| Summary: | 博士 === 長庚大學 === 臨床醫學研究所 === 101 === Background: Hepatitis B virus (HBV) associated end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) are the leading cause of liver transplantation (LT) in Taiwan. However, relapse of HBV infection or recurrence of HCC after LT increases graft failure and reduces patient survival. The aim of this study was to evaluate the clinical, pathological and virological factors associated with clinical outcome after LT in HBV surface antigen (HBsAg) positive patients.
Methods: Between September 2002 and August 2009, 150 consecutive HBsAg positive patients underwent LT were retrospectively studied. Among them, 78 patients also diagnosed with HCC. All patients received short-term hepatitis B immunoglobulin (HBIG) and lamivudine (LAM) for prophylaxis. The amount of HBV DNA was measured using pre-LT serum samples and the virological factors were assayed including viral genotype, presence of the HBV precore stop codon G1896A mutation, basal core promoter A1762T/G1764A (BCP) mutation, and large (> 100 base pairs) or small fragment of pre-S deletions (LFpreSDel or SFpreSDel). The pathological factors including hepatitis severity by ISHAK score and the tissue expression of HBsAg or HBcAg from explanted liver by immunohistochemistry were also reviewed. We investigated the risk factors of HBV relapse or HCC recurrence using univariate and multivariate analysis.
Results: To survey the risk factors associated with HBV relapse after LT, Kaplan-Meier analyses discovered that pre-operative lamivudine treatment ≦ 3 months; membranous distribution and higher expression of tissue HBsAg in liver explants; preoperative viral load ≧ 106 copies/ml; and presence of LFpreSDel correlated significantly with hepatitis B relapse. Multivariate cox regression analysis showed that the presence of LFpreSDel (P = 0.001) and viral load ≧106 copies/mL (P = 0.023) were independent predictors for hepatitis B relapse. Only five of 76 (6.6%) patients without these two risk factors experienced HBV relapse after transplantation. To survey the post transplantation outcome of patients with HBV related HCC, we also found that HBV relapse exhibited a close association with HCC recurrence (P = 0.004) and led to unfavorable overall survival after LT. Moreover, with the exception of advanced tumor characteristics, the BCP mutation was found to be an important prognostic factor that affected HCC recurrence after LT (P = 0.042).
Conclusions: The amount of HBV-DNA and presence of pre-S large fragment deletion were two independent predictors for HBV relapse after LT in HBsAg positive patients. Except advanced tumor characteristics, the HBV-BCP mutation was identified as an important predictor of post-LT clinical outcomes in patients with HBV-related HCC. Therefore, we recommend that aggressive antiviral treatment may be considered for patients associated with this risk factor.
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