Published online Nov 27, 2020. doi: 10.4254/wjh.v12.i11.1076
Peer-review started: June 2, 2020
First decision: June 15, 2020
Revised: June 23, 2020
Accepted: September 4, 2020
Article in press: September 4, 2020
Published online: November 27, 2020
Processing time: 174 Days and 20.9 Hours
Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues (NAs) rarely achieve hepatitis B surface antigen (HBsAg) loss.
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.
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.
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.
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.
Core Tip: The functional cure of chronic hepatitis B defined as the loss of the hepatitis B surface antigen is the optimal end-point with the currently available therapies. However, it is rarely achieved in hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues (NAs). In the present study, we report that the addition of pegylated interferon (Peg-IFN) to NAs during forty-eight weeks caused a greater and faster decrease of hepatitis B surface antigen levels compared to NA monotherapy. No changes in hepatitis B core-related antigen were observed. However, the low applicability and poor tolerance of Peg-IFN make difficult its use in clinical practice.