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The end\u2010point of therapy is to persistently suppress viral replication to halt progression of liver disease. Two different treatment strategies are currently available: a short\u2010term course of pegylated interferon alpha (<jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>) or long\u2010term therapy with nucleot(s)ide analogues (<jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>), i.e. entecavir or tenofovir. Young patients with mild\u2010to\u2010moderate stages of liver disease can benefit from a 48\u2010week course of <jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>, while <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content> may be preferred in patients with more severe liver disease, in older patients, and in those who do not respond, are unwilling or have contraindications to <jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>. Nucleot(s)ide analogues provide persistent viral suppression and biochemical normalization in almost all patients, together with the regression of fibrosis and the prevention of decompensation, but the effect on hepatocellular carcinoma rates is limited. Thus, <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>s have become the most popular treatment strategy worldwide but lifelong administration is associated with high cost, unknown safety and adherence issues and an unknown risk of drug\u2010resistance over time as well as limited rates of HBsAg seroclearance. On the other hand, <jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content> treatment may achieve a SVR in nearly a quarter of patients ultimately leading to HBsAg loss in almost 30\u201350%. Interestingly, response rates to <jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content> may further increase with more careful patient selection based on age, <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content> levels at baseline and by applying early on\u2010treatment stopping rules based on <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content> and HBsAg kinetics. The combination of <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content> is not currently recommended but numerous studies are ongoing.<\/jats:p>","DOI":"10.1111\/liv.12717","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T10:26:34Z","timestamp":1419243994000},"page":"107-113","source":"Crossref","is-referenced-by-count":21,"title":["Optimal therapy of chronic hepatitis B: how do I treat my HBeAg\u2010negative patients?"],"prefix":"10.1111","volume":"35","author":[{"given":"Mauro","family":"Vigan\u00f2","sequence":"first","affiliation":[{"name":"Hepatology Division Ospedale San Giuseppe Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"First Division of Gastroenterology Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico \u2018A.M. e A. 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