A qualitative exploration of enablers for hepatitis B clinical management among ethnic Chinese in Australia.

An estimated 18% of people living with chronic hepatitis B (CHB) in Australia were born in China. While guideline-based care, including regular clinical monitoring and timely treatment, prevent CHB-related cirrhosis, cancer and deaths, over three-quarters of people with CHB do not receive guideline-based care in Australia. This qualitative study aimed to identify enablers to engagement in CHB clinical management among ethnic Chinese people attending specialist care. Participants self-identified as of Chinese ethnicity and who attended specialist care for CHB clinical management were interviewed in Melbourne in 2019 (n = 30). Semi-structured interviews covered experiences of diagnosis and engagement in clinical management services, and advice for people living with CHB. Interviews were recorded with consent; data were transcribed verbatim and thematically analysed. Receiving clear information about the availability of treatment and/or the necessity of long-term clinical management were the main enablers for participants to engage in CHB clinical management. Additional enablers identified to maintain regular clinical monitoring included understanding CHB increases risks of cirrhosis and liver cancer, using viral load indicators to visualize disease status in patient-doctor communication; expectations from family, peer group and medical professionals; use of a patient recall system; availability of interpreters or multilingual doctors; and largely subsidized healthcare services. In conclusion, to support people attending clinical management for CHB, a holistic response from community, healthcare providers and the public health sector is required. There are needs for public health programmes directed to communicate (i) CHB-related complications; (ii) availability of effective and cheap treatment; and that (iii) long-term engagement with clinical management and its benefits.

The Yin and the Yang of Treatment for Chronic Hepatitis B-When to Start, When to Stop Nucleos(t)ide Analogue Therapy.

Over 257 million individuals worldwide are chronically infected with the Hepatitis B Virus (HBV). Nucleos(t)ide analogues (NAs) are the first-line treatment option for most patients. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both potent, safe antiviral agents, have a high barrier to resistance, and are now off patent. They effectively suppress HBV replication to reduce the risk of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Treatment is continued long-term in most patients, as NA therapy rarely induces HBsAg loss or functional cure. Two diverging paradigms in the treatment of chronic hepatitis B have recently emerged. First, the public health focussed "treat-all" strategy, advocating for early and lifelong antiviral therapy to minimise the risk of HCC as well as the risk of HBV transmission. In LMICs, this strategy may be cost saving compared to monitoring off treatment. Second, the concept of "stopping" NA therapy in patients with HBeAg-negative disease after long-term viral suppression, a personalised treatment strategy aiming for long-term immune control and even HBsAg loss off treatment. In this manuscript, we will briefly review the current standard of care approach to the management of hepatitis B, before discussing emerging evidence to support both the "treat-all" strategy, as well as the "stop" strategy, and how they may both have a role in the management of patients with chronic hepatitis B.

Vitamin D deficiency impacts on expression of toll-like receptor-2 and cytokine profile: a pilot study.

BACKGROUND: Vitamin D is believed to play an important role outside the endocrine system in the regulation of the immune system, and in cellular proliferation and differentiation. The aim of the study was to investigate the impact of vitamin D levels on innate immunity. METHODS: Participants for this prospective, longitudinal study were recruited amongst otherwise healthy staff of a large hospital in Victoria, Australia. Those fulfilling the inclusion criteria, including a vitamin D level of <50 nmol/L, were supplemented. Using flow cytometry, expression of the innate immune receptors TLR2, TLR4 and CD86 was measured on peripheral blood mononuclear cells (PBMCs) collected prior to vitamin D treatment and then at 1 and 3 months. Additonally, PBMCs at each timepoint were stimulated with specific TLR ligands and resultant supernatants were assayed for the cytokines TNFα, IL-6, IFN-α and IP-10. RESULTS: In participants whose vitamin D level was >100 nmol/L post supplementation (n=11), TLR2 expression on PBMCs increased significantly, with no change noted in TLR4 or CD86 expression. Stimulation of vitamin D deficient samples with TLR ligands produced a number of proinflammatory cytokines, which were significantly reduced upon vitamin D normalisation. In patients whose levels returned to a deficient level at 3 months despite ongoing low-level supplementation, an increase in the pro-inflamamtory state returned. This suggests that vitamin D may play an important role in ensuring an appropriate baseline pro-inflammatory state. CONCLUSIONS: This ex-vivo pilot study adds clinical evidence supporting a possibly important role for vitamin D in innate immunity. If confirmed, this unique clinical study has potentially significant implications for the treatment of a variety of inflammatory conditions, where achieving optimal vitamin D levels may help reduce inflammation.