核苷(酸)类似物及干扰素治疗对慢性HBV感染者远期肝癌和死亡风险的影响

Long-term effect of nucleoside(tide) analogues and interferon treatment on hepatocellular carcinoma occurrence and death in chronic HBV-infected patients

目的观察核苷(酸)类似物(NAs)和α干扰素(IFN-α)抗病毒治疗对慢性乙型肝炎(CHB)和代偿期肝硬化(LC)患者远期发生肝细胞癌(HCC)及死亡风险的影响。方法采用回顾性-前瞻性双向队列研究设计,自2008年1月起,对1998年8月至2007年12月间住院的慢性HBV感染者通过回顾性调查建立研究队列,并随访至2013年5月。共2 035例患者纳入队列研究,其中NAs治疗组380例,IFN-α治疗组153例,未治疗(对照)组1 502例。结果 IFN-α治疗组中位随访时间10.08(IQR:7.96~11.67)年,HCC发生率为2.70/1 000人年;NAs治疗组中位随访时间7.58(IQR:6.08~9.67)年,HCC发生率为6.76/1 000人年;对照组中位随访时间9.2(IQR:7.0~11.33)年,HCC发生率为13.02/1 000人年。在CHB患者中,IFN-α治疗组的HCC累积发生率显著低于对照组(P=0.008)和NAs治疗<5年的患者(P=0.039),其累积肝病相关病死率亦显著低于对照组(P=0.001)和NAs治疗<5年(P=0.007)的患者;NAs治疗≥5年患者的累积肝病相关病死率显著低于对照组(P=0.019)和NAs治疗<5年的患者(P=0.034)。在基线代偿期LC患者中,NAs治疗≥5年的患者HCC累积发生率显著低于对照组(P=0.028)及NAs治疗<5年患者(P=0.031);同时其累积肝病死亡率亦显著低于对照组(P=0.001)及NAs治疗<5年患者(P=0.017)。结论 IFN-α治疗能显著降低CHB患者远期发生HCC和死亡的风险,而NAs长期治疗可以减少CHB患者的死亡风险,并显著降低代偿性肝硬化患者HCC的发生风险及死亡率。

Objective To investigate the long-term effect of nucleos(t)ide analogues(NAs)and interferon-alpha(IFN-α)treatment on hepatocellular carcinoma(HCC)occurrence and mortality in patients with chronic hepatitis B(CHB)and compensated liver cirrhosis(LC)patients.Methods CHB and compensated LC patients admitted in our hospital from August 1998 to December 2007 were enrolled for the clinical cohort in January 2008,and followed up untill May 2013.Results A total of 2 035 cases were enrolled in the cohort,including 380 NAs-treated patients,153 IFN-treated patients and 1 502 non-antiviral treated cases(control group).Median follow-up period of IFN-treated group,NAs-treated group and control group was 10.08 years(IQR:7.96-11.67 years),7.58 years(IQR:6.08-9.67 years)and 9.2 years(IQR:7.0-11.33 years),respectively.Incidence of HCC among the three groups were 2.70/1 000 person-years,6.76/1 000person-years and 13.02/1 000 person-years,respectively.In IFN-treated group,the cumulative incidence of HCC and cumulative liver-specific death were both significantly lower than those in control group and patients treated with NAs for less than 5 years.In CHB patients treated with NAs for more than 5 years,the cumulative liver-specific mortality was significantly lower than that in control group(P=0.019)and short-term(<5 years)NAs-treated patients(P=0.034).In the compensated LC patients treated with long-term(≥ 5 years)NAs,the cumulative incidence of HCC and cumulative liver-specific mortality were lower than those in control group and short-term(<5 years)NAs-treated group.ConclusionIFN-treatment can significantly reduce the risk of HCC and liver-specific mortality in CHB Patients.Long-term NAs treatment(≥ 5 years)can not only prevent the occurrence of HCC in compensated LC patients,but also improve the survival in both CHB and compensated LC patients.