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BackgroundComputerized medical records (CMR) are used in most Australian general practices. Although CMRs have the capacity to amalgamate and provide data to the clinician about their standard of care, there is little research on the way in which they may be used to support clinical governance: the process of ensuring quality and accountability that incorporates the obligation that patients are treated according to best evidence. ObjectiveThe objective of this study was to explore the capability, capacity, and acceptability of CMRs to support clinical governance. MethodsWe conducted a realist review of the role of seven CMR systems in implementing clinical governance, developing a four-level maturity model for the CMR. We took Australian primary care as the context, CMR to be the mechanism, and looked at outcomes for individual patients, localities, and for the population in terms of known evidence-based surrogates or true outcome measures. ResultsThe lack of standardization of CMRs makes national and international benchmarking challenging. The use of the CMR was largely at level two of our maturity model, indicating a relatively simple system in which most of the process takes place outside of the CMR, and which has little capacity to support benchmarking, practice comparisons, and population-level activities. Although national standards for coding and projects for record access are proposed, they are not operationalized. ConclusionsThe current CMR systems can support clinical governance activities; however, unless the standardization and data quality issues are addressed, it will not be possible for current systems to work at higher levels.

Background and Aims: Accurate biomarkers to predict outcomes following discontinuation of nucleos(t)ide analogue (NA) therapy are needed. We evaluated serum hepatitis B core-related antigen (HBcrAg) level as a biomarker for predicting outcomes after NA discontinuation., Methods: Patients with HBeAg-negative chronic hepatitis B (CHB) without cirrhosis were enrolled in a prospective trial evaluating clinical outcomes until 96 weeks after NA discontinuation. End of treatment (EOT) and off-treatment levels of serum HBcrAg, HBsAg, HBV RNA and HBV DNA were used to predict key clinical outcomes including hepatitis flare (ALT ≥5 × ULN and HBV DNA > 2000 IU/mL). The SCALE-B score was calculated for the purposes of model validation., Results: HBcrAg was tested amongst 65 participants. The median age was 54 years, 54% were male and 83% were Asian. HBcrAg was detectable in 86% patients. HBcrAg level ≥4 log U/mL at EOT was predictive of hepatitis flare [8/10 (80%) vs. 17/55 (31%), p = .001]. The presence of either HBcrAg ≥4 log U/mL or detectable HBV RNA at EOT predicted for both biochemical relapse and hepatitis flare. The SCALE-B model at EOT predicted for virological relapse, biochemical relapse, hepatitis flare and HBsAg loss in this cohort. An increase in the serum HBcrAg level off-treatment was also associated with hepatitis flare. No participant with EOT HBcrAg level ≥4 log U/mL achieved HBsAg loss., Conclusions: High levels of serum HBcrAg predict for hepatitis flare after stopping NA therapy and low likelihood of HBsAg loss at week 96. People with high levels of serum HBcrAg are not suitable candidates for NA discontinuation., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background and Aims: HBV RNA in peripheral blood reflects HBV cccDNA transcriptional activity and may predict clinical outcomes. The prospective Melbourne HBV-STOP trial studied nucleot(s)ide analog discontinuation in HBeAg-negative non-cirrhotic participants with long-term virological suppression. Ninety-six weeks after stopping treatment, the proportion of participants with virological relapse (HBV DNA > 2000 IU/mL), biochemical relapse (ALT > 2 × ULN and HBV DNA > 2000 IU/mL), or hepatitis flare (ALT > 5 × ULN and HBV DNA > 2000 IU/mL) was 89%, 58%, and 38%, respectively. We evaluated the ability of serum HBV RNA levels to predict these outcomes., Approach Results: HBV RNA levels were measured using the Roche cobas 6800/8800 HBV RNA Investigational Assay. Sixty-five participants had baseline and longitudinal off-treatment specimens available for RNA testing. HBV RNA was detectable at baseline in 25% of participants and was associated with a higher risk of biochemical relapse (81% vs. 51%, p value 0.04) and hepatitis flare (63% vs. 31%, p value 0.04). Participants who had undetectable serum HBV RNA as well as HBsAg ≤ 100 IU/mL at baseline were less likely to experience virological relapse (4 of 9, 44%) than participants with detectable HBV RNA and HBsAg level > 100 IU/mL (15/15, 100%; p value 0.0009). Off-treatment levels of HBV RNA were correlated with HBV DNA and were associated with the risk of hepatitis flare., Conclusions: Serum HBV RNA may be a useful biomarker for guiding clinical decision-making before stopping nucleot(s)ide analog therapy. Baseline HBV RNA and HBsAg levels are associated with the risk of clinical relapse, hepatitis flare, and disease remission off-treatment., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: We evaluated the patterns of peripheral Toll-like receptor (TLR) signaling activity and the expression of TLRs and natural killer (NK) cell activation in a cohort of patients experiencing severe hepatitis flares after stopping nucleot(s)ide analogues (NAs) therapy., Methods: Samples were collected longitudinally from patients with chronic hepatitis B who were enrolled in a prospective study of NA discontinuation. Patients experiencing hepatitis flares were compared with patients with normal alanine aminotransferase. Peripheral blood mononuclear cells (PBMCs) were stimulated with TLR ligands and cytokine secretion in the cell culture supernatant measured. Expression of TLR2/4, NKG2D, NKp46, and triggering receptor expressed on myeloid cells 1 (TREM-1) on monocytes, NK, and NK-T cells was measured., Results: Seventeen patients with severe reactivation hepatitis flares were compared to 12 nonflare patients. Hepatitis flares were associated with increased activity of TLR2-8 and TLR9 signaling in PBMCs at the time of peak flare compared to baseline. Hepatitis flares were also associated with (1) upregulation of TLR2 and (2) TREM-1 receptor expression on NK. There were no differences at baseline between flare patients and nonflare patients., Conclusions: Hepatitis flares off NA therapy have a significant innate inflammatory response with upregulation of TLR signaling on peripheral monocytes and TLR2 and TREM-1 expression on NK cells. This implicates the innate immune system in the immunopathogenesis of hepatitis B flares., Competing Interests: Potential conflicts of interest. K. V. received speaker fees from Gilead and consulting fees from Antios Pharmaceuticals. K. V. is on the Advisory Board for Gilead and ViiV Health Care; A. J. T. received funding from Roche Diagnostics, which did not support the current work. A. J. T. received speaker fees from Gilead Sciences and is on their Advisory Board; P. A. R. is an executive for the Australian Centre for HIV and Hepatitis Virology and the International Coalition to Eliminate Hepatitis B Virus; G. M. received funding from Gilead Sciences, Abbvie, and ViiV Health Care. G. M. received consulting fees from Astra Zeneca and speaker fees from Janssen. G. M. is on the Gilead Advisory Board and has a leadership role in ASHM; M. S. received funding from Mallinckrodt; M. C. N. is a member for the board of directors of ANZAC Research Institute; S. I. S. received funding from Gilead, Abbvie, BMS, MSD, Eisai, Astra Zeneca, CSL Behring, Cheisi, Roche, Pfizer, and Norgine. S. I. S. has leadership roles in The Liver Foundation, GESA, and APASL; A. J. N. received speaker fees from Astra Zeneca, Roche, and Eisai. A. J. N. is on the Ipsen Advisory Board; J. S. L. is on the Advisory Board for Gilead, Abbvie, and Bayer. J. S. L. has a leadership role in GESA; M. T. L. received funding from Gilead Sciences and Abbvie. M. T. L. received speaker fees from Gilead and Falk. M. T. L. is on the Advisory Board for Abbvie, Gilead, and Ipsen. M. T. L. has a leadership role in GESA. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Sustained virological suppression and hepatitis B surface antigen (HBsAg) loss have been described after nucleot(s)ide analogue (NA) discontinuation for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We performed a meta-analysis of the clinical outcomes after NA discontinuation for HBeAg-negative CHB., Methods: Studies involving NA cessation in HBeAg-negative CHB individuals with a median follow-up of ≥12 months were included. Participants were HBeAg-negative at the time of NA initiation. Random effects meta-analyses were performed for the following clinical outcomes: (1) virological relapse (VR) at 6 and 12 months; (2) clinical relapse (CR) at 6 and 12 months and (3) HBsAg loss. Effect of other variables was estimated using subgroup analysis and meta-regression. Studies including patients stopping entecavir (ETV) and/or tenofovir disoproxil fumarate (TDF) were considered separately to studies including patients stopping older generation NA., Results: N=37 studies met inclusion criteria. Cumulative incidence of VR and CR after stopping ETV/TDF was 44% and 17% at 6 months and 63% and 35% at 12 months. Similar relapse rates were observed after stopping older NAs. Among patients stopping ETV/TDF, TDF cessation was associated with increased CR rates at 6 months versus ETV. There was an association between follow-up ≥4 years and HBsAg loss rates when stopping older NAs. Hepatic decompensation and hepatocellular carcinoma were rare but occurred more frequently in studies including cirrhotic individuals., Conclusion: VR is common after NA discontinuation, however, CR was only seen in one-third of patients at 12 months. Stopping NA therapy can be followed by HBsAg clearance, and rates are higher with longer follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Current guidelines recommend long-term nucleot(s)ide analogue (NA) therapy for patients with HBeAg-negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss., Methods: We performed a prospective multi-centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg-negative CHB, the absence of cirrhosis and HBVDNA5× ULN occurred in 35 (32%); ALT flares were not associated with HBsAg loss. There were no unexpected safety issues., Conclusion: Virological reactivation was very common after stopping NA therapy and occurred earlier after stopping TDF versus ETV. The majority of patients had ALT <2× ULN at week 96, but only one-third achieved disease remission and HBsAg loss was rare. Very low HBsAg levels at baseline were uncommon but predicted for HBsAg loss and disease remission., (© 2022 John Wiley & Sons Ltd.)

Background: International guidelines recommend screening for hepatitis B virus (HBV) infection prior to administration of rituximab, due to high risk of HBV reactivation in at-risk patients., Aims: To determine: (i) adherence to the South Australian (SA) protocol for HBV screening; (ii) HBV prevalence in patients receiving rituximab; and (iii) outcomes of patients at risk of HBV reactivation., Methods: All patients commenced on rituximab at the six major SA public hospitals during a 12-month period were included in the study. Adherence was assessed by documentation of both hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) prior to initiation of rituximab. Patients were observed for a minimum of 6 months following rituximab initiation., Results: Four hundred and thirty eight patients were included in the study. The main indication for rituximab therapy was haematological malignancy (76.0%). Two hundred and nine (47.7%) failed to receive appropriate HBV screening, 86 (19.6%) had neither HBsAg nor HBcAb performed, and 119 (27.2%) had only HBsAg performed. The identified prevalence of at-risk cases (either HBsAg- or HBcAb-positive) within the study population was 4.6% (20/438 cases). One case of HBV reactivation was identified, but none led to acute liver failure, transplantation or death., Conclusions: Poor adherence to HBV screening protocols suggests the need for targeted clinician education and system redesign. While the rate of reactivation was low, the prevalence of at-risk patients in this population was high and justifies further initiatives to increase adherence rates to HBV screening pre-rituximab., (© 2018 Royal Australasian College of Physicians.)