scholarly journals Efficacy of Entecavir-Tenofovir Combination Therapy for Chronic Hepatitis B Patients with Multidrug-Resistant Strains

2014 ◽  
Vol 58 (11) ◽  
pp. 6710-6716 ◽  
Author(s):  
Yun Bin Lee ◽  
Jeong-Hoon Lee ◽  
Dong Hyeon Lee ◽  
Hyeki Cho ◽  
Hongkeun Ahn ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Combination Therapy ◽  
Treatment Period ◽  
Rescue Therapy ◽  
Antiviral Drug ◽  
Multidrug Resistant ◽  
Cox Proportional Hazards ◽  
Cumulative Probability ◽  
Virologic Suppression ◽  
Genotypic Resistance

ABSTRACTThe emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 with strains resistant to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 with strains resistant to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7 to 31.7) months. Seventy-four of 93 patients (79.6%) achieved complete virologic suppression, after a median of 4.5 (95% confidence interval, 3.0 to 6.0) months. The cumulative probability of complete virologic suppression at month 6 was 63.6% (55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively). During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P= 0.072 andP= 0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.

scholarly journals Is Combination Antiviral Therapy Mandatory for Maintenance Therapy in Fully Suppressed Multidrug-Resistant Hepatitis B Patients?

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Sung Won Chung ◽  
Young Chang ◽  
Hyo Young Lee ◽  
Eun Ju Cho ◽  
Jeong-Hoon Lee ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Combination Therapy ◽  
Maintenance Therapy ◽  
Multidrug Resistant ◽  
Combination Group ◽  
Virologic Suppression ◽  
Single Group ◽  
Virologic Breakthrough ◽  
Immortal Time Bias ◽  
Cox Proportional Hazard Regression

Aim. The efficacy of tenofovir disoproxil fumarate (TDF) monotherapy as maintenance therapy in multidrug-resistant (MDR) hepatitis B virus (HBV) patients after complete virologic suppression (CVS) has not been well evaluated. We evaluated the efficacy of maintenance TDF monotherapy compared with conventional TDF plus entecavir combination therapy after CVS of MDR HBV. Methods. In this single-center retrospective study, patients with MDR HBV who were previously treated with entecavir plus TDF combination therapy and achieved CVS were included. Patients were either maintained on entecavir plus TDF combination therapy or switched to TDF monotherapy after CVS. The primary endpoint was the virologic breakthrough, and secondary outcomes were liver cirrhosis (LC) or hepatocellular carcinoma (HCC) development. To overcome immortal time bias, time-varying Cox proportional hazard regression analysis was performed. Results. A total of 201 patients were included, and 153 patients were maintained on entecavir plus TDF combination therapy (combination group); 48 patients were converted from combination therapy to TDF monotherapy (single group) after CVS. Five patients experienced a virologic breakthrough, one patient in the single group owing to poor transient compliance and four patients in the combination group (P=0.51). One new case of LC developed in the single group; five cases of LC developed in the combination group (P=0.35). No new HCC development occurred in the single group, while seven cases of HCC developments were noted in the combination group. However, these results were not statistically significant (P=0.54). Conclusions. For patients with suppressed HBV DNA, the efficacy of TDF monotherapy as maintenance therapy is comparable to that of entecavir plus TDF combination therapy.

Clonal evolution of multidrug resistant hepatitis B virus during entecavir rescue therapy

2015 ◽  
Vol 35 (11) ◽  
pp. 2370-2383 ◽  
Author(s):  
Young E. Chon ◽  
Bora Jin ◽  
Sang H. Ahn ◽  
Seungtaek Kim ◽  
Nam D. Kim ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Rescue Therapy ◽  
Clonal Evolution ◽  
Multidrug Resistant ◽  
B Virus

Prediction of virologic response to tenofovir mono-rescue therapy for multidrug resistant chronic hepatitis B

2015 ◽  
Vol 88 (6) ◽  
pp. 1027-1034 ◽  
Author(s):  
Sangheun Lee ◽  
Jun Yong Park ◽  
Do Young Kim ◽  
Beom Kyung Kim ◽  
Seung Up Kim ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Rescue Therapy ◽  
Multidrug Resistant ◽  
Virologic Response

Tenofovir plus entecavir as rescue therapy for multidrug-resistant chronic hepatitis B

2011 ◽  
Vol 32 (1) ◽  
pp. 171-172 ◽  
Author(s):  
Gaetano Scotto ◽  
Giovanna D'Addiego ◽  
Adele Giammario ◽  
Francesca Campanale ◽  
Vincenzina Fazio
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Rescue Therapy ◽  
Multidrug Resistant

The partial virological response to Tenofovir monotherapy in naïve patients with chronic hepatitis B

2020 ◽  
pp. 1-12
Author(s):  
Habip Gedik ◽  
Muge Sonmezisik
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Partial Response ◽  
Combination Therapy ◽  
Chronic Hepatitis B ◽  
Antiviral Drug ◽  
Sustained Viral Response ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Partial Virological Response

Abstract We report two treatment-naïve cases, a 26-year-old female patient and a 59-year-old male patient who were followed up for chronic hepatitis B (CHB) at the Department of Infectious Diseases and Clinical Microbiology. A partial response subsequent to 12 months of Tenofovir Disoproksil (TDF) monotherapy presumably due to an antiviral-drug resistance was noted. A sustained viral response with TDF (245 mg) or Tenofovir Alafenamide (TAF, 25 mg) + Entecavir (ETV, 1 mg) combination therapy was observed after failure with TDF monotherapy. A combination therapy with TDF (245 mg) or TAF (25 mg) +ETV (1 mg) is efficacious in naïve patients with a partial response to TDF monotherapy. Keywords: Chronic hepatitis B, Tenofovir, partial response, Entecavir, combination therapy

scholarly journals Efficacy of Adefovir-Based Combination Therapy for Patients with Lamivudine- and Entecavir-Resistant Chronic Hepatitis B Virus Infection

2013 ◽  
Vol 57 (12) ◽  
pp. 6325-6332 ◽  
Author(s):  
Yun Bin Lee ◽  
Jeong-Hoon Lee ◽  
Won-mook Choi ◽  
Young Youn Cho ◽  
Jeong-ju Yoo ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Propensity Score ◽  
Hepatitis B ◽  
Combination Therapy ◽  
Hbv Dna ◽  
Nucleoside Analogues ◽  
Virologic Suppression ◽  
Lower Baseline ◽  
B Virus

ABSTRACTTreatment strategies for entecavir (ETV)-resistant chronic hepatitis B (CHB) patients are not yet well established. The aim of this study was to evaluate overall antiviral efficacy and to compare the efficacy of combination therapy with adefovir (ADV) plus nucleoside analogues (lamivudine [LAM], telbivudine [LdT], or ETV) in patients infected with LAM- and ETV-resistant hepatitis B virus (HBV) variants. Virologic, biochemical, and serologic responses during combination therapy with ADV plus nucleoside analogues were assessed. Propensity score analysis was used to select a matched group of patients for the comparison of rescue therapy regimens. A total of 67 consecutive patients were analyzed. Complete virologic suppression was achieved in 27 patients. The overall cumulative incidence of complete virologic suppression at month 24 was 47.4%: 44.3% in the LAM or LdT plus ADV group and 51.4% in the group given ETV and ADV. There was no significant difference between these two groups (P= 0.234). The cumulative incidences of complete virologic suppression were still comparable between the two groups selected and matched using the propensity score model (P= 0.419). Virologic breakthrough was observed in 9 patients, and rtA181V substitution was newly detected in one patient. Hepatitis B e antigen (HBeAg) negativity and lower baseline HBV DNA level were associated with complete virologic suppression in univariate analysis. In multivariate analysis, lower baseline HBV DNA level remained an independent predictor. In conclusion, combination therapy with ADV plus nucleoside analogues fails to show sufficient antiviral efficacy in CHB patients with resistance to both LAM and ETV. Further study is warranted to evaluate the efficacy of a more potent tenofovir-based regimen in such patients.

scholarly journals Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response

2020 ◽  
Vol 26 (3) ◽  
pp. 352-363
Author(s):  
Hyun Young Woo ◽  
Jun Yong Park ◽  
Si Hyun Bae ◽  
Chang Wook Kim ◽  
Jae Young Jang ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Combination Treatment ◽  
Rescue Therapy ◽  
Controlled Trial ◽  
Virologic Response ◽  
Hbv Dna ◽  
Genotypic Resistance ◽  
Prospective Randomized Controlled Trial ◽  
B Virus ◽  
New Treatment

Background/Aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV.Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded.Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], <i>P</i><0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs. -0.37 log10 IU/mL, <i>P</i><0.001). Multivariate analysis indicated that high baseline HBV DNA level (<i>P</i>=0.005) and LAM/LdT+ADV maintenance therapy (<i>P</i>=0.001) were negatively associated with virologic response. At week 48, additional ADV- or ETV-associated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/LdT+ADV group (P=0.106). The two groups had similar rates of adverse events.Conclusions: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).

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