Diverticulosis morphology is associated with risk of diverticulitis.

The size, number and distribution of diverticula vary greatly in patients with diverticulosis. We aimed to study the association between the morphology of diverticulosis assessed on colonoscopy and the risk of diverticulitis. We performed a retrospective, case-control study of cases with a history of diverticulitis and controls with diverticulosis without diverticulitis matched on sex, age (within 5 years) and year of colonoscopy. Diverticulosis characteristics were obtained from endoscopy reports and were categorized according to severity, extent, number and size. We used conditional logistic regression on matched pairs to calculate the odds of diverticulitis among patients with diverticulosis according to differing morphologic characteristics. We identified 85 cases with computed tomography-documented diverticulitis and 85 matched controls with diverticulosis without a diagnosis of diverticulitis. In cases, 60% had left-sided only diverticulosis, 2% had right-sided only and 38% had both right and left-sided diverticulosis; whereas in controls, the distribution was 53%, 18% and 29%, respectively. Cases were more likely to have large diverticula [odds ratio (OR), 3.33; 95% confidence interval (CI), 1.30-8.56 for left colon only and 1.89, 95% CI, 0.78-4.57 for both right and left]. Similarly, when the severity of diverticulosis was compared between the groups, cases were more likely to have moderate or severe diverticulosis (OR, 3.44; 95% CI, 1.51-7.84 for moderate and OR, 8.87; 95% CI, 2.98-26.37 for severe). Diverticulitis cases were more likely to have large diverticula and severe diverticulosis when compared to controls suggesting that size and severity are novel risk factors for diverticulitis.

Temporal change in aetiology and clinical characteristics of hepatocellular carcinoma in a large cohort of patients in New South Wales, Australia.

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.

Smoking and Alcohol Consumption and Risk of Incident Diverticulitis in Women.

BACKGROUND & AIMS: Much of what is known about the effects of alcohol and tobacco use on diverticular disease derives from studies of asymptomatic diverticulosis or complicated diverticulitis. We examined smoking and alcohol consumption and risk of incident diverticulitis in a large cohort of women. METHODS: We conducted a prospective study of 84,232 women in the Nurses' Health Study II (NHS II) who were 39-52 years old and without known diverticulitis at baseline in 2003. Smoking was ascertained every 2 years and alcohol use every 4 years. We used Cox proportional hazards regression to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 1,139,660 person-years of follow up, we identified 3018 incident cases of diverticulitis. After adjustment for other risk factors, current (HR, 1.20; 95% CI, 1.04-1.39) and past smoking (HR, 1.20; 95% CI, 1.11-1.30) were associated with increased risk of diverticulitis when compared with never smokers. Women who consumed ≥30 g/d of alcohol had a multivariate HR of 1.26 (95% CI, 1.05-1.50) when compared with women who did not drink. A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥15 g/d of alcohol were at highest risk of diverticulitis (multivariate HR, 1.60; 95% CI, 1.16-2.21), compared with participants who never smoked and reported no alcohol use. CONCLUSIONS: In this large prospective study of women, smoking and alcohol consumption were associated with an increased risk of incident diverticulitis. These data highlight additional modifiable risk factors for diverticulitis that may aid in prevention.

Broadening and strengthening the health providers caring for patients with chronic hepatitis C may improve continuity of care.

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.

Baseline serum HBV RNA is associated with the risk of hepatitis flare after stopping nucleoside analog therapy in HBeAg-negative participants.

BACKGROUND AND AIMS: HBV RNA in peripheral blood reflects HBV cccDNA transcriptional activity and may predict clinical outcomes. The prospective Melbourne HBV-STOP trial studied nucleot(s)ide analog discontinuation in HBeAg-negative non-cirrhotic participants with long-term virological suppression. Ninety-six weeks after stopping treatment, the proportion of participants with virological relapse (HBV DNA > 2000 IU/mL), biochemical relapse (ALT > 2 × ULN and HBV DNA > 2000 IU/mL), or hepatitis flare (ALT > 5 × ULN and HBV DNA > 2000 IU/mL) was 89%, 58%, and 38%, respectively. We evaluated the ability of serum HBV RNA levels to predict these outcomes. APPROACH RESULTS: HBV RNA levels were measured using the Roche cobas 6800/8800 HBV RNA Investigational Assay. Sixty-five participants had baseline and longitudinal off-treatment specimens available for RNA testing. HBV RNA was detectable at baseline in 25% of participants and was associated with a higher risk of biochemical relapse (81% vs. 51%, p value 0.04) and hepatitis flare (63% vs. 31%, p value 0.04). Participants who had undetectable serum HBV RNA as well as HBsAg ≤ 100 IU/mL at baseline were less likely to experience virological relapse (4 of 9, 44%) than participants with detectable HBV RNA and HBsAg level > 100 IU/mL (15/15, 100%; p value 0.0009). Off-treatment levels of HBV RNA were correlated with HBV DNA and were associated with the risk of hepatitis flare. CONCLUSIONS: Serum HBV RNA may be a useful biomarker for guiding clinical decision-making before stopping nucleot(s)ide analog therapy. Baseline HBV RNA and HBsAg levels are associated with the risk of clinical relapse, hepatitis flare, and disease remission off-treatment.

Frailty predicts mortality in patients with upper gastrointestinal bleed: a prospective cohort study.

BACKGROUND AND AIM: Evidence on the impact of frailty in patients with upper gastrointestinal bleed (UGIB) is limited. This study aims to define the role of frailty as defined by Canadian Study of Health and Aging clinical frailty scale (CSHA-CFS) in predicting mortality in UGIB. METHODS: A prospective single-center cohort study was conducted over 21 months on all consecutive patients with UGIB. Data on demographics, lab parameters, Glasgow Blatchford score, CSHA-CFS, Charlson Comorbidity Index, and AIMS65 score was recorded. The primary outcome was all-cause inpatient mortality. The secondary outcomes were all-cause 30-day mortality, 30-day rebleeding, 30-day readmission, hospital length of stay (LoS), intensive care unit (ICU) admission, need for repeat endoscopy, and need for blood transfusion. The data were evaluated using univariate and multivariate analysis. RESULTS: There were 298 eligible patients, of which 63% were males, median age was 68 years, 44% were from non-English-speaking background, and 72% had major comorbidities. The all-cause inpatient and 30-day mortality were 9.4% and 10.7%, respectively. In the multivariate analysis, CHSA-CFS was the independent predictor of all-cause inpatient mortality (OR 1.66; 95% CI 1.13-2.143; P = 0.010) and all-cause 30-day mortality (OR 1.83; 95% CI 1.26-2.67; P = 0.002). CHSA-CFS was not a significant predictor of 30-day rebleed, 30-day readmission, ICU admission, hospital LoS, or need for blood transfusion. CONCLUSION: Frailty is an important independent predictor of mortality in patients with UGIB. Frailty assessment can guide clinical decision making and allow targeting of health-care resource (Australia/New Zealand Clinical Trial Registry number: ACTRN12622000821796).

Predicting hepatitis B e Antigen seroconversion after pregnancy-The SydPregScore.

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 log10 IU/mL (IQR 6.3-8.2 log10 IU/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 log10 IU/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 log10 IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression.

Routine screening of emergency admissions at risk of chronic hepatitis (SEARCH) identifies and links hepatitis B cases to care.

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.

Liver Disease and Poor Adherence Limit Hepatitis C Cure: A Real-World Australian Treatment Cohort.

BACKGROUND AND AIMS: In 2016, direct-acting antiviral (DAA) treatment for hepatitis C (HCV) became available through Australia's universal health care system, with the aim of HCV elimination. We report real-world effectiveness of DAA HCV treatment in Australia from a clinically well-informed cohort, enriched for cirrhosis and prior HCV treatment. METHODS: 3413 patients were recruited from 26 hospital liver clinics across Australia from February 2016 to June 2020. Clinical history and sustained viral response (SVR) were obtained from medical records and data linkage to the Australian Pharmaceutical Benefits Scheme. Factors associated with SVR were assessed by multivariable logistic regression (MVR). RESULTS: At recruitment, 32.2% had cirrhosis (72.9% Child Pugh class B/C), and 19.9% were treatment experienced. Of the 2,939 with data, 93.3% confirmed SVR. 137 patients received second-line therapy. Patients with cirrhosis had lower SVR rate (88.4 vs. 95.8%; p < 0.001). On MVR, failure to achieve SVR was associated with Genotype 3 (adj-OR = 0.42, 95%CI 0.29-0.61), male gender (adj-OR = 0.49, 95%CI 0.31-0.77), fair/poor adherence (adj-OR = 0.52, 95%CI 0.28-0.94), cirrhosis (adj-OR = 0.57, 95%CI 0.36-0.88), FIB-4 > 3.25 (adj-OR = 0.52, 95%CI 0.33-0.83) and MELD score ≥ 20 (adj-OR = 0.25, 95%CI 0.08-0.80). Consistent results were seen in cirrhotic sub-analysis. CONCLUSIONS: Excellent SVR rates were achieved with DAAs in this real-world cohort of patients with chronic HCV infection. More advanced liver disease and clinician impression of poor adherence were associated with HCV treatment failure. Supports to improve liver fibrosis assessment skills for non-specialist DAA prescribers in the community and to optimize patient adherence are likely to enable more effective pursuit of HCV elimination in Australia.

Finding Cases of Hepatitis C for Treatment Using Automated Screening in the Emergency Department is Effective, but What Is the Cost?

Case detection remains a major challenge for hepatitis C virus (HCV) elimination. We have previously published results from a pilot of an emergency department (ED) semiautomated screening program, SEARCH; Screening Emergency Admissions at Risk of Chronic HCV. Several refinements to SEARCH have been developed to streamline and reduce cost. All direct costs of HCV testing until direct-acting antiviral (DAA) therapy initiation were calculated. Cost was assessed in 2018 Australian Dollars. A cost analysis of the initial program and refinements are presented. Sensitivity analysis to understand impact of variation in staff time, laboratory test cost, changes in HCV antibody (Ab) prevalence, RNA positivity percentage, and rate of linkage to care was conducted. Impact of refinements (SEARCH (2)) to cost is presented. The total SEARCH pilot, testing 5000 patients was estimated to cost $110,549.52 (range $92,109.79-$129,581.24) comprising of $68,278.67 for HCV Ab testing, $21,568.99 for follow-up and linkage to care of positive patients and $20,701.86 to prepare HCV RNA positive patients for treatment. Internal program refinements resulted in a 25% cost reduction. Following refinements, the cost of HCV antibody screening was $8.46 per test and the total cost per positive HCV Ab, positive HCV RNA, and per treated patient were $611.77, $2,168.64, and $3,566.11, respectively. Our sensitivity analysis indicates costs per HCV case found are modest so long as HCV Ab prevalence was at least 1%. ED screening is an affordable strategy for HCV case detection and elimination.

Monitoring quality of care in hepatocellular carcinoma: A modified Delphi consensus.

Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two-round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system-level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival.

Hepatitis B Virus Flares After Nucleot(s)ide Analogue Cessation Are Associated With Activation of Toll-Like Receptor Signaling Pathways.

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.

Lenvatinib for the treatment of hepatocellular carcinoma-a real-world multicenter Australian cohort study.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia. METHODS: We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes. RESULTS: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59-75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8-14.0) and 5.3 months (95% CI: 2.8-9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child-Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%). CONCLUSIONS: Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.

Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study.

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

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.

Stopping nucleot(s)ide analogues in non-cirrhotic HBeAg-negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels.

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.

Plasma and breast milk pharmacokinetics of tenofovir alafenamide in mothers with chronic hepatitis B infection.

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.