrombin time normalized in 51%, 81%, 76%, and 56% of posttransplantation patients, respectively. Among wait-listed patients who underwent on-study liver transplantation, protection from graft reinfection over a median of 35 weeks was similar among patients who did (n = 34) or did not (n = 23) receive hepatitis B immunoglobulin (HBIg). Hepatitis B surface antigen was detected on the first measurement only in 6% and 9% of patients who did or did not receive HBIg, respectively. Serum HBV DNA was detected on consecutive visits in 6% and 0% of patients who did or did not receive HBIg, respectively. Treatment-related adverse events led to discontinuation of adefovir dipivoxil in 4% of patients. Cumulative probabilities of resistance were 0%, 2%, and 2% at weeks 48, 96, and 144, respectively. In conclusion, adefovir dipivoxil is effective and safe in wait-listed or posttransplantation CHB patients with lamivudine-resistant HBV and prevents graft reinfection with or without HBIg. Liver Transpl 13:349-360, 2007. © 2007 AASLD. [source] Living donor liver transplantation for hepatitis B cirrhosisLIVER TRANSPLANTATION, Issue 11 2003Yasuhiko Sugawara The living donor liver transplantation (LDLT) experience for patients with hepatitis B virus (HBV) infection is still limited. Because LDLT can be performed electively, it can provide an appropriate length of time to reduce HBV DNA levels before the operation. This study aims to examine the feasibility of our protocol for preventing HBV reinfection after LDLT. Of 20 patients analyzed, 15 patients had detectable serum HBV DNA when referred to our hospital. Thirteen patients had hepatocellular carcinoma. All patients were treated with lamivudine (100 mg/d) before LDLT. After LDLT, hepatitis B immunoglobulin (HBIG) was administered to maintain serum antibody to hepatitis B surface antigen titers at greater than 1,000 IU/mL for 1 year and 200 IU/mL thereafter. Lamivudine was not administered postoperatively, except for three patients with detectable serum HBV DNA just before LDLT. All patients survived the operation. One patient died 229 days after LDLT of carcinoma recurrence. In the other 19 patients, liver function has remained normal and no viral relapse occurred postoperatively during a median follow-up of 19 months. Perioperative use of lamivudine and indefinite HBIG administration in the postoperative period might be a rational strategy for preventing HBV reinfection after LDLT. [source] | ||||||||||||||||||||||