Viral dynamics in hepatitis B virus infection.

Nowak, Martin A.; Bonhoeffer, Sebastian; Hill, Andrew; Boehme, Richard; Thomas, Howard; McDade, Hugh

doi:10.1073/pnas.93.9.4398

Cited by 952 publications

(814 citation statements)

References 21 publications

Supporting

Mentioning

784

Contrasting

Unclassified

Order By: Relevance

“…HBV DNA showed a biphasic decline in the combination therapy group, as has previously been described for nucleoside analogues in chronic hepatitis B. [24][25][26][27][28] For PEG-IFN monotherapy we found significantly less decline of HBV DNA throughout the treatment period as compared to combination therapy. Despite these differences in HBV DNA decline, loss of HBeAg and HBsAg at the end of follow-up were similar in both treatment groups.…”

Section: Discussionsupporting

confidence: 51%

Patterns of viral decline during PEG-interferon alpha-2b therapy in HBeAg-positive chronic hepatitis B: Relation to treatment response

et al. 2006

View full text Add to dashboard Cite

In chronic hepatitis B, it is difficult to predict an early therapeutic response. We investigated the viral decline during therapy with pegylated interferon alpha-2b (PEG-IFN) with or without lamivudine in 266 HBeAg-positive chronic hepatitis B patients. In patients treated with PEG-IFN and lamivudine, a uniform biphasic viral decline pattern was found during therapy and there were no marked differences in viral load between those who lost HBeAg at the end of follow-up (response) or not. In contrast, those treated with PEG-IFN monotherapy exhibited different viral decline patterns. A delayed decline of at least two log from baseline HBV DNA after week 4 but before week 32 was associated with the highest response rate (63%). In comparison, response was 52% for patients with an early decline (week 0-4), 38% for a late decline (week 32-52), 27% for a posttreatment decline (week 52-78) and 11% for patients with no substantial decline. The HBsAg loss was 22% in the delayed decline pattern compared to 4% for those with early decline and none for other decline patterns. In conclusion, different patterns of decline in viral load during treatment with PEG-IFN monotherapy were associated with different rates of HBeAg and HBsAg loss at the end of follow-up. Since there was a considerable response, even in patients with a late or posttreatment decline pattern, prediction of response based on viral decline during the first months of therapy was difficult. (HEPATOLOGY 2006;44:721-727.) Abbreviations: HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; IFN, interferon alpha; ALT, alanine aminotransferase; HBsAg, hepatitis B surface antigen; antibody to hepatitis B surface antigen; antibody to hepatitis B e antigen; ROC, receiver operating characteristic. From the

show abstract

Section: Discussionsupporting

confidence: 51%

Patterns of viral decline during PEG-interferon alpha-2b therapy in HBeAg-positive chronic hepatitis B: Relation to treatment response

et al. 2006

View full text Add to dashboard Cite

show abstract

“…From another perspective, since the serum viral genome obtained even at the late phase of AE was also identical to the intrahepatic one, we therefore speculate that the viral variant that emerged during AE most likely originated from the liver. The results were compatible with the rapid turnover of HBV in the circulation, more than 10 11 virions/day, 14 that are most likely produced by and released from the liver. denotes the viral nucleotide sequence of serum clone-1.…”

Section: Discussionsupporting

confidence: 71%

Origin of serum hepatitis B virus in acute exacerbation: Comparison with HBV in the liver and from other exacerbation

et al. 2004

View full text Add to dashboard Cite

Acute exacerbation (AE) of chronic hepatitis B is usually preceded by reemergence or increase of hepatitis B virus (HBV) in the serum. To investigate the origin of the reemergence or increase, we compared the identity of the serum viral genome to that in the liver and in previous AE by full-length sequencing. The full-length viral genome and extent of quasispecies were obtained from serum and liver biopsy specimens at the same time from 9 subjects with hepatitis B exacerbation (group I). Composition of viral quasispecies was compared by the genetic diversity and the average number of nucleotide substitutions within and between different viral sources. Another 2 patients with repeated AEs (group II) were also enrolled, and their serial serum alanine aminotransferase, HBV DNA levels and full-length sequences were determined. In all group I patients, serum viral genome was identical to that in the liver. The genetic diversity and the average number of nucleotide difference were also comparable between serum and liver tissue. In 2 group II patients, the viral variant that emerged after previous AE was not identical to that caused by the subsequent AE. Dominant viral strains for serial AEs in a single patient did not show a sequential evolution, but presented as a horizontal selection of a minor population from the original viral pool. In conclusion, the findings suggest that viral strain in serum reflects the intrahepatic strain of the AE. Random reactivation of the original HBV pool, rather than a sequential evolution of one strain, also contributes to the onset of repeated AE. A cute exacerbation (AE) occurs frequently in hepatitis B surface antigen carriers. 1 The exacerbation can accelerate the progression of liver disease. 2 Hepatitis B virus (HBV) evolves rapidly in chronic hepatitis B patients, and the correlation of HBV variation with the onset of AE has been extensively studied. [3][4][5] Previously, we investigated sequential full-length viral sequences in patients with AE 6,7 and found that most exacerbations were preceded by an upsurge of serum HBV identical to the preexisting HBV strain. After exacerbation, however, about half of the patients were repopulated by a different viral variant in the circulation.The pathogenesis of AE actually takes place in the liver. Therefore, it is better to directly characterize the viral genome from the liver biopsy specimen. As noted previously, some potential pathogenic strains may replicate actively within the liver but not be released into the circulation. 8 Thus, HBV genomic changes that are correlated with the development of hepatitis B exacerbation might occur and be retained within the liver but not be detected in the specimens obtained from the circulation. To resolve these questions, the representation of the serum viral genome to the corresponding intrahepatic one was first determined by comparing the dominant viral nucleotide sequence and genetic complexity of the viral quasispecies between both tissue specimens obtained si-

show abstract

“…Initial HBV DNA response was defined as HBV DNA level B10 5 copies/ml or 2 log 10 reduction from baseline HBV DNA level at 6 months [17,18]. VBT was defined as [1 log 10 copies increase in HBV DNA from nadir after an initial virologic response or HBV DNA could be detected again after the previous report of under the detection limit [7].…”

Section: Definitionsmentioning

confidence: 99%

Pretreatment and on-treatment predictors of viral breakthrough in lamivudine therapy for chronic hepatitis B

et al. 2008

View full text Add to dashboard Cite

Purpose There are remarkable advances in the treatment of chronic hepatitis B (CHB) in the last few years. Unfortunately, prolonged antiviral treatment is associated with increasing risk of drug resistance/viral breakthrough (VBT), which may lead to flare-up and rapid decompensation. We have designed this study to predict the pretreatment and on-treatment factors responsible for development of VBT. Methods This study was conducted during the period of February 2000 to November 2007. We have included 423 patients who received lamivudine (LAM) therapy for at least 1 year and at least 2 follow-ups at 6 months' interval. Follow-up period was 12-78 months. Chi-square test, student's t test, and logistic regression analysis were performed to prove the validity. Results Of the 423 study cases, 367 (86.8%) were of male patients and 261 (61.7%) patients were HBeAg positive; the age of the patients was 30.8 ± 12.9 years. Development of VBT was 4. 4, 22.8, 45.3, and 74% at 1, 2, 3, and 4 or more years, respectively. Pretreatment high HBV DNA (P = 0.005) and female sex (P = 0.01) were associated with VBT and pretherapy ALT (P = 0.698), HBeAg status (P = 0.273), and age (P = 0.059) were not associated. Duration of treatment, failure to lose HBeAg at 1 year, and HBV DNA nonresponder at 6 months were significantly (P = 0.001) associated with development of VBT. Conclusion Persistence of HBeAg at 1 year and HBV DNA nonresponder at 6 months are good predictors of development of VBT.

show abstract

Viral dynamics in hepatitis B virus infection.

Abstract: Treatment of chronic hepatitis B virus (HBV) infections with the reverse transcriptase inhibitor lamivudine leads to a rapid decline in plasma viremia and provides estimates for crucial kinetic constants of HBV replication. We

Cited by 952 publications

References 21 publications

Patterns of viral decline during PEG-interferon alpha-2b therapy in HBeAg-positive chronic hepatitis B: Relation to treatment response

Patterns of viral decline during PEG-interferon alpha-2b therapy in HBeAg-positive chronic hepatitis B: Relation to treatment response

Origin of serum hepatitis B virus in acute exacerbation: Comparison with HBV in the liver and from other exacerbation

Pretreatment and on-treatment predictors of viral breakthrough in lamivudine therapy for chronic hepatitis B

Contact Info

Product

Resources

About