[130] The effect of eliminating HBV-infected hepatocytes is weak. NAs currently approved by medical insurance system in Japan comprise 3 agents: lamivudine, adefovir and entecavir. In Japan, lamivudine, the http://www.selleckchem.com/products/Decitabine.html first of the NAs, were approved by medical insurance in 2000, followed by adefovir in 2004 and entecavir in 2006 (Table 2). If administration of the NAs is ceased, in many cases the HBV DNA levels rise again, returning to pretreatment

levels.[131-134] Even in cases where HBeAg seroconversion occurred during administration of a NA (lamivudine), it was found similarly that HBV DNA quantity rose again and HBeAg reappeared.[135, 136] Furthermore, after treatment ceases, cases have been reported where ALT levels rose www.selleckchem.com/products/abc294640.html to ≥500 U/L, and total bilirubin rose to ≥2.0 mg/dL.[137] Accordingly, in order to achieve the aim of improved long term outcomes, in general it is necessary not to stop administration

of the NAs, and provide continuous maintenance treatment to inhibit HBV reproduction. Lamivudine is a reverse transcriptase inhibitor, originally developed for treatment of human immunodeficiency virus (HIV). Like HIV, HBV passes through a transcriptase process in its lifecycle, so a reverse transcriptase inhibitor has therapeutic effect. Lamivudine has a structure (3TC-TP) similar to deoxycytidine triphosphate (dCTP), which is used as a foundation substance when reverse transcriptase synthesizes DNA using RNA as a template. For this reason lamivudine binds to reverse transcriptase during DNA synthesis and inhibits further DNA synthesis. This mechanism inhibits reproduction of the HBV virus and reduces HBV selleck inhibitor DNA levels. The dosage of lamivudine is 100 mg per day. Lamivudine has almost no adverse reactions and is very safe. Reported therapeutic results for lamivudine in HBeAg positive patients in Asian and other overseas countries are ALT normalization rates of 40–87% 1 year after commencement of treatment, 85% after 2 years, and HBV DNA negative conversion rates (solution-hybridization or branched

chain DNA assays) of 44–87% after 1 year, and 74% after 2 years.[131, 138, 139] Reported HBeAg seroconversion rate are 17–28% after 1 year, 25–29% after 2 years, 40% after 3 years, and 50% after 5 years.[138-141] Furthermore, histological improvement is also reported 1 year after commencement of treatment.[142] The short term effects of lamivudine are also favorable in HBeAg negative patients.[134, 143, 144] In a Japanese study,[139] the HBV DNA negative conversion rate (HBV DNA <0.5 Meq/mL) was 94% after 1 year of treatment and 92% after 2 years, and the ALT normalization rate was 89% after 1 year, and 82% after 2 years. However, the HBV DNA negative conversion rate decreases over the long term.[96] A major problem with lamivudine is the occurrence of drug resistance (YMDD motif mutation).