scholarly journals Prior Exposure to Lamivudine Increases Entecavir Resistance Risk in Chronic Hepatitis B Patients without Detectable Lamivudine Resistance

2014 ◽  
Vol 58 (3) ◽  
pp. 1730-1737 ◽  
Author(s):  
Jeong-Hoon Lee ◽  
Yuri Cho ◽  
Dong Hyeon Lee ◽  
Minjong Lee ◽  
Jeong-ju Yoo ◽  
...  

ABSTRACTThe efficacy of entecavir (ETV) treatment in chronic hepatitis B (CHB) patients who were exposed to lamivudine (LAM) but had no detectable LAM resistance (LAM-R) is not well evaluated. In this study, we aimed to evaluate whether the probability of developing genotypic resistance to ETV in LAM-exposed patients with or without LAM-R is comparable to that in antiviral-naive patients. This retrospective cohort study included 500 consecutive patients with CHB who started ETV monotherapy at a single tertiary hospital in Korea. The patients were divided into three groups: nucleos(t)ide analogue (NA)-naive patients (group 1,n= 142), patients who were previously exposed to LAM and had no currently or previously detected LAM-R (group 2,n= 233), and patients with LAM-R when starting ETV (group 3,n= 125). The overall median ETV treatment duration was 48.7 months. The probabilities of virologic breakthrough were significantly increased not only in group 3 (hazard ratio [HR] = 14.4,P< 0.001) but also in group 2 (HR = 5.0,P< 0.001) compared to group 1. Genotypic ETV resistance (ETV-R) developed more frequently in group 2 (HR = 13.0,P= 0.013) as well as group 3 (HR = 43.9,P< 0.001) than in group 1: the probabilities of developing ETV-R in groups 1, 2, and 3 were <1.0%, 8.0%, and 28.2%, respectively, at month 48. The results of this study indicate that ETV-R occurred more frequently in LAM-exposed patients, even though they had no detectable LAM-R, than in NA-naive patients. Therefore, LAM-exposed CHB patients, regardless of the presence or absence of LAM-R, should be monitored more cautiously for the development of ETV-R during ETV monotherapy.

Author(s):  
Yi-Wen Huang ◽  
Chao-Wei Hsu ◽  
Sheng-Nan Lu ◽  
Ming-Lung Yu ◽  
Chien-Wei Su ◽  
...  

Abstract Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to 8–14 isomers of other on-market pegylated interferon, allowing injection every two or more weeks with higher tolerability. It received European Medicines Agency and Taiwan marketing authorization in 2019 and 2020, for treatment of polycythemia vera. This phase I/II study aimed to have preliminary evaluation of safety and efficacy in chronic hepatitis B. Methods Thirty-one HBeAg-positive and 31 HBeAg-negative were stratified by HBeAg status and randomized at 1:1:1 ratio to q2w ropeginterferon alfa-2b 350 μg (group 1), q2w 450 μg (group 2) or q1w PEG-IFN alfa-2a 180 μg (group 3). Each patient received 48-week treatment (TW48) and 24-week post-treatment follow-up (FW24). Results The baseline demographics were comparable among the three groups, except for mean HBeAg in HBeAg-positive patients (2.90, 2.23, 2.99 log10 S/CO, respectively). Cumulative HBeAg seroconversion rate at follow-up period was 27.3% (3/11), 36.4% (4/11), and 11.1% (1/9) with time to HBeAg seroconversion starting from TW24, TW16, and TW48 in group 1, 2, and 3, respectively. The rate of HBV DNA < 2000 IU/mL and HBsAg levels < 1500 IU/mL at FW24 were comparable in all groups. Ropeginterferon alfa-2b (group 1 & 2) had numerically lower incidence of rash (9.5% and 4.5%) as compared to PEG-IFN alfa-2a (36.8%). Ropeginterferon alfa-2b 350 μg (group 1) had more ALT elevation (38.1%), however the rate was comparable in group 2 (9.1%) and group 3 (10.5%). Conclusion In this preliminary study, ropeginterferon alfa-2b, although in only half the number of injections, is as safe and effective as pegylated interferon alfa-2a for chronic hepatitis B. Graphic abstract


2018 ◽  
Vol 2 (2) ◽  
Author(s):  
Hong Yu ◽  
Pingyan Chen ◽  
Jilin Chen ◽  
Wei Dai ◽  
Zhimin Wu ◽  
...  

Background: Ozone therapy has a long history. Some studies proved that ozone therapy was useful in treatment of virus hepatitis.Objective: To evaluate the efficacy and safety of new medical ozone therapy system for the treatment of chronic hepatitis B.Method One hundred eighty-nine patients with chronic hepatitis B were included in this open-label, phase 3 study, and randomly assigned to receive ozone autohemotherapy with experimental ozone generator TianYi (group 1) or with ozone generator Humares (group 2) or oral diammonium glycyrrhizinate capsules (group 3) in a 1:1:1 ratio for 12 weeks. The primary efficacy end point was sera HBV DNA level of less than 1×103 IU/ml or having a more than 2 log10 reduction in HBV DNA level at the end of 12 weeks treatment as compared to baseline HBV DNA level. Secondary end points included HBeAg seroconversion, biochemical response, and combined response.Results At the end of 12 weeks treatment, the proportion of patients reached the primary end point of virologic response in group 1, group 2, and group 3 were 22.4% (13/58, 95% CI, 12.5 to 35.3), 14.7 (9/61, 95% CI, 7.0 to 26.2) and 3.9% (2/51, 95% CI, 0.5 to 13.5), respectively (p=0.021) in the pre-protocol population. Virologic response occurred in more patients receiving ozone therapy with experimental device than patients receiving oral diammonium glycyrrhizinate capsules (mean difference 18.5%, 95% CI 6.3 to 31.5, p=0.005). However, there was no statistical difference in VR12 rates between the treatment of medical ozone therapy system with experimental device (group 1) and with Humares (group 2) (mean difference 7.7%, 95% CI -6.5 to 22.0, p=0.282). More HBeAg seroconversion in patients treated by Tianyi ozone therapy system than those treated by Humares ozone therapy device and oral diammonium glycyrrhizinate capsules (14.8%, 5.1% and 7.3%, respectively, P = 0.272). Higher biochemical response rate was observes in patients receiving ozone therapy than oral diammonium glycyrrhizinate capsules (31.6%, 36.7% and 24.0%, respectively, p = 0.359). The safety profile was similar for the three treatment groups and adverse events were .scare infrequent and mild.Conclusions: Ozone therapy had superior antiviral efficacy with a similar safety profile as compared with oral diammonium glycyrrhizinate capsules through week 12 treatment. Ozone therapy is also associated with normalized ALT and AST levels, demonstrating that ozone therapy could benefit the patients with chronic hepatitis B.


QJM ◽  
2021 ◽  
Author(s):  
N W Chew ◽  
J N Ngiam ◽  
S M Tham ◽  
Z Y Lim ◽  
T Y W Li ◽  
...  

Summary Background/Introduction There are little data on outcomes of COVID-19 patients with the presence of fever compared to the presence of symptoms. Aim We examined the associations between symptomology, presence of fever and outcomes of a COVID-19 cohort. Design and Methods Between 23 January and 30 April 2020, 554 COVID-19 patients were admitted to a tertiary hospital in Singapore. They were allocated into four groups based on symptomology and fever—Group 1: asymptomatic and afebrile, Group 2: symptomatic but afebrile, Group 3: febrile but asymptomatic and Group 4: symptomatic and febrile. The primary outcomes were intensive care unit (ICU) admissions and mortality. The composite end-point included ICU admissions, mortality or any COVID-19 related end-organ involvement. Results There were differences in ferritin (P=0.003), C-reactive protein (CRP) levels (P&lt;0.001) and lymphopenia (P=0.033) across all groups, with the most favourable biochemical profile in Group 1, and the least in Group 4. Symptomatic groups (Groups 2 and 4) had higher ICU admissions (1.9% and 6.0%, respectively, P=0.003) than asymptomatic groups (Groups 1 and 3). Composite end-point was highest in Group 4 (24.0%), followed by Group 3 (8.6%), Group 2 (4.8%) and Group 1 (2.4%) (P&lt;0.001). The presence of fever (OR 4.096, 95% CI 1.737–9.656, P=0.001) was associated with the composite end-point after adjusting for age, pulse rate, comorbidities, lymphocyte, ferritin and CRP. Presence of symptoms was not associated with the composite end-point. Discussion/Conclusion In this COVID-19 cohort, presence of fever was a predictor of adverse outcomes. This has implications on the management of febrile but asymptomatic COVID-19 patients.


2012 ◽  
Vol 4 (12) ◽  
pp. 389 ◽  
Author(s):  
Min-Ning Song ◽  
Mei-Zhu Hong ◽  
Dan-Qing Luo ◽  
Wen-Qi Huang ◽  
Feng Min ◽  
...  

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.


2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Tanya FM Dahl ◽  
Benjamin C Cowie ◽  
Beverley-Ann Biggs ◽  
Karin Leder ◽  
Jennifer H MacLachlan ◽  
...  

2013 ◽  
Vol 84 (6) ◽  
pp. 810
Author(s):  
Kyung Ho Ha ◽  
Dong Wook Joo ◽  
Ji Suk Kim ◽  
Byung Seok Kim ◽  
Chang Hyeong Lee

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