慢性HBV感染不确定期患者的临床治疗现状及展望

Clinical treatment of chronic hepatitis B virus infection in indeterminate phase:Current status and future prospects

慢性乙型肝炎病毒(chronic hepatitis B virus,HBV)感染的自然病程通常分为4个阶段:免疫耐受期、乙肝e抗原(hepatitis B e antigen,HBeAg)阳性慢性乙型肝炎(chronic Hepatitis B,CHB)(即免疫清除期)、免疫控制期、HBeAg阴性CHB(即再活动期).根据HBeAg、乙肝病毒脱氧核糖核酸(HBV deoxyribonucleic acid,HBV DNA)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)和肝脏组织学表现,将不适合上述任何一个阶段的不确定期患者分为以下四组:(1)免疫耐受期相关不确定期:其余指标符合免疫耐受期,但HBV DNA<10^(6)IU/mL或肝脏有显著炎症和纤维化;(2)免疫清除期相关不确定期:其余指标符合免疫清除期,但HBV DNA<2×10^(4)IU/mL或ALT 1-2倍正常值上限(the upper limits of normal,ULN);(3)免疫控制期相关不确定期:其余指标符合免疫控制期,但HBV DNA>2×10^(3)IU/mL或有显著炎症和纤维化;(4)再活动期相关不确定期:其余指标符合再活动期,但HBV DNA<2×10^(3)IU/mL或ALT 1-2 ULN.据统计我国约有7000万人感染了慢性HBV,其中约有2000-3000万是CHB患者.此外我国肝硬化和肝细胞癌(hepatocellular carcinoma,HCC)患者中,由HBV感染引起的比例分别为77%和84%.慢性HBV感染严重威胁着人民的生命健康并给国家医疗卫生体系带来沉重的经济负担.虽然现有指南建议动态监测这部分不确定期患者血清ALT和HBV DNA水平并评估肝脏组织学,但是否对这部分患者进行抗病毒治疗仍存有争议.本文主要介绍了CHB免疫控制期及与其相关不确定期患者的临床治疗现状,和对这部分患者进行抗病毒治疗的展望.

The natural history of chronic hepatitis B virus(HBV)infection is usually divided into four stages:Immune tolerant phase(IT),hepatitis B e antigen(HBeAg)positive chronic hepatitis B(CHB)(i.e.,immune clearance phase),immune control(IC)phase,and HBeAg negative CHB(i.e.,reactivation phase).Patients whose HBeAg,alanine aminotransferase(ALT),HBV DNA,and hepatic histopathology fall into an indeterminate phase are divided into the following four groups:(1)Indeterminate phase related to IT:HBV DNA<10^(6)IU/mL or significant inflammation and fibrosis,while other indicators are in line with IT;(2)Indeterminate phase related to HBeAg positive CHB:HBV DNA<2×10^(4)IU/mL or ALT 1-2 times the upper limit of normal(ULN),while the rest indicators are consistent with HBeAg positive CHB;(3)Indeterminate phase related to IC:HBV DNA>2×10^(3)IU/mL or significant inflammation and fibrosis,while other indicators meet IC;and(4)Indeterminate phase related to HBeAg negative CHB:HBV DNA<2×10^(3)IU/mL or ALT 1-2 ULN,while the remaining indicators are in accordance with HBeAg negative CHB.In China,it is estimated that about 70 million people have chronic HBV infection,of which about 20-30 million are CHB patients.The percentage of liver cirrhosis and hepatocellular carcinoma caused by HBV infection is 77%and 84%,respectively.Chronic HBV infection brings severe burden to people’s life and health as well as the national health care system.Although existing guidelines recommend dynamic monitoring of serum ALT and HBV DNA levels and assessment of liver histology of indeterminate zone,whether to initiate antiviral therapy in these patients remains controversial.This review mainly introduces the clinical treatment status of CHB patients in IC and indeterminate phase related to IC,and the future prospects of antiviral treatment for these patients.