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

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.

Circulating Type I Interferon Levels and COVID-19 Severity: A Systematic Review and Meta-Analysis

“…IFN-I is used to treat various diseases, including hepatitis C ( 45 , 46 ) and B ( 47 ), multiple myeloma ( 48 ), polycythemia Vera ( 49 ), and are also tested for the treatment of COVID-19. Studies carried out with inhaled or intramuscularly administered IFN-α2b have demonstrated that treatment can accelerate viral clearance and reduce circulating IL-6 and CRP levels ( 50 ), in addition to preventing disease progression ( 51 ).…”

On-therapy HBsAg kinetics can predict HBsAg loss after nucleos(t)ide analogues interruption in HBeAg-negative patients. The cup is half full and half empty

“…Thus, we consider that NA type should be considered for the monitoring after interruption. Another interesting point of our cohort was that 37% added-on Peg-IFN two years before EoT [17] . Patients with add-on Peg-IFN showed faster HBsAg decline despite no differences in HBsAg loss rate were found.…”

“…However, patients treated with TDF compared to those treated with ETV showed earlier VR (4 vs. 12 weeks; p < 0.001), SVR (12 vs. 30 weeks; p < 0.001) and CR (10 vs. 48 weeks; p = 0.14). In patients who had received Peg-IFN ( n = 19) [17] the add-on therapy was finished a median of 2.3 years before EoT and no differences in HBsAg loss rate were found (5.3 vs. 15.2%; p = ns). However, patients with add-on Peg-IFN showed faster ( −0.10 vs. −0.05 log10 IU/mL/year; p = 0.02) and greater HBsAg decline ( −0.74 vs. −0.46 log10IU/mL; p = 0.056).…”

“…The assay ranged from 0.05 to 52,0 0 0 IU/mL. In highly concentrated samples above the upper limit, the value of manual dilution was multiplied by the dilution factor [17] . In patients who started NA treatment before July 2014, the HBsAg was analysed in cryopreserved serum samples part of the private collection (C.0 0 0 0956) of the IMIM (Hospital del Mar Medical Research Institute) and were extracted in fasting conditions and centrifuged at 30 0 0 rpm before preservation at −30 °C [5] .…”

“…From January 1999 to December 2017, 148 CHB HBeAg-negative patiens started NA treatment in our hospital. Twenty-seven (18.2%) were lost during follow-up and 9 (6.2%) lost the HBsAg during therapy (6 under NA treatment [5] and 3 under pegylated interferon [peg-IFN] add-on strategy [17] ). Therefore, 112 patients were evaluated, and sixty were excluded: 20 ( 1 .…”