Sequential combination therapy with pegylated interferon leads to loss of hepatitis B surface antigen and hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients receiving long-term entecavir treatment.
Nucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of patients. We assessed the effect of sequential combination therapy with Peg-IFN-α2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-α2a added to ongoing entecavir therapy (sequential combination [S-C] therapy; n = 81) for 48 weeks or remaining on entecavir monotherapy (n = 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%; P < 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was ≥200 S/CO (64.2% versus 17.9%; P < 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of ≥0.5 log10 IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.
Department of Hepatology, the Second Hospital of Yinzhou of Ningbo, Ningbo, China.
Guo-Jun
GJ
Li
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Yi-Qi
YQ
Yu
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Shao-Long
SL
Chen
Department of Hepatology, PLA Hospital, Ningbo, China.
Ping
P
Fan
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Ling-Yun
LY
Shao
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Jia-Zhen
JZ
Chen
Department of Hepatology, the Second Hospital of Yinzhou of Ningbo, Ningbo, China.
Chang-Shui
CS
Li
Department of Hepatology, the Second Hospital of Yinzhou of Ningbo, Ningbo, China.
Bin
B
Yi
Department of Hepatology, the Second Hospital of Yinzhou of Ningbo, Ningbo, China.
Wei-Cun
WC
Chen
Department of Hepatology, the Second Hospital of Yinzhou of Ningbo, Ningbo, China.
Shu-Yuan
SY
Xie
Department of Hepatology, the Second Hospital of Yinzhou of Ningbo, Ningbo, China.
Xiao-Na
XN
Mao
Department of Hepatology, the Second Hospital of Yinzhou of Ningbo, Ningbo, China.
He-Hui
HH
Zou
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China Institutes of Biomedical Sciences, Fudan University, Shanghai, China MOH and MOE Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai, China zhangwenhong@fudan.edu.cn.
Wen-Hong
WH
Zhang
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D023381:Endpoint Determination; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D000069078:Seroconversion; D016896:Treatment Outcome; D055815:Young Adult
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; C100416:peginterferon alfa-2a