Prediction for HBsAg seroconversion in children with chronic hepatitis B

Background To establish a prediction of HBsAg seroconversion in children with chronic hepatitis B (CHB), so as to help clinicians to choose therapeutic strategy. Methods A total of 63 children with HBeAg-positive CHB aged 1 to 17 years, who admitted to the fifth medical center of Chinese PLA general hospital and treated with interferon α (IFNα) 48 weeks were enrolled, the clinical data were measured. Based on the results of HBsAg seroconversion (HBsAg < 0.05 IU/mL and anti-HBsAg > 10 IU/L) at week 48, the patients were divided into HBsAg seroconversion (S) group and non-HBsAg seroconversion (NS) group. Multivariate COX regression was used to identify the impact factors associated with HBsAg seroconversion. A novel prediction index was established and the area under the receiver operating characteristic curve (AUROC) was used to assess the prediction for HBsAg seroconversion. Results The 63 patients were divided into S group (20.6%, 13/63) and NS group (79.4%, 50/63). Univariate and multivariate analysis identified age, baseline intrahepatic cccDNA and serum HBsAg levels were independent impact factors for HBsAg seroconversion. Intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.464, p = 0.000). AUROC of HBV cccDNA was 0.83 (95% CI 0.71 to 0.95) and AUROC of baseline HBsAg was 0.77 (95% CI 0.61 to 0.92). Intrahepatic cccDNA ≤ 0.08 log10 copies/106 cell is regarded as cutoff value, the positive predictive value(PPV) and negative predictive value(NPV) for HBsAg seroconversion were 86.8% and 60.0%, respectively, with a sensitivity of 92.0% and specificity of 56.2%. HBsAg ≤ 3.68 log10 IU/mL is used as cut off value, the PPV and NPV for HBsAg seroconversion were 91.2% and 56.3%, respectively; the sensitivity and specificity was 86.0% of 69.2%, respectively. There was no statistical difference between them for predicting HBsAg seroconversion (p = 0.146). Conclusions HBsAg seroconversion can be predicted by the baseline serum HBsAg or intrahepatic cccDNA in children with CHB. Using the index, clinicians can choose more reasonable therapeutic strategy and reduce the waste of medical resources.

ETIOTROPIC THERAPY FOR DIFFERENT FORMS OF HEPATITIS B

Background. Currently, etiotropic therapy of hepatitis B in most cases is carried out using nucleot(s)ide analogues. The ultimate goal of the therapy depends on the period of its administration – in acute or chronic hepatitis. The influence of the molecular genetic profile of the hepatitis B virus on the effectiveness of therapy in both acute and chronic forms of the disease has not yet been established, which requires further research. Objective. To assess the possibilities of modern etiotropic therapy in acute and chronic forms of hepatitis B. Material and methods. The article analyzes the indicators of clinical, laboratory and instrumental data of patients who received etiotropic therapy with nucleot(s)ide analogues. Results. Etiotropic therapy resulted in a viral load decrease to an undetectable level in all patients regardless of the course of hepatitis B and infection with either a "mutant" or "wild" virus strain. In acute hepatitis B, HBV DNA was not detected in 100% of cases after 24 weeks of therapy, in HBsAg seroconversion - after 36 weeks; in chronic hepatitis B - after 36 weeks without HBsAg seroconversion. Six months after the completion of the treatment, the patients with chronic hepatitis B developed relapse in 89.7% of cases, but the viral load was less than 2000 IU / ml, and the severity of liver fibrosis was insignificant. In the rest of the cases, resumption of therapy was required. Conclusions. It was found that mutations of the hepatitis B virus do not affect the effectiveness of etiotropic therapy. The rate of viral load decrease correlates with the form of hepatitis B and is significantly higher in acute disease.

Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment

ObjectiveWe examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520.DesignThe present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4–9 4 weekly doses of MD ARC-520 and entecavir. Liver biopsies were performed in six patients. Intrahepatic and serum HBV DNA, HBV RNA and viral antigens were measured.ResultsAll patients had 28.9–30.4 months of follow-up after the last MD. All three hepatitis B e antigen (HBeAg)-positive patients had profound reductions in hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen and HBV RNA with two undergoing HBeAg seroconversion. One further achieved HBsAg seroconversion (anti-HBs level of 25.1 IU/L) and the remaining two had HBsAg reductions of −1.7 and −3.5 log IU/mL >30 months after MD. Among the five HBeAg-negative patients, four had modest HBsAg reduction >29 months after completion of MD and one achieved HBsAg seroconversion (anti-HBs level of 152.5 IU/L) and was negative for liver HBsAg staining. Entecavir was successfully stopped in this patient 12 months after HBsAg seroconversion. Temporally related alanine aminotransferase elevations preceded by HBsAg reductions were observed in three patients suggesting immune activation. HBcAg staining was negative in all six biopsied patients. Two patients with <10% HBsAg positive staining of hepatocytes had correspondingly low serum HBsAg levels of 1.5 and 11.5 IU/mL.ConclusionsMD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable.Trial registration numberNCT02065336.

B cells were related to HBsAg seroconversion in inactive HBsAg carriers following peginterferon therapy

Our recent study showed high rate of HBsAg seroconversion achieved in inactive HBsAg carriers (IHCs) treated with peginterferon (PEG-IFN). To better understand the immune-mediated component to the HBsAg seroconversion, we investigated the role of B cells in this study. A total of 44 IHCs were given 48 weeks of PEG-IFN. Fifteen cases achieve HBsAg seroconversion (R group), whereas 29 failed (NR group). The proportion of total B cells and plasma B cells were measured before and during treatment. We found that the proportion of total B cells and plasma B cells was no significant between R group and NR group at baseline, but significantly higher in R group than NR group during PEG-IFN treatment, even when the exact age-, sex-, and treatment period-match was made. In conclusion, we demonstrated the increase of total B cell and plasma B cells during PEG-IFN treatment favored HBsAg seroconversion for IHC, and B cells may play a role in HBV seroconversion.

Contribution of NK cells to HBsAg seroconversion in inactive HBsAg carriers following pegylated IFN therapy

Our recent study showed a high rate of HBsAg seroconversion in inactive HBsAg carriers (IHCs) treated with pegylated IFN (PEG-IFN). To understand the immune-mediated component of the HBsAg seroconversion better, this study investigated the role of NK cells. A total of 44 IHCs were given 48 wk of PEG-IFN. Fifteen cases achieved HBsAg seroconversion (R group), whereas 29 failed (NR group). The proportion and activity (CD107α and IFN-γ production) of NK cells were measured before and during treatment. We found that the proportion of NK cells in the R group was higher than in the NR group at baseline and during PEG-IFN treatment, even when patients were matched for age, sex and treatment period. IFN- γ secretion and CD107α expression from NK cells in cases who achieved HBsAg seroconversion were significantly higher than patients matched for age, sex, HBsAg and treatment period in the NR group at baseline and during PEG-IFN treatment. We also found that in HBsAg seroconversion cases, NK cells activity increased after PEG-IFN treatment, especially before HBsAg seroconversion. These effects were not found in non-responders. In conclusion, we demonstrated that the increase of NK cells accompanied by enhanced activity during PEG-IFN treatment favoured HBsAg seroconversion for IHC, and that NK cells may play a role in HBV seroconversion.

Long-term nucleoside analogue therapy can lead effective HBV DNA inhibition in patients with chronic HBV infection in immune tolerate phase

Background and Aims The efficacy and safety of long-term antiviral therapy with nucleoside analogues (NAs) for chronic hepatitis B (CHB) patients in immune tolerate (IT) phase is uncertain.We retrospectively evaluated the efficacy and safety of 61 CHB patients in IT phase receiving NAs therapy from 2013 through 2018. Methods We performed a retrospective study of CHB patients who had high HBV DNA, normal or minimum alanine aminotransferase (ALT), liver biopsy confirmed light necro-inflammation and received NAs therapy from 2012 through 2018.All patients received NAs at least 12 months. Patients on-treatment monitoring were in accordance with the roadmap concept and were followed after their treatment start date to the treatment end date (if any) or 6 years at least once every 6 months. The median follow-up time was 36(16; 52) months. We assessed the virological response (the proportions of patients with plasma HBV DNA loads less than the limit of quantification,100IU/ml) and serological endpoints (HBeAg loss and seroconcersion to anti-HBe, and HBsAg loss and seroconversion to anti-HBs). Safety and tolerability, including serious events, were regularly assessed. Results At 48 weeks on treatment, 55.6%(95%confidence interval(CI):37.0-70.0%) patients with CHB in IT phase achieved HBV DNA less than quantitative limit(<100IU/ml), and the accumulate proportion of patients who achieved HBV DNA less than quantitative limit was 76.7%(95%CI: 58-90.0%) and 95.8%(95%CI: 79-100%) at 96 weeks and ≥144weeks on treatment, respectively. The HBeAg loss or seroconversion rate in patients with CHB in IT phase on NAs treatment at 48, 96 and ≥144weeks was 2.7%(95%CI: 0-14.0%), 13.3% (95%CI: 4-31.0%) and 29.2%(95%CI: 13-51%), respectively. During the study only one patient achieved HBsAg seroconversion after 3years NAs therapy and only one patient experienced drug-related breakthrough during the study. Conclusion Patients with CHB in IT phase have relatively preferable safety and HBV DNA inhibition efficacy on long-term NAs treatment.

The efficiency of low-dose Hepatitis B Immunoglobulin plus nucleos(t)ide analogs in preventing post-transplant HBV recurrence

Background/aim: In this study, the efficiency of using low-dose HBIG plus antiviral treatment according to individual needs have been evaluated in post-transplant HBV patients. Material and methods: We retrospectively evaluated 179 patients who admitted between 2009-2014. Five thousand IU IV HBIG was given in anhepatic phase, and 400 IU/day IM HBIG was given in the post-transplant period. After HBsAg seroconversion 400 IU IM HBIG every two weeks as prophylaxis was continued. Results: Average follow-up period was 26 (2-65) months. Seventy patients had hepatocellular carcinoma (HCC). The HBV recurrence was 4.5% in the 1st year, and 5.8% in the 3rd year. The HBsAg became negative in 11 (2-63) days, and anti-HBs became positive in 9 (1-31) days. HBsAg positivity occurred in 6 patients during the follow-up period. Five of these patients were those who were transplanted due to HCC. In 5 of the HCC patients whose HBsAg became positive, tumor recurrence was observed after 0.3-9.9 months. HBsAg positivity was more frequently detected in patients with HCC (p=0.009). Conclusion: The HBV recurrence should be evaluated as a predictor of HCC recurrence in patients who were transplanted due to HCC.