Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B

Lee, Jung Min; Park, Jun Yong; Kim, Do Young; Nguyen, Thang; Hong, Sun; Kim, Soo Ok; Chon, Chae Yoon; Han, Kwang Hyub; Ahn, Sang Hoon

doi:10.3851/imp1510

Cited by 61 publications

(48 citation statements)

References 34 publications

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“…When genotypic resistance to ETV was suspected, it was analyzed with the method of restriction fragment mass polymorphism. 26 Endpoints and Definitions. The primary endpoint of this study was the serial analysis of qHBsAg and qHBeAg profiles in patients receiving ETV.…”

Section: Methodsmentioning

confidence: 99%

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

et al. 2011

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Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen-positive [HBeAg(1)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/ mL), and 1.71 Paul Ehrlich (PE) IU/mL (20.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(1) patients, baseline alanine aminotransferase (P 5 0.013), HBV DNA (P 5 0.040), and qHBsAg levels (P 5 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(1) group versus the SR(2) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(1) patients. Conclusion: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(1) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated. (HEPATOLOGY 2011;53:1486-1493 C hronic infection with hepatitis B virus (HBV) is a worldwide health problem, with more than 400 million people thought to be infected.Moreover, these patients are at increased risk for disease progression to cirrhosis and hepatocellular carcinoma. 1 Large cohort studies have shown that elevated levels of Abbreviations: ALT, alanine aminotransferase; anti-HBs, antibody to hepatitis B surface antigen; AUC, area under the curve; AUROC, area under the receiver operating characteristic

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Section: Methodsmentioning

confidence: 99%

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

et al. 2011

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“…[16][17][18] Likewise, high baseline DNA level (cut-off level of 10 5 -10 8 copies/mL) caused insufficient viral suppression, and even frequent emergence of resistance in ADV treatment for LAM-resistance CH-B patients. 8,10,19,20 Those phenomena may have resulted from a high replication rate and subsequent selection of a resistant strain. In this study, a chance to achieve IVR increased sharply by a log10 copies/mL decrement of HBV DNA level.…”

Section: Discussionmentioning

confidence: 99%

“…1,5,6 However, not all LAM-resistant hepatitis B patients respond well to ADV treatment, some of them show partial or non-response and sometimes represent resistant mutations such as rtN236T and rtA181V/T. [7][8][9][10] Moreover, it is harder to manage CH-B showing combined resistance against LAM and ADV. The aim of this study was to identify factor(s) related to the efficacy of ADV treatment for LAM-resistant CH-B patients.…”

Section: Introductionmentioning

confidence: 99%

A Low Viral Load Predicts a Higher Initial Virologic Response to Adefovir in Patients with Lamivudine-Resistant Chronic Hepatitis B

Shin¹,

Koh²,

Gwak³

et al. 2010

Gut Liver

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Background/Aims: Adefovir (ADV) is the preferred drug for treating lamivudine (LAM)-resistant hepatitis B. However, not all patients who face virologic breakthrough during LAM treatment respond to ADV. The aim of this study was to determine the factors associated with efficacy of ADV in LAM-resistant hepatitis B patients. Methods: The medical records of 231 patients who received ADV due to LAM-resistance were reviewed. Efficacy was assessed by the initial virologic response (IVR), defined as hepatitis B virus (HBV) DNA not being undetectable by real-time PCR at 6 months of ADV treatment. Results: Seventy patients (30%) achieved IVR. While 'add-on' modality, hepatitis B e antigen (HBeAg) negativity, and low baseline HBV DNA levels were associated with IVR in univariate analysis, multivariate analysis revealed HBeAg status and the DNA level to be the significant factors. The probability of IVR achievement increased sharply per each log10 copies/mL decrement in the baseline viral load, which was 133 times in patients who had HBV DNA ＜10 5 copies/mL compared with those who had ≥10 8 copies/mL. Conclusions: Factors associated with the IVR were HBeAg negativity and a low baseline viral load. Therefore, when virologic breakthrough with genotypic resistance emerges during LAM therapy, ADV treatment should be considered immediately before further increases in viral load. Additional long-term follow-up data are warranted.(Gut Liver 2010;4:530-536)

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“…Because of the unavailability of TDF in many Asian countries, ADV has been used widely as a combination treatment regimen. However, due to the weak antiviral activity of ADV [28] and poor susceptibility for drug-resistant viral strains, suboptimal response is particularly common in patients who received LAM + ADV [29,30] . Evidence has shown that the persistence of suboptimal response during long-term antiviral treatment is associated with the emergence of multi-drug resistant viral strains, which could result in poorer clinical outcomes [31,32] .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of switching to telbivudine plus adefovir in suboptimal responders to lamivudine plus adefovir

Park

Kim

et al. 2013

WJG

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Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B

Cited by 61 publications

References 34 publications

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

A Low Viral Load Predicts a Higher Initial Virologic Response to Adefovir in Patients with Lamivudine-Resistant Chronic Hepatitis B

Efficacy of switching to telbivudine plus adefovir in suboptimal responders to lamivudine plus adefovir

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