Carcinoma hepatocelular como fator de risco para recorrência da infecção pelo vírus da hepatite B após o transplante de fígado: possível envolvimento das células neoplásicas na replicação viral

Abstract

Background and aims: In the last years, ortothopic liver transplantation (OLT) has become an important modality of treatment for hepatitis B virus (HBV)-related liver disease patients. However, HBV infection may recur in the transplanted liver and prophylactic measures are necessary to avoid this recurrence. The aims of this study were to investigate the role of hepatocellular carcinoma (HCC) in HBV recurrence after OLT and to assess HBV replication by cccDNA (covalently closed circular DNA)and total HBV DNA quantification in HCC and non-tumor cells from the native liver of HBsAg-positive transplanted patients. Methods: 113 HBsAg-positive transplanted patients were retrospectively studied. All patients received hyperimmune anti-HBs globulins (HBIG) after OLT and 56 also received lamivudine and/or adefovir. Median follow-up was 53 months (range 0.25 to 125). 33 patients (29.2%) had HCC. TotalHBV DNA and cccDNA were quantified in HCC and in non-tumor cells from the native liver of 16 patients by a real time polymerase chain reaction assay. CccDNA was quantified in HCC cells in three patients who presented HBV and HCC recurrences. Results: 14 patients (12.4%) presented HBV recurrence after OLT. The independent risk factors for HBV recurrence were HCC, serum levels of hepatitis B virus DNA = 30,000 copies/mL at the time of OLT, and HBIG monoprophylaxis (vscombined prophylaxis). CccDNA was detected in HCC cells from 11 patients and in non-tumor cells from 12 out of 16 patients on the explanted liver. CccDNA was detected in HCC metastatic cells after tumoral recurrence in two out of three tested patients who presented HBV and HCC recurrences. Conclusions: HCC, hepatitis B virus DNA viral load = 30,000 copies/mL at the time of liver transplantation and HBIGmonoprophylaxis were independent risk factors for HBV recurrence after OLT. HBV replication in HCC cells is strongly suggested by the concomitant recurrence of HCC and HBV infection and by the detection of cccDNA and HBV DNA in tumor tissues. These facts are probably implicated in HBV recurrence and other studies are necessary to investigate this association.