Section 14. Combination of entecavir plus low-dose on-demand hepatitis B immunoglobulin is effective with very low hepatitis B recurrence after liver transplantation.
OBJECTIVE
Antiviral prophylaxis with hepatitis B immunoglobulin (HBIg) plus lamivudine reduces the risk of hepatitis B virus (HBV) recurrence after HBV-related liver transplant (LT). However, HBIg is expensive, and lamivudine therapy is limited by drug resistance. This study assessed a pilot study of entecavir plus low-dose, on-demand HBIg in preventing HBV recurrence after LT.


METHODS
Between 2006 and May 2011, approximately 145 patients undergoing HBV-related LT and receiving entecavir plus low-dose, on-demand HBIg were enrolled and followed for a median of 36 months. A historical control group of 171 patients undergoing HBV-related LT between 1998 and 2010 and receiving lamivudine plus HBIg were followed for a median of 77 months. The primary end point was the proportion of patients with recurrent HBsAg-positivity.


RESULTS
In the entecavir cohort, 2 (1.37%) of 145 patients experienced HBV recurrence, none of which had evidence of viral resistance. In the lamivudine cohort, 11 (6.4%) of 171 cases of HBV recurrence were observed, 5 of which were associated with lamivudine resistance. The cumulative probabilities of HBV recurrence were significantly different between both cohorts (P=0.055). HBsAg recurrence was associated with lower overall survival (P<0.001), even in patients with undetectable HBV DNA. Using pooled data from both cohorts, predictors of HBV recurrence were nucleoside selection, pre-LT hepatocellular carcinoma, post-LT low anti-HBs, male sex, and HBsAg-positivity in the explant liver tissue.


CONCLUSIONS
Entecavir plus low-dose, on-demand HBIg resulted in a low rate of HBV recurrence without evidence of resistance development and provided an effective and cost-saving strategy for patients having HBV-related LT.
1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gang Memorial Hospital, Taiwan. 2 Department of Surgery, Kaohsiung Chang Gang Memorial Hospital, Taiwan. 3 Department of Pathology, Kaohsiung Chang Gang Memorial Hospital, Taiwan. 4 Address correspondence to: Chao-Long Chen, M.D., Liver Transplant Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan.
Tsung-Hui
TH
Hu
Chao-Long
CL
Chen
Chih-Che
CC
Lin
Chih-Chi
CC
Wang
King-Wah
KW
Chiu
Chee-Chien
CC
Yong
Yueh-Wei
YW
Liu
Hock-Liew
HL
Eng
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006509:Hepatitis B / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; C413685:entecavir; D006147:Guanine; C045213:hepatitis B hyperimmune globulin