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This phase is followed by immune clearance, which is characterized by active inflammation of the liver and high or fluctuating serum alanine transaminase levels and fluctuating, but progressively decreasing, HBV-DNA levels. An important outcome of the immunoactive phase is seroconversion from HBeAg to anti-HBe, that marks the transition to the next phase of HBV natural history. The patient we describe was born and lived in Bangladesh until he moved to Italy and in April 2012, at the time of first evaluation, he was in the immune tolerant learn more phase of chronic HBV infection, with positive serum HBeAg, high levels of HBV DNA, normal ALT levels and normal/near normal histological picture with undetectable cytoplasmic/membranous HBsAg, and rare nuclear HBcAg staining at immune-histochemical evaluation of liver biopsy [Chu and Liaw, 1997]. It seems reasonable that HBV infection was acquired during childhood via vertical or early horizontal transmission. The mechanism(s) triggering the loss of immune tolerance are still unknown, however, the majority of patients enter the immune clearance phase between 20 and 40 years of age [Chu and Liaw, 1997; Liaw et al., 2003]. Among 300 Chinese subjects with immune clearance followed-up for 10�C50 months, 181 cases achieved spontaneous HBeAg seroconversion to anti-HBe, and the younger the patient, the shorter the time to anti-HBe development (P?Mdm2 dysfunction of the innate and adaptive systems in which immune activation and immune suppression, with poor development of adaptive immunity, coexist [Bortolotti et al., 2006; Kato et al., 2008; Vaziri et al., 2012]. Interestingly, in June 2012 the patient entered the immunoclearance phase, as demonstrated by ALT flare associated with the presence of low-titer anti-HBcIgM and significantly decreased HBV-DNA levels. The two most important changes in his lifestyle were the control of uremia by dialysis and the improvement of living conditions and nutritional status, both of whom may Cyclopamine manufacturer have contributed to trigger the immune clearance phase. The prompt administration of entecavir at the very beginning of this phase produced an unexpected result since after only 3 months of antiviral treatment the patient reached anti-HBe seroconversion and became HBsAg negative, and after 6 months he achieved anti-HBs seroconversion. In children who acquired HBV infection early during childhood, spontaneous HBeAg seroconversion occurs at an average rate of 14�C16% per year during the first 10 years of follow-up [Fabrizi et al., 2010] and ALT flares are often observed before seroconversion. However, the large majority of patients become inactive carriers, while HBsAg clearance is rarely observed [Chu and Liaw, 2007].