scholarly journals Antiviral Therapy in Lamivudine-Resistant Chronic Hepatitis B Patients: A Systematic Review and Network Meta-Analysis

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.


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.


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.


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.


2012 ◽  
Vol 1 (4) ◽  
pp. 216-223
Author(s):  
Zhen Ye ◽  
Min Zhao ◽  
He Jiao ◽  
Yang Feng ◽  
Ying-zi Li ◽  
...  

Objective To evaluate the therapeutic effects of telbivudine and entecavir on patients with chronic hepatitis B by meta-analysis method. Methods Databases including the Cochrane Library, PubMed, EMBASE and HighWire were searched from January 2008 to October 2012. Randomized controlled trials on treatment of chronic hepatitis B with telbivudine and entecavir were included. According to the Cochrane systematic reviews, the methodological quality of the included studies was evaluated and effective data was extracted from these studies and analyzed. Results Six studies were included eventually. The telbivudine group included 417 cases and the entecavir group included 396 cases. For 12-week antiviral treatment of chronic hepatitis B, the rate of undetectable HBV DNA was 39.1% with telbivudine and 38.6% with entecavir [OR = 1.04, 95% CI (0.62, 1.73), P > 0.05]; for treatment of HBeAg (+) hepatitis B, the HBeAg clearance rate was 23.8% with telbivudine and 3.8% with entecavir [OR= 8.07, 95% CI (2.69, 24.21), P < 0.05], and the HBeAg seroconversion rate was 6.7% with telbivudine and 3.8% with entecavir [OR = 4.95, 95% CI (1.60, 15.31), P < 0.05]; the ALT normalization rate was 54.3% with telbivudine and 58.5% with entecavir [OR = 0.84, 95% CI (0.49, 1.45), P > 0.05]; and for early-stage treatment, the incidence of adverse events was 17.2% with telbivudine and 22.0% with entecavir [OR = 0.66, 95% CI (0.33, 1.32), P > 0.05]. For 1-year antiviral treatment of chronic hepatitis B, the rate of undetectable HBV DNA was 79.4% with telbivudine and 89.7% with entecavir [OR = 0.46, 95% CI (0.28, 0.74), P < 0.05]; for treatment of HBeAg (+) hepatitis B, the HBeAg clearance rate was 28.9% with telbivudine and 15.6% with entecavir [OR = 2.21, 95% CI (1.06, 4.58), P < 0.05], and the HBeAg seroconversion rate was 31.2% with telbivudine and 18.5% with entecavir [OR = 2.31, 95% CI (1.23, 4.31), P < 0.05]; the ALT normalization rate was 85.8% with telbivudine and 84.9% with entecavir [OR = 0.90, 95% CI (0.29, 2.84), P > 0.05]; and the resistance rate was 6.0% with telbivudine and 0.76% with entecavir [OR = 5.71, 95% CI (1.67, 19.47), P < 0.05]. Conclusions For 1-year treatment of chronic hepatitis B, the difference in ALT normalization between telbivudine and entecavir was not statistically significant; and telbivudine was superior over entecavir in terms of HBeAg undetectable and HBeAg seroconversion; entecavir was superior over telbivudine in terms of HBV DNA undetectable and resistance; and both drugs had similar rates of adverse events in early-stage treatment and no severe adverse event was noted. Both telbivudine and entecavir are effective antiviral drugs against hepatitis B.


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.


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.


2006 ◽  
Vol 50 (5) ◽  
pp. 1642-1648 ◽  
Author(s):  
Seng Gee Lim ◽  
Zahary Krastev ◽  
Tay Meng Ng ◽  
Grigor Mechkov ◽  
Iskren Andreev Kotzev ◽  
...  

ABSTRACT Emtricitabine (FTC) is approved for the treatment of human immunodeficiency virus. FTC and clevudine (CLV) have activity against hepatitis B virus (HBV). This report summarizes the results of a double-blind, multicenter study of patients with chronic hepatitis B who had completed a phase 3 study of FTC and were randomized 1:1 to 200 mg FTC once daily (QD) plus 10 mg CLV QD or 200 mg FTC QD plus placebo for 24 weeks with 24 weeks of follow-up. One hundred sixty-three patients were treated (82 with FTC plus CLV [FTC+CLV] and 81 with FTC); 72% were men, 53% were Asian, 47% were Caucasian, and 52% were hepatitis B e antigen positive, and the median baseline HBV DNA level was 6 log10 copies/ml. After 24 weeks of treatment, 74% (FTC+CLV) versus 65% (FTC alone) had serum HBV DNA levels of <4,700 copies/ml (P = 0.114) (Digene HBV Hybrid Capture II assay). Twenty-four weeks posttreatment, the mean change in serum HBV DNA levels from baseline was −1.25 log10 copies/ml (FTC+CLV), 40% had undetectable viremia (versus 23% for FTC alone), and 63% had normal alanine aminotransferase levels (versus 42% for FTC alone) (P ≤ 0.025 for all endpoints). The safety profile was similar between arms during treatment, with less posttreatment exacerbation of hepatitis B in the combination arm. In summary, after 24 weeks of treatment, no significant difference between arms was observed, but there was a significantly greater virologic and biochemical response 24 weeks posttreatment in the FTC+CLV arm.


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