Different Kinetics of HBV-DNA and HBsAg in HCV Coinfected Patients during DAAs Therapy

Piero Colombatto; Elena Palmisano; Gabriele Ricco; Daniela Cavallone; Filippo Oliveri; Barbara Coco; Antonio Salvati; Veronica Romagnoli; Lidia Surace; Marialinda Vatteroni; Mauro Pistello; Agostino Virdis; Ferruccio Bonino; Maurizia Rossana Brunetto

doi:10.3390/jcm11051406

Different Kinetics of HBV-DNA and HBsAg in HCV Coinfected Patients during DAAs Therapy

J Clin Med. 2022 Mar 4;11(5):1406. doi: 10.3390/jcm11051406.

Authors

Affiliations

¹ Hepatology Unit, Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy.
² Internal Medicine Unit, University of Pisa, 56126 Pisa, Italy.
³ Virology Unit, University Hospital of Pisa, 56124 Pisa, Italy.
⁴ Institute of Biostructure and Bioimaging, National Research Council, 80145 Naples, Italy.
⁵ Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.

Abstract

Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) may induce hepatitis B virus (HBV) reactivations in co-infected patients, whose dynamics and outcomes could depend on the phase of HBV infection. We investigated HBsAg and HBV-DNA kinetics in fifteen untreated HBeAg Negative Infection (ENI) (4F-11M, 62.1y) and eight Nucleos(t)ide Analogs (NAs) treated Chronic Hepatitis B (CHB) (3F-6M, 54.8y) with HCV co-infection, receiving DAAs-regimens including Sofosbuvir (13) or not (10). All achieved a sustained virologic response (SVR) and normalized alanine-aminotransferase (ALT). At the direct acting antivirals’ (DAAs) baseline (BL), the HBV-DNA was undetectable (<6 IU/mL) in eight ENI and all CHB, the mean Log-HBsAg was lower in ENI than CHB (0.88 vs. 2.42, p = 0.035). During DAAs, HBV-DNA increased in untreated ENI by >1 Log in five and became detectable in two. Accordingly, mean BL Log-HBV-DNA (0.89) increased at week-4 (1.78; p = 0.100) and at the end of therapy (1.57; p = 0.104). Mean Log-HBsAg decreased at week-4 in ENI (from 0.88 to 0.55; p = 0.020) and CHB (from 2.42 to 2.15; p = 0.015). After DAAs, the HBsAg returned to pre-treatment levels in CHB, but not in ENI (six cleared HBsAg). Female gender and SOF were associated with a greater HBsAg decline. In conclusion, HBV reactivations during DAAs in HCV co-infected ENI caused moderate increases of HBV-DNA without ALT elevations. The concomitant HBsAg decline, although significant, did not modify individual pre-treatment profiles.

Keywords: HBeAg negative infection; chronic hepatitis B; co-infection; direct acting antivirals; hepatitis B surface antigen; hepatitis B virus; hepatitis C virus; interferon γ-induced protein 10; kinetics; reactivation.