scholarly journals Efficacy of different nucleoside analog rescue therapies for entecavir-resistant chronic hepatitis B patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin Shang ◽  
Juan Zhou ◽  
Huan Liu ◽  
Rili M. Ise ◽  
You Tu ◽  
...  

Abstract Background Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue. Methods Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups. Results The rate of ETV resistance among all HBV-resistant variants increased from 6.04% in 2011 to 15.02% in 2017. TDF monotherapy and TDF combination groups showed similar rates of negative HBV DNA at 48 weeks (74.07% vs 70.00%, P > 0.05), while the ETV and ADV group showed the worst virologic response (28.00%). Also, TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function among the three groups. Conclusions TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.

2020 ◽  
Author(s):  
Jin Shang ◽  
Juan Zhou ◽  
Huan Liu ◽  
You Tu ◽  
Jinqiu Ran ◽  
...  

Abstract Background Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue. Methods Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups. Results The rate of ETV resistance increased form 6.04% in 2011 to 15.02% in 2017. Regarding the rates of negative HBV DNA at 48 weeks, no significant differences occurred in the TDF monotherapy and TDF combination groups (74.07% vs 70.00%), while the ETV and ADV group showed the worst virologic response (28.00%). TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function between the three groups. Conclusions TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.


2020 ◽  
Author(s):  
Jin Shang ◽  
Juan Zhou ◽  
Huan Liu ◽  
You Tu ◽  
Jinqiu Ran ◽  
...  

Abstract Background: Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue. Methods: Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups.Results: The rate of ETV resistance increased form 6.04% in 2011 to 15.02% in 2017. Regarding the rates of negative HBV DNA at 48 weeks, no significant differences occurred in the TDF monotherapy and TDF combination groups (74.07% vs 70.00%), while the ETV and ADV group showed the worst virologic response (28.00%). TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function between the three groups. Conclusions: TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.


2014 ◽  
Vol 59 (2) ◽  
pp. 972-978 ◽  
Author(s):  
Yun Bin Lee ◽  
Eun Uk Jung ◽  
Bo Hyun Kim ◽  
Jeong-Hoon Lee ◽  
Hyeki Cho ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hui-Lian Wang ◽  
Xi Lu ◽  
Xudong Yang ◽  
Nan Xu

The relative efficacy of different strategies for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) has not yet been systematically studied. Clinical trials were searched in PUBMED, MEDLINE, EMBASE, and CNKI databases up to February 15, 2016. Nine trials including 764 patients met the entry criteria. In direct meta-analysis, TDF showed a stronger antiviral effect than any one of ETV, LAM/ADV, and ADV against LAM-R hepatitis B virus. LAM/ADV therapy was superior to ADV in suppressing viral replication. ETV achieved similar rate of HBV DNA undetectable compared to ADV or LAM/ADV. In network meta-analysis, TDF had higher rates of HBV DNA undetectable compared to ETV (OR, 24.69; 95% CrI: 5.36–113.66), ADV (OR, 37.28; 95% CrI: 9.73–142.92), or LAM/ADV (OR, 21.05; 95% CrI: 5.70–77.80). However, among ETV, ADV, and LAM/ADV, no drug was clearly superior to others in HBV DNA undetectable rate. Moreover, no significant difference in the rate of ALT normalization or HBeAg loss was observed compared the four rescue strategies with each other. TDF appears to be a more effective rescue therapy than LAM/ADV, ETV, or ADV. LAM plus ADV therapy was a better treatment option than ETV or ADV alone for patients with LAM-R.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Zhe Chen ◽  
Xiao Ma ◽  
Yanling Zhao ◽  
Jiabo Wang ◽  
Yaming Zhang ◽  
...  

Objective. To evaluate the efficacy and safety of Kushenin (KS) combined with nucleoside analogues (NAs) for chronic hepatitis B (CHB).Methods. Randomized controlled trials (RCTs) of KS combined with NAs for CHB were identified through 7 databases. Frequencies of loss of serum HBeAg, HBeAg seroconversion, undetectable serum HBV-DNA, ALT normalization, and adverse events at 48 weeks were abstracted by two reviewers. The Cochrane software was performed to assess the risk of bias in the included trials. Data were analyzed with Review Manager 5.3 software.Results. 18 RCTs involving 1684 subjects with CHB were included in the analysis. KS combined with NAs including lamivudine (LAM), entecavir (ETV), adefovir dipivoxil (ADV), and telbivudine (TLV) showed different degree of improvement in CHB indices. KS combined with NAs increased the frequency of loss of serum HBeAg, HBeAg seroconversion, undetectable HBV-DNA levels, and ALT normalization compared with single agents. It also decreased serum ALT and AST level after one-year treatment. However, KS combined with TLV did not show a significant difference in CHB indices. The side-effects of KS combined with NAs were light and of low frequency.Conclusion. KS combined with NAs improves the efficacy of NAs in CHB.


2019 ◽  
Vol 35 (3) ◽  
Author(s):  
Mustafa Kerem Calgin ◽  
Yeliz Cetinkol

Background & Objective: Liver and intestines are anatomically and physiologically linked. Zonulin is a protein modulating intercellular tight junctions and regulating intestinal permeability. Copeptin was studied as a marker of systemic circulation disorders in research about vasopressin and was associated with liver disease prognosis. Serum zonulin and copeptin levels were measured in patients with diagnosis of chronic hepatitis B (CHB) with the aim of easing antiviral treatment management in clinical applications and to investigate the association with normal population and viral load. Methods: Analysis included the serum of 30 CHB patients and 17 controls. HBV-DNA real-time PCR tests were completed. CHB patients were divided into three subgroups according to viral load in serum. Zonulin and copeptin levels were measured using ELISA kits. Results: Serum zonulin and copeptin levels were significantly low in CHB patients compared to controls (p<0.001). When CHB subgroups are investigated in terms of serum zonulin and copeptin levels, there was an inverse correlation observed with significant difference (p<0.01, p<0.05). Conclusion: The negative correlation between serum zonulin and copeptin with HBV-DNA load revealed in our study shows they may be used to monitor treatment. Zonulin and copeptin assays provide the possibility of developing new approaches to CHB diagnosis and monitoring. doi: https://doi.org/10.12669/pjms.35.3.144 How to cite this:Calgin MK, Cetinkol Y. Decreased levels of serum zonulin and copeptin in chronic Hepatitis-B patients. Pak J Med Sci. 2019;35(3):---------. doi: https://doi.org/10.12669/pjms.35.3.144 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2019 ◽  
Author(s):  
jingmao Yang ◽  
Liping Chen ◽  
Yajie Wang ◽  
Bei Lv ◽  
Hong Zhao ◽  
...  

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.


2011 ◽  
Vol 17 (4) ◽  
pp. 268 ◽  
Author(s):  
Joon Chang Song ◽  
Bo Young Min ◽  
Jin-Wook Kim ◽  
Jong Yeop Kim ◽  
Yeo Myeong Kim ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Hong Shi ◽  
Mingxing Huang ◽  
Guoli Lin ◽  
Xiangyong Li ◽  
Yuankai Wu ◽  
...  

Objectives. To compare entecavir (ETV) and tenofovir disoproxil fumarate (TDF) effects in chronic hepatitis B (CHB) patients with high HBV DNA.Method. 96 patients treated initially with tenofovir (TDF group) or entecavir (ETV group) were included in this retrospective study. The following parameters were assessed: HBeAg and hepatitis B e antibody (anti-HBe) status, serum alanine aminotransferase (ALT), and HBV-DNA levels at weeks 4, 12, 24, 36, 48, 60, 72, and 96; time to ALT normalization, undetectable HBV-DNA levels, and HBeAg seroconversion; total duration of follow-up and adverse reactions.Results. The patients included 66 (69%) and 30 (31%) individuals administered ETV and TDF, respectively, comprising 75% males. They were35.1±4.5and33.7±4.6years old in ETV and TDF groups, respectively. At 36 weeks, the response rate was significantly higher in the TDF group than in ETV treated patients (90% versus 69.7%,p=0.03). At 48 weeks, less patients administered ETV showed undetectable HBV-DNA levels compared with the TDF group (86.4% versus 96.7%), a non-statistically significant difference (p=0.13). Only 1 ETV treated patient developed virological breakthrough at 48–96 w. No adverse reactions were found.Conclusion. ETV and TDF are comparable in efficacy and safety to suppress HBV-DNA replication in HBeAg-positive CHB patients with high HBV DNA.


2014 ◽  
Vol 8 (12) ◽  
pp. 1601-1608 ◽  
Author(s):  
Ertugrul Guclu ◽  
Nazan Tuna ◽  
Oguz Karabay ◽  
Sıla Akhan ◽  
Hurrem Bodur ◽  
...  

Introduction: Although pegylated interferons (pegIFNs) alpha-2a and alpha-2b have been used in chronic hepatitis B (CHB) treatment for many years, there are few studies concerning predictors of sustained virologic response (SVR) to pegIFN therapy. In this study, we aimed to investigate the predictors of response to pegIFN treatment in cases with HBeAg-negative CHB infection. Methodology: Seventeen tertiary care hospitals in Turkey were included in this study. Data from consecutively treated HBeAg-negative CHB patients, who received either pegIFN alpha-2a or alpha-2b, were collected retrospectively. SVR is defined as an HBV DNA concentration of less than 2,000 IU/mL six months after the completion of therapy Results: SVR was achieved in 40 (25%) of the 160 HBeAg-negative CHB patients. Viral loads in patients with SVR were lower compared to those with no SVR, beginning in the third month of treatment (p < 0.05). The number of cases with a decline of 1 log10 IU/mL in viral load after the first month of treatment and with a serum HBV DNA level under 2,000 IU/mL after the third month of treatment was higher in cases with SVR (p < 0.05). The number of patients who had undetectable HBV DNA levels at week 48 among responders was significantly greater than among post-treatment virological relapsers (p < 0.05). Conclusions: Detection of a 1 log10 decline in serum HBV DNA level at the first month of treatment and a serum HBV DNA level < 2000 IU/mL at the third month of therapy may be predictors of SVR.


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