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

Abstract

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

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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