Serum hepatitis B virus RNA levels as a predictor of HBeAg seroconversion during treatment with peginterferon alfa-2a

Abstract

Background Hepatitis B e antigen (HBeAg) seroconversion represents an endpoint of treatment of chronic hepatitis B virus (HBV) infections. Methods We have studied whether levels of serum hepatitis B virus ribonucleic acid (HBV RNA) during pegylated interferon alfa-2a treatment might be helpful for predicting HBeAg seroconversion. 61 HBeAg-positive chronic hepatitis B (CHB) patients treated with pegylated interferon alfa-2a alone or in combination with adefovir (10 mg/day) for 48 weeks were included in this retrospective analysis. Response was defined as HBeAg seroconversion at 24 weeks posttreatment. Receiver operating characteristic analyses were used to identify baseline and on-treatment HBV RNA levels associated with response. Results Twenty-two of 61 (36.1%) patients achieved a response. Baseline HBV RNA levels were lower in responders than in nonresponders (4.55 ± 1.19 and 5.90 ± 1.13 copies/mL, respectively, P = 0.001). Baseline HBV RNA cut off level (200,000 copies/mL) provided a positive predictive value (PPV) of 56.0% and a negative predictive value (NPV) of 77.8%. HBV RNA level (3000 copies/mL) at week 12 provide a PPV of 75.0% and a NPV of 82.8%. Moreover, HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in patients with HBV RNA ≤ 200,000 copies/mL at baseline and HBV RNA ≤ 3000 copies/mL at week 12 (92.9%) versus others (12.5%) (All P < 0.05). Conclusions In Conclusions, serum HBV RNA levels may serve as a novel tool for prediction of HBeAg seroconversion during therapy with pegylated interferon alfa-2a in HBeAg-positive CHB patients. Electronic supplementary material The online version of this article (10.1186/s12985-019-1152-6) contains supplementary material, which is available to authorized users.

Serum HBV RNA Correlated with Intrahepatic cccDNA More Strongly than other HBV Markers During Peg-Interferon Treatment

“…In previous studies, both serum HBV RNA and HBcrAg were reported to be potential surrogate biomarkers of cccDNA in predicting the outcomes of peg-IFN or NAs treatments [4,20,21]. The correlation of cccDNA with HBV RNA has also been studied before and after nucleos(t)ide analog treatment [5,21,22].…”

“…Nowadays, the approved agents for the treatment of chronic HBV infections mainly belong to two classes: pegylated interferon (peg-IFN) and nucleotide/nucleoside analogs (NAs) [3]. Among these agents, peg-IFN, which has the effects of suppressing HBV replication and immunomodulation, is still widely used in the clinic as the rst-line therapeutic option for patients with HBeAg-positive chronic hepatitis B (CHB) [4].…”

“…Recently, due to being transcribed from cccDNA, serum HBV RNA has also been reported as a potential surrogate marker for re ecting the activity of intrahepatic cccDNA in CHB patients, as well as during NAs therapy [12][13][14]. Serum HBV RNA was also identi ed as a good predictor of HBeAg seroconversion in HBeAg-positive patients during therapy with peg-IFN [4]. In addition, a mouse model experiment revealed that HBV RNA correlated positively with cccDNA before treatment, whereas no correlation between them after 6 weeks of peg-IFN therapy [12].…”

Comparison of Serum Hepatitis B Virus RNA Levels and Quasispecies Evolution Patterns between Entecavir and Pegylated-Interferon Mono-treatment in Chronic Hepatitis B Patients

“…Luo et al reported that serum HBV RNA levels could predict HBeAg seroconversion during ETV treatment, but their sample size was relatively small (22). Jia et al found that serum HBV RNA levels might be helpful for predicting HBeAg seroconversion in patients treated with Peg-IFN alone or in combination with adefovir (23). In the present study, we expanded the sample size and compared the prediction value of serum HBV RNA between ETV and Peg-IFN mono-treatment.…”

Role of Biomarkers in Guiding Cure of Viral Hepatitis B

“…In several small studies, low HBV RNA levels at baseline and during therapy predicted HBeAg seroconversion. 77,89 Recently, data have emerged regarding a potential role of HBV RNA in future HBV treatments. In a phase I study, RO7049389, a core protein allosteric modulator resulting in formation of aberrant core protein aggregates, was associated with a median HBV RNA decline from baseline of 1.6 and 2.3 log copies/mL in all the 14 untreated CHB patients receiving either the 200 or 400 mg dose.…”