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Entecavir
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Entecavir is a first-line therapy for treatment of immune-active HBV infection, for both patients with and without detectable hepatitis B e antigen (HBeAg) (Terrault et al., 2016; EASL, 2012). Entecavir efficacy in comparison with lamivudine was studied in three large phase III trials, and a number of supporting studies (Chang et al., 2006; Lai et al., 2006; Sherman et al., 2006; Lok et al., 2016; see Table 254.6). All phase III studies were randomized, double-blinded, and placebo controlled and included patients > 16 years of age with elevated ALT (1.3 to 10 times the upper limit of normal [ULN]) and with compensated liver disease; patients with HIV infection, co-infected with hepatitis C or D viruses were excluded. Nucleoside-naive patients were given 0.5 mg entecavir daily, whereas lamivudine-refractory patients were treated with 1 mg daily.
Developments in pharmacotherapeutic agents for hepatitis B – how close are we to a functional cure?
Published in Expert Opinion on Pharmacotherapy, 2023
Naoshin Khan, Mohamed Ramzi Almajed, Mary Grace Fitzmaurice, Syed-Mohammed Jafri
Entecavir (ETV) is another agent used to treat chronic hepatitis B with similar efficacy to tenofovir [23]. ETV is a cyclopentyl guanosine analog, and like other analogs, ETV is phosphorylated to its active triphosphate form. It has potent selective inhibition of the three main functions of the HBV polymerase: priming, DNA-dependent synthesis, and reverse transcription. ETV is typically administered at 0.5 mg daily and has shown efficacy in both HBeAg positive and negative patients. In HBeAg-positive patients, a significant reduction in HBV DNA was seen. HBeAg seroconversion was also seen in 20% of patients that have not been previously treated with other analogs; this was demonstrated after three years of continuous ETV therapy [29]. In HBeAg-negative patients, patients achieved undetectable HBV DNA by PCR, ALT normalization, and a decrease in inflammation, especially when compared to older agents such as lamivudine [30]. Special considerations need to be made for patients previously treated with lamivudine due to lower efficacy and increased risk of developing ETV resistance. ETV should be avoided in patients with prior lamivudine monotherapy. Prior studies have shown approximately 50% of patients developed ETV resistance after 5 years of treatment in lamivudine-treated patients. In the setting of patients previously treated with other analogs or with decompensated liver disease, ETV can be used, but the dose is increased to 1 mg daily.
Pharmacotherapy options for managing hepatitis B in children
Published in Expert Opinion on Pharmacotherapy, 2021
Haruki Komatsu, Ayano Inui, Sachiyo Yoshio, Tomoo Fujisawa
A retrospective study compared the efficacy of entecavir with that of lamivudine in children with chronic HBV infection. The cumulative rate of virologic response (undetectable HBV DNA) was significantly higher in the children treated with entecavir than in the children treated with lamivudine. The cumulative rate of virologic breakthrough was significantly lower in the children treated with entecavir compared to the children treated with lamivudine. However, the cumulative rate of HBeAg seroconversion in the children treated with entecavir was not significantly different from that of the children treated with lamivudine [118]. Because entecavir provides a robust suppression of HBV replication and has a low genetic barrier to resistance, entecavir should be used as the first-line treatment if children aged 2 years to ˂12 years meet the criteria of treatment with NAs. Lamivudine-resistance substitutions reduce the efficacy of entecavir and the genetic barrier of entecavir to resistance [119–121]. A double dose of entecavir is therefore needed for children with a lamivudine-resistant strain.
Association of KIR Genotypes and Haplotypes in HBeAg-positive Chronic Hepatitis B Patients Treated with Entecavir
Published in Immunological Investigations, 2019
YunLong Zhuang, XiXi Li, Xiaohua Li, HuiCong Xu, Hui Ye, Di Sun, XiangZhong Liu, GuiJie Ren
Hepatitis B virus (HBV) infection still remains a major health issue worldwide, which approximately 350 million people (more than 200 million in China) suffer the virus (Lu et al., 2008). Clinically, HBV infection often leads to severe consequences such as liver failure, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) since it can persist in the host for the whole life (Huang et al., 2017). Entecavir (ETV) is recommended as one of first line drugs in the treatment of chronic hepatitis B (CHB) due to their higher antiviral potency and higher genetic barriers than other antiviral agents (European Association for the Study of the Liver, 2012; Leung et al., 2009), and the antiviral therapy could ameliorate progression of liver injury, cirrhosis and HCC (Jang et al., 2015; Papatheodoridis et al., 2015; Wu et al., 2012). The amounts of HBV DNA was less than 300 copies/mL inhibited by ETV at 0.5 mg daily in 80% of hepatitis B e-Antigen (HBeAg) positive patients through 96 weeks (Gish et al., 2007). However, there are still some portions of HBeAg-positive CHB patients who don’t respond to the treatment with ETV, which the molecular mechanism remains largely unknown.