Highly significant differences in HBsAg kinetics among patients with two types of hepatitis B flare, with and without retreatment

Background Off-therapy hepatitis flare may be detrimental or, conversely, facilitate hepatitis B surface antigen (HBsAg) decline. Retreatment decisions are crucial. Methods HBsAg was quantified before and during flares, at peak/retreatment start and at Months 6 and 12 in 336 entecavir/tenofovir-retreated and 105 non-retreated hepatitis B e antigen (HBeAg)-negative patients. Increasing HBsAg during ALT flare defined a ‘virus-dominating flare’ and decreasing HBsAg a ‘host-dominating flare’. Results Two hundred and eighty-eight retreated patients with a virus-dominating flare showed greater 1 year HBsAg decline (−1.0 versus −0.01 log10 IU/mL; P < 0.0001), more frequent rapid decline (69.8% versus 8.3%; P < 0001) and higher 3 year incidence of HBsAg < 100 IU/mL (32% versus 12%; P = 0.026) than 48 patients with a host-dominating flare, of whom 16 (33.3%) showed 3.8-fold (2 to 52-fold) HBsAg rebound on retreatment (versus 2/288; P < 0.0001). Compared with non-retreated controls, 1 year HBsAg decline was greater (−1.0 versus −0.47 log10 IU/mL; P < 0.0001) and faster (69.8% versus 42.5%; P < 0.0001) in patients with a virus-dominating flare, whereas 1 year HBsAg decline (−0.01 versus −0.16 log10 IU/mL) and 3 year HBsAg loss rate (0% versus 21%; P = 0.009) were lower in patients with a host-dominating flare. Conclusions Entecavir/tenofovir retreatment effectively decreases HBsAg level in patients with a virus-dominating flare but is ineffective/worse in patients with a host-dominating flare. These results support the use of combined HBsAg/ALT kinetics for the decision to retreat patients with a virus-dominating flare and withhold retreatment for patients with a host-dominating flare.

Hepatitis B Viral Markers in the Human Milk of HBsAg-Positive Mothers: An Observational Study

Background: Quantification of viral antigens and viral loads in human milk samples from mothers infected with hepatitis B virus is largely unknown. Research Aim: The aim of the study was to quantitatively measure the levels of viral antigens and deoxyribonucleic acid of hepatitis B virus in human milk from mothers infected with hepatitis B virus. Methods: Fifty-five pairs of milk and serum samples from mothers with positive hepatitis B surface antigen, including 11 hepatitis B e antigen positive, were quantitatively tested to measure viral antigens by microparticle enzyme immunoassay and viral loads by real-time polymerase chain reaction assay. Results: The median level of hepatitis B surface antigen in the human milk samples of mothers with positive or negative hepatitis B e antigen was each lower than that in the sera, respectively (1.10 vs. 4.32 log10 IU/ml, t = 10.693, p < .001; -0.77 vs. 2.53 log10 IU/ml, t = -25.135, p < .001). The titers of hepatitis B surface antigen or hepatitis B e antigen in the human milk samples were each correlated with that in maternal serum. The detectable level of deoxyribonucleic acid of hepatitis B virus in human milk ranged from 1.42–5.27 log10 IU/ml, whereas that in maternal sera was 1.44–8.66 log10 IU/ml. The viral level in human milk was not correlated with that in maternal circulation. Conclusion: The present study data illustrate the relatively low titers of viral markers in the milk of mothers with positive hepatitis B surface antigen.

Serum miR-192-5p Levels Predict the Efficacy of Pegylated Interferon Therapy for Chronic Hepatitis B

We examined the association between serum miRNA (-192-5p, -122-3p, -320a and − 6126-5p) levels and the efficacy of pegylated interferon (Peg-IFN) monotherapy for chronic hepatitis B (CHB) patients. We enrolled 61 CHB patients treated with Peg-IFNα-2a weekly for 48 weeks, of whom 12 had a virological response (VR) and 49 did not VR (non-VR). A VR was defined as HBV DNA < 2,000 IU/ml, hepatitis B e antigen (HBeAg)-negative, and nucleos(t)ide analogue free at 48 weeks after the end of treatment. The non-VR group showed a significantly higher HBeAg-positivity rate, ALT, HBV DNA, and serum miR-192-5p levels at baseline (P = 0.024, P = 0.020, P = 0.007, P = 0.021, respectively). Serum miR-192-5p levels at 24 weeks after the start of treatment were also significantly higher in the non-VR than the VR group (P = 0.011). Multivariate logistic regression analysis for predicting VR showed that miR-192-5p level at baseline was an independent factor. Serum miR-192-5p levels were significantly correlated with the levels of HBV DNA, hepatitis B core-related antigen, and hepatitis B surface antigen (r = 0.484, 0.384 and 0.759, respectively). The serum miR-192-5p level was useful as a biomarker for the therapeutic efficacy of Peg-IFN in CHB treatment.