聚乙二醇干扰素对核苷(酸)类似物经治与未治的HBsAg低水平慢性乙型肝炎患者48周疗效比较

摘要/Abstract

摘要： 目的比较聚乙二醇干扰素α(PegIFNα)对核苷(酸)类似物(NA)经治与未治HBsAg低水平慢性乙型肝炎(CHB)患者的疗效。方法纳入2018至2022年金陵医院就诊的CHB患者49例,患者的HBsAg＜5000 IU/mL 、HBV DNA＜10⁴ IU/mL。分为NP组(NA经治1年以上联合PegIFNα-2b)、P组(初治单用PegIFNα)、C组(未使用任何抗病毒药物)。比较3组患者基线、PegIFNα-2b治疗12周及48周的血清HBV DNA、HBsAg、抗HBs、HBeAg及肝脏生化指标。结果 NP组20例,P组17例,C组12例。NP、P、C组基线HBsAg分别为201.06(47.82~863.06)、184.15(50.79~386.17)、77.70(19.22~839.27)IU/mL,差异无统计学意义(P=0.58); NP、P及C组各有19例、15例、11例患者基线HBsAg水平<1500 IU/mL。48周末NP组、P组、C组的HBsAg清除例数分别为7、5、0例(P<0.017)。NP组HBsAg清除率稍高于P组,但差异无统计学意义(P>0.05)。治疗48周获得HBsAg清除的12例CHB患者基线HBsAg为79.71(6.10~206.59)IU/mL低于未获得者的202.09(115.73~9.81)IU/mL(H=226.00, P=0.01);且前者12周HBsAg为1.76(1.08~13.20)IU/mL亦低于后者的107.99(1.96~318.80)IU/mL(H=224.00,P=0.02)。这12例中基线HBsAg水平最高为484.64 IU/mL。NP组基线血清HBV DNA均<50 IU/mL;P组及C组HBV DNA水平差异无统计学意义(2.66±0.61)lgIU/mL比(2.78±0.71)lgIU/mL(t=-0.51, P=0.62)。48周后,P组HBV DNA 均＜50 IU/mL,C组仅1例患者HBV DNA＜50 IU/mL (P<0.01)。NP组有4例患者HBeAg弱阳性(分别为4.04、4.05、2.92和 1.52 S/CO),48周时有1例HBeAg阴转;P组及C组HBeAg均阴性。结论在NA经治基础上加用PegIFNα-2b治疗CHB与单用PegIFNα-2b治疗48周时的HBsAg清除率相近,但前者更易获得HBsAg清除。基线HBsAg水平越低,PegIFNα-2b治疗后越易获得HBsAg清除,尤其基线HBsAg<500 IU/mL者。

关键词: HBsAg清除, 功能性治愈, 核苷(酸)类似物, 聚乙二醇干扰素, 单用, 联合使用

Abstract: Objective This is a side by side comparative study (SSS) on the efficiency of functional cure (HBsAg clearance) by pegylated interferon alpha (PegIFNα) treatment between nucleos(t)ide analogue (NA)-treated and NA treatment-naive chronic hepatitis B (CHB) patients with low baseline HBsAg levels, and explored the related factors for HBsAg clearance. Methods Forty-nine CHB patients with serum HBsAg<5000 IU/mL (especially<1500 IU/mL) and HBV DNA<10⁴ IU/mL collected from 2018 to 2022 were divided into three groups, including group NP (NA treated-patients for more than one year in combination with PegIFNα-2b), group P (NA treatment-naïve patients with PegIFNα-2b monotherapy), and group C (patients without receiving any antiviral treatment). Serum HBV DNA, HBsAg, anti-HBs, HBeAg and liver function tests were measured and compared at baseline, week 12 and week 48. Results Twenty, seventeen and twelve patients were distributed into group NP, group P and group C respectively. The baseline HBsAg levels had no significant difference among the three groups (median, interquartile range: 201.06, 47.82~863.06 vs 184.15, 50.79~386.17 vs 77.70, 19.22~839.27, respectively, P=0.58). There were 19, 15 and 11 patients with baseline HBsAg<1500 IU/mL in group NP, P and C, respectively. After 48 weeks PegIFNα-2b therapy, a significant higher HBsAg clearance rate was observed in patients of NP and P groups than that of C group (35.00% vs 29.41% vs 0.00%, P<0.017). A tendency of higher HBsAg clearance rate was found in patients of NP group compared with that of P group (P>0.05). All the 12 patients who achieved HBsAg clearance had significant lower baseline HBsAg level (79.71, 6.10~206.59) than that of patients without HBsAg clearance (202.09, 115.73~9.81, H=224.00, P=0.02). They also had lower HBsAg levels at week 12 (1.76, 1.08~13.20 vs 107.99, H=224.00, P=0.02). Among the 12 patients who achieved HBsAg clearance, the highest baseline HBsAg level was 484.64 IU/mL. The Baseline level of serum HBV DNA (log10) in group NP were all <50 IU/mL, while the levels were 2.66±0.61 IU/mL and 2.78±0.71 IU/mL in group P and C, respectively (t=-0.51, P=0.62). At week 48, serum HBV DNA level in all of the 17 patients in group P was <50 IU/mL; however, only one patient in group C had HBV DNA<50 IU/mL (P<0.01). Four patients in group NP were HBeAg-positive (4.04, 4.05, 2.92 and 1.52 S/CO) at baseline. Only one of them had serum HBeAg-reversion at week 48. All of the patients in group P and C were HBeAg-negative. Conclusion Patients with PegIFNα-2b added on continuous NA treatment had a similar HBsAg clearance rate as that of patients with PegIFNα-2b monotherapy, but the former seemed to have higher HBsAg clearance potential. The lower the baseline HBsAg, the greater the likelihood of “functional cure” achieved by PegIFNα-2b treatment, especially when a baseline level of HBsAg was less than 500 IU/mL in both sides with or without NA treatment.

Key words: HBsAg clearance, functional cure, neucleoside/neucleotide (NA), pegylated interferon (PegIFN), monotherapy, combination therapy

郝坤艳, 陈宇星, 汪文洋, 朱浩, 沈敏, 阳文新, 于乐成. 聚乙二醇干扰素对核苷(酸)类似物经治与未治的HBsAg低水平慢性乙型肝炎患者48周疗效比较[J]. 肝脏, 2024, 29(6): 635-640.

HAO Kun-yan, CHEN Yu-xing, WANG Wen-yang, ZHU Hao, SHEN Min, YANG Wen-xin, YU Yue-cheng. A side-by-side comparative study on the efficacy of HBsAg clearance by PegIFN therapy for 48 weeks on NA-treated and treatment naive CHB patients with low baseline HBsAg levels[J]. Chinese Hepatolgy, 2024, 29(6): 635-640.

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