Jung Min Lee, Sang Hoon Ahn, Hyon Suk Kim, Hana Park, Hye Young Chang, Do Young Kim, Seong Gyu Hwang, Kyu Sung Rim, Chae Yoon Chon, Kwang-Hyub Han, and Jun Yong Park 1 Prof. 심재준 / R2 이민혜 Hepatology 2011;53: Quantitative Hepatitis B Surface Antigen and Hepatitis B e Antigen Titers in Prediction of Treatment Response to Entecavir

Chronic hepatits B (CHB) More than 400 million infected people Progression to cirrhosis and hepatocellular carcinoma Quantitative hepatitis B surface antigen (qHBsAg) and Quantitative hepatitis B e antigen (qHBeAg) titers Pegylated interferon (PEG-IFN) therapy Useful tools for predicting virological response (VR) and serological response (SR) Oral nucleoside analogues Adefovir and lamivudine (LAM) : low potency in decreasing qHBsAg levels Entecavir (ETV) : little is known about qHBsAg 2 B ACKGROUND

P ATIENTS AND M ETHODS All patients with chronic hepatitis B (CHB) at Severance Hospital or CHA Bundang Medical Center Started on ETV (0.5 mg once a day) between January 2007 and June 2008 Starting time at ETV HBV DNA level > 10,000 copies/mL ALT level > 2 times the upper limit of normal Biopsy showed significant fibrosis/cirrhosis VR(virological response) : HBV DNA level undetectable by a real-time PCR assay (<60 copies/mL) at 24 months SR(serological response) : loss of HBeAg at 24 months in HBeAg(+) patients 3

P ATIENTS AND M ETHODS 4 Inclusion criteria Presence of serum HBsAg for 6 or more months HBV genotype C Age greater than 16 years Previous lack of treatment with a subsequent ETV treatment period of at least 24 months Exclusion criteria Coinfection with hepatitis C virus or human immunodeficiency virus History of organ transplantation Decompensated liver cirrhosis Concurrent use of immunomodulatory drugs or corticosteroids

R ESULTS 5  95 patients, 475 serial samples  Median age = 48 years, 68(71.6%) patients male, 57(60.0%) patients HBeAg(+)  ALT = 66 IU/L, log HBV DNA = 6.73 copies/mL,  log qHBsAg = 3.58 IU/L, log qHBeAg = 1.71 PE IU/mL

R ESULTS HBeAg(+) patients VR(+) group 3.48±0.65  3.33±0.55 IU/mL (P=0.097) VR(-) group 4.22±0.68  3.80±0.54 IU/mL (P=0.005) Significant differences in qHBsAg levels (P < 0.005) HBeAg(-) patient VR(+) group 3.40±0.48  3.20±0.50 IU/mL (P=0.007) VR(-) group 3.77±0.73  3.60±0.75 IU/mL (P=0.058) Not significant differences in qHBsAg levels 6 Fig. 1. Serial values of qHBsAg in (A) HBeAg(+) patients and (B) HBeAg(-) patients receiving ETV therapy according to the VR status.

R ESULTS 7 Fig. 2. Serial values of qHBeAg according to the (A) VR and (B) SR status in HBeAg(+) patients receiving ETV therapy VR status VR(+) group 1.11±1.04  -0.01±0.71 PE IU/mL (P<0.001) VR(-) group 2.11±0.65  1.26±0.95 PE IU/mL (P<0.001) Significant differences in qHBeAg reduction (P<0.001) SR status SR(+) group 1.44±1.10  -0.72±0.46 PE IU/mL (P=0.003) SR(-) group 1.45±1.04  0.60±0.94 PE IU/mL (P<0.001) Statistical differences from month 6 in qHBeAg reduction (P<0.05)

R ESULTS Significantly associated with VR Higher ALT levels (P=0.013) Lower HBV DNA levels (P=0.040) Lower qHBsAg levels (P=0.033) 8

R ESULTS 9 Fig. 3. ROC curves of (A) baseline characteristics used to predict VR and (B) an on-treatment factor used to predict SR The accuracy of predicting VR was highest at log qHBsAg=3.98 IU/mL Sensitivity : 86.8% Specificity : 78.9% The accuracy of predicting SR was highest with a reduction of log qHBeAg to 1.00 PE IU/mL Sensitivity : 75.0% Specificity : 89.8%

C ONCLUSION HBeAg(+) Patients treated with ETV Useful in predicting VR Baseline level of qHBsAg Useful in predicting SR On-treatment decline of qHBeAg Determination of qHBsAg and qHBeAg Inexpensive and simple assays Help us to select the appropriate strategy for the management of patients with CHB 10