19 The cccDNA levels at the end of therapy are indeed predictive

of a sustained off-treatment response,20 but the clinical utility is limited because these can only be assessed invasively. Recent studies report an excellent correlation between decline in intrahepatic cccDNA and serum HBsAg levels in HBeAg-positive patients.5, 21 A decline in serum HBsAg levels may therefore reflect the efficacy of PEG-IFN in decreasing intrahepatic cccDNA and consequently predict a sustained off-treatment response. The aims of our study were to investigate the effects of 1 year of PEG-IFN with or without lamivudine (PEG-IFN ± LAM) therapy on serum HBsAg levels in patients with HBeAg-positive CHB, and to describe the relationship between on-treatment HBsAg decline and a sustained off-treatment response. ALT,

Natural Product Library cost alanine aminotransferase; AUC, area under the receiver-operating characteristic curve; cccDNA, covalently closed circular DNA; CHB, chronic hepatitis B; HBV, hepatitis Omipalisib B virus; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; LAM, lamivudine; LTFU, long-term follow-up; PEG-IFN, pegylated interferon; ULN, upper limit of normal. In this study, serum HBsAg levels were assessed in HBeAg-positive CHB patients who were previously enrolled in an investigator-initiated multicenter randomized controlled trial and a subsequent long-term follow-up (LTFU) study.12, 13 Patients were eligible for the initial study if they had been HBsAg-positive for at least 6 months prior to randomization, were HBeAg-positive on two occasions within 8 weeks prior to randomization, had elevated serum alanine aminotransferase (ALT) levels of 2-10 times the upper limit of normal (ULN), and had a serum HBV DNA

concentration above 1.0 × 105 copies/mL. Key exclusion criteria were: antiviral therapy within 6 medchemexpress months prior to randomization, presence of viral coinfections, preexisting cytopenia, or decompensated liver disease. Treatment comprised of PEG-IFN alfa-2b 100 μg weekly (PegIntron; Schering-Plough, Kenilworth, NJ) in combination with placebo or LAM (Zeffix; GlaxoSmithKline, Greenford, UK) 100 mg daily for 52 weeks. To limit the probability of early treatment discontinuation, the dose of PEG-IFN was reduced to 50 μg per week after 32 weeks of treatment. Patients attended the outpatient clinic at least every 4 weeks for routine examinations and laboratory assessments during both the treatment and the posttreatment follow-up phase of the initial study. For the LTFU study, patients were reevaluated at one additional visit at the local participating center. The mean duration of follow-up was 3 years.12 Inclusion criteria for the present analysis were completion of the 26-week follow-up phase of the main study and availability of a baseline serum sample for HBsAg quantification.