Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients

Ono, Atsushi; Suzuki, Fumitaka; Kawamura, Yusuke; Sezaki, Hitomi; Hosaka, Tetsuya; Akuta, Norio; Kobayashi, Masahiro; Suzuki, Yoshiyuki; Saitou, Satoshi; Arase, Yasuji; Ikeda, Kenji; Kobayashi, Mariko; Watahiki, Sachiyo; Mineta, Rie; Kumada, Hiromitsu

doi:10.1016/j.jhep.2012.04.037

Cited by 152 publications

(136 citation statements)

References 29 publications

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“…About 84% of the patients with PVR achieved VR through prolonged therapy without adaptation. These results were consistent with previous ETV therapy studies (15,16). Our results support previous studies suggesting that continuous ETV therapy is an effective and promising choice (15,16).…”

Section: Discussionsupporting

confidence: 93%

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

Lee

Kwon

et al. 2015

Antimicrob Agents Chemother

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The 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). C urrently, treatment guidelines for both HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) patients recommend treatment with pegylated interferon or nucleos(t)ide analogs (NAs) (1-4). Although pegylated interferon has advantages, including a finite treatment duration and the absence of viral resistance, adherence to treatment is poor due to frequent side effects and the need for frequent subcutaneous injections (5). Given the increased risk of virological failure from poor adherence to pegylated interferon treatment, NAs have been widely used in clinical practice. Among several NAs, entecavir (ETV) and tenofovir (TDF) are especially potent inhibitors of hepatitis B virus (HBV) reverse transcriptase and DNA polymerase with minimal or no drug resistance (6-8). Therefore, ETV has been confidently used as a first-line therapy. Despite its efficacy, about 10 to 20% patients treated with ETV showed partial virological response (PVR) (9, 10). Unfortunately, HBV cannot be eradicated, and NAs must be continued until HBsAg seroclearance. Sustained viremia may ultimately result in HBV variants with genotypic resistance and clinical breakthrough. Therefore, it is related to subsequent therapeutic failure. In contrast to the frequently described genotypic re...

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Section: Discussionsupporting

confidence: 93%

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

Lee

Kwon

et al. 2015

Antimicrob Agents Chemother

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“…While our results coincide with data from Far east and Middle of Asia [18][19][20][21][22]. Chang et al from Taiwan, showed in their 5 year follow up study of 146 Entecavir treated patients that 94% (88/94) had HBV-DNA <300 copies/mL and 80% (78/98) had normalized ALT levels [19].…”

Section: Discussionsupporting

confidence: 91%

“…Data from Japan, by Atsushi and his colleagues assured the antiviral potency and viral resistance rate after 4 years of continuous Entecavir treatment in patients with CHB infection. They reported 96% chance of undetectable HBV-DNA with similar rates of HBeAg sero-conversion and HBsAg loss [22].…”

Section: Discussionmentioning

confidence: 97%

Retrospective-Prospective Study on Efficacy & Safety of Entecavir in Chronic Hepatitis B West Asian Patients with Genotype D

Akrouf¹,

Gad²,

Ibraheem³

et al. 2017

J Clin Infect Dis Pract

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Aim: To assess the long term efficacy and safety of Entecavir in the treatment of CHB in Asian-Arabic patients with genotype D, for both nucleoside-naïve as well as experienced, comparing HBeAg positive and negative group. Methods:This study included 70 CHB consecutive patients who were maintained on Entecavir for at least 36 months retrospectively and followed up prospectively every 3 months for a total of 18 months, at 2 centers in Kuwait (October 2012 and April 2014).Results: It showed that 23 (32.8%) were HBeAg +ve. All were found to be HBV genotype D, 47.1% naive, 22 (31.4%) females, with a mean age of 42.9 ± (13), 14 (20%) cirrhotic and 1(1.4%) decompensated. There were no significant differences in the pre-treatment HBV-DNA level among HBeAg+ve and HBeAg-ve group, with a mean± SD log 10 of 7.9 ± 5.4 and 7.4 ± 5.0 respectively (P=0.237). There was a significant viral load reduction in both groups after 6 months of treatment with Entecavir. The reduction was more pronounced in the HBeAg-ve compared to HBeAg +ve group. In HBeAg +ve, 19 patients (82.61%) had complete HBV-DNA suppression after a median period of 7 month, while in HBeAg -ve group; all (100%) had complete HBV-DNA suppression after a median period of 5 month duration (P<0.05). None showed primary non response to Entecavir in both groups. In the HBeAg-ve group; one (2.13%) had HBsAg loss at 45 month compared to non in HBeAg+ve group (P<0.001), while in the HBeAg+ve group; 5 (21.74%) showed HBeAg clearance after a median of 16 month during Entecavir treatment. Multivariate analysis identified HBeAg negative status, pre-treatment as the only independent factor affecting complete viral suppression on Entecavir treatment. The drug showed 100% safety, as there were no serious adverse events throughout 54 month of follow up. None showed hepatic decompensation, HCC or need for liver transplantation during follow up. Also, there was no reported death throughout study period in both groups. Conclusions:In real life data; long term Entecavir treatment for up to 54 months in West Asian CHB patients, with genotype D suppressed HBV-DNA to an undetectable level in 100% of HBeAg-ve, compared to 82% in HBeAg +ve group. Entecavir is considered an effective and safe choice on long term use for treatment CHB patients.

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“…The serum HBV DNA-negative conversion and serum ALT normalization rates of entecavir for 48 to 96 wk were superior to those in response to lamivudine for both HBeAg-positive and HBeAg-negative patients [66,67,70,77] . With entecavir administration for 3 to 5 years, the serum HBV DNA-negative conversion rates were 55% to 88%/1 year, 83% to 93%/2 years, 89% to 95%/3 years, and 91% to 96%/4 years, 94%/5 years; the serum ALT normalization rates were 65% to 84%/1 year, 78% to 88%/2 years, 77% to 90%/3 years, 86%/4 years, and 80%/5 years; and the HBeAg seroconversion rates were 12% to 22%/1 year, 18% to 41%/2 years, 29% to 44%/3 years and 38%/4 years [69,[74][75][76]78] . The resistance mutant emergence rates were reported to be 0.2%/1 year, 0.5%/2 years, and 1.2%/3 to 5 years for the NUCs-treatment-naive patients [69,78] .…”

Section: Entecavirmentioning

confidence: 97%

Current and future directions for treating hepatitis B virus infection

Tawada

Yokosuka

2015

WJH

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Hepatitis B virus (HBV) persistently infects approximately 350 million people, and approximately 600000 liverrelated deaths are observed per year worldwide. HBV infection is also one of the major risk factors for hepatocellular carcinoma (HCC). The persistence of serum hepatitis B e antigen (HBeAg) and high level of serum HBV DNA are thought to reflect a high HBV replication status in hepatocytes, causing cirrhosis, HCC and liver-related deaths. It has been reported that antiviral therapy, such as peginterferon and nucleos(t)ide analogues (NUCs), could suppress liver-related death by inhibiting the HBV DNA levels and inducing seroconversion from HBeAg to antibody to HBe antigen. Currently, peginterferon is widely used, but there are also several disadvantages in the use of peginterferon, such as various adverse events, the administration route and duration. It is difficult to predict the effects of treatment and interferon is contraindicated for the patients with advanced fibrosis of the liver and cirrhosis. With respect to NUCs, entecavir and tenofovir disoproxil fumarate are current the first-choice drugs. NUCs can be administered orally, and their anti-viral effects are stronger than that of peginterferon. However, because cessation of NUC administration leads to high levels of viral replication and causes severe hepatitis, they must be administered for a long time. On the other hand, the use of both interferon and NUCs cannot eliminate covalently closed circular DNA of HBV. In this review, we evaluate the natural course of chronic HBV infection and then provide an outline of these representative drugs, such as peginterferon, entecavir and tenofovir disoproxil fumarate.

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Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients

Cited by 152 publications

References 29 publications

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

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

Retrospective-Prospective Study on Efficacy & Safety of Entecavir in Chronic Hepatitis B West Asian Patients with Genotype D

Current and future directions for treating hepatitis B virus infection

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