慢性乙型肝炎抗病毒治疗的挑战与策略——如何实现临床治愈最大化

Challenges and strategies of antiviral therapy for chronic hepatitis B-how to achieve the maximization of clinical cure?

HBV感染是全球重要的公共卫生问题,抗病毒治疗是阻止慢性乙型肝炎(CHB)患者疾病进展和改善预后的关键治疗方案。全球多个指南均推荐强效低耐药核苷和核苷酸类药物(NAs)及长效干扰素(PEG-IFN)为一线抗病毒治疗方案。但长期服用NAs存在疗程长、较低的HBeAg血清学转换率、极低的HBsAg清除或血清学转换率、安全性及耐药性等一系列弊端。因此,提高NAs经治患者的HBeAg和HBsAg血清学转换率,实现临床治愈是目前CHB治疗中需要关注的一个重要问题。近年来,多项全球性随机临床试验如OSST、Switch及ARES等均提示NAs联合或者序贯PEG-IFN能够提高CHB患者HBeAg及HBsAg的血清学转换率,实现临床治愈,为NAs治疗CHB患者提供了新方向。

Hepatitis B virus infection is still a major public health issue in the world,and antiviral therapy is the key therapeutic regimen to delay disease progression and improve outcome in patients with chronic hepatitis B（ CHB）. Various international guidelines recommend nucleos（ t） ide analogues（ NAs） and long-acting interferon as the first-line antiviral therapy. However,long-term administration of NAs has the disadvantages of long course of treatment,low HBeAg seroconversion rate,extremely low HBsAg clearance or seroconversion rate,low safety,and drug resistance. Therefore,it is an important issue to increase the seroconversion rates of HBeAg and HBsAg in treatment-experienced patients and realize clinical cure in the treatment of CHB. In recent years,many global randomized clinical trials including OSST,Switch,and ARES have shown that a combination of NAs and PEG-IFN or sequential therapy with NAs and PEG-IFN can increase the seroconversion rates of HBeAg and HBsAg in CHB patients and realize clinical cure,which provides a new direction for NAs in the treatment of CHB patients.