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.

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 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 ETV add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial

2019 ◽  
Author(s):  
jingmao Yang ◽  
Liping Chen ◽  
Yajie Wang ◽  
Bei Lv ◽  
Hong Zhao ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Combination Therapy ◽  
Transient Elastography ◽  
Therapy Group ◽  
Hbeag Seroconversion ◽  
Virologic Response ◽  
Combination Group ◽  
Combination Therapy Group ◽  
Monotherapy Group ◽  
Positive Role

Abstract Background and Aim The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding Peg-interferon to ongoing ETV treatment leads to a better curative effect or not. Methods Eligible HBV patients (n=144) were randomly divided (1:1) to receive either ETV monotherapy (n=70) or peg-interferon add-on therapy from weeks 26 to 52 (n=74). Patients were followed-up for 2 years. We evaluated hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response (SVR), transient elastography value, and histological scores. Results At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase (ALT)and aspartate aminotransferase (AST) levels and transient elastography values decreased significantly compared with baseline. Both group showed a favorable decrease in alpha fetoprotein(AFP) (monotherapy:23.4±77.3 vs 2.4±0.91, P=0.149; combination therapy: 33.3±96.9 vs 4.3±5.5,P=0.085) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group(mean transient elastography value 7.5±3.4 kPa [SD 1.9] vs. 12.8±13.9 kPa [SD 1.9], P=0.037). But this research didn’t show significant difference in HBsAg conversion rate (1.79% (1/56) vs 4.11% (3/73), P=0.632) as well as HBV-DNA sustained virologic response(93.2% vs 98.5%,P=0.15) between two groups. Conclusions Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better antiviral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.

scholarly journals ETV add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial

2019 ◽  
Author(s):  
Jingmao Yang ◽  
Liping Chen ◽  
Yajie Wang ◽  
Bei Lv ◽  
Hong Zhao ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Combination Therapy ◽  
Transient Elastography ◽  
Therapy Group ◽  
Hbeag Seroconversion ◽  
Virologic Response ◽  
Combination Group ◽  
Combination Therapy Group ◽  
Monotherapy Group ◽  
Positive Role

Abstract Background and Aim The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding Peg-interferon to ongoing ETV treatment leads to a better curative effect or not. Methods Eligible HBV patients (n=144) were randomly divided (1:1) to receive either ETV monotherapy (n=70) or peg-interferon add-on therapy from weeks 26 to 52 (n=74). Patients were followed-up for 2 years. We evaluated hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response (SVR), transient elastography value, and histological scores. Results At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase (ALT)and aspartate aminotransferase (AST) levels and transient elastography values decreased significantly compared with baseline. Both group showed a favorable decrease in alpha fetoprotein(AFP) (monotherapy:23.4±77.3 vs 2.4±0.91, P=0.149; combination therapy: 33.3±96.9 vs 4.3±5.5,P=0.085) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group(mean transient elastography value 7.5±3.4 kPa [SD 1.9] vs. 12.8±13.9 kPa [SD 1.9], P=0.037). But this research didn’t show significant difference in HBsAg conversion rate (1.79% (1/56) vs 4.11% (3/73), P=0.632) as well as HBV-DNA sustained virologic response(93.2% vs 98.5%,P=0.15) between two groups. Conclusions Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better antiviral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.

scholarly journals Tenofovir Monotherapy versus Tenofovir plus Lamivudine or Telbivudine Combination Therapy in Treatment of Lamivudine-Resistant Chronic Hepatitis B

2014 ◽  
Vol 59 (2) ◽  
pp. 972-978 ◽  
Author(s):  
Yun Bin Lee ◽  
Eun Uk Jung ◽  
Bo Hyun Kim ◽  
Jeong-Hoon Lee ◽  
Hyeki Cho ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Combination Therapy ◽  
Chronic Hepatitis B ◽  
Therapy Group ◽  
Virologic Suppression ◽  
Combination Therapy Group ◽  
Monotherapy Group ◽  
Treatment Groups ◽  
Hbv Variants

ABSTRACTTenofovir disoproxil fumarate (TDF) monotherapy is a therapeutic option for chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV) variants resistant to lamivudine (LAM). We evaluated the antiviral efficacy and safety of TDF alone compared to those of TDF plus LAM or telbivudine (LdT) combination in patients harboring HBV variants with genotypic resistance to LAM. This multicenter retrospective study included consecutive patients who had LAM-resistant HBV variants and were treated with TDF alone (monotherapy group) or TDF combined with LAM or LdT (combination therapy group) for at least 6 months. Inverse probability of treatment weighting (IPTW) for the entire cohort was applied to control for treatment selection bias. Overall, 153 patients (33 in the monotherapy group and 120 in the combination therapy group) were analyzed. The overall probability of achieving complete virologic suppression at month 12 was 91.6%: 88.6% in the monotherapy group and 92.6% in the combination therapy group. Combination therapy was not superior to monotherapy in viral suppression before and after IPTW (P= 0.562 andP= 0.194, respectively). Hepatitis B e antigen (HBeAg) loss, biochemical response, and virologic breakthrough did not differ between treatment groups. The probabilities of complete virologic suppression were comparable between treatment groups in the subsets according to HBeAg status and HBV DNA levels at baseline. No patient experienced any significant renal dysfunction during the treatment period. In conclusion, TDF monotherapy has antiviral efficacy comparable to that of TDF plus LAM or LdT combination therapy, with a favorable safety profile in CHB patients with LAM-resistant HBV variants.

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