Hepatocellular carcinoma is associated with an increased risk of hepatitis B virus recurrence after liver transplantation.
OBJECTIVE
Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) is significantly reduced by prophylaxis with hyperimmune antibody to hepatitis B surface antigen (anti-HBs) globulins (HBIG) and antiviral drugs. The role of hepatocellular carcinoma (HCC) in HBV recurrence remains unclear. We investigated the association between HCC pre-OLT and HBV recurrence post-OLT.


METHODS
We studied 99 hepatitis B surface antigen-positive patients who underwent OLT for cirrhosis. The median follow-up period was 43 months. All patients received HBIG, and 51 also received lamivudine and/or adefovir. Of these 99 patients, 31 had HCC before OLT. Total HBV DNA and covalently closed circular (ccc)-DNA were measured in tumor and nontumor tissues from the explanted livers of 16 of these 31 HCC patients and, also, in a context of tumor recurrence, in 3 patients who developed HBV/HCC recurrence.


RESULTS
Fourteen patients (14.1%) developed HBV recurrence within a median period of 15 months post-OLT. HCC at OLT, a pre-OLT HBV DNA viral load > or = 100,000 copies/mL, and HBIG monoprophylaxis were independently associated with HBV recurrence post-OLT. Eleven out of the 31 patients with HCC at OLT presented with HBV recurrence and 3 out of the 68 patients without HCC had HBV recurrence (P < .0001). HBV recurrence was more frequent in patients who developed HCC recurrence (7/8 patients, 87.5%) than in those who did not (4/23 patients, 17.4%) (P < .0001). In the 16 explanted livers, cccDNA was detectable in HCC cells in 11 and in nontumor cells in 12. cccDNA was detected in a context of HCC recurrence in 2 of the 3 patients tested who developed HBV/HCC recurrence.


CONCLUSIONS
The associations of HCC pre-OLT, and HCC recurrence with HBV recurrence post-OLT, and the detection of HBV DNA and cccDNA in HCC suggest that HBV replication in tumor cells may contribute to HBV recurrence post-OLT.
Faria
Luciana C
LC
INSERM, U 785, Villejuif, France.
Gigou
Michelle
M
Roque-Afonso
Anne M
AM
Sebagh
Mylene
M
Roche
Bruno
B
Fallot
Guillaume
G
Ferrari
Teresa C A
TC
Guettier
Catherine
C
Dussaix
Elisabeth
E
Castaing
Denis
D
Brechot
Christian
C
Samuel
Didier
D
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000601:surgery / Q000821:virology*; D004270:DNA, Circular / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000601:surgery; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use; D007150:Immunohistochemistry; D019259:Lamivudine / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000601:surgery / Q000821:virology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000821:virology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention; D017422:Sequence Analysis, DNA; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication
D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine; C045213:hepatitis B hyperimmune globulin