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.

Occult HBV Infection in Patients Infected by HIV or HCV: Comparison between HBV-DNA and Two Assays for HBsAg

“…Those patients showed a higher rate of OBI compared to HIV-positive individuals ( Table 1 ) and a much higher frequency of HBV active infection, either OBI or overt (HBsAg-positive), compared to subjects with HIV (10.2% vs. 0.6%; p < 0.001). From a virological and clinical standpoint, in most cases, HCV/HBV coinfection appears to inhibit HBV replication, and accordingly, clearance of the HCV infection, either spontaneous or driven by treatment with IFN-based regimens or with DAAs, can be associated with HBV reactivations leading to hepatitis flares [ 21 ].…”

“…The spectrum and features of HBV Infection in patients with an active infection by HCV require attention since current data and evidence have shown a non-negligible incidence of HBV reactivation in patients with chronic hepatitis C when treatment with directly acting antivirals (DAAs) is started to eradicate HCV and during the follow-up period after treatment [ 9 , 21 , 22 ]. The spectrum of clinical manifestations associated with HBV reactivation is wide, ranging from laboratory abnormalities with minimal evidence of liver disease to life-threatening hepatitis that is more frequent in HBV-endemic areas.…”

“…However, quite interestingly, four subjects were confirmed positive for HBsAg with an undetectable HBV-DNA. This may depend on the different kinetics of and fluctuations in the two parameters [ 21 ], but a limitation of our study is that its cross-sectional nature did not allow us to ascertain the behavior of HBsAg and HBV-DNA over time. Our results suggest that monitoring HCV in patients coinfected by HBV using both HBV-DNA and HBsAg via highly sensitive assays shall be strongly recommended.…”

“…On the other side, finding four samples that were positive for HBsAg and negative for HBV-DNA suggests that the adoption of HBsAg assays with greater sensitivity may help to better define the pattern of HBV infection and will reduce the frequency of OBI. HBsAg and HBV-DNA have different kinetics both in untreated subjects and in patients treated with antivirals [ 9 , 12 , 21 , 24 ], and infectivity from samples positive for HBsAg and negative for HBV-DNA has been documented [ 25 ].…”

Insight on the hepatitis B virus and host immune mechanisms in the context of occult hepatitis

“…15 HCV coinfection was connected to much greater spontaneous HBsAg clearance rates than HBV infection alone, showing that the two viruses/viral proteins interact. 69 Another research, on the other hand, showed no substantial interactions between the two viruses in coinfected hepatocytes, showing that host responses play a crucial role in viral dominance in coinfected cells. 70 HBV promoters and enhancers are activated by the hepatitis B virus X protein (HBx).…”