High risk of hepatocellular carcinoma in anti-HBe positive liver cirrhosis patients developing lamivudine resistance.
The emergence of drug-resistant virus in hepatitis B virus patients treated with lamivudine is well documented. However, its clinical impact in the long-term treatment of anti-HBe positive compensated cirrhotic patients is not well known. In this study, we treated 22 consecutive patients with anti-HBe compensated cirrhosis with lamivudine for a median period of 42 months. All patients responded to lamivudine, but viral breakthrough occurred in 13 patients (59%) between 9 and 42 months of therapy due to the emergence of a mutant strain. During the follow-up, 11 developed hepatocellular carcinoma. Of these, 10 occurred soon after the emergence of viral resistance, generally showing aggressive behaviour, and one in the nine long-term responder patients (P = 0.013). Lamivudine resistance was the only independent predictor of hepatocellular carcinoma development (risk ratio: 10.4; 95% CI: 1.3-84.9). Our study suggests that the occurrence of lamivudine resistance increases the risk of hepatocellular carcinoma in anti-HBe positive cirrhosis and warrants further research.
Andreone
P
P
Semeiotica Medica, Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, Università di Bologna, 40138 Bologna, Italy. andreone@med.unibo.it
Gramenzi
A
A
Cursaro
C
C
Biselli
M
M
Cammà
C
C
Trevisani
F
F
Bernardi
M
M
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D018570:Risk Assessment
D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine