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Introduction and objective: The aim of the present study was to investigate the significance of serum HBsAg levels in treatment cessation of nucleoside analogues (NAs) in patients with chronic hepatitis B (CHB) infection. Methods: In 158 CHB patients with long-term NAs treatment, 74 patients were in HBeAg negative and had a HBsAg level 1000 IU/mL relapsed. HBsAg of patients with a sustained response decreased slowly. In contrast, HBsAg levels increased gradually in relapsed patients, and the increase of HBsAg was precedent to relapses of HBV DNA and ALT. Multivariate analysis suggested that only HBsAg level showed a close correlation with HBV DNA relapses. ROC curve analysis suggested that the increase of HBsAg level in the 3rd and 6th month after NAs cessation had a great predictive value for relapses. Conclusion: Monitoring of base line HBsAg level can predict outcomes of NAs cessation in HBeAg-negative chronic hepatitis B. HBsAg

Molecular epidemiologic studies have indicated the possible existence of mixed infection of different hepatitis B virus (HBV) genotypes in chronic hepatitis B (CH-B) carriers, but the effect of dual HBV genotype B and C infection on the efficacy of lamivudine therapy remains unclear. We report four CH-B patients with dual HBV genotype B and C infection and acute exacerbation who received lamivudine monotherapy for about 18 months. None of them had achieved a sustained response at the end of the 18-month trial of treatment.

Background and Aims: Previous studies suggested spontaneous seroclearance of hepatitis B surface antigen (HBsAg) was still associated with an increased risk of hepatocellular carcinoma (HCC), in patients ⩾50years of age. This study aimed to evaluate the risk of HCC after HBsAg seroclearance and the impact of gender on HCC., Methods: All chronic hepatitis B patients under medical care in Hospital Authority, Hong Kong who had cleared HBsAg between January 2000 and August 2016 were identified. The age of the patient at HBsAg seroclearance, gender, and subsequent development of HCC were analyzed., Results: A total of 4,568 patients with HBsAg seroclearance were identified; 793 (17.4%) were treated by nucleos(t)ide analogues and 60 (1.3%) had received interferon treatment. At a median (interquartile range) follow-up of 3.4 (1.5-5.0)years, 54 patients developed HCC; cumulative incidences of HCC at 1, 3 and 5years were 0.9%, 1.3% and 1.5%, respectively. Age above 50years (adjusted hazard ratio 4.31, 95% confidence interval 1.72-10.84; p=0.002) and male gender (2.47, 1.24-4.91; p=0.01) were two independent risk factors of HCC. Female patients aged ⩽50years (n=545) had zero risk of HCC within 5years of follow-up. Male patients aged ⩽50years (n=769), female patients aged >50years (n=1,149) and male patients aged >50years (n=2,105) had a 5-year cumulative incidence of HCC 0.7%, 1.0% and 2.5%, respectively. Similar findings were observed in patients with spontaneous and antiviral treatment-induced HBsAg seroclearance., Conclusions: Female patients aged 50years or below have zero risk of HCC after HBsAg seroclearance, whereas female patients aged above 50years and all male patients are still at risk of HCC. Lay summary: We investigated 4,568 patients with hepatitis B surface antigen (HBsAg) seroclearance. Female patients aged 50years or below have zero risk of hepatocellular carcinoma (HCC) after HBsAg seroclearance, whereas female patients aged above 50years and all male patients are still at risk of HCC., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: It is uncertain if nucleos(t)ide analogue (NA)-induced hepatitis B surface antigen (HBsAg) seroclearance is durable. We investigated the impact of hepatitis B surface antibody (anti-HBs) and duration of consolidation antiviral therapy on the durability of HBsAg seroclearance., Methods: A territory-wide cohort study was conducted using data from the Hospital Authority, Hong Kong. We identified all subjects with positive HBsAg between January 1, 2000 and August 31, 2016. NA use, liver biochemistries, serial HBsAg and anti-HBs results were retrieved. The primary endpoint was confirmed HBsAg seroclearance, defined least two negative HBsAg test results, with the last HBsAg test being negative in patients with chronic hepatitis B (CHB)., Results: A total of 4,080 CHB patients were included for analysis. In patients with spontaneous HBsAg seroclearance (n=3,563), 1,771 patients (49.7%) had confirmed HBsAg seroclearance and 75 patients (2.1%) had HBsAg seroreversion. In patients with NA-induced HBsAg seroclearance (n=475), 320 patients (67.4%) had confirmed HBsAg seroclearance and 14 patients (2.9%) had HBsAg seroreversion. The five-year cumulative probability of confirmed HBsAg seroclearance was comparable in patients with spontaneous and NA-induced HBsAg seroclearance (88.1% vs. 92.2%; Log-rank test, p=0.964); it was also similar in patients with or without anti-HBs in NA-treated patients (95.4% vs. 95.5%, Log-rank test, p=0.602). HBsAg seroreversion was only observed in 3 (2.0%) patients who had received consolidation therapy for 6-12months and none of those who had received it for ≥12months., Conclusions: NA-induced HBsAg seroclearance is as durable as spontaneous HBsAg seroclearance. NA-treated patients may not need to have positive anti-HBs before stopping treatment. Longer consolidation NA treatment may result in more durable HBsAg seroclearance., Lay Summary: We investigated 4,080 patients with hepatitis B surface antigen (HBsAg) seroclearance. HBsAg seroreversion occurred in 2.1% of patients with spontaneous and 2.9% of those with nucleos(t)ide analogues-induced HBsAg seroclearance., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Finite treatment with nucleos(t)ide analogues (NAs) remains a great challenge for chronic hepatitis B in the clinic. This study aimed to investigate the relationship between intrahepatic quasispecies heterogeneity and the NAs off-treatment outcomes in a prospective cohort. Eighteen HBeAg-positive patients with chronic hepatitis B who achieved the cessation criteria underwent liver biopsy, and stopped treatment thereafter. Patients were followed up prospectively for 1 year. The reverse transcriptase (RT) gene of intrahepatic hepatitis B virus (HBV) was cloned and sequenced. Intrahepatic quasispecies heterogeneity and specific gene mutations were analysed using bioinformatic methods. Ten patients achieved sustained response, and eight patients developed viral relapse. The intrahepatic quasispecies Shannon entropy and nucleotide diversity within either RT or the surface (S) region of patients with sustained response were significantly higher (p < 0.05) than those of patients who had a viral relapse. Intrahepatic quasispecies Shannon entropy at the nucleotide level predicted the sustained off-treatment response (area under receiver operating characteristics curve 0.925; 95% CI 0.807-1.000; p 0.003). More positive selection sites and N-glycosylation mutations within the S region were found in patients with sustained response than in the patients with viral relapse (p < 0.01). Most of the positive selection sites in patients with sustained response were located in reported HLA-I-restricted or HLA-II-restricted epitopes. Intrahepatic quasispecies heterogeneity at the end of treatment was correlated with off-treatment outcomes in HBeAg-positive patients with chronic hepatitis B. More immune escape mutations were found within the S region in patients with sustained response. The higher intrahepatic quasispecies heterogeneity indicated a more robust immune control over HBV, which in turn maintained a sustained response after withdrawal of NAs., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response., Methods: In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months., Results: Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm., Conclusions: These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients., (Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)