Introduction: Stopping nucleo(s)tide analogue (NA) treatment in selected non-cirrhotic Chronic Hepatitis B (CHB) often leads to virus-induced flares, which may result to life-threatening liver failure. Aim: to identify predictive parameters of off-NAs response at the end of treatment and their association with HBsAg loss or HBsAg < 100IU/ml, for a safe discontinuation of treatment. Materials and Methods: 38 non-cirrhotic CHB patients, with complete virological suppression ( > 4 years), were prospectively monitored after suspending NA treatment for a median (IQR) time of 16 (10-19) months. Plasma samples at suspension date (baseline, BL) were collected and used to quantify serum HBV-DNA by highly sensitive droplet digital PCR (ddPCR). HBsAg was quantified by the ARCHITECT HBsAg assay at BL, every 2 weeks from suspension in the first month, followed by every month until the sixth month, then every 3 months. Results: At BL, 28 (73.7%) pts had detectable serum HBV-DNA (median[ IQR] 5[2-11] IU/mL), while 10 (26.3%) were completely negative to HBV-DNA. After NA suspension, 7 (18.4%) achieved HBsAg < 100IU/mL (median [IQR]: 43 [35-53]IU/ml) and 8 (21.1%) lost HBsAg at last follow-up. Patients achieving HBsAg loss had lower HBsAg levels at BL (140 [70-480]IU/ml with vs 1162 [439- 3135] without HBsAg loss, p = 0.014). The negativity to HBV-DNA by ddPCR at BL strongly correlated with the achievement of HBsAg < 100IU/mL or HBsAg loss after NA suspension (70% [7/10] with vs 28.6% [8/28] without negative BL HBV-DNA; OR [95%CI]: 5.8 [1.3- 23.6], p = 0.03).The combination of HBsAg < 500IU/mL + negativity HBV-DNA by ddPCR at BL was the best predictor for achieving HBsAg < 100IU/mL or HBsAg loss (85.7% with vs 27.6% without this combination; OR [95%CI]: 15.8 (1.6-152.2; p = 0.008; PPV = 86%; NPV = 72%). Conclusions: Residual HBV replicative activity at NA suspension, measured by highly sensitive assays, provides an added value in identifying patients more prone to achieve HBV functional cure.
Serum HBsAg and ddPCR HBV-DNA as predictive parameters of HBsAg loss after nucleo(s)tide analogue (NA) treatment discontinuation in non-cirrhotic patients with Chronic Hepatitis B / Guerra, A. F.; Tomassoli, G.; Piermatteo, L.; D’Anna, S.; Salpini, R.; Svicher, V.; Abbati, G.; Pietrangelo, A.; Ventura, P.. - In: DIGESTIVE AND LIVER DISEASE. - ISSN 1590-8658. - 54:Supplement 1(2022), p. 34. (Intervento presentato al convegno 54th A.I.S.F. - Italian Association for the Study of the Liver - Annual Meeting 2022 tenutosi a Roma nel 24-25 Marzo 2022) [10.1016/j.dld.2022.01.065].