Changes in the S/L proteins ratio may lead to the retention of surface proteins within the hepatocytes, although this event may not affect virion secretion.18-23 Several recent studies suggest that circulating HBsAg levels might reflect intrahepatic HBV activity and that their decline under treatment might predict a response to antiviral therapies in chronic hepatitis B (CHB) patients.24-27 HBsAg titer has been proposed as a surrogate marker for HBV covalently closed circular DNA (cccDNA),24, 25, 27 the intranuclear replicative intermediate that constitutes the reservoir responsible

for viral persistence. However, studies evaluating HBsAg titers have PI3K Inhibitor Library not considered the possible emergence of preS/S HBV mutants as dominant infecting viral populations, and in particular, they have not

taken into consideration the possible influence of preS/S gene variability on circulating levels of HBsAg. The aims of this study were to investigate whether infection with preS/S variants may influence the amounts of circulating HBsAg and HBV DNA in CHB patients and to perform a phenotypic characterization of naturally occurring preS/S variant isolates. aa, amino acid; anti-HBe, antibody to hepatitis B e antigen; BCP, basal core HCS assay promoter; cccDNA, covalently closed circular DNA; CHB, chronic hepatitis B; ER, endoplasmic reticulum; HBeAg, hepatitis e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; L, large; M, medium; mt, mutant; mRNA, messenger RNA; PC, precore; PCR, polymerase chain reaction; S, small; WT, wild-type. We studied N-acetylglucosamine-1-phosphate transferase serum samples collected

prior to any antiviral treatment from 40 patients with HBV-related chronic liver disease (26 men and 14 women; mean age, 43 ± 14.6 years), consecutively admitted to the outpatient service of the Liver Unit of the Messina University Hospital (Italy) in 2008. All of the patients were Italian and were infected with HBV genotype D (n = 36 patients) or A (n = 4). Eleven of the patients were HBV e antigen (HBeAg)-positive, and 29 were positive for the corresponding antibody (anti-HBe). Thirteen patients had cirrhosis and 27 had CHB. The diagnosis was performed through needle liver biopsy in 17 cases and through clinical/biochemical/ultrasonographic evaluation in 23 cases (Table 1). All patients were negative for hepatitis delta virus, hepatitis C virus, and human immunodeficiency virus serum markers. The study protocol was performed according to the principles of the Declaration of Helsinki, and written informed consent was obtained from all patients. Serum HBV DNA was quantified using the COBAS AmpliPrep-COBAS TaqMan HBV test (Roche Diagnostics, Monza, Italy) with a lower limit of detection of 12 IU/mL. HBsAg was quantified on the same sera using the ARCHITECT HBsAg Assay (Abbott; Abbott Laboratories, Chicago, IL) according to the manufacturer’s instructions.