HBV的基因型、突变、病毒载量是否对HBV引起的HCC患者的预后起决定性作用，仍存在争议。研究HBV对HBV引起的肝癌手术切除后患者预后的影响，调查抗病毒治疗是否可以抵消病毒因素所致的不利影响。333例HBV相关的HCC接受肿瘤切除的患者。分析其HBV DNA水平、突变、抗病毒治疗，及其他变量与术后复发的关系。经中位随访45.9个月，208例术后复发。5年总生存率和无复发生存率分别为55.4％和35.3％。多因素分析显示，吲哚绿15 min保留率在10％以上，GGT水平>60 U/L，肉眼和镜下的浸润、抗病毒治疗的缺乏，为影响复发的危险因素。抗病毒治疗可以降低早期HCC患者的复发率，而对于BCLC C期复发的患者效果不明显。在术后没有接受抗病毒治疗的患者，HBV DNA水平>106拷贝/毫升，GGT>60 U/L，则成为预测复发的危险因素。其中216例未接受抗病毒治疗的患者，73例 pre-S抗原缺失、突变。在具有较高HBV DNA水平的患者中，pre-S抗原缺失的患者有较高的复发率。多因素分析显示，多结节，肉眼所见浸润，肝硬化，进展期肿瘤细胞的分化，pre-S抗原缺失，为预测复发的危险因素，持续HBV复制和pre-S缺失是确定手术后肿瘤复发的关键。
BACKGROUND:
Whether or not hepatitis B virus (HBV) genotypes, mutations, and viral loads determine outcomes for patients with HBV-induced hepatocellular carcinoma (HCC) remains controversial.
AIMS:
To study the influence of HBV viral factors on prognoses for patients with HBV-induced HCC after resection surgery and investigate if antiviral therapy could counteract the adverse effects of viral factors.
METHODS:
A total of 333 HBV-related HCC patients who underwent tumor resection were enrolled retrospectively. Serum HBV DNA levels,mutations, anti-viral therapy, and other clinical variables were analyzed for their association with post-operative recurrence.
RESULTS:
After a median follow-up of 45.9 months, 208 patients had HCC recurrence after resection. The 5-year overall survival and recurrence-free survival rates were 55.4% and 35.3%, respectively. Multivariate analysis showed indocyanine green retention rate at 15 minutes >10%, gamma-glutamyltransferase (GGT) level >60 U/L, macroscopic and microscopic venous invasion, and the absence of anti-viral therapy were significant risk factors for recurrence. Anti-viral therapy could decrease recurrence in patients with early stage HCC, but the effect was less apparent in those with the Barcelona-Clinic Liver Cancer stage C HCC. For patients without antiviral therapy after resection, serum HBV DNA levels >106 copies/mL, GGT >60 U/L, and macroscopic and microscopic venous invasion were significant risk factors predicting recurrence. Among the 216 patients without anti-viral therapy but with complete HBV surface gene mapping data, 73 were with pre-S deletion mutants. Among patients with higher serum HBV DNA levels, those with pre-S deletion had significantly higher rates of recurrence. Moreover, multivariate analysis showed multi-nodularity, macroscopic venous invasion, cirrhosis, advanced tumor cell differentiation, and pre-S deletion were significant risk factors predictive of recurrence.
CONCLUSIONS:
Ongoing HBV viral replication and pre-S deletion are crucial for determining post-operative tumor recurrence. Anti-viral therapy can help reduce recurrence and improve prognosis, especially for those with early stage HCC.
吉林大学第一医院肝病科 穆雪峰 摘译
本文首次发表于[PLoS One,2013,8(6):e66457]
本文首次发表于[PLoS One,2013,8(6):e66457]
The Influence of Hepatitis B Viral Load and Pre-S Deletion Mutations on Post-Operative Recurrence of Hepatocellular Carcinoma and the Tertiary Preventive Effects by Anti-Viral Therapy.
AbstractBACKGROUND:
Whether or not hepatitis B virus (HBV) genotypes, mutations, and viral loads determine outcomes for patients with HBV-induced hepatocellular carcinoma (HCC) remains controversial.
AIMS:
To study the influence of HBV viral factors on prognoses for patients with HBV-induced HCC after resection surgery and investigate if antiviral therapy could counteract the adverse effects of viral factors.
METHODS:
A total of 333 HBV-related HCC patients who underwent tumor resection were enrolled retrospectively. Serum HBV DNA levels,mutations, anti-viral therapy, and other clinical variables were analyzed for their association with post-operative recurrence.
RESULTS:
After a median follow-up of 45.9 months, 208 patients had HCC recurrence after resection. The 5-year overall survival and recurrence-free survival rates were 55.4% and 35.3%, respectively. Multivariate analysis showed indocyanine green retention rate at 15 minutes >10%, gamma-glutamyltransferase (GGT) level >60 U/L, macroscopic and microscopic venous invasion, and the absence of anti-viral therapy were significant risk factors for recurrence. Anti-viral therapy could decrease recurrence in patients with early stage HCC, but the effect was less apparent in those with the Barcelona-Clinic Liver Cancer stage C HCC. For patients without antiviral therapy after resection, serum HBV DNA levels >106 copies/mL, GGT >60 U/L, and macroscopic and microscopic venous invasion were significant risk factors predicting recurrence. Among the 216 patients without anti-viral therapy but with complete HBV surface gene mapping data, 73 were with pre-S deletion mutants. Among patients with higher serum HBV DNA levels, those with pre-S deletion had significantly higher rates of recurrence. Moreover, multivariate analysis showed multi-nodularity, macroscopic venous invasion, cirrhosis, advanced tumor cell differentiation, and pre-S deletion were significant risk factors predictive of recurrence.
CONCLUSIONS:
Ongoing HBV viral replication and pre-S deletion are crucial for determining post-operative tumor recurrence. Anti-viral therapy can help reduce recurrence and improve prognosis, especially for those with early stage HCC.
