Utilisation of hepatocellular carcinoma screening in Australians at risk of hepatitis B virus-related carcinoma and prescribed anti-viral therapy.

AIMS AND OBJECTIVES: To investigate hepatocellular carcinoma screening utilisation and factors associated with utilisation among patients prescribed hepatitis B virus anti-viral therapy and at risk of hepatocellular carcinoma. BACKGROUND: The incidence of hepatocellular carcinoma has increased in Australia over the past three decades with chronic hepatitis B virus infection a major contributor. hepatocellular carcinoma surveillance programs aim to detect cancers early enabling curative treatment options, longer survival and longer times to recurrence. DESIGN: Multi-site cross-sectional survey. METHODS: An online study questionnaire was administered to eligible participants attending three Sydney tertiary hospitals. Data were grouped into six mutually exclusive hepatocellular carcinoma risk factor categories as per American Association for the Study of Liver Diseases guidelines. All analyses were undertaken in STATA. Logistic regression was used to assess the associations between covariates and screening utilisation. Multivariate models described were assessed using the Hosmer-Lemeshow goodness of fit. RESULTS: Of the 177 participants, 137 (77.4%) self-reported that US had been performed in the last six months. Awareness that screening should be performed and knowing the correct frequency of US screening were independently associated with screening utilisation. Participants who knew that screening should be undertaken were three times more likely to have had pretreatment education or were prescribed hepatitis B virus anti-viral treatment for >4 years. Participants reporting a family history of hepatocellular carcinoma were less likely to know that screening should be undertaken every 6 months. CONCLUSION: While utilisation of hepatocellular carcinoma surveillance programs was higher in this study than in previous reports, strategies to further improve surveillance remain necessary. RELEVANCE TO CLINICAL PRACTICE: Findings from this research form the basis for proposing strategies to improve utilisation of hepatocellular carcinoma screening, inform hepatitis B virus-related clinical practice and for the delivery of care and nursing education to people receiving hepatitis B virus anti-viral therapy and at risk of developing hepatocellular carcinoma.

Factors associated with non-adherence to HBV antiviral therapy.

BACKGROUND: HBV antiviral therapy has the potential to reduce the burden of HBV-related liver disease by suppressing HBV DNA replication to undetectable levels, reducing the progression of liver fibrosis and reducing the risk of hepatocellular carcinoma (HCC) development. Treatment outcomes and long-term benefits require adherence to medication regimens. This study aimed to identify the prevalence and factors associated with non-adherence to antiviral therapy. METHODS: A cross-sectional survey of patients receiving HBV antiviral therapies was conducted in three Sydney hospitals. Participants were asked to complete an online questionnaire. Logistic regression was used to assess the associations between non-adherence (defined as missing more than 1 day of medication in the last 30 days) and demographic, socio-economic, disease, treatment, health-care system and individual-related factors. RESULTS: Of the 277 participants, 66 (23.8%) were non-adherent, missing a mean 1.7 days of medication (sd 4.8) in the last 30 days. In multivariate analysis, non-adherent behaviour declined with age (odds ratio [OR] 0.9, 95% CI 0.97, 0.99; P<0.013). Participants who reported having no established routine to take their medication (OR 5.0, 95% CI 1.4, 17.4; P<0.012) and having inadequate health literacy (OR 2.7, 95% CI 1.3, 5.5; P<0.007) were more likely to be non-adherent. CONCLUSIONS: Almost a quarter of participants in the current study were non-adherent. Adherence is potentially modifiable through person-centred education, collaborative models of patient care and interventions designed to improve health literacy and establish medication routines. Findings have the potential to improve health service delivery to patients at risk of non-adherence to HBV antiviral therapy.

Factors associated with HBV virological breakthrough.

BACKGROUND: Little is known about non-adherence to HBV therapy. This study aimed to investigate the relationship between self-reported missed days of antiviral therapy and HBV virological breakthrough and factors associated with virological breakthrough. METHODS: A cross-sectional survey of 211 HBV patients receiving oral antiviral therapies was undertaken at three tertiary hospitals in Sydney, Australia. Associations between 0 to >6 missed days in the last 30 days and virological breakthrough (defined as >10-fold rise in serum HBV DNA above nadir or after achieving virological response in the last 12 months) were examined. Logistic regression analyses determined the number of missed days most strongly associated with virological breakthrough and the associated factors. We report odds ratios (ORs) and relative risks (RRs). RESULTS: Of the 204, 32 participants (15.6%) had quantifiable HBV DNA levels (>20 IU/ml); 15 (46.8%) of them experienced virological breakthrough. Participants reported never missing medication (n=130, 63.7%) or missing 1 day (n=23, 11.3%), >1 day (n=23, 11.3%), 2-6 days (n=15, 7.3%) and >6 days (n=13, 6.4%). The most discriminating definition of non-adherence was missing >1 day of medication (RR=8.3; OR=10.2, 95% CI 3.1, 33.8, receiver operating characteristic curve 0.76). Factors independently associated with virological breakthrough included non-adherence (OR=9.0, 95% CI 2.5, 31.9) diagnosed with HBV ≤14 years (OR=5.3, 95% CI 1.0, 26.2) and age ≤47 years (OR=5.4, 95% CI 1.1, 26.9). CONCLUSIONS: Results provide an evidence-based definition of non-adherence to inform clinical practice and provide a basis for key patient education messages. Closer monitoring of groups at risk of viral breakthrough is required.

Efficacy and safety of tenofovir disoproxil fumarate in pregnancy to prevent perinatal transmission of hepatitis B virus.

BACKGROUND & AIMS: Perinatal transmission of hepatitis B virus still occurs despite immunoprophylaxis in approximately 9% of children from highly viraemic mothers. Antiviral therapy in this setting has been suggested, however with limited evidence to direct agent choice. METHODS: We conducted a multi-centre, prospective, opt-in observational study of antiviral safety and efficacy in pregnant women with high viral load (>7 log IU/ml); lamivudine was used from 2007 to 2010 and tenofovir disoproxil fumarate (TDF) from late 2010. Outcomes of treated and untreated cohorts were compared. RESULTS: 120 women with 130 pregnancies used TDF (58), lamivudine (52 including four who switched due to TDF intolerance) and no therapy (20). 96% were HBeAg positive, with baseline viral load mean 7.8 log IU/ml (±0.72) and ALT median 25 U/L (18.75-33). Duration of antiviral theraphy before birth was mean 58 days (±19) TDF and 53 (±14) lamivudine. Viral load declined by 3.64 log IU/ml (±0.9) TDF and 2.81 log IU/ml (±1.33) lamivudine. Virologic failure (birth viral load >7 IU/ml) occurred in 3% and 18% respectively. Congenital abnormality rate and neonatal growth centiles were similar across cohorts. Perinatal transmission reduced significantly to 2% and 0% in TDF and lamivudine cohorts, compared with 20% in untreated. CONCLUSIONS: TDF in this setting is safe, effective and more potent than lamivudine. Antiviral therapy did not adversely impact obstetric or infant parameters. More TDF intolerance occurred than expected. Perinatal transmission was significantly reduced in antiviral therapy cohorts.