[Clinical trial of sequential antiviral therapy for patients with chronic hepatitis B in China].
OBJECTIVE
To establish a sequential antiviral regime and evaluate its efficacy in patients with chronic hepatitis B using a controlled trial.


METHODS
Seventy-four patients with chronic hepatitis B were divided into 3 groups: 30 cases were enrolled in the sequential antiviral group in which patients received eight-week treatment with thymosin alpha1 (1.6 mg/time, subcutaneous injection, 2 times/week), six-month treatment with interferon (500 MU/ times, muscle inject, every other day) begun in the fifth week of the therapeutic course, and lamivudine treatment (100 mg/days) begun 2 months later after HBeAg seroconversion or just after the withdrawal of interferon to more than eighteen months. Fourteen cases were enrolled in combination group in which patients received six-month treatment with interferon and thymosin alpha1 simultaneously in the same manner as in sequential antiviral group. Thirty cases were enrolled in lamivudine group in which patients received more than eighteen-month treatment with lamivudine.


RESULTS
The temporary rates of HBeAg seroconversion and normalization of alanine aminotransferase (effective rate) in sequential antiviral group, combination group and lamivudine group were 76.7%, 78.6% and 13.3%, respectively. The effective rates of sequential group and combination group were very similar, and significantly higher than that of lamivudine group (P less than 0.01). Long-term efficacy rates were 76.7%, 57.1% and 16.7% among the three groups, respectively. The long-term effective rate of sequential group was relatively higher. The rate of liver damage sensitive period in sequential antiviral group and combination group was 47.7%. The time of onset was from 2 to 8 weeks after the treatment begun, earlier than that from 6 to 8 weeks after the beginning of interferon alone in the literature.


CONCLUSIONS
Sequential antiviral therapy had much higher rates of long-term HBeAg seroconversion, undetectable HBV DNA and normalization of alanine aminotransferase with good cost-effectiveness. Its mechanism to promote the antiviral effect might be dependent on the immunoregulatory action of thymosin alpha1 in the earlier period and the specific inhibition of HBV DNA replication by lamivudine in the later period of the therapeutic course.
Lei
Chun-liang
CL
The No.8 Hospital of Guangzhou, Guangzhou 510060, China.
Peng
Xiao-mou
XM
Tang
Xiao-ping
XP
Yang
Zhan
Z
Fan
Hui-min
HM
Yuan
Xiao-zhen
XZ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage*; D002681:China; D004359:Drug Therapy, Combination; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D019259:Lamivudine / Q000008:administration & dosage*; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D016898:Interferon-alpha; D019259:Lamivudine; D013947:Thymosin; D000077596:Thymalfasin