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

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.

Figure 1

Kinetics of HBV-DNA, HBsAg and ALT across Direct Acting Antivirals (DAAs) treatment is reported for the 15 patients with concomitant HBeAg Negative Infection (ENI). None of these patients received antiviral therapy for HBV. Data are represented as mean values (points) with Standard Deviation (dashed lines). The baseline (BL) values were compared to the other time points (−12 w: 12 weeks before BL; 4 w: week 4 of DAAs therapy; EOT: End of Therapy; FU12, FU24 and FU48: Follow Up week 12, 24 and 48) using the Student’s t-test for means of paired data (p values of the most relevant comparisons are showed on the top of each graph; ns: not significant).

Figure 2

Correlation between maximum HBsAg decline during DAAs therapy (◊) and maximum increase of HBV-DNA in the same period. Higher increase of Log HBV-DNA correlates with lower decline of Log HBsAg in 10/15 patients with HBeAg Negative Infection and measurable HBV-DNA levels; in 5 patients without measurable HBV-DNA levels during therapy the maximum HBV-DNA increase was not computable.

Figure 3

Kinetics of HBV-DNA, HBsAg and ALT across Direct Acting Antivirals (DAAs) treatment is reported for the 8 patients with concomitant HBeAg Negative Chronic Hepatitis B (CHB). All these patients were on Nucleoside Analogs (NAs) therapy before starting DAAs and continued treatment; HBV-DNA remained undetectable in all time points. Data are represented as mean values (points) with Standard Deviation (dashed lines). The baseline (BL) values were compared to the other time points (−12 w: 12 weeks before BL; 4w: week 4 of DAAs therapy; EOT: End of Therapy; FU12, FU24 and FU48: Follow Up week 12, 24 and 48) using the Student’s t-test for means of paired data (p values of the most relevant comparisons for HBsAg changes are shown on the top of the graph; ns: not significant).

Figure 4

Maximum HBsAg decline observed during DAAs treatment in 22 patients. SOF: Sofosbuvir (full columns); NO SOF: No Sofosbuvir (columns with stripes). Columns without color fill represent patients of female gender. * indicates CHB patients on NAs treatment.