Population-level interventions to improve the health outcomes of people living with hepatitis B: an Evidence Check brokered by the Sax Institute for the NSW Ministry of Health, 2022.

Background An estimated 292 million people are living with chronic hepatitis B virus (HBV) infection globally, including 223,000 people in Australia. HBV diagnosis and linkage of people living with HBV to clinical care is suboptimal in Australia, with 27% of people living with HBV undiagnosed and 77% not receiving regular HBV clinical care. This systematic review aimed to characterize population-level interventions implemented to enhance all components of HBV care cascade and analyse the effectiveness of interventions. Review questions Question 1: What population-level interventions, programs or policy approaches have been shown to be effective in reducing the incidence of hepatitis B; and that may not yet be fully rolled out or evaluated in Australia demonstrate early effectiveness, or promise, in reducing the incidence of hepatitis B? Question 2: What population-level interventions and/or programs are effective at reducing disease burden for people in the community with hepatitis B? Methods Four bibliographic databases and 21 grey literature sources were searched. Studies were eligible for inclusion if the study population included people with or at risk of chronic HBV, and the study conducted a population-level interventions to decrease HBV incidence or disease burden or to enhance any components of HBV care cascade (i.e., diagnosis, linkage to care, treatment initiation, adherence to clinical care), or HBV vaccination coverage. Studies published in the past 10 years (since January 2012), with or without comparison groups were eligible for inclusion. Studies conducting an HBV screening intervention were eligible if they reported proportion of people participating in screening, proportion of newly diagnosed HBV (participant was unaware of their HBV status), proportion of people received HBV vaccination following screening, or proportion of participants diagnosed with chronic HBV infection who were linked to HBV clinical care. Studies were excluded if study population was less than 20 participants, intervention included a pharmaceutical intervention or a hospital-based intervention, or study was implemented in limited clinical services. The records were initially screened by title and abstract. The full texts of potentially eligible records were reviewed, and eligible studies were selected for inclusion. For each study included in analysis, the study outcome and corresponding 95% confidence intervals (95%CIs) were calculated. For studies including a comparison group, odds ratio (OR) and corresponding 95%CIs were calculated. Random effect meta-analysis models were used to calculate the pooled study outcome estimates. Stratified analyses were conducted by study setting, study population, and intervention-specific characteristics. Key findings A total of 61 studies were included in the analysis. A large majority of studies (study n=48, 79%) included single-arm studies with no concurrent control, with seven (12%) randomised controlled trials, and six (10%) non-randomised controlled studies. A total of 109 interventions were evaluated in 61 included studies. On-site or outreach HBV screening and linkage to HBV clinical care coordination were the most frequent interventions, conducted in 27 and 26 studies, respectively. Question 1 We found no studies reporting HBV incidence as the study outcome. One study conducted in remote area demonstrated that an intervention including education of pregnant women and training village health volunteers enhanced coverage of HBV birth dose vaccination (93% post-intervention, vs. 81% pre-intervention), but no data of HBV incidence among infants were reported. Question 2 Study outcomes most relevant to the HBV burden for people in the community with HBV included, HBV diagnosis, linkage to HBV care, and HBV vaccination coverage. Among randomised controlled trials aimed at enhancing HBV screening, a meta-analysis was conducted including three studies which implemented an intervention including community face-to-face education focused on HBV and/or liver cancer among migrants from high HBV prevalence areas. This analysis demonstrated a significantly higher HBV testing uptake in intervention groups with the likelihood of HBV testing 3.6 times higher among those participating in education programs compared to the control groups (OR: 3.62, 95% CI 2.72, 4.88). In another analysis, including 25 studies evaluating an intervention to enhance HBV screening, a pooled estimate of 66% of participants received HBV testing following the study intervention (95%CI: 58-75%), with high heterogeneity across studies (range: 17-98%; I-square: 99.9%). A stratified analysis by HBV screening strategy demonstrated that in the studies providing participants with on-site HBV testing, the proportion receiving HBV testing (80%, 95%CI: 72-87%) was significantly higher compared to the studies referring participants to an external site for HBV testing (54%, 95%CI: 37-71%). In the studies implementing an intervention to enhance linkage of people diagnosed with HBV infection to clinical care, the interventions included different components and varied across studies. The most common component was post-test counselling followed by assistance with scheduling clinical appointments, conducted in 52% and 38% of the studies, respectively. In meta-analysis, a pooled estimate of 73% of people with HBV infection were linked to HBV clinical care (95%CI: 64-81%), with high heterogeneity across studies (range: 28-100%; I-square: 99.2%). A stratified analysis by study population demonstrated that in the studies among general population in high prevalence countries, 94% of people (95%CI: 88-100%) who received the study intervention were linked to care, significantly higher than 72% (95%CI: 61-83%) in studies among migrants from high prevalence area living in a country with low prevalence. In 19 studies, HBV vaccination uptake was assessed after an intervention, among which one study assessed birth dose vaccination among infants, one study assessed vaccination in elementary school children and 17 studies assessed vaccination in adults. Among studies assessing adult vaccination, a pooled estimate of 38% (95%CI: 21-56%) of people initiated vaccination, with high heterogeneity across studies (range: 0.5-93%; I square: 99.9%). A stratified analysis by HBV vaccination strategy demonstrated that in the studies providing on-site vaccination, the uptake was 78% (95%CI: 62-94%), significantly higher compared to 27% (95%CI: 13-42%) in studies referring participants to an external site for vaccination. Conclusion This systematic review identified a wide variety of interventions, mostly multi-component interventions, to enhance HBV screening, linkage to HBV clinical care, and HBV vaccination coverage. High heterogeneity was observed in effectiveness of interventions in all three domains of screening, linkage to care, and vaccination. Strategies identified to boost the effectiveness of interventions included providing on-site HBV testing and vaccination (versus referral for testing and vaccination) and including community education focussed on HBV or liver cancer in an HBV screening program. Further studies are needed to evaluate the effectiveness of more novel interventions (e.g., point of care testing) and interventions specifically including Indigenous populations, people who inject drugs, men who have sex with men, and people incarcerated.