Farrell G C, Teoh N C
Department of Gastroenterology and Hepatology, The Canberra Hospital and Department of Medicine, Australian National University, Canberra, Australian Capital Territory, Australia.
Intern Med J. 2006 Feb;36(2):100-13. doi: 10.1111/j.1445-5994.2006.01027.x.
When assessing patients with chronic hepatitis B virus (HBV) infection, consider the state of viral replication, the immune response and whether viral mutations could be present, as well as evidence for liver disease or extrahepatic manifestations. In wild-type infections, loss of hepatitis B e antigen (HBeAg), gain of anti-HBe and disappearance of HBV DNA from serum indicate immunosuppression of viral replication, or 'nonreplicative chronic HBV infection'. This 'healthy carrier' state must be distinguished from HBeAg-negative chronic hepatitis B (CHB) resulting from precore and core promoter mutations. HBeAg-negative CHB is common with genotypes D (Mediterranean region, south Asia) and C (north Asia) infections. Age, disease activity (alanine aminotransferase level) and severity (fibrosis stage, cirrhosis) influence treatment decisions. Following the marginal effectiveness of interferon and often temporary effectiveness of lamivudine due to drug resistance, treatment of CHB is entering a new era. Adefovir, entecavir, tenofovir, telbivudine and clevudine have equal or superior antiviral efficacy to lamivudine, whereas several agents are effective against lamivudine-resistant HBV. Pegylated-interferon (peginterferon) is superior to conventional interferon for obtaining sustained immunosuppression of HBV without drug resistance. Antiviral suppression of HBV replication for 2-5 years reverses hepatic fibrosis, prevents cirrhosis and, when cirrhosis is established, improves liver function, prevents hepatic decompensation and lowers the risk of liver cancer. Before embarking on immunosuppressive chemotherapy or organ transplantation in patients with chronic HBV infection, it is important to start antiviral therapy to prevent hepatitis flares. Antiviral therapy can be effective against membranous glomerulonephritis and polyarteritis nodosa caused by HBV. Further improvements in treatment of CHB are needed to prevent drug resistance and permanently suppress viral replication by eradicating viral templates or stimulating host immune responsiveness to HBV.
在评估慢性乙型肝炎病毒（HBV）感染患者时，要考虑病毒复制状态、免疫反应、是否可能存在病毒突变，以及肝病或肝外表现的证据。在野生型感染中，乙肝e抗原（HBeAg）消失、抗-HBe出现以及血清中HBV DNA消失表明病毒复制受到免疫抑制，即“非复制性慢性HBV感染”。这种“健康携带者”状态必须与前核心和核心启动子突变导致的HBeAg阴性慢性乙型肝炎（CHB）相区分。HBeAg阴性CHB常见于D型（地中海地区、南亚）和C型（北亚）基因型感染。年龄、疾病活动度（丙氨酸转氨酶水平）和严重程度（纤维化阶段、肝硬化）会影响治疗决策。由于干扰素疗效有限且拉米夫定常因耐药性而疗效短暂，CHB治疗正进入一个新时代。阿德福韦、恩替卡韦、替诺福韦、替比夫定和克拉夫定的抗病毒疗效与拉米夫定相当或更优，而几种药物对拉米夫定耐药的HBV有效。聚乙二醇化干扰素（聚乙二醇干扰素）在获得持续的无耐药性HBV免疫抑制方面优于传统干扰素。对HBV复制进行2至5年的抗病毒抑制可逆转肝纤维化、预防肝硬化，在肝硬化已形成时可改善肝功能、预防肝失代偿并降低肝癌风险。在慢性HBV感染患者开始免疫抑制化疗或器官移植之前，启动抗病毒治疗以预防肝炎发作很重要。抗病毒治疗对HBV引起的膜性肾小球肾炎和结节性多动脉炎有效。需要进一步改进CHB的治疗，以防止耐药性并通过消除病毒模板或刺激宿主对HBV的免疫反应来永久抑制病毒复制。
