The High Incidence of the Emergence of Entecavir-Resistant Mutants among Patients Infected with Lamivudine-Resistant Hepatitis B Virus

Nagasaki, Futoshi; Niitsuma, Hiroaki; Ueno, Yoshiyuki; Inoue, Jun; Kogure, Takayuki; Fukushima, Koji; Shimosegawa, Tooru

doi:10.1620/tjem.213.181

Cited by 9 publications

(9 citation statements)

References 29 publications

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“…Two cases had LAM-resistant mutations before onset of therapy (rtM204I/V ± rtL180M). Previous studies have confirmed that the presence of rtM204I/V and rtl180 M can reduce the genetic resistance barrier to ETV [33,34]. Therefore, pretreatment resistance testing may be useful in detecting viral mutations.…”

Section: Discussionmentioning

confidence: 95%

Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil therapy versus entecavir monotherapy for the treatment-naive patients with chronic hepatitis B: a meta-analysis

Liu

Wang

Fang

et al. 2014

Virol J

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BackgroundCurrently, there is no consensus on the efficacy and resistance of de novo combination therapy versus monotherapy for treatment naive patients of chronic hepatitis B (CHB).ObjectivesThe aim of this study was to evaluate the effectiveness and resistance of de novo combination of lamivudine (LAM) and adefovir dipivoxil (ADV) compared with entecavir (ETV) monotherapy for nucleos(t)ide–naive patients with CHB.Study designPublications on the effectiveness and resistance of LAM plus ADV versus ETV monotherapy for nucleos(t)ide-naive patients with CHB were identified by a search of PubMed, Embase, the Cochrane Library, Web of science, OVID, and CBM (Chinese Biological Medical Literature) until May 1, 2013. Biochemical response, hepatitis B e antigen seroconversion, and viroligic response were extracted and combined to obtain an integrated result. Viral resistance and safety were reviewed.ResultsFive eligible studies (328 patients in total) were included in the analysis. LAM plus ADV combination therapy produced more rapid HBV DNA reduction rate at 12 weeks than that of ETV monotherapy. At 48 weeks, the combination group had superior viroligic response rates compared with ETV group (90.0% vs. 78.9%, P=0.01). The difference in the ALT normalization and HBeAg seroconversion rates was not found. At week 96, LAM + ADV was more effective than ETV in ALT normalization [RR = 1. 11, 95% CI (1.02, 1.21), P =0.01] and HBeAg seroconversion [RR = 2.00, 95% CI (1.26, 3.18, P=0.003)], and no significant difference was found in the virologic response (P =0.23). No viral resistance occurred in combination therapy and six patients in ETV group were experienced with viral breakthrough. Both groups were well tolerated.ConclusionThe de novo LAM plus ADV combination therapy for treatment-naïve patients with CHB was greater than ETV monotherapy in both biochemical response and HBeAg seroconversion rate up to 96 weeks. The rate of emergence of viral resistance in the combination group was less than that in the ETV monotherapy.

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Section: Discussionmentioning

confidence: 95%

Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil therapy versus entecavir monotherapy for the treatment-naive patients with chronic hepatitis B: a meta-analysis

Liu

Wang

Fang

et al. 2014

Virol J

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“…However, their long-term efficacies have not been established yet. In particular, the usage of entecavir for lamivudine-resistant mutants has shown similar mechanisms with regard to the development of resistant mutations (66). PegIFN-a-2a has been shown to be superior to conventional IFN-a and lamivudine in the treatment of both HBeAg-positive and -negative chronic hepatitis B patients (67).…”

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confidence: 99%

Correlation between Hepatitis B Virus Genotypes and Clinical Outcomes

Shi¹

2012

Jpn J Infect Dis

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“…In the same study, naïve patients who had received three years of ETV treatment had <1% resistance; however the resistance rate became 30% after three years of ETV treatment, in the LAM-resistant group. Nagasaki et al [17] have reported that in 3 out of 4 LAM-resistant subjects, resistance developed in the period from the 52nd to the 130th week. In the study conducted by Tilmann [18] in Germany, 9% of the subjects with LAM resistance developed resistance after 2 years.…”

Section: Discussionmentioning

confidence: 99%

Tenofovir therapy in chronic hepatitis B infection: 48-week results from Izmir Province, Turkey

Köse¹

2012

JMID

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BackgroundIn the present study, we aimed to present the initial results of chronic hepatitis B patients who received entecavir (ETV) therapy in our hospital in Izmir, Turkey.MethodsA total of 52 patients were enrolled in the study. ETV was given in a dosage of 0.5 mg/day and 1 mg/day to 50 patients without Lamivudine/Adefovir (LAM/ADV) resistance and to 2 patients with LAM resistance, respectively. ETV was given in a dose of 0.5mg/day every three days to one patient with a renal transplant. The treatment duration was 48 weeks.ResultsOut of a total of 52 patients, 23 (44.23%) were hepatitis B e antigen (HBeAg)-positive, and 29 (55.77%) of them were HBeAg-negative. In 29 HBeAg-negative patients, early biochemical and virological responses were 82.6% and 100%, respectively. These responses were 97% and 79.3% in the 12th month. In HBeAg-positive patients, early biochemical and virological responses were found to be 78.3% and 82.6%, respectively. They were 100% and 52.2% in the 12th month. HBeAg s oconversion developed in 4.5% of HBeAg-positive patients.ConclusionsAccording to our one-year ETV treatment results, both HBeAg-negative and -positive patients had high biochemical and virological response rates. Their HBeAg seroconversion rate was 4.5%. In conclusion, more studies of longer duration are needed to understand the required duration of treatment, to assess its long-term effectiveness, and to check the resistance and side effects of ETV. There is also a need to have late-phase results after treatment.

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The High Incidence of the Emergence of Entecavir-Resistant Mutants among Patients Infected with Lamivudine-Resistant Hepatitis B Virus

Cited by 9 publications

References 29 publications

Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil therapy versus entecavir monotherapy for the treatment-naive patients with chronic hepatitis B: a meta-analysis

Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil therapy versus entecavir monotherapy for the treatment-naive patients with chronic hepatitis B: a meta-analysis

Correlation between Hepatitis B Virus Genotypes and Clinical Outcomes

Tenofovir therapy in chronic hepatitis B infection: 48-week results from Izmir Province, Turkey

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