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Clinical Trial
. 2020 Nov 27;12(11):1076-1088.
doi: 10.4254/wjh.v12.i11.1076.

Hepatitis B surface antigen and hepatitis B core-related antigen kinetics after adding pegylated-interferon to nucleos(t)ids analogues in hepatitis B e antigen-negative patients

Teresa Broquetas  1 , Montserrat Garcia-Retortillo  1 , Miquel Micó  2 , Lidia Canillas  1 , Marc Puigvehí  1 , Nuria Cañete  1 , Susana Coll  1 , Ana Viu  1 , Juan Jose Hernandez  2 , Xavier Bessa  1 , José A Carrión  1
Affiliations
Clinical Trial

Hepatitis B surface antigen and hepatitis B core-related antigen kinetics after adding pegylated-interferon to nucleos(t)ids analogues in hepatitis B e antigen-negative patients

Teresa Broquetas et al. World J Hepatol. .

Abstract

Background: Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues (NAs) rarely achieve hepatitis B surface antigen (HBsAg) loss.

Aim: To evaluate if the addition of pegylated interferon (Peg-IFN) could decrease HBsAg and hepatitis B core-related antigen (HBcrAg) levels and increase HBsAg loss rate in patients under NAs therapy.

Methods: Prospective, non-randomized, open-label trial evaluating the combination of Peg-IFN 180 µg/week plus NAs during forty-eight weeks vs NAs in monotherapy. Hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients of a tertiary hospital, under NAs therapy for at least 2 years and with undetectable viral load, were eligible. Patients with hepatitis C virus, hepatitis D virus or human immunodeficiency virus co-infection and liver transplanted patients were excluded. HBsAg and HBcrAg levels (log10 U/mL) were measured at baseline and during ninety-six weeks. HBsAg loss rate was evaluated in both groups. Adverse events were recorded in both groups. The kinetic of HBsAg for each treatment group was evaluated from baseline to weeks 24 and 48 by the slope of the HBsAg decline (log10 IU/mL/week) using a linear regression model.

Results: Sixty-five patients were enrolled, 61% receiving tenofovir and 33% entecavir. Thirty-six (55%) were included in Peg-IFN-NA group and 29 (44%) in NA group. After matching by age and treatment duration, baseline HBsAg levels were comparable between groups (3.1 vs 3.2) (P = 0.25). HBsAg levels at weeks 24, 48 and 96 declined in Peg-IFN-NA group (-0.26, -0.40 and -0.44) and remained stable in NA group (-0.10, -0.10 and -0.10) (P < 0.05). The slope of HBsAg decline in Peg-IFN-NA group (-0.02) was higher than in NA group (-0.00) (P = 0.015). HBcrAg levels did not change. Eight (22%) patients discontinued Peg-IFN due to adverse events. The HBsAg loss was achieved in 3 (8.3%) patients of the Peg-IFN-NA group and 0 (0%) of the NA group.

Conclusion: The addition of Peg-IFN to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy. Side effects of Peg-IFN can limit its use in clinical practice.

Keywords: Chronic hepatitis B; Hepatitis B core-related antigen; Hepatitis B e antigen-negative; Hepatitis B surface antigen; Nucleos(t)ids analogues; Pegylated-interferon.

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Conflict of interest statement

Conflict-of-interest statement: Authors declare no conflict-of-interest.

Figures

Figure 1
Figure 1
Flowchart of patients and study design. HBeAg: Hepatitis B e antigen; CHB: Chronic hepatitis B; Peg-IFN: Pegylated interferon; NAs: Nucleos(t)ids analogues.
Figure 2
Figure 2
Hepatitis B surface antigen delta (Δ) (log10 IU/mL) at wk 24, 48 and 96 according to treatment group. Peg-IFN: Pegylated interferon; NA: Nucleos(t)ids analogue.
Figure 3
Figure 3
Hepatitis B surface antigen delta (Δ) (log10 IU/mL) according to interleukin 28B polymorphism and treatment group. A: Hepatitis B surface antigen delta (Δ) in interleukin 28B CC patients (n = 22); B: Hepatitis B surface antigen delta (Δ) in interleukin 28B CT/TT patients (n = 26). NS: Not significant; NA: Nucleos(t)ids analogue; Peg-IFN: Pegylated interferon.
Figure 4
Figure 4
Linear regression model of hepatitis B surface antigen levels according to treatment group. NA: Nucleos(t)ids analogue; Peg-IFN: Pegylated interferon; LR: Linear regression.
Figure 5
Figure 5
Rate of patients with low hepatitis B surface antigen levels (Hepatitis B surface antigen < 100 IU/mL and 100-1000 IU/mL) according to treatment group. A: NA group; B: Peg-IFN-NA group. NS: Not significant; NA: Nucleos(t)ids analogue; Peg-IFN: Pegylated interferon.
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