[Study of the relapse of patients with chronic hepatitis B undergoing first and repeated recombinant interferon-alpha therapy during long-term follow up].
OBJECTIVE
To investigate the relapse of patients with chronic hepatitis B (CHB) undergoing first and repeated recombinant interferon-alpha (rIFN-alpha) therapy during long-term follow up.


METHODS
Five hundred and twenty three patients with chronic hepatitis B including 403 hepatitis B e-antigen (HBeAg) positive patients and 120 HBeAg negative ones were treated with 5MU recombinant interferon-alpha 1b (rIFN-alpha1b) subcutaneously thrice weekly for 6 - 25 (median 10) months. For each patient, serum alanine aminotransferase (ALT) was measured biochemically and serum HBV DNA level was detected by fluorescent-quantitative PCR, HBeAg with enzyme immunoassay every 1 - 3 month during therapy and every 3 - 6 month during the follow up period. Some of the individuals who relapsed during the follow-up period were treated with interferon-alpha repeatedly.


RESULTS
Ratios of early response to interferon-alpha were similar in HBeAg positive patients (55.8%, 225/403), and HBeAg negative patients (64.2%, 77/120) at the end of naive treatment (chi(2) = 2.633, P = 0.105). 39.4% (119/302) of early responders relapsed during 39 +/- 22-month follow up, and relapse rates in HBeAg negative group (55.8%, 43/77) were higher than those in HBeAg positive group (33.8%, 76/225) at the end of follow up (chi(2) = 19.335, P = 0.000). Divided the follow-up period into six fragments as 1 - 12 months, 13 - 24 months, 25 - 36 months, 37 - 48 months, 48 - 60 months and > or = 61 months, we found that the differences of relapse incidence were significant (chi(2) = 73.518, df = 5, P = 0.000), and accumulative relapse rates were significant too (chi(2) = 32.167, df = 5, P = 0.000) in all follow-up periods. Constituent ratios of HBeAg in relapsed patients of every follow-up period were similar. 57 relapsed individuals (25 in HBeAg positive group and 32 in HBeAg negative group) were retreated with interferon-alpha, and complete response were achieved in all cases at the end of repeated therapy. The relapse rates in HBeAg positive group (52.0%, 13/25) were higher than in HBeAg negative group (21.9%, 7/32) during the follow-up period after the end of retreatment (chi(2) = 5.592, P = 0.018).


CONCLUSIONS
Rates of early response to interferon-alpha therapy were similar in HBeAg positive and HBeAg negative patients at the end of nave treatment, and relapse rates in HBeAg negative group were higher than in HBeAg positive group during long term follow-up. Combined response was achieved in all relapse cases received repeated interferon-alpha therapy at the end of retreatment. The relapse rates in HBeAg positive group were higher than in HBeAg negative group during the follow-up period after repeated therapy.
Liu
Ding-li
DL
Department of Infectious Diseases, Nanfang Hospital, the Southern Medical University, Guangzhou 510515, China.
Luo
Kang-xian
KX
Feng
Xiao-rong
XR
Fu
Qun-xiang
QX
Hou
Jin-lin
JL
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D007124:Immunoenzyme Techniques; D007370:Interferon Type I / Q000627:therapeutic use*; D008297:Male; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D007370:Interferon Type I; D011994:Recombinant Proteins; D000410:Alanine Transaminase