Department of Hepatology, Toronto Western Hospital Liver Centre, McLaughlin Rotman Centre for Global Health, University of Toronto, Toronto, Canada.
Semin Liver Dis. 2013 May;33(2):157-66. doi: 10.1055/s-0033-1345719. Epub 2013 Jun 8.
Chronic hepatitis B infection (CHB) is common and can lead to serious consequences including liver cirrhosis, failure, and hepatocellular carcinoma (HCC). The hepatitis B virus (HBV) has a simple genome, but a complex lifecycle that includes the production of covalently closed circular DNA (cccDNA). Currently approved antiviral treatments for CHB include interferon (IFN) and nucleos(t)ide analogues. These drugs work either by stimulating the immune system to eliminate virus-infected cells or to inhibit viral replication, respectively. The drugs do not affect the cccDNA pool in the nucleus; therefore, this molecule represents a persistent source of recurrent infection that is difficult to eradicate. With longer-term follow-up of patients treated with antiviral therapy, investigators have looked at whether treatment can prevent the development of HCC. Unfortunately, the data are fairly heterogeneous in terms of both quality and conclusions. IFN appears to reduce the risk of HCC, but the benefit seems to be restricted to cirrhotic patients who have a lasting response to therapy. Oral agents successfully suppress HBV DNA replication and slow or even reverse hepatic fibrosis. Studies suggest that long-term therapy reduces the risk of HCC in patients with active disease and again primarily in those with advanced fibrosis or cirrhosis. The mechanism by which any of the therapies reduce the risk of HCC is not clear. The authors review the lifecycle of HBV and mechanisms by which the virus may be carcinogenic followed by a review of the literature on the efficacy of therapy in reducing the risk of HCC.
慢性乙型肝炎感染（CHB）很常见，可导致严重后果，包括肝硬化、衰竭和肝细胞癌（HCC）。乙型肝炎病毒（HBV）具有简单的基因组，但具有复杂的生命周期，包括共价闭合环状 DNA（cccDNA）的产生。目前批准的 CHB 抗病毒治疗包括干扰素（IFN）和核苷（酸）类似物。这些药物分别通过刺激免疫系统消除病毒感染细胞或抑制病毒复制来发挥作用。这些药物不会影响核内的 cccDNA 池；因此，这种分子代表了难以根除的持续感染的来源。随着对接受抗病毒治疗的患者进行更长期的随访，研究人员研究了治疗是否可以预防 HCC 的发生。不幸的是，无论在质量还是结论方面，数据都相当不一致。IFN 似乎降低了 HCC 的风险，但获益似乎仅限于对治疗有持久反应的肝硬化患者。口服药物可成功抑制 HBV DNA 复制并减缓甚至逆转肝纤维化。研究表明，长期治疗可降低活动期患者和再次主要是纤维化或肝硬化患者 HCC 的风险。任何治疗方法降低 HCC 风险的机制尚不清楚。作者回顾了 HBV 的生命周期以及病毒致癌的机制，然后对文献中治疗降低 HCC 风险的疗效进行了综述。
