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]

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]