scholarly journals Pradefovir Treatment in Patients with Chronic Hepatitis B: Week 24 Results from a Multicenter, Double-blind, Randomized, Noninferiority, Phase 2 Trial

2021 ◽  
Author(s):  
Yanhang Gao ◽  
Fei Kong ◽  
Xinwen Song ◽  
Jia Shang ◽  
Lvfeng Yao ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Adverse Events ◽  
Chronic Hepatitis B ◽  
Hbv Dna ◽  
Phase 2 ◽  
Double Blind ◽  
Phase 2 Trial ◽  
Hbeag Loss ◽  
Treatment Naïve

Abstract Objectives Pradefovir is a liver-targeted prodrug of adefovir, a nucleotide analog with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30mg, 45mg, 60mg, and 75mg) versus tenofovir disoproxil fumarate (TDF; 300mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. Methods Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible. Results A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were HBeAg positive and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/ml with pradefovir doses of 30mg, 45mg, 60mg, and 75mg, respectively, compared to 5.12 log10 IU/ml with TDF. However, HBeAg loss was attained by more participants who received 45mg, 60mg or 75mg pradefovir than those receiving TDF (12%, 6%, 9% vs. 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30mg or 45mg groups, and serum phosphate levels were comparable among all groups. Most adverse events were mild (grade 1). No treatment-related severe adverse events were reported. Overall, adverse events and laboratory abnormalities were comparable to the TDF group. Conclusions Pradefovir exhibited comparable reductions in HBV DNA levels to TDF. All treatments were safe and well tolerated.

scholarly journals Lingmao Formula Combined with Entecavir for HBeAg-Positive Chronic Hepatitis B Patients with Mildly Elevated Alanine Aminotransferase: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Xiao-Jun Zhu ◽  
Xue-Hua Sun ◽  
Zheng-Hua Zhou ◽  
Shun-Qing Liu ◽  
Hua Lv ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Treatment Group ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Alanine Aminotransferase ◽  
Hbv Dna ◽  
Control Group ◽  
Hbeag Loss ◽  
Histological Improvement ◽  
Positive Chronic Hepatitis

Objective. To determine the efficacy and safety of Lingmao Formula combined with entecavir for HBeAg-positive chronic hepatitis B patients with mildly elevated alanine aminotransferase (ALT).Methods. 301 patients were randomly assigned to receive Lingmao Formula combined with entecavir (treatment group) or placebo combined with entecavir (control group) for 52 weeks. The outcomes of interest included the reduction of serum HBV DNA level, HBeAg loss, HBeAg seroconversion, ALT normalization, and histological improvement.Results. The mean decrease of serum HBV DNA level from baseline and the percentage of patients who had reduction in serum HBV DNA level ≥2 lg copies/mL in treatment group were significantly greater than that in control group (5.5 versus 5.4 lg copies/mL,P=0.010; 98.5% versus 92.6%,P=0.019). The percentage of HBeAg loss in treatment group was 22.8%, which was much higher than a percentage of 12.6% in control group (P=0.038). There was no significant difference between the two groups in histological improvement. Safety was similar in the two groups.Conclusions. The combination of Lingmao Formula with entecavir could result in significant decrease of serum HBV DNA and increase of HBeAg loss for HBeAg-positive chronic hepatitis B patients with mildly elevated ALT without any serious adverse events. Clinical trial registration number isChiCTR-TRC-09000594.

scholarly journals Observation of genotype C infected chronic hepatitis B patients in clinical practice

2011 ◽  
Vol 5 (12) ◽  
pp. 882-889 ◽  
Author(s):  
Myo Nyein Aung ◽  
Wattana Leowattana ◽  
Noppadon Tangpukdee ◽  
Chatporn Kittitrakul
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Clinical Information ◽  
Hbv Dna ◽  
Hbv Genotype ◽  
Surrogate Outcome ◽  
Treatment Naïve ◽  
Genotype C ◽  
One Year

Introduction: Hepatitis B virus (HBV) genotype C is prevalent in many areas of the world including Thailand and Southeast Asia. It is a strong risk for hepatocellular carcinoma (HCC) by evidence. We aimed to describe the baseline clinical information of treatment naïve genotype C infected chronic hepatitis B (CHB) patients and to describe the treatment response by surrogate outcome markers in genotype C infected CHB patients after one year of nucleos(t)ide analogues (NA) treatment Methodology:  Thirty-four genotype C CHB patients were studied at the Hospital for Tropical Diseases, Bangkok, including 12 patients treated with lamivudine, 11 with telbivudine, 8 with adefovir, and 3 with entecavir. Serum HBV DNA levels, serum alanine amino transferase ( ALT ) levels, HBeAg status, and alpha-feto protein (AFP) levels were recorded at the start and after twelve months of ongoing treatment. HBV genotyping was performed by line-probe assay. Results: About half of the patients (58.8%) were HBeAg positive. Mean HBV viral load was 6.53 + 1.15 log10 copies per ml at baseline and reduced to 3.63 + 1.3 log10 copies per ml after one year of NA treatment. Serum HBV DNA levels became undetectable in 47.1 % of the patients and serum ALT was normalized in 23.5 % of the patients. Conclusion: Most of the genotype C patients were aged above 40 years. More than half of the genotype C infected patients did not achieve virological response and biochemical remission. Among the CHB patients, genotype C infected patients are a high priority group for intervention.

20. Correlation between quantitative HBsAg and serum HBV DNA levels in treatment naïve chronic hepatitis B patients

2018 ◽  
Vol 8 ◽  
pp. S22-S23
Author(s):  
Shashank Wanjari ◽  
Vasudha Goel ◽  
Deepak Sharma ◽  
Sudhir Maharshi ◽  
Gaurav Gupta ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hbv Dna ◽  
Treatment Naïve

Entecavir plasma concentrations are inversely related to HBV-DNA decrease in a cohort of treatment-naïve patients with chronic hepatitis B

2016 ◽  
Vol 48 (3) ◽  
pp. 324-327 ◽  
Author(s):  
Lucio Boglione ◽  
Amedeo De Nicolò ◽  
Jessica Cusato ◽  
Gabriele Bonifacio ◽  
Giuseppe Cariti ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Plasma Concentrations ◽  
Hbv Dna ◽  
Treatment Naïve

scholarly journals Efficacy of 24-week Administration of Tenofovir Disoproxil Fumarate in the Management of Naïve Chronic Hepatitis B

2020 ◽  
Vol 8 (B) ◽  
pp. 1005-1009
Author(s):  
Darmadi Darmadi ◽  
Gontar Alamsyah Siregar
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Tenofovir Disoproxil Fumarate ◽  
Deoxyribonucleic Acid ◽  
Hbv Dna ◽  
B Virus ◽  
Hbeag Loss ◽  
Undetectable Serum ◽  
Envelope Antigen

   BACKGROUND: Chronic hepatitis B (CHB) is becoming a common liver abnormality worldwide. Thus, a series of good management is needed to prevent the progression and complications of hepatitis B infection. Tenofovir disoproxil fumarate (TDF) is one of the drugs of choice that’s used for CHB management. AIM: Limited studies were found regarding the efficacy of tenofovir in dealing with CHB. Hence, the aim of this study is to determine the efficacy of TDF administration for 24 weeks in subjects with naïve CHB in Medan, Indonesia. METHODS: Retrospective study was conducted in Haji Adam Malik Hospital Medan, Indonesia, between January and December 2019. Subjects were CHB patients aged 18 years or older and were treated TDF for 24 weeks. Demographic, clinical, and CHB disease progression parameters (serum alanine aminotransferase [ALT], hepatitis B envelope antigen [HBeAg], and hepatitis B virus deoxyribonucleic acid [HBV DNA]) data were obtained. RESULTS: One hundred and twenty subjects were obtained and divided into 2 groups: HBeAg positive and HBeAg negative. Mean age of subjects was 46.5 ± 10.36 years in HBeAg positive group and 48.6 ± 10.67 years HBeAg negative group, with predominant males’ subjects in both groups (58.3% vs. 61.7%, respectively). Serum ALT normalization and undetectable serum HBV DNA were observed in more than 70% and 65% of subjects in both groups, respectively (both p < 0.001). Serum HBeAg loss was achieved in 10.8% subjects (p < 0.001). No subject showed serum HbsAg loss. CONCLUSION: Our results are consonant with current clinical guidelines and other evidence literature. For both HBeAg-positive and HBeAg-negative populations, TDF administration for 24 weeks has good efficacy in naïve CHB patients.

scholarly journals Role of the line probe assay INNO-LiPA HBV DR and ultradeep pyrosequencing in detecting resistance mutations to nucleoside/nucleotide analogues in viral samples isolated from chronic hepatitis B patients

2013 ◽  
Vol 94 (12) ◽  
pp. 2729-2738 ◽  
Author(s):  
Sevim Mese ◽  
Muzaffer Arikan ◽  
Aris Cakiris ◽  
Neslihan Abaci ◽  
Ergun Gumus ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Early Stage ◽  
Hbv Dna ◽  
Line Probe Assay ◽  
Resistance Mutations ◽  
Nucleotide Analogues ◽  
Treatment Naïve ◽  
Probe Assay

Despite the effectiveness of nucleoside/nucleotide analogues in the treatment of chronic hepatitis B (CHB), their long-term administration is associated with the emergence of resistant hepatitis B virus (HBV) mutants. In this study, mutations resulting in antiviral resistance in HBV DNA samples isolated from 23 CHB patients (nine treatment naïve and 14 treated previously) were studied using a line probe assay (INNO-LiPA HBV DR; Innogenetics) and ultradeep pyrosequencing (UDPS) methods. Whilst the INNO-LiPA HBV DR showed no resistance mutations in HBV DNA samples from treatment-naive patients, mutations mediating lamivudine resistance were detected in three samples by UDPS. Among patients who were treated previously, 19 mutations were detected in eight samples using the INNO-LiPA HBV DR and 29 mutations were detected in 12 samples using UDPS. All mutations detected by the INNO-LiPA HBV DR were also detected by UDPS. There were no mutations that could be detected by INNO-LiPA HBV DR but not by UDPS. A total of ten mutations were detected by UDPS but not by INNO-LiPA HBV DR, and the mean frequency of these mutations was 14.7 %. It was concluded that, although INNO-LiPA HBV DR is a sensitive and practical method commonly used for the detection of resistance mutations in HBV infection, UDPS may significantly increase the detection rate of genotypic resistance in HBV at an early stage.

scholarly journals Prolonged Entecavir Therapy Is Not Effective for HBeAg Seroconversion in Treatment-Naive Chronic Hepatitis B Patients with a Partial Virological Response

2015 ◽  
Vol 59 (9) ◽  
pp. 5348-5356 ◽  
Author(s):  
Hyun Woong Lee ◽  
Jae-Cheol Kwon ◽  
In Soo Oh ◽  
Hye Young Chang ◽  
Young Joo Cha ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Virological Response ◽  
Hbeag Seroconversion ◽  
Hbv Dna ◽  
Duration Of Treatment ◽  
Genotypic Resistance ◽  
Treatment Naïve ◽  
Partial Virological Response

ABSTRACTThe aims of this study were to investigate the efficacy of prolonged entecavir (ETV) therapy in treatment-naive chronic hepatitis B (CHB) patients and to determine whether continuous ETV therapy is feasible to achieve HBeAg seroconversion, particularly in patients with partial virological response (PVR). A total of 142 treatment-naive patients with CHB were enrolled. The mean duration of treatment was 65 (range, 26 to 90) months, and 86 patients (60.6%) were HBeAg positive. PVR was defined as detectable hepatitis B virus (HBV) DNA (>116 copies/ml) at year 1. The cumulative incidence of virological response (VR) increased from 54.9% at year 1 to 98.2% at year 7. HBeAg positivity (odds ratio [OR], 4.146;P= 0.001) and initial alanine aminotransferase (ALT) (OR, 0.997;P= 0.004) were independent risk factors for PVR. Among the 64 patients with PVR, 47 patients (73.4%) achieved VR within 4 years after prolonged ETV therapy without treatment adaptation. Three patients (2.1%) experienced virological breakthrough and HBV variants with genotypic resistance. The cumulative rate of HBeAg seroconversion was significantly higher in the patients with VR than in the patients with PVR (P= 0.018). None of the PVR patients with HBV DNA at ≥5,000 copies/ml at year 1 ever experienced HBeAg seroconversion. Multivariate analysis identified VR at year 1 as the only determinant of HBeAg seroconversion (hazard ratio [HR], 3.009;P= 0.010). In conclusion, although there were patients with PVR, prolonged ETV therapy showed excellent VR, with only 2.1% emergence of viral resistance during a 7-year follow-up. However, to achieve HBeAg seroconversion, drug modification is needed for HBeAg-positive patients with PVR (especially those with HBV DNA at ≥5,000 copies/ml at year 1).

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