Wong Grace L-H, Chan Henry L-Y
Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, the Hong Kong SAR, China.
Drugs. 2009 Nov 12;69(16):2167-77. doi: 10.2165/11319850-000000000-00000.
The ultimate goal of treatment for chronic hepatitis B is to reduce liver-related complications and mortality. Sustained hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) clearance 6-12 months after stopping treatment are the short-term surrogate outcomes for interferon or peginterferon therapy. As most patients require long-term nucleos(t)ide analogue treatment, which also has the risk of drug resistance in the case of incomplete viral suppression, maintained hepatitis B virus (HBV) DNA suppression to an undetectable level is the appropriate surrogate outcome. Because no antiviral treatment is perfect, it is desirable for treatment response to be predicted and the treatment regimen modified accordingly. At baseline, high ALT and low HBV DNA levels can predict response to both (peg)interferon and nucleos(t)ide analogues. Genotype A HBV responds best to peginterferon but HBV genotype has no predictive value for nucleos(t)ide analogue treatment. HBV DNA is a good on-treatment predictor of response for nucleos(t)ide analogues but not for (peg)interferon. The data supporting the use of quantitative HBsAg and HBeAg to predict response to peginterferon is stronger than that for nucleos(t)ide analogues. In conclusion, predictors of response are useful to provide the most appropriate antiviral therapy to the most suitable patients, in order to achieve the best response and improve the clinical outcome of chronic hepatitis B patients.
慢性乙型肝炎治疗的最终目标是减少肝脏相关并发症和死亡率。停止治疗后6 - 12个月实现持续的乙肝e抗原（HBeAg）血清学转换和乙肝表面抗原（HBsAg）清除是干扰素或聚乙二醇干扰素治疗的短期替代结局。由于大多数患者需要长期核苷（酸）类似物治疗，且在病毒抑制不完全时存在耐药风险，因此将乙肝病毒（HBV）DNA抑制维持在不可检测水平是合适的替代结局。由于没有一种抗病毒治疗是完美的，所以期望能够预测治疗反应并相应地调整治疗方案。在基线时，高ALT水平和低HBV DNA水平可预测对（聚乙二醇）干扰素和核苷（酸）类似物的反应。A型HBV对聚乙二醇干扰素反应最佳，但HBV基因型对核苷（酸）类似物治疗没有预测价值。HBV DNA是核苷（酸）类似物治疗反应的良好治疗期预测指标，但对（聚乙二醇）干扰素则不然。支持使用定量HBsAg和HBeAg预测聚乙二醇干扰素反应的数据比对核苷（酸）类似物的更强。总之，反应预测指标有助于为最合适的患者提供最恰当的抗病毒治疗，以实现最佳反应并改善慢性乙型肝炎患者的临床结局。
