Search

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. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct‐acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2‐year survival for patients receiving HCV DAA therapy. Methods: Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016–2021 were followed up for 2 years. Risky alcohol use was defined by a combination of self‐report (≥40 g/day of ethanol), physician‐reported history of problematic alcohol use, and anti‐craving medication prescription via population‐based database linkage. We examined factors associated with advanced liver fibrosis and survival using multivariable logistic and Cox regression. Results: Among 1634 patients (62.3%) with risky alcohol use, 24.6% reported consuming ≥40 g/day of alcohol, 98.3% physician‐reported problematic alcohol use; only 4.1% were dispensed naltrexone/acamprosate. One hundred and forty‐three patients with cirrhosis reported ≥40 g/day of alcohol, 6 (4.3%) were prescribed naltrexone/acamprosate. Risky alcohol use was associated with advanced fibrosis (adjusted‐odds ratio 1.69, 95% confidence interval 1.32–2.17) and patients were over‐represented for cirrhosis (45.1% vs. 25.6% in no‐risky alcohol use [p < 0.001]) and hepatocellular carcinoma (5.7% vs. 2.5% [p < 0.001]). Sustained viral response (p = 0.319) and 2‐year survival (adjusted‐hazard ratio 1.98, 95% confidence interval 0.84–4.63) after DAA therapy were not associated with risky alcohol use. Discussion and Conclusions: Risky alcohol use in HCV patients was prevalent, but did not reduce HCV cure. Treatment for alcohol dependence was low. Risky alcohol use may be under‐recognised in liver clinics. Better integration of addiction medicine into liver services and increased resourcing and addiction medicine training opportunities for hepatologists may help address this. [ABSTRACT FROM AUTHOR]

Background: Viral hepatitis, alcohol‐related liver disease (ARLD) and nonalcoholic fatty liver disease (NAFLD) are the main risk factors for hepatocellular carcinoma (HCC) in many countries. In Australia, given the access to hepatitis C virus (HCV) direct‐acting antiviral (DAA) therapy since 2016, a temporal change in HCC aetiology was hypothesized. This study evaluated the temporal change in the aetiology and characteristics of HCC in New South Wales (NSW). Methods: Patients diagnosed with HCC, admitted to three public hospitals in NSW between 2008 and 2021, were included in the analyses. We assessed the annual frequency of each HCC aetiology and the distribution of HCC characteristics in participants. Results: Among 1370 patients, the most common HCC etiologies were HCV (n = 483, 35%), ARLD (n = 452, 33%), NAFLD (n = 347, 25%) and hepatitis B virus (n = 301, 22%). The proportion of HCV‐related HCC was the highest in 2011–2016 (41%) and significantly declined to 30% in 2017–2021 (odds ratio [OR], 0.53 [95% confidence interval (CI), 0.35–0.79]; P = 0.002). The proportion of HCC diagnosed at an early stage (Barcelona Clinic Liver Cancer stage O/A) increased from 41% in 2008–2009 to 56% in 2020–2021 (OR per annum, 1.05 [95% CI, 1.02–1.08]; P = 0.002), and the proportion of patients receiving potentially curative HCC management increased from 29% in 2008–2009 to 41% in 2020–2021 (OR per annum, 1.06 [95% CI, 1.03–1.10]; P < 0.001). Conclusion: The contribution of HCV to HCC burden has been decreasing in the DAA era, suggesting the role of HCV elimination in decreasing HCC risk. Increasing frequency of less advanced HCC at diagnosis over time suggests improved HCC surveillance. [ABSTRACT FROM AUTHOR]

Background: Direct‐acting antiviral (DAA) therapies for hepatitis C virus infection (HCV) lead to excellent rates of sustained virological response (SVR). However, loss to follow‐up (LTFU) for SVR testing remains a challenge. We examine factors associated with LTFU in a real‐world setting. Methods: Adults who received DAA therapy for HCV in one of 26 centers across Australia during 2016–2021 were followed up for 2 years. Data sources included the patient medical records and the national Pharmaceutical and Medicare Benefits Schemes. Linkage to Medicare provided utilization data of other health‐care providers and re‐treatment with DAAs. LTFU was defined as no clinic attendance for SVR testing by at least 52 weeks after DAA treatment commencement. Multivariable logistic regression assessed factors associated with LTFU. Results: In 3619 patients included in the study (mean age 52.0 years; SD = 10.5), 33.6% had cirrhosis (69.4% Child–Pugh class B/C), and 19.3% had HCV treatment prior to the DAA era. Five hundred and fifteen patients (14.2%) were LTFU. HCV treatment initiation in 2017 or later (adj‐OR = 2.82, 95% confidence interval [CI] 2.25–3.54), younger age (adj‐OR = 2.63, 95% CI 1.80–3.84), Indigenous identification (adj‐OR = 1.99, 95% CI 1.23–3.21), current injection drug use or opioid replacement therapy (adj‐OR = 1.66, 95% CI 1.25–2.20), depression treatment (adj‐OR = 1.49, 95% CI 1.17–1.90), and male gender (adj‐OR = 1.31, 95% CI 1.04–1.66) were associated with LTFU. Conclusions: These findings stress the importance of strengthening the network of providers caring for patients with HCV. In particular, services targeting vulnerable groups of patients such as First Nations Peoples, youth health, and those with addiction and mental health disorders should be equipped to treat HCV. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Significant barriers exist with hepatitis B (HBV) case detection and effective linkage to care (LTC). The emergency department (ED) is a unique healthcare interaction where hepatitis screening and LTC could be achieved. We examined the efficacy and utility of automated ED HBV screening for Overseas Born (OB) patients. Methods: A novel‐automated hepatitis screening service "SEARCH" (Screening Emergency Admissions at Risk of Chronic Hepatitis) was piloted at a metropolitan hospital. A retrospective and comparative analysis of hepatitis testing during the SEARCH pilot compared to a period of routine testing was conducted. Results: During the SEARCH pilot, 4778 OB patients were tested for HBV (86% of eligible patient presentations), compared with 1.9% of eligible patients during a control period of clinician‐initiated testing. SEARCH detected 108 (2.3%) hepatitis B surface antigen positive patients including 20 (19%) in whom the diagnosis was new. Among 88 patients with known HBV, 57% were receiving medical care, 33% had become lost to follow‐up and 10% had never received HBV care. Overall, 30/88 (34%) patients with known HBV were receiving complete guideline‐based care prior to re‐engagement via SEARCH. Following SEARCH, LTC was successful achieved in 48/58 (83%) unlinked patients and 19 patients were commenced on anti‐viral therapy. New diagnoses of cirrhosis and hepatocellular carcinoma were made in five and one patient(s) respectively. Conclusions: Automated ED screening of OB patients is effective in HBV diagnosis, re‐diagnosis and LTC. Prior to SEARCH, the majority of patients were not receiving guideline‐based care. [ABSTRACT FROM AUTHOR]

Background and Aims: Achieving Hepatitis B e antigen seroconversion (HBeAg SC) at an earlier age confers a better prognosis. We examined baseline and post‐partum factors associated with HBeAg SC after pregnancy. We developed a tool, the SydPregScore, to estimate the likelihood of HBeAg SC in the years after pregnancy. Methods: A retrospective analysis of an HBeAg‐positive pregnant cohort was conducted. Variables including baseline age, parity, alanine aminotransferase level, HBV viral load, quantitative HBsAg, use of antiviral therapy and post‐partum flare were collected. Univariate and multivariate Cox regression analyses to determine predictors of HBeAg SC and develop a predictor score were performed. Results: We analysed HBeAg SC rates in 220 pregnancies to 149 HBeAg‐positive women from 2006 to 2019. At baseline, their median age was 33 (IQR 29–37), ALT 23 U/L (IQR 17–33) and viral load 8 log10IU/mL (IQR 6.3–8.2 log10IU/mL). The majority (133/198, 67.2%) received short‐course antiviral therapy to prevent mother‐to‐child transmission, and 109/192 (56.8%) had a post‐partum flare. HBeAg SC occurred in 74/220 (33.6%) after pregnancy (median follow‐up 814 days, IQR 405–1531). Multivariate analysis identified baseline viral load <8 log10IU/mL (HR 2.426 [1.224–4.809], p =.011), baseline ALT ≥2 ULN (HR 2.726 [1.299–5.721], p =.008) and age <35 (HR 2.859 [1.255–6.513], p =.012) to be positive predictors of HBeAg SC. The 'SydPreg Score' estimated the probability of HBeAg SC at 2000 days as 10%, 30%, 70% and 80% for 0, 1, 2, and 3 predictors respectively. Conclusion: The SydPreg Score allows the prediction of HBeAg SC in the years after pregnancy. Even in those without elevated ALT, age <35 and viral load <8 log10IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression. [ABSTRACT FROM AUTHOR]

Summary: Background: Antenatal antiviral therapy (AVT) is effective in preventing mother‐to‐child transmission (MTCT) in chronic hepatitis B (CHB); tenofovir disoproxil fumarate (TDF) is the preferred agent. Tenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) similar to TDF, with improved bone and renal safety. There are no data on TAF breast milk pharmacokinetics and exposure to breastfeeding infants in CHB. Aim: To assess the pharmacokinetics of TAF/TFV in breastfeeding women with CHB on TAF monotherapy. Methods: Pregnant women with CHB requiring AVT commenced TAF 25 mg daily at third trimester or postpartum. Sample collection occurred while breastfeeding and taking TAF for minimum 4 weeks. Maternal blood, breast milk and infant urine samples were collected. Drug concentrations were measured by LCMS/MS analyses using validated methods. Non‐compartmental analyses were performed to quantify the pharmacokinetic parameters. Results: Eight women provided samples. In breast milk and plasma, median TAF half‐life was 0.81 and 0.94 h, respectively, and Cmax 1.69 and 120.5 ng/ml, respectively. Median maternal breast milk to plasma (M/P) ratio of TAF was 0.029; for and TFV it was 2.809. The relative infant dose of TAF was 0.005% of maternal dose, well below safety threshold of 5–10%. TFV was detectable in three out of seven infant urine samples with median steady‐state concentration of 5 ng/ml being 300–2500 times less than reported adult steady‐state urine concentrations in those taking TAF and TDF, respectively. Conclusions: In this first pharmacokinetic study of TAF monotherapy in breastfeeding women with CHB, concentrations of TAF and TFV were low in breast milk with negligible infant exposure, supporting the use of TAF to prevent MTCT. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatitis C virus (HCV) cure with direct‐acting antiviral (DAA) therapy improves survival in patients with HCV‐related hepatocellular carcinoma (HCC). We hypothesized that HCV‐HCC survival has increased in the DAA era, more than other aetiologies of HCC. We aimed to evaluate survival following HCC diagnosis in the pre‐DAA and DAA eras, across each aetiology of HCC. Methods: Patients with HCC at three tertiary referral hospitals were included retrospectively (January 2008 to December 2019). Patients were categorized as HCV‐HCC, hepatitis B virus (HBV)‐HCC, or non‐viral HCC. For each aetiology, the risk of death following incident HCC among patients diagnosed in the DAA era (2015–2019) was compared with patients diagnosed in the pre‐DAA era (2008–2014). Results: Among 1161 patients, there were 422 (36%) patients with HCV‐HCC, 227 (20%) with HBV‐HCC, and 512 (44%) with non‐viral HCC. In adjusted analysis, the risk of death was lower in patients with HCV‐HCC diagnosed in 2015–2019, compared with patients diagnosed in 2008–2014 (adjusted hazard ratio [aHR]: 0.68; 95% confidence interval [CI]: 0.52–0.89; P = 0.005). In contrast, there was no difference in the risk of death between time periods for patients with HBV‐HCC (HR: 0.91; 95% CI: 0.64–1.29; P = 0.602) or non‐viral HCC on adjusted analysis (aHR: 0.92; 95% CI: 0.74–1.15; P = 0.476). Although patients with HBV‐HCC had better survival compared with patients with HCV‐HCC in 2008–2014 (aHR: 0.74; 95% CI: 0.55–0.98; P = 0.037), this difference disappeared in 2015–2019 (aHR: 1.26; 95% CI: 0.90–1.77; P = 0.175). Conclusions: Hepatitis C virus‐related HCC survival has increased in the DAA era, whereas adjusted survival remained stable for HBV‐HCC and non‐viral HCC. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths both globally and in Australia. Surveillance for HCC in at‐risk populations allows diagnosis at an early stage, when potentially curable. However, most Australians diagnosed with HCC die of the cancer or of liver disease. In the changing landscape of HCC management, unique challenges may lead to clinical practice variation. As a result, there is a need to identify best practice management of HCC in an Australian context. This consensus statement has been developed for health professionals involved in the care of adult patients with HCC in Australia. It is applicable to specialists, general medical practitioners, nurses, health coordinators and hospital administrators. Methods and recommendations: This statement has been developed by specialists in hepatology, radiology, surgery, oncology, palliative care, and primary care, including medical practitioners and nurses. The statement addresses four main areas relevant to HCC management: epidemiology and incidence, diagnosis, treatment, and patient management. A modified Delphi process was used to reach consensus on 31 recommendations. Principal recommendations include the adoption of surveillance strategies, use of multidisciplinary meetings, diagnosis, treatment options and patient management. Changes in management as a result of this statement: This consensus statement will simplify HCC patient management and reduce clinical variation. Ultimately, this should result in better outcomes for patients with HCC. [ABSTRACT FROM AUTHOR]

The impact of hepatitis C virus (HCV) cure on survival in patients with HCV‐related hepatocellular carcinoma (HCC) has been examined, although many studies have been subject to survivor treatment selection bias. We assessed the impact of HCV cure before HCC diagnosis on overall survival. Patients with HCV‐related HCC at three referral hospitals in Australia were included retrospectively (January 2008 to December 2019). The risk of death following HCC diagnosis among patients who achieved HCV cure before HCC diagnosis was compared to patients who were viraemic at diagnosis. Among 422 patients with HCV‐related HCC, 101 (24%) achieved HCV cure before HCC diagnosis, 37 with interferon (IFN) and 64 with direct‐acting antiviral (DAA) therapy. Patients with HCV cure were more likely to have no cirrhosis or Child‐Pugh A liver disease (83% vs. 66%, p =.002), surveillance detection (71% vs. 48%, p <.001), HCC stage O or A (64% vs. 45%, p <.001) and receive curative initial HCC management (51% vs. 28%, p <.001), compared with patients who were viraemic at diagnosis. The 5‐year overall survival was 51% in the HCV cure group and 22% in the viraemic group. In adjusted analysis, risk of death was lower in patients with HCV cure before HCC diagnosis compared with patients who were viraemic at diagnosis (adjusted hazard ratio: 0.63; 95% CI: 0.44–0.91; p =.013). Patients with HCV‐related HCC who have achieved HCV cure before HCC diagnosis have improved overall survival compared with patients who were viraemic at diagnosis. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kayes et al papers. To view these articles, visit https://doi.org/10.1111/apt.17040 [ABSTRACT FROM AUTHOR]

Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration. Such properties suggest a pro-fibrotic role for this peptidase but this hypothesis needs in vivo examination. Experimental liver injury was induced with carbon tetrachloride (CCl4) in DPP4 gene knockout (gko) mice. DPP4 gko had less liver fibrosis and inflammation and fewer B cell clusters than wild type mice in the fibrosis model. DPP4 inhibitor-treated mice also developed less liver fibrosis. DNA microarray and PCR showed that many immunoglobulin (Ig) genes and some metabolism-associated transcripts were differentially expressed in the gko strain compared with wild type. CCl4-treated DPP4 gko livers had more IgM+ and IgG+ intrahepatic lymphocytes, and fewer CD4+, IgD+ and CD21+ intrahepatic lymphocytes. These data suggest that DPP4 is pro-fibrotic in CCl4-induced liver fibrosis and that the mechanisms of DPP4 pro-fibrotic action include energy metabolism, B cells, NK cells and CD4+ cells. [ABSTRACT FROM AUTHOR]

Objective: To examine the chronic hepatitis B (CHB) assessment and management practices of general practitioners in the Sydney and South Western Sydney Local Health Districts, areas with a high prevalence of CHB, and to obtain their views on alternative models of care.Design, Setting and Participants: We used a descriptive, cross-sectional study design to survey GPs who had seen at least one patient aged 18 years or over who had been notified as having CHB to the Public Health Unit between 1 June 2012 and 31 May 2013. There were 213 eligible GPs; the response rate was 57.7%.Main Outcome Measures: The CHB assessment, management and referral practices of the GPs, and their opinions about different models of care.Results: Most GPs (78.9%) were at least reasonably confident about managing CHB. GPs were generally most comfortable with a model of care that involved initial referral to a specialist; managing CHB without specialist input or with only review by a specialised nurse practitioner were less popular.Conclusion: These results suggest that barriers, including dependence on specialist input, still hinder the appropriate assessment and management of CHB patients by GPs. Well designed and targeted support programs that include specialist support are needed if there is to be a successful shift to an increased role for GPs in the model of care for managing CHB. [ABSTRACT FROM AUTHOR]

A number of antiviral agents used against Human Immunodeficiency Virus (HIV) infection and hepatitis B virus (HBV) mono or co-infection have been associated with real nephrotoxicity (including tenofovir disoproxil fumarate (TDF), atazanavir, indinavir and lopinavir) or apparent changes in renal function (e.g. cobicistat, ritonavir, rilpivirine and dolutegravir). Patients with HIV are at higher risk of acute and chronic renal dysfunction, so baseline assessment and ongoing monitoring of renal function is an important part of routine management of patients with HIV. Given the paucity of evidence in this area, we sought to establish a consensus view on how routine monitoring could be performed in Australian patients on ART regimens, especially those involving TDF. A group of nephrologists and prescribers (an HIV physician and a hepatologist) were assembled by Gilead to discuss practical and reasonable renal management strategies for patients particularly those on TDF-based combination regimens (in the case of those with HIV-infection) or on TDF-monotherapy (in the case of HBV-mono infection). The group considered which investigations should be performed as part of routine practice, their frequency, and when specialist renal referral is warranted. The algorithm presented suggests testing for serum creatinine along with plasma phosphate and an assessment of urinary protein (rather than albumin) and glucose. Here we advocate baseline tests of renal function at initiation of therapy. If creatinine excretion inhibitors (e.g. cobicistat or rilpivirine) are used as part of the ART regimen, we suggest creatinine is rechecked at 4 weeks and this value used as the new baseline. Repeat testing is suggested at 3-monthly intervals for a year and then at least yearly thereafter if no abnormalities are detected. In patients with abnormal baseline results, renal function assessment should be performed at least 6 monthly. In HBV mono-infected patients advocate that a similar testing protocol may be logical. [ABSTRACT FROM AUTHOR]

Background: First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection.Methods: Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016-2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU.Results: Compared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger (p < 0.001), morel likely to reside in most disadvantaged (p = 0.002) and in regional/remote areas (p < 0.001), and had similar liver disease severity. Medicines for mental health conditions were most commonly dispensed among First Nations Peoples (55.2% vs. 42.8%; p = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients; p = 0.51) and 'good' adherence (90.0% vs. 86.9%, respectively; p = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients (p < 0.001). Among First Nations Peoples, younger age (adj-OR = 0.93, 95% CI 0.87-0.99) and treatment initiation in 2018-2019 vs. 2016 (adj-OR = 5.14, 95% CI 1.23-21.36) predicted LTFU, while higher fibrosis score was associated with better engagement in HCV care (adj-OR = 0.71, 95% CI 0.50-0.99).Conclusions: Our data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed. [ABSTRACT FROM AUTHOR]

Issue Addressed: Increasing the uptake of hepatitis C treatment by injecting drug users (IDUs) is a key strategy in addressing the escalating disease burden of chronic hepatitis C virus (HCV) infection in Australia. Little is known about barriers to treatment uptake among culturally diverse groups of IDUs. Indo-Chinese IDUs represent a marginalised group with high rates of incident and prevalent HCV infection.Methods: An ethnographic study was conducted to explore barriers to HCV treatment uptake experienced by Indo-Chinese IDUs and inform the development of policies and practices that promote access to treatment. Following a baseline interview, participants (n=23) received a brief intervention about HCV treatment and an offer of facilitated referral to a tertiary liver clinic. Follow-up interviews were conducted three and six months post intervention, to explore decision-making about treatment-seeking and experiences accessing the clinic.Results: While 'getting rid of' HCV was regarded as highly desirable, only three participants were assessed for treatment. For most participants, seeking treatment was not seen as feasible given social and structural barriers related to their drug use, lack of resources and support. Institutional barriers included the clinic's administrative procedures, limited flexibility and apparent reluctance to consider current IDUs suitable candidates for treatment.Conclusions: Resources and support, fexible, low threshold approaches to assessment and a willingness to provide treatment to current IDUs, would promote equitable access to treatment among these groups. [ABSTRACT FROM AUTHOR]

Issue addressed: Increasing the uptake of hepatitis C treatment by injecting drug users (IDUs) is a key strategy in addressing the escalating disease burden of chronic hepatitis C virus (HCV) infection in Australia. Little is known about barriers to treatment uptake among culturally diverse groups of IDUs. Indo-Chinese IDUs represent a marginalised group with high rates of incident and prevalent HCV infection. Methods: An ethnographic study was conducted to explore barriers to HCV treatment uptake experienced by Indo-Chinese IDUs and inform the development of policies and practices that promote access to treatment. Following a baseline interview, participants (n=23) received a brief intervention about HCV treatment and an offer of facilitated referral to a tertiary liver clinic. Follow-up interviews were conducted three and six months post intervention, to explore decision-making about treatment-seeking and experiences accessing the clinic. Results: While 'getting rid of' HCV was regarded as highly desirable, only three participants were assessed for treatment. For most participants, seeking treatment was not seen as feasible given social and structural barriers related to their drug use, lack of resources and support. Institutional barriers included the clinic's administrative procedures, limited flexibility and apparent reluctance to consider current IDUs suitable candidates for treatment. Conclusions: Resources and support, flexible, low threshold approaches to assessment and a willingness to provide treatment to current IDUs, would promote equitable access to treatment among these groups. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the rate of perinatal hepatitis B virus (HBV) transmission in Australia, along with the maternal virological factors associated with risk of transmission. The study included pregnant women attending Sydney South West Area Health Service antenatal clinics who were hepatitis B surface antigen (HBsAg) positive, and their babies. It discovered that HBV perinatal transmission is prevalent in hepatitis B "e" antigen (HBeAg)-positive mothers with very high viral loads.

The hallmarks of chronic liver diseases are chronic inflammation, cellular damage, regeneration and fibrosis. An appreciation of intrahepatic molecular expression patterns in normal and diseased liver provides clues for understanding pathogenic pathways whilst studies of the structure and function of molecules implicated in liver disease provide insights into their potential as therapeutic targets. We have examined the expression, function, molecular structure and structure-function relationships of type IV dipeptidyl aminopeptidases. In particular, the roles of CD26/DPPIV in T-cell proliferation and chemotaxis and of fibroblast activation protein in human cirrhosis are discussed. We have investigated the pathogenesis of liver disease by chracterising patterns of cytokine and growth factor expression in experimental and human cirrhosis. We have quite recently expanded this approach to use differential gene expression analyses to elucidate overall pathways of gene activation and suppression in human cirrhosis. In addition, our detailed molecular and cellular studies of the mechanisms of spontaneous liver transplant tolerance have generated novel insights into this process. This review touches on these diverse aspects of liver function and disease. [ABSTRACT FROM AUTHOR]

Examines the binding of human dipeptidyl peptidase IV by adenosine deaminase and antibodies. Inhibition of ligand binding; Modification on the biological activities for chemokines and neuropeptides; Analysis of mutation using transient transfection into monkey kidney fibroblast cells.

LINKED CONTENT This article is linked to Toyoda et al papers. To view these articles, visit https://doi.org/10.1111/apt.15490 and https://doi.org/10.1111/apt.15546. [ABSTRACT FROM AUTHOR]

Humans usually acquire Fasciola infection by eating contaminated aquatic vegetation, such as watercress. After ingestion, Fasciola metacercariae excyst in the duodenum. In contrast to other liver flukes (Clonorchis and Opisthorchis) that migrate through the ampulla of Vater and ascend the biliary tree, Fasciola metacercariae penetrate the duodenal wall, migrate through the peritoneal cavity, and enter the liver. After a period of migrating randomly through the liver parenchyma, they eventually reach the larger biliary ducts and mature into adults. We present a case that illustrates this migration route of Fasciola. After ingestion, fasciola metacercariae penetrate the duodenal wall, migrate through the peritoneal cavity and enter the liver. After a period migrating randomly through the liver parenchyma, they eventually reach the larger biliary ducts and mature into adults. We present a case that illustrates this migration route of Fasciola. [ABSTRACT FROM AUTHOR]

Viral hepatitis contributes to significant morbidity and mortality worldwide. While acute infection may be self-limiting, unrecognised chronic infection and under-utilisation of guideline-based approaches to therapy contribute to increasing rates of cirrhosis, hepatocellular carcinoma and death. Our aim was to review the current evidence for screening, diagnosis and treatment in hepatitis A to E. Evidence for this review was sourced from international and Australian guidelines and high-quality clinical trials. MEDLINE was searched using structured key word strategy and retrieved articles were reviewed methodically to inform a brief and up-to-date synopsis of hepatitis A to E. We share some of the recent developments in viral hepatitis, specifically the new therapies for hepatitis C. Direct-acting antiviral therapies are safe, well-tolerated and effective. Subsidies allow access for all Australians with most strains of hepatitis C. We outline evidence underpinning efficacy and safety of treatment for hepatitis B, while clarifying some of the nuances in the setting of pregnancy and immunosuppression. We provide a simplified concept to facilitate understanding of the five phases of hepatitis B; practical for real-world setting. Hepatitis A to E is a broad topic, not all aspects of these viruses can be covered in this short review. We provided suggestions for evidence based guidelines, which are a suitable supplement to this article. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a study by Elke Wiseman and colleagues on their 9 month virological follow-up of babies born to women who tested positive for hepatitis B surface antigen.